COMPLICATIONS OF DIALYSIS - PART 9 doc

700 Miles and Friedman
predisposition of diabetic patients to access thrombosis
in earlier reports.
F. Vascular Steal Syndromes
An arteriovenous access (particularly a brachiocephalic
access or a side-to-side radiocephalic fistula) creates a
low-pressure run-off system, which may short-circuit
blood from the palmar arch and ulnar arteries to such
a degree that a steal syndrome results. With the pre-
existing, severe medial arterial calcinosis of the ulnar
and digital arteries, which is common in diabetic di-
alysis patients (19), progressive ischemic pain leading
to dry gangrene of one or more fingers may develop
days to weeks after placement of the access. Nonheal-
ing wounds of the fingers may also be a manifestation
of vascular steal (20), and in cases of clinical uncer-
tainty, digital pressures of <50 mmHg on noninvasive
vascular studies and arteriography help to confirm the
diagnosis. In severe cases of arterial steal syndromes,
the onset may be more acute, within hours of creation
of the access, and signs of acute arterial insufficiency
such as pallor and pulselessness may be seen. Ligation
of the distal limb of the radial artery in a side-to-side
radiocephalic fistula or ligation or removal of a bra-
chiocephalic access is necessary to correct the syn-
drome. Amputation of one or more digits and even be-
low elbow amputation may sometimes be necessary.
G. Ischemic Monomelic Neuropathy
The term ischemic monomelic neuropathy was coined
in 1983 by Wilbourn (21). It is a complication of vas-
cular access seen almost exclusively in diabetic patients

(22) and refers to the development of acute pain, weak-
ness, and paralysis of the muscles of the forearm and
hand, often with sensory loss, developing immediately
after placement of an arteriovenous access, usually in
the brachiocephalic or antecubital location. The con-
dition results from diversion of the blood supply to the
nerves of the forearm and hand, the ischemic insult
being severe enough to damage nerve fibers but insuf-
ficient to produce necrosis of other tissues. Hence, un-
like in vascular steal syndromes, the radial pulse is usu-
ally present, digital pressures normal or only mildly
decreased, and necrosis, ulcers, and gangrene of the
digits are absent. The propensity to development of the
complication with brachiocephalic accesses relates to
the fact that the brachial artery constitutes the sole ar-
terial inflow to the forearm and hand and, in the ab-
sence of collateral vessels about the elbow, diversion
of all or most brachial arterial blood through a fistula
or graft results in distal ischemia. Nerve conduction
studies are helpful in diagnosing the syndrome, and
early access removal or ligation is necessary to prevent
permanent paralysis of the hand. Unfortunately, even
with prompt access closure, paralysis of the hand may
be permanent.
H. Venous Hypertension
Chronic swelling of the hand, and especially of the
thumb (‘‘sore thumb’’ syndrome), related to the pres-
ence of the distal segment of the vein used for creation
of the access, may occur in both diabetic and nondi-
abetic patients. Venous hypertension occurs in associ-

ation with venous stenosis of the access or a more
proximal stenosis at the level of the subclavian vein,
which may have been previously catheterized for tem-
porary vascular access. Ligature of the distal venous
limb of the fistula or graft will usually correct the
problem.
III. BONE DISEASE
Adynamic bone disease is a form of renal osteodystro-
phy commonly seen in diabetics, particularly those on
peritoneal dialysis (23). It is characterized by low rates
of bone turnover without excess unmineralized osteoid
and is associated with parathyroid hormone levels be-
low 100 pg/mL. Decreased osteoblast proliferation and
defective mineralization contribute to a low rate of
bone formation in diabetic rats (24), and a similar
mechanism may underlie adynamic bone disease in hu-
mans. Diabetic dialysis patients also tend to experience
higher rates of low-turnover bone disease associated
with aluminum deposition: reduced bone formation
may allow time for enhanced deposition of aluminum
on the ossification front, and within 1 year of hemo-
dialysis, aluminum deposition (usually related to use of
aluminum-containing phosphate binders) is observed
on bone surfaces in diabetics, and symptoms of bone
pain and fractures related to aluminum bone disease
may start as early as 2 years after initiation of hemo-
dialysis (25). Aluminum bone disease may also be un-
masked or accelerated after parathyroidectomy. Alu-
minum-containing phosphate binders should therefore
be avoided in diabetics, and all diabetics with bone

pain and/or fractures should have plasma aluminum
levels measured before and after a single infusion of
desferrioxamine. Aluminum-associated bone disease in
Complications of Dialysis in Diabetic Patients 701
hemodialyzed diabetics responds to a regimen of vita-
min D, calcium, and desferrioxamine.
IV. DIABETIC RETINOPATHY
Visual loss in diabetic ESRD patients is most com-
monly related to proliferative retinopathy with associ-
ated vitreous hemorrhage and retinal detachment but
may also result from macular edema, glaucoma, cata-
racts, and corneal disease. The presence of proliferative
retinopathy is correlated with age of onset and duration
of diabetes, glycemic control, and degree of blood pres-
sure control. Heparin use during hemodialysis is no
longer considered a significant contributor to progres-
sion of diabetic retinopathy or to intraocular hemor-
rhage. No reports definitively link heparin use on di-
alysis with progression of diabetic retinopathy or visual
loss. Indeed, in a study of 112 diabetics followed for
20 months, progression of retinopathy was shown to be
independent of dialysis modality (hemo- or peritoneal
dialysis), while the significant correlation between
blood pressure control and vision preservation was re-
inforced (26). In addition, because of the rarity (0.05%)
of intraocular hemorrhage in diabetics treated with
thrombolytic agents, diabetic retinopathy is not consid-
ered a contraindication to thrombolytic therapy for
acute myocardial infarction (27). Focal or panretinal
laser photocoagulation can reduce the incidence of se-

rious visual loss in patients with proliferative retinop-
athy, and vitrectomy may restore vision in patients with
vitreous hemorrhage.
V. UNDERNUTRITION
Malnutrition is frequently seen in diabetic hemodialysis
patients, particularly in the presence of intercurrent ill-
nesses. Causes of malnutrition in diabetics on hemo-
dialysis include (a) poor glycemic control leading to
gluconeogenesis and catabolism of muscle, (b) gastro-
paresis leading to nausea and vomiting, (c) diabetic di-
arrhea, and (d) underdialysis related to difficulties with
vascular access or to repeated early termination of di-
alysis sessions caused by recurrent hypotension (28). A
diet of 25–30 kcal/kg/day, with 50% of the calories
coming from complex carbohydrates, and protein con-
tent of 1.3–1.5 g/kg/day is recommended for hemodi-
alyzed diabetics. In diabetic hemodialysis patients who
develop intercurrent illnesses (e.g., sepsis), early and
intensive nutritional support with enteral or peripheral
parenteral nutrition is necessary. Dialysate fluid should
contain at least 200 mg/dL glucose because use of glu-
cose-free dialysate results in rapid glucose loss, hypo-
glycemia, and production of acute starvation with aci-
dosis and hyperkalemia (29).
VI. HYPERGLYCEMIA
Insulin requirements after beginning maintenance he-
modialysis vary (30), and it is important to teach pa-
tients home glucose monitoring so as to determine
changing insulin requirements. Most diabetic patients
with ESRD experience reduction in insulin needs due

to decreased renal excretion and catabolism of injected
and endogenous insulin. Many diabetics who start di-
alysis will no longer need insulin, and some type 2
diabetics previously on insulin may achieve glycemic
control with a small dose of a short-acting sulfonylurea
drug such as glyburide or glipizide, or indeed with no
hypoglycemic medications at all. The new oral hypo-
glycemic agent troglitazone has been approved for use
in type 2 diabetics to decrease insulin requirements or
for use alone or in combination with a sulfonylurea to
prevent need for insulin therapy. The drug works by
increasing the sensitivity of peripheral tissues to insulin
and decreasing hepatic glucose production. It under-
goes hepatic metabolism and hence does not require
dose reduction in renal failure. It is effective in only
50% of treated patients, however, and produces mild
liver injury in 1.9% of patients and sporadic cases of
fulminant hepatic failure requiring liver transplantation.
Liver function tests should be monitored at the start of
therapy with troglitazone and at monthly intervals for
the first 6 months of therapy, and then every 2 months
for the remainder of the first year. Rosiglitazone ap-
pears to be a safer option with equivalent efficacy.
With control of uremia by dialysis, improved appe-
tite and weight gain in some diabetics may result in
increased insulin needs. In addition, noncompliance
with hypoglycemic medications related to depression
in the often stormy period surrounding dialysis initia-
tion may contribute to hyperglycemia. Hyperosmolar
coma is uncommon in diabetics on dialysis unless there

is significant residual renal function. Ketoacidosis is
also not frequently seen but may occur in association
with sepsis or other severe intercurrent illness. Both
conditions are managed by low-dose hourly regular in-
sulin infusions for blood sugar levels above 450–500
mg/dL. It is usually possible to achieve rapid control
of blood sugar, and indeed in some patients an initial
single dose of 10 units of regular insulin may suffice
702 Miles and Friedman
if the patient is not seriously ill. The usual fluid re-
plenishment regimens for nonuremic diabetics are of
course not required unless the patient is in shock. Usu-
ally, fluid replacement during hemodialysis suffices.
VII. COMPLICATIONS OF PERITONEAL
DIALYSIS IN DIABETIC PATIENTS
Eleven percent of diabetics entering renal replacement
programs in the United States are treated with some
form of peritoneal dialysis (2). In other countries such
as Canada, the percentage of diabetic ESRD patients
treated by peritoneal dialysis (PD) is much higher, in-
deed, PD is the treatment of choice for diabetics with
ESRD in these countries. Physician bias, national re-
sources, patient preference, and the presence of severe
cardiovascular disease are the major factors that deter-
mine the selection of PD over hemodialysis in diabet-
ics. The more gentle ultrafiltration afforded by CAPD
will prevent or ameliorate hypotension in diabetics so
prone because of left ventricular dysfunction or auto-
nomic neuropathy.
Diabetic hemodialysis patients younger than 60

years have a similar or lower relative risk of death than
diabetics of the same age on CAPD (31,32). In diabetic
CAPD patients older than 60 years, there is a 19%
higher relative risk of death compared with diabetic
hemodialysis patients (26). The higher death rate in el-
derly diabetics treated with CAPD is related to ad-
vanced atherosclerotic cardiovascular and cerebrovas-
cular disease. Diabetics are subject to a similar
spectrum and rate of technique-related complications as
in nondiabetics on CAPD, and a discussion of some of
the most common problems of diabetics on PD follows.
A. Peritonitis
Within the first year of starting PD, 49% of patients
will switch to another modality of renal replacement
therapy (33), while only 37% of hemodialysis patients
change treatment modality during the first year. It is
more likely that a CAPD or continuous cyclic PD
(CCPD) patient will switch to hemodialysis (15.6%)
than that a hemodialysis patient will switch to CAPD
(4.4%) (34). The high technique failure rate on CAPD
is due mainly to peritonitis (35). Recurrent peritonitis,
usually caused by Staphylococcus epidermidis or
Staphylococcus aureus, often in association with exit
site infections, is the major disadvantage of CAPD.
Peritonitis in diabetic CAPD patients occurs at a rate
of one episode per 11–21 patients per month
(26,29,36). Diabetics on CAPD need twice the number
of hospitalization days as nondiabetic CAPD patients
(37), and peritonitis accounts for 30–50% of the hos-
pitalization days (38). Fungal peritonitis is seen more

commonly in diabetic than in nondiabetic CAPD pa-
tients and usually requires removal of the peritoneal
catheter. There is, however, no overall increased risk
of peritonitis in diabetics over nondiabetics (39), and
the rates of catheter replacement are the same in both
groups.
Because of delayed wound healing, dialysate leak-
age and exit site infections may occur in diabetics if a
newly implanted Tenchoff catheter is used too early;
and we recommend that, if possible, at least 2–3 weeks
elapse before starting regular CAPD exchanges through
a newly implanted Tenchoff catheter in a diabetic. Al-
ternatively, starting nighttime cycling exchanges 1–2
weeks after catheter insertion and leaving the abdomen
dry during the daytime to reduce intra-abdominal pres-
sure during ambulation may reduce the risk of dialysate
leakage. The Moncrief-Popovich peritoneal catheter is
a recently introduced double-cuffed catheter with an
external cuff, which is longer than that of the standard
Tenchoff catheter, and whose external segment (exter-
nal cuff and tubing) is buried subcutaneously for 4–6
weeks before being externalized and used (40). Be-
cause tissue ingrowth into the external cuff has oc-
curred during the period of subcutaneous implantation,
it is anticipated that the rates of leaks and peritonitis
will be less with this catheter, and indeed we have had
excellent results, with no dialysate leaks so far with
this catheter.
B. Underdialysis
Patients on CAPD tend to have higher levels of blood

urea nitrogen and creatinine than hemodialysis patients,
and there is concern about the adequacy of CAPD as
long-term uremia therapy (41). Based on peritoneal
equilibration testing, a minimum clearance of 6–7 L/
day is recommended for patients on peritoneal dialysis.
The amount of dialysis delivered on CAPD may have
to be increased with time as residual renal function is
lost, and peritoneal clearance decreases owing to ad-
vanced vascular disease or recurrent episodes of peri-
tonitis. Microangiopathy and increased vascular per-
meability to small and large molecules and resultant
increased diffusive transport of glucose (42) may pro-
duce type I ultrafiltration failure in some diabetic
patients.
Complications of Dialysis in Diabetic Patients 703
C. Undernutrition
Malnutrition may occur in up to 40% of long-term
CAPD patients (43,44). Malnutrition in CAPD-treated
diabetics may occur because of (a) reduced appetite
caused by the large glucose load in dialysate or by
early satiety from increased intra-abdominal pressure
or (b) large protein losses (8–10 g/day) in the dialysate
effluent that may lower serum albumin and total protein
levels (45). Loss of protein through the peritoneal
membrane is increased during episodes of peritonitis
and may worsen with time because of a generalized
increase in permeability related to diabetic microangio-
pathy involving the peritoneal vessels or nausea and
vomiting related to diabetic gastroparesis. To maintain
adequate nutrition, CAPD patients should ingest at

least 1.5 g protein/kg/day and between 130 and 150 g
carbohydrates/day.
D. Hyperglycemia
Blood glucose control may sometimes be difficult in
diabetics on CAPD because of the absorption of a mean
of 182 Ϯ 61 g glucose/day from the peritoneal cavity
(46). A combination of subcutaneous and intraperito-
neal insulin administration usually results in adequate
glucose control, however. The total dose of intraperi-
toneal regular insulin required is usually two to three
times the usual subcutaneous total dose. Oral antidi-
abetic agents (sulfonylureas with short half-lives and
hepatic metabolism, e.g., glipizide, glyburide) to reduce
the risk of prolonged hypoglycemia may be used in
patients requiring less than 20–25 units of insulin per
day.
VIII. SUMMARY
Diabetic dialysis patients require extra effort on the part
of nephrologists to prevent and treat macro- and mi-
crovascular disease, to manage intradialytic complica-
tions, and to achieve the usually difficult goal of main-
taining good vascular access. A multidisciplinary team
approach is required, and the services of an experi-
enced vascular access surgeon are invaluable. As the
epidemic of type 2 diabetes mellitus afflicting devel-
oped countries continues and diabetics comprise an in-
creasing percentage of incident and prevalent ESRD
patients, nephrologists must target the problems pecu-
liar to, or prevalent in the diabetic dialysis population
in order to reduce morbidity and mortality in this high-

risk group.
REFERENCES
1. U.S. Renal Data System, USRDS 1997 Annual Data
Report. Bethesda, MD: National Institutes of Health,
National Institute of Diabetes and Digestive and Kidney
Diseases, 1991.
2. Miles AMV, Friedman EA. Managing co-morbid dis-
orders in the uremic diabetic patient. Sem Dial 1997;
10:225–230.
3. Shideman JR, Buselmeier TJ, Kjellstrand CM. Hemo-
dialysis in diabetics. Arch Intern Med 1976; 136:1126–
1130.
4. Collins AL, Liao A, Umen A, Hanson G, Keshaviah P.
Diabetic hemodialysis patients treated with a high Kt/
V have a lower risk of death than standard Kt/V. J Am
Soc Nephrol 1991; 2:318.
5. Nakamoto M. The mechanism of intradialytic hypoten-
sion in diabetic patients. Nippon Jinzo Gakkai Shi. Jap
J Nephrol 1994; 36:374–381.
6. Ritz E, Strumpf C, Katz F, et al. Hypertension and car-
diovascular risk factors in hemodialyzed diabetic pa-
tients. Hypertension 1985; 7(suppl II):118–124.
7. Daugirdas JT. Dialysis hypotension: A hemodynamic
analysis. Kidney Int 1991; 39:223–246.
8. Gotch FA, Keen ML, Yarian SR. An analysis of thermal
regulation in hemodialysis with one and three com-
partment models. Trans Am Soc Artif Intern Organs
1989; 35:622–624.
9. Dorhout Mees EJ. Rise in blood pressure during he-
modialysis ultrafiltration: a paradoxical situation? Int J

Artificial Organs 1996; 19:569–570.
10. Ifudu O, Dulin A, Lundin AP, et al. Diabetics manifest
excess weight gain on maintenance hemodialysis. Am
Soc Artif Intern Org 1992; 21:85.
11. Jones R, Poston R, Hinestrota A, et al. Weight gain
between dialysis in diabetics. Possible significance of
raised intracellular sodium content. Br Med J 1980; 1:
153–154.
12. U.S. Renal Data System. USRDS 1997 Annual Data
Report. Bethesda, MD: National Institutes of Health,
National Institute of Diabetes and Digestive and Kidney
Diseases, 1997.
13. Miles AMV, Hong JH, Sumrani N, et al. Outcome and
complications of vascular access placement in elderly
diabetic patients with end stage renal disease. J Korean
Am Med Assoc 1996; 2:25–28.
14. Taber TE, Maikranz PS, Haag BW, et al. Maintenance
of adequate hemodialysis access. Prevention of neoin-
timal hyperplasia. ASAIO J 1995; 41:842–846.
15. Gensini GF, Abbate R, Favilla S, Neri Serneri GC.
Changes of platelet function and blood clotting in dia-
betes mellitus. Thromb Hemost 1979; 42:983–993.
16. Halushka PV. Increased platelet thromboxane. J Lab
Clin Med 1981; 97:87–92.
17. U.S. Renal Data System. USRDS 1993 Annual Data
Report. Bethesda, MD: National Institutes of Health.
704 Miles and Friedman
National Institute of Diabetes and Digestive and Kidney
Diseases, 1993.
18. Woods JD, Turenne MN, Strawderman RL, et al. Vas-

cular access survival among incident hemodialysis pa-
tients in the United States. Am J Kidney Dis 1997; 30:
50–57.
19. Tzamaloukas AH, Murata GH, Harford AM, et al. Hand
gangrene in diabetic patients on chronic dialysis. Trans
Am Soc Artif Intern Organs 1991; 37:638–643.
20. Redfern AB, Zimmerman NB. Neurologic and ischemic
complications of upper extremity vascular access for
dialysis. J Hand Surg 1995; 20:199–204.
21. Wilbourn AJ, Furlan AJ, Hulley W, Ruschhaupt W. Is-
chemic monomelic neuropathy. Neurology 1983; 33:
447–451.
22. Riggs JE, Moss AH, Labosky DA, Liput JH, et al. Up-
per extremity ischemic monomelic neuropathy: a com-
plication of vascular access procedures in uremic dia-
betic patients. Neurology 1989; 39:997–998.
23. Vincenti F, Arnaud SB, Recker R, et al. Parathyroid and
bone response of the diabetic patient to uremia. Kidney
Int 1984; 25:677–682.
24. Weiss RE, Reddi AH. Influence of experimental dia-
betes and insulin on matrix-induced cartilage and bone
differentiation. Am J Physiol 1980, 238:E200–E207.
25. Andress DL, Kopp JB, Maloney NA, et al. Early dep-
osition of aluminum in bone in diabetic patients on he-
modialysis. N Engl J Med 1987; 316:292–296.
26. Diaz-Buxo JA, Burgess WP, Greenman M, et al. Visual
function in diabetic patients undergoing dialysis: com-
parison of peritoneal had hemodialysis. Int J Artificial
Organs 1984; 7:257–262.
27. Mahaffey KW, Granger CB, Toth CA, et al. Diabetic

retinopathy should not be a contraindication to throm-
bolytic therapy for acute myocardial infarction: review
of ocular hemorrhage incidence and location in the
GUSTO-I trial. J Am Coll Cardiol 1997; 30:1606–
1610.
28. Cheigh J, Raghavan J, Sullivan J, et al. Is insufficient
dialysis a cause for high morbidity in diabetic patients.
J Am Soc Nephrol 1991; 2:317.
29. Davis M, Comty C, Shapiro F. Dietary management of
patients with diabetes treated by hemodialysis. J Am
Diet Assoc 1979; 75:265–269.
30. Davis M, Comty C, Shapiro F. Dietary management of
patients with diabetes treated by hemodialysis. J Am
Diet Assoc 1979; 75:265–269.
31. Maiorca R, Vonesh EF, Cavalli PL, et al. A multicenter,
selection-adjusted comparison of patient and technique
survivals on CAPD and hemodialysis. Perit Dial Int
1991; 11:118–127.
32. Gokal R, Jakubowski C, Hunt L. Multicenter study of
outcome of CAPD and hemodialysis patients. Nephrol
Dial Transplant 1986; 1:111–114.
33. Held PJ, Port FK, Blagg CR, et al. The United States
renal data systems annual data report. Am J Kidney Dis
1990; 16(suppl 2):34–43.
34. Yuan ZY, Balaskas E, Gupta A, et al. Is CAPD or he-
modialysis better for diabetic patients? CAPD is more
advantageous. Semin Dialysis 1992; 5:181–188.
35. Nolph KD. Continuous ambulatory peritoneal dialysis
as long term treatment for end stage renal disease. Am
J Kidney Dis 1991; 17:154–157.

36. Scarpioni LL, Balocchi S, Castelli A, et al. Continuous
ambulatory peritoneal dialysis in diabetic patients. Con-
trib Nephrol 1990; 84:50–74.
37. Khanna R, Oreopoulos DG. Continuous ambulatory
peritoneal dialysis in diabetics with end stage renal dis-
ease. A combined experience of 2 North American cen-
ters. In: Friedman EA, L’Esperance FA, eds. Diabetic
Renal Retinal Syndrome. New York: Grune and Strat-
ton, 1986; 363–381.
38. Rottemburg J. Peritoneal dialysis in diabetics. In: Nolph
KD, ed. Peritoneal Dialysis. Boston: Martinus Nijhoff,
1985:365–379.
39. Rubin J, Oreopoulos DG, Blair RDG, et al. Chronic
peritoneal dialysis in the management of diabetics with
terminal renal failure. Nephron 1977; 19:265–270.
40. Moncrief JW et al. The Moncrief-Popovich catheter. A
new peritoneal access technique for patients on peri-
toneal dialysis. ASAIO J 1993; 39:62.
41. Diaz-Buxo JA. Is continuous ambulatory peritoneal di-
alysis adequate long-term therapy for end-stage renal
disease? A critical assessment. J Am Soc Nephrol 1992;
3:1039–1048.
42. Lin JJ, Wadhwa NK, Suh H, et al. Increased peritoneal
solute transport in diabetic peritoneal dialysis patients.
Adv Peritoneal Dial 1995; 11:63–66.
43. Young GA, Kopple JD, Lindholm B, et al. Nutritional
assessment of chronic ambulatory peritoneal dialysis
patients: an international study. Am J Kidney Dis 1991;
17:462–471.
44. Rotellar C, Black J, Winchester JF, et al. Ten years

experience with continuous ambulatory peritoneal di-
alysis. Am J Kidney Dis 1991; 17:158–164.
45. Blumenkrantz MJ, Gahl GM, Kopple JD, et al. Protein
losses during peritoneal dialysis. Kidney Int 1981; 19:
593–602.
46. Grodstein GP, Blumenkrantz MJ, Kopple JD, et al. Glu-
cose absorption during continuous ambulatory perito-
neal dialysis. Kidney Int 1981; 19:564–567.
705
40
Problems of Women on Dialysis
Susan S. Hou
Loyola University School of Medicine, Maywood, Illinois
Susan Grossman
St. Vincent’s Medical Center of Richmond, Staten Island, New York
The care of dialysis patients has been focused first on
survival and then on decreased morbidity. Rehabilita-
tion has generally emphasized return to employment or
family and community activities. Pregnancy and child-
bearing have been regarded as unfortunate accidents
rather than as goals of treatment. Our attention to gy-
necological problems affecting dialysis patients has
been overshadowed by attention to cardiovascular dis-
ease, infection, and other life-threatening complications
of dialysis. Pregnancy in dialysis patients is still un-
common and carries a high risk for both mother and
fetus. However, with the increasing length of survival
of young dialysis patients and the increasing wait for
transplantation, the problems associated with child-
bearing and contraception have become more impor-

tant. The possibility and implications of conception
need to be addressed with each patient. While rarely
life-threatening, the problems of sexual dysfunction,
dysfunctional uterine bleeding, and gynecological in-
fections contribute to a diminished quality of life. Gy-
necological neoplasms are life-threatening when they
occur, although they are not the most common cause
of death in dialysis patients.
I. CONTRACEPTION
Early literature reported that only 10% of female di-
alysis patients of childbearing age menstruated (1), but
a more recent report (2) indicates that the frequency of
menses has increased to 42%. It is not certain how
many of these women could conceive, but the risks and
possibility of pregnancy and the need for contraception
should be discussed with all dialysis patients of child-
bearing age.
Oral contraceptives offer many advantages for di-
alysis patients. Many dialysis patients are estrogen de-
ficient, and women with irregular periods may be ex-
posed to the effects of unopposed estrogen for
prolonged periods of time. Estrogen deficiency is added
to the many other factors that contribute to bone dis-
ease, and unopposed estrogen may increase the risk of
endometrial cancer. The use of oral contraceptives
would not only prevent pregnancy but would treat es-
trogen deficiency and allow for regular hormonal cy-
cling. Oral contraceptives should be used with caution
in hypertensive women and women at risk for throm-
boembolic disease. These drugs may increase the risk

for lupus flares in women whose end-stage renal dis-
ease is secondary to lupus.
Mechanical methods of contraception can be used
in women for whom estrogen is contraindicated. Intra-
uterine devices may be associated with increased uter-
ine bleeding when patients are heparinized, and an in-
crease in the risk of peritonitis would be expected in
peritoneal dialysis patients. Other mechanical methods
of birth control are acceptable in dialysis patients.
II. PREGNANCY
A. Frequency of Conception
Fertility is markedly reduced in dialysis patients. Esti-
mates of the frequency of conception in dialysis pa-
706 Hou and Grossman
tients range from 1.4% per year in Saudi Arabia (3) to
0.5% in the United States (4) and 0.3% in Belgium (5).
The estimates from the United States and Saudi Arabia
are based on surveys that covered only half the women
of childbearing age treated with dialysis, while the sur-
vey from Belgium included a response from all of the
dialysis units in the country. Only the report from the
American National Registry for Pregnancy in Dialysis
Patients (NRPDP) included a substantial number of
peritoneal dialysis patients (4). Of note is that the fre-
quency of conception in hemodialysis patients was
two to three times higher than in peritoneal dialysis
patients.
The reasons for the rarity of pregnancy in dialysis
patients are not well understood. The hormonal
changes in dialysis patients are reviewed elsewhere in

this book. Nonhormonal causes of infertility have not
been investigated.
It is not clear whether the difference in the frequency
of conception between hemodialysis patients and
CAPD patients is the result of endocrine differences or
is in some way related to peritoneal dialysis itself. Re-
current peritonitis might be expected to cause tubal ob-
struction in peritoneal dialysis patients, but if tubal
damage were a major contributor to infertility, an in-
crease in tubal pregnancies would be expected. Few
tubal pregnancies have been described in dialysis pa-
tients and none in peritoneal dialysis patients. It is pos-
sible that hypertonic dextrose damages the ovum or
that the volume of fluid in the intraperitoneal space
interferes with transport of the ovum from the ovary to
the fallopian tubes.
Most pregnancies occur during the first few years on
dialysis, but conception rates as a function of time on
dialysis have not been determined. Pregnancy has oc-
curred in women who have been on dialysis as long as
20 years. Repeat pregnancies in women who become
pregnant on dialysis are not uncommon. In the 318
women whose pregnancies are recorded by the NRPDP,
8 became pregnant twice, 8 became pregnant three
times, and one conceived four times (4). Although it
would be expected that pregnancy would be more
likely in women with regular menses, pregnancy has
been reported in a woman after 9 years of amenorrhea.
In contrast to dialysis patients, approximately 12% of
women transplant recipients of childbearing age be-

come pregnant.
B. Outcome of Pregnancy in Dialysis Patients
In 1980, the European Dialysis and Transplant Asso-
ciation reported 115 pregnancies in dialysis patients
(6). Of those that were not electively terminated, only
23% resulted in surviving infants. Success rate for
pregnancy in dialysis patients has improved since the
EDTA report. In Saudi Arabia 30% of pregnancies re-
sulted in surviving infants. The NRPDP recorded 222
pregnancies in women who were receiving dialysis at
the time of conception. Of the 141 pregnancies that
reached the second trimester, 55% resulted in surviving
infants. Eighteen percent of live-born infants died in
the neonatal period; 8.5% of pregnancies reaching the
second trimester resulted in stillbirth, and 22% resulted
in spontaneous abortion. The four induced abortions
done in the second trimester were done for life-threat-
ening maternal problems (three hypertension and one
critical aortic stenosis) rather than for social reasons or
anticipated problems.
C. Maternal Complications
1. Maternal Death
There have been three maternal deaths reported to the
NRPDP. One death resulted from lupus cerebritis in a
woman who started dialysis after conception. There
were two deaths in women who conceived after starting
dialysis, one as a result of hypertension and one from
unknown causes. All three infants survived.
2. Hypertension
Hypertension is the most common life-threatening

complication of pregnancy in dialysis patients. Of 57
case reports published in the medical literature in
which blood pressure was noted in a pregnant dialysis
patient, only 30% of women were normotensive
throughout pregnancy (7). Sixty percent of women had
blood pressures over 140/90 at some time during preg-
nancy, and in 25% the blood pressure exceeded 170/
110. Ten percent were treated with antihypertensive
medications, but blood pressure was not specified.
In cases reported to the NRPDP, approximately 80%
of the 68 women for whom blood pressure measure-
ments were available either had a blood pressure
greater than 140/90 or required antihypertensive med-
ication at some time during pregnancy (4). In over half
of hypertensive pregnant dialysis patients, the blood
pressure exceeds 170/110. Five of these women re-
quired intensive care unit admissions in addition to the
maternal one death. Thirty-eight percent of patients
who developed severe hypertension did so in the first
trimester. In such cases, it was usually possible to con-
trol the blood pressure without terminating the preg-
nancy. Fifty percent of women with severe hyperten-
Problems of Women on Dialysis 707
sion reached blood pressures of >170/110 in the second
trimester. These cases were problematic in that pre-
eclampsia could not be excluded and the fetus was still
not viable. Three of 16 women required therapeutic
abortion for hypertension. Of note, severe hypertension
could be seen as late as 6 weeks postpartum.
3. Anemia

A drop in hematocrit is almost invariable in dialysis
patients who become pregnant. In pregnancies reported
to the NRPDP, 33% of women treated with erythro-
poietin and 77% of women not treated with erythro-
poietin required transfusion (4). Iron stores usually
dropped, but there were several instances in which the
hematocrit dropped despite iron saturation, which re-
mained at acceptable levels.
D. Prematurity and Growth Restriction
Eighty-five percent of infants born to women who con-
ceived after starting dialysis reported to the NRPDP
were born before 37 weeks gestation (mean gestational
age 32.4 weeks). Thirty-six percent weighed less than
1500 g at birth, and 28% were small for gestational
age. Their neonatal course was complicated by respi-
ratory distress and other complications of prematurity.
Eleven of 116 live-born infants and 1 stillborn infant
reported to the NRPDP had congenital anomalies (4).
Eleven of 49 infants for whom follow-up data were
available had long-term medical or developmental
problems, most of which appeared to be the result of
prematurity rather than an azotemic intrauterine envi-
ronment. The mean gestational age was lower for in-
fants who had long-term problems compared to those
with normal growth and development (30.6 vs. 34.3
weeks).
III. MANAGEMENT ISSUES IN
PREGNANT DIALYSIS PATIENTS
A. Preconception Counseling
Counseling of dialysis patients who are attempting

pregnancy is all but impossible. The infrequency of
conception makes it impossible to plan except in
women who have already conceived once on dialysis.
Even if a woman is actively trying to become pregnant,
the likelihood of conception is low enough that changes
in dialysis regimen cannot be justified. However, folic
acid supplementation should be increased and good
blood sugar control should be achieved in diabetic
women who are attempting conception.
B. Diagnosis of Pregnancy
Pregnancy is usually diagnosed late in dialysis patients.
Irregular menses are common and abdominal com-
plaints are often attributed to other causes. A high index
of suspicion is required to make the diagnosis early.
Urine tests for human chorionic gonadotropin (hcg) are
inaccurate even in women who have residual renal
function. Small amounts of hcg are made by somatic
cells, and because the hormone is partially excreted by
the kidney, serum tests for
␤
hcg are sometimes bor-
derline or falsely positive in women who are not preg-
nant (8). The titers of
␤
hcg may be higher than ex-
pected for the stage of gestation. The diagnosis and
stage of gestation must be confirmed by ultrasound.
C. Management of Hypertension
Dialysis patients, particularly those on home treatment
modalities, should measure their own blood pressure

twice daily since severe increases in blood pressure can
be abrupt. As with dialysis patients who are not preg-
nant, the first line of treatment is correction of volume
overload. Assessment of volume status is difficult be-
cause of the expected 9 L increase in total body water
during pregnancy, but cautious fluid removal should be
attempted when hypertension develops. If fluid removal
does not correct blood pressure, pharmacological treat-
ment can be started. There is experience with a wide
variety of antihypertensive medications in pregnancy
(Table 1). Of the widely used antihypertensive drugs,
only angiotensin-converting enzyme (ACE) inhibitors
and, by inference, angiotensin receptor blockers are
strongly contraindicated in pregnancy.
1. Angiotensin-Converting Enzyme Inhibitors
This group of drugs has been associated with oligo-
hydramnios, which results in a number of complica-
tions. Amniotic fluid is necessary for fetal lung devel-
opment, and the most serious consequence of
oligohydramnios is pulmonary hypoplasia leading to
neonatal death as a result of respiratory failure (9). Oli-
gohydramnios also accounts for limb contractures in
infants exposed to the drug. Direct pressure of the uter-
ine muscle on the fetal skull is thought to result in
abnormal calcification of the skull. Several instances of
patent ductus have been described. This effect is
708 Hou and Grossman
Table 1 Antihypertensive Drugs Used in Pregnancy
Drug (category) Comments
Chronic Hypertension

ACE inhibitors (D) Contraindicated; 2nd and 3rd trimester use associated with pulmonary hypoplasia,
hypocalvaria, renal dysplasia, neonatal anuria, contractures; no known harm in
1st trimester
␣
Methyl dopa (C) Safe; 40 year use; careful developmental testing of children at ages 4 and 7; rare
Coombs ϩ hemolytic anemia, rare hepatitis
␤
Blockers (C) Probably safe; fetal bradycardia, hypoglycemia, respiratory depression at birth,
intrauterine growth restriction? ↓ fetal tolerance of anoxic stress
Labetolol (C) Limited first trimester experience; less bradycardia and growth restriction than
␤
blockers
Clonidine (C) Probably safe; limited 1st trimester experience
Calcium channel blockers (C) Profound ↓ BP with when used with magnesium; limited experience; reserve for
severe hypertension
Hydralazine (C) Safe; long experience with use in pregnancy; no ↑ birth defects; ineffective as a
single agent
Minoxidil (C) Very limited experience; hypertricosis and congenital anomalies in one the infant
Prazocin (C) Limited experience; no problems noted
Thiazide diuretics (D) ↑ congenital anomalies with chlorthaldone; subnormal intravascular volume
expansion, neonatal thrombocytopenia, hemolytic anemia,
electrolyte abnormalities
Hypertensive Crisis
Hydralazine (C) Used for 40 years without serious side effects
Labetolol (C) Shorter length of use; appears safe
Nitroprusside (C) Fetal cyanide toxicity
Diazoxide (C) Fatal maternal hypotension reported; limit dose to 30 mg boluses; ↓ uterine
contraction; neonatal hyperglycemia
thought to be the result of the effects of ACE inhibitors
on prostaglandin metabolism.

While exposure to ACE inhibitors in the second and
third trimesters may have serious consequences, no ill
effects have been identified as a result of first trimester
exposure. Two studies, one involving 46 infants and
one involving 86 infants, showed no adverse effect of
exposure to ACE inhibitors in the first trimester (10).
In the latter report there were four congenital anoma-
lies, a number that was not significantly different from
the expected three. Women with inadvertent first tri-
mester exposure need not be advised to terminate the
pregnancy.
There is less experience with angiotensin II receptor
blockers, but it is expected that problems caused by
decreased angiotensin effect will be similar to those
seen in women treated with ACE inhibitors.
2. Other Antihypertensive Drugs
a.
␣
Methyl Dopa
␣
Methyl dopa has been used in pregnant women for
over 40 years and is still the drug of first choice for
essential hypertension. Careful developmental studies
have been done at 4 and 7 years of age in children
exposed to the drug in utero, and no problems have
been found (11).
b.
␤
Blockers
There are several case reports of neonatal bradycardia,

hypoglycemia, and respiratory depression associated
with
␤
blockers, but these problems are generally easily
managed by the neonatologist (12). There are mixed
data concerning whether blockers are associated with
intrauterine growth restriction. There are reports of
small-for-gestational-age infants of mothers treated
with
␤
blockers for diseases not usually associated with
growth restriction (13). There are also data from animal
models suggesting a decreased ability of the fetus to
withstand anoxic stress (14). None of these problems
has turned out to be a major contraindication to the use
of this category of drugs in pregnant humans. Fetal
bradycardia may make it difficult to interpret antenatal
monitoring, which depends on changes in fetal heart
rate.
Problems of Women on Dialysis 709
c. Labetolol
Labetolol is not associated with fetal bradycardia and
growth restriction and, it is widely used in preference
to
␤
blockers. Nonetheless, data on first trimester ef-
fects of the drug are still limited (10). Moreover, con-
trolled studies have not shown it to be superior to other
antihypertensive agents (15).
d. Clonidine

Clonidine is a centrally acting
␣
2
-agonist, which has
been reported in one study to have efficacy and safety
similar to methyl dopa (16). In view of the limited
experience with it, there is no reason to use it in pref-
erence to
␣
methyl dopa.
e. Prazocin
No adverse effects on the fetus have been demonstrated
with prazocin, but the experience with it is more lim-
ited than with labetolol,
␣
methyl dopa, and
␤
blockers,
and it does not appear to offer any advantage. The drug
can be continued in women whose blood pressure is
well controlled on it at the time of conception.
f. Calcium Channel Blockers
Nifedipine, nicardipine, and verapamil have been used
in severe hypertension. They do not appear to be as-
sociated with any increase in congenital anomalies
when used in the first trimester. These drugs have been
used for treatment of premature labor in the third tri-
mester. Experience with diltiazem is more limited. Cal-
cium channel blockers may potentiate the hypotensive
effects and neuromuscular blockade of magnesium and

the interaction should be kept in mind when the drugs
are used in women with a possibility of developing
preeclampsia (17,18). Because of the limited experi-
ence with all members of this group of drugs, their use
is best limited to severe hypertension unresponsive to
other drugs.
g. Vasodilators
Hydralazine has been used safely during pregnancy for
40 years. It is ineffective as a single oral agent but can
be added to a first-line drug if the latter does not ade-
quately control blood pressure. The more potent vaso-
dilator, minoxidil has been associated with hypertri-
chosis and congenital anomalies in one case report
(19). It is ineffective unless combined with a diuretic
and a sympatholytic agent.
3. Drugs for Hypertensive Emergencies
a. Hydralazine
Intravenous hydralazine in doses of 5–10 mg every
20–30 minutes is the drug of first choice for hyperten-
sive crisis in pregnancy. A single study has shown a
high frequency of malignant ventricular arrhythmias in
eclamptic women treated with hydralazine than in
women treated with labetolol (20). Nine studies com-
paring hydralazine with other drugs, most often intra-
venous labetolol, have found no advantage of one drug
regimen over another (21).
b. Labetolol
Intravenous labetolol given either as a 20 mg loading
dose followed by 20 mg every 30 minutes or a 1–2
mg/min drip is the second most commonly used regi-

men for treating hypertensive emergencies in pregnant
women. There are occasional reports of fetal bradycar-
dia, and the newborn should be monitored for hypo-
tension.
c. Diazoxide
There is extensive experience with the use of diazoxide
in pregnancy, but the drug is now primarily of historic
interest. In doses of 150–300 mg it has been associated
with at least one maternal fatality from hypotension. It
is also associated with decreased uterine contractions
and neonatal hyperglycemia. Its only advantage is a
long duration of action, which may make it useful in a
woman who must be transported with minimal moni-
toring capability or when other drugs have failed. It
should be used only in 30 mg boluses every 1–2
minutes until the desired blood pressure is reached.
D. Infections
Pregnant hemodialysis patients are probably at no more
risk of infection than those who are not pregnant, but
the use of antibiotics will be influenced by pregnancy.
Most penicillins are safe during pregnancy. First-gen-
eration cephalosporins such as cephazolin and cephal-
exin are safe in pregnancy (10). Cephalosporins with a
methyltetrathiazole moiety (cefoperozone, cefotetan,
moxalactam, and cefamandole) are usually avoided in
pregnancy because studies have shown infertility in an-
imals (22). Sulfa drugs, such as sulfamethoxiazole, can
be used in the early part of pregnancy but should be
avoided in the latter part of pregnancy because there is
a risk of kernicterus. Trimethoprim and trimethoprim-

sulfamethoxiazole combinations are generally avoided
710 Hou and Grossman
because of the teratogenicity of folic acid antagonists.
In practice, significant increases in congenital anoma-
lies have not been noted with these drugs. The quino-
lone antibiotics should be avoided in pregnancy be-
cause they have been associated with weakened
cartilage in young animals. Aminoglycosides should
also be avoided because of their association with 8th
nerve damage.
E. Peritonitis
The anatomic connection between the uterus and the
intraperitoneal cavity raises the concern that peritonitis
will result in intrauterine infection and vice versa.
There have been few cases reported of peritonitis in
pregnant CAPD patients. In three cases reported, per-
itonitis was followed by labor in two (23,24). One
pregnancy resulted in a premature baby, who survived,
and the other resulted in a stillbirth. Five additional
cases of peritonitis have been reported to the NRPDP.
There was only one fetal loss, which was remote from
the time of peritonitis. There is one report of postpar-
tum Escherichia coli peritonitis requiring removal of
the peritoneal catheter resulting from ascending infec-
tion in a woman with chorioamnionitis (25).
F. Erythropoietin
There are limited but reassuring data on the use of
erythropoietin during pregnancy (26). There have been
no reports of teratogenicity. Since conception is not
usually expected in dialysis patients, these women are

generally being treated with erythropoietin and are well
into the period of organogenesis when pregnancy is
diagnosed. The drug has not been associated with in-
creased difficulty controlling hypertension or with
polycythemia in the infants. Dialysis patients who are
not treated with erythropoietin almost always require
transfusions (4). Erythropoietin requirements increase
in pregnancy, and a 50–100% increase in the dose can
be prescribed as soon as pregnancy is diagnosed.
G. Iron
Serum iron and ferritin usually drop during pregnancy
in dialysis patients, and iron deficiency may play a role
in anemia later in pregnancy. The safety of intravenous
iron has not been established, but it has been widely
used. There are old data indicating that iron may be
transferred disproportionately to the fetus, and if intra-
venous iron is used, it seems prudent to give it in small
doses to minimize the risk of acute iron toxicity. The
outcome of pregnancy in dialysis patients treated with
intravenous iron is not different from women who have
not received iron.
H. Dialysis Regimens
1. Choice of Modality
When the first cases of pregnancy in peritoneal dialysis
patients were reported, it appeared that the outcome
was better for peritoneal dialysis patients than for he-
modialysis (27). With the accumulation of more data,
it has become clear that the apparent superiority of
peritoneal dialysis simply reflected the overall im-
provement in outcome for pregnancies in dialysis pa-

tients compared to earlier reports.
There are theoretical advantages to peritoneal dial-
ysis in that there are no rapid metabolic changes and
volume removal is gradual. There may be disadvan-
tages with difficulty maintaining adequate nutrition for
pregnancy. There is no reason to switch a woman who
is stable on either hemodialysis or peritoneal dialysis
to another modality because of pregnancy per se. When
starting dialysis during pregnancy, the usual criteria for
choosing a dialysis modality can be used. Peritoneal
dialysis has been successfully used in women with end-
stage renal disease secondary to diabetic nephropathy.
It might be relatively contraindicated in nondiabetic
women who are at high risk for gestational diabetes.
2. Hemodialysis
a. Intensive Dialysis
The value of intensive dialysis (daily dialysis) in im-
proving the outcome of pregnancy in dialysis patients
has not been established, but there are theoretical rea-
sons to support its use. Women who begin dialysis dur-
ing pregnancy and have residual renal function have a
better pregnancy outcome (75–80% vs. 40% infant sur-
vival) (4). It is not known whether residual excretory
function or endocrine function is responsible for the
better outcome, but an attempt to lower the fetal ex-
posure to metabolic waste products seems reasonable.
With daily dialysis, interdialytic weight gains are mod-
est and the risk of hypotension with fluid removal is
decreased. Polyhydramnios is common in dialysis pa-
tients. A recent report of 17 pregnancies in dialysis pa-

tients from University of Sa˜o Paulo noted polyhydram-
nios in 17 (28). Uterine distension associated with
polyhydramnios may contribute to premature labor. A
high blood urea nitrogen in the fetus that has normal
kidneys may cause an osmotic diuresis, which aggra-
vates polyhydramnios. This hypothesis is supported by
Problems of Women on Dialysis 711
Table 2 Dietary Guidelines for Pregnant Dialysis Patients
Protein HD: 1.2 g/kg ideal body wt ϩ 10 g/d
PD: 2.4 g/kg ideal body weight ϩ 10 g/d
Calories: 35 kcal/kg ϩ 300 k/cal
Sodium: 3 g/d
Potassium: 2–3 g/d
Phosphorus: 1200 mg/d
Calcium: 1–2 g as phosphate binders; 2 g/d if 2.5 mEq/L
bath is used
Vitamin A and E: no supplement
Folate: 1.8 mg/d
Vitamin C: 170 mg/d
Thiamine: 3 mg/d
Riboflavin: 3.4 mg/d
Niacin: 20 mg/d
B6: 5 mg
Biotin: 600 mg
Zinc: 15 mg
Carnitine: 330 mg
the observation that a urea diuresis is usual in infants
born to mothers on dialysis. A report of 27 pregnancies
in women in Saudi Arabia found a significantly longer
dialysis time in women with successful pregnancies

compared to women with unsuccessful pregnancies (12
h vs. 10 h) (3). Limited data from the NRPDP indicate
that dialysis must be increased to at least 20 hours per
week to achieve any improvement in outcome.
b. Dialysis Bath
If intensive dialysis is used, several adjustments in the
dialysate composition may be necessary. Serum potas-
sium may drop if dietary increases in potassium do not
offset increased losses, and the dialysate potassium
may need to be raised. With daily dialysis, hypercal-
cemia may occur if a bath containing 3.5 mEq/L of
calcium is used, and 2.5 mEq/L is usually preferable.
While potassium and calcium in the dialysate are rel-
atively easy to adjust, bicarbonate is more problematic.
The dialysate bicarbonate of 35 mEq/L is designed to
offset 2 days of acid production. Daily dialysis may
result in excessive bicarbonate gain. The situation is
further complicated by the normal respiratory alkalosis
of pregnancy in which the appropriate serum bicarbon-
ate is 18–20 mEq/L rather than 25 mEq/L. If serious
alkalosis develops, an individually formulated dialysis
solution may be necessary.
c. Anticoagulation
In the past, recommendations have been made to min-
imize anticoagulant dose in pregnant women. However,
the usual practice in all dialysis patients is to give the
smallest amount of anticoagulation possible. An at-
tempt at lowering heparin doses results in the same
problems of clotting of the extracorporeal circuit that
it does in nonpregnant patients. Although direct com-

parisons have not been made, clotting problems may
even be increased because pregnancy is a hyperco-
agulable state. Heparin does not cross the placenta and
is not teratogenic (29). We recommend that heparin-
free dialysis be limited to women with bleeding prob-
lems. Coumadin does cross the placenta, is teratogenic
in the first trimester, and may cause bleeding in the
fetus in the third trimester (10). Women treated with
coumadin either for recurrent access clotting or for
other reasons should be switched to subcutaneous hep-
arin in doses adequate for full anticoagulation.
3. Peritoneal Dialysis
In late pregnancy it becomes difficult for a woman to
tolerate her usual exchange volume (27). Volume must
be reduced and the number of exchanges increased. It
may become difficult to maintain even the previous
level of dialysis. To increase the amount of dialysis
delivered, it is necessary to use a combination of day-
time CAPD and nighttime CCPD. There is not enough
data to determine whether increasing the amount of
peritoneal dialysis delivered improves outcome.
I. Calcium and Phosphorus
Thirty grams of calcium are necessary for calcification
of the fetal skeleton. If the patient is dialyzed on a bath
containing more than 3.5 mEq/L of calcium, dialysis
easily provides this amount. If she is dialyzed on a
lower calcium bath, enough calcium should be ab-
sorbed from phosphate binders to provide the necessary
calcium if she takes at least 2 g of calcium daily. 1,25-
Dihydroxyvitamin D preparations, either oral or intra-

venous, are usually continued, although their effect in
pregnancy is not well understood. The placenta does
convert some 25-OH
2
D
3
to 1,25-OH
2
D
3
(30). High
doses of 1,25-OH
2
D
3
have been used in one patient
with hypoparathyroidism without ill effects on the fetus
(31).
J. Nutritional Considerations
Guidelines for nutritional care of a pregnant dialysis
patient are still in a state of evolution (Table 2).
712 Hou and Grossman
I. Weight Gain
It is almost impossible to prescribe weight gain. The
task confronting the health care team is usually to de-
termine how much of observed weight gain is either
pregnancy related increase in soft tissue or increased
total body water appropriate for pregnancy and how
much is fluid overload that should be removed with
dialysis. Normal pregnancy is accompanied by an in-

crease in total body water of approximately 9 L, most
of it in the extracellular space. Fluid retention occurs
to some extent in dialysis patients. A common obser-
vation early in pregnancy and occasionally a clue to
the diagnosis is hypotension in response to the attempt
to remove fluid. The patient should be examined care-
fully on a weekly basis for evidence of fluid overload,
and if signs of excessive volume expansion are present,
a careful attempt to remove fluid with dialysis should
be made.
2. Protein and Calories
Practically, with intensive dialysis, no protein restric-
tion is necessary during pregnancy, and provision of
adequate protein and calories is frequently a problem.
Supplements are often required, and several instances
in which intradialytic parenteral nutrition was used
have been reported (32).
3. Fluid Restriction
Daily dialysis allows for decreasing but not eliminating
a fluid restriction. One goal of daily dialysis is to avoid
the need to remove more than 1–2 L during a single
treatment.
4. Water-Soluble Vitamins
The requirements for water-soluble vitamins increase
during pregnancy, and increased frequency of dialysis
increases the loss of water-soluble vitamins above the
usual for dialysis patients.
Folic acid is necessary for the increased hematopoi-
esis that occurs during pregnancy. Preconception sup-
plementation with 0.8 mg of folic acid has been shown

to reduce the risk of neural tube defects (33). The usual
renal diet is frequently low in fruits and vegetables and
thus low in folate. The usual supplement for dialysis
patients is 1 mg/day, and we recommend increasing the
supplement to 1.8–2 mg/day.
Requirements for all vitamins are increased during
pregnancy and an additional increase is required for
pregnancy with additional increases required in dialysis
patients. Vitamin C dose should be increased. Defi-
ciency has been associated with neonatal scurvy.
5. Fat-Soluble Vitamins
Supplements of vitamin A are usually prescribed in
normal pregnancy but should not be prescribed in preg-
nant dialysis patients. Excretion is decreased in dial-
ysis patients, and it is not removed by dialysis. Very
high doses of vitamin A have been associated with con-
genital anomalies similar to those seen with isoretinoin
(34).
Standard preparations of vitamin D have little effect
on dialysis patients, and their presence in vitamin prep-
arations has little relevance.
Vitamin E supplements are not required in pregnant
dialysis patients.
6. Zinc
Zinc is necessary for human reproduction, and its de-
ficiency has been associated with teratogenesis (34).
Later in pregnancy it has been associated with prema-
ture birth and atonic uterine bleeding. A supplement
should be given particularly to patients taking oral iron.
IV. OBSTETRIC MANAGEMENT

Care of the pregnant dialysis and transplant patient re-
quires close cooperation between the nephrologist and
a perinatologist experienced in taking care of women
with renal disease. A referral to a high-risk obstetrician
should be made as soon as pregnancy is diagnosed.
Because of the high frequency of severe prematurity, a
level three nursery should be available.
A. Premature Labor
Prematurity is the greatest cause of morbidity and mor-
tality in the infants of women with renal disease. There
are several special considerations to bear in mind with
the most commonly used treatments for premature la-
bor. Magnesium can be used, but as in its use for pre-
eclampsia, extreme caution must be used to avoid mag-
nesium toxicity and respiratory depression in women
with renal insufficiency (35). In dialysis patients, a
loading dose can be given and supplemented after each
dialysis treatment or when the magnesium level has
been documented to fall below 5 mg/dL. Continuous
infusion should not be used in dialysis patients.
Indomethacin has been used to treat premature labor
in women with renal disease and may be especially
Problems of Women on Dialysis 713
effective in women with polyhydramnios (26). How-
ever, in women with renal insufficiency or in dialysis
patients with residual renal function, there may be a
loss of renal function, causing hyperkalemia and re-
quiring initiation or increase in dialysis.
Premature labor usually occurs early enough that it
is desirable to delay delivery longer than the usual 72

hours that indomethacin is used. The fetus should be
monitored for any evidence of right heart strain, and
the mother should be monitored for polyhydramnios.
Midtrimester losses are common in dialysis patients,
and there have been a few reports of incompetent cer-
vix. Dialysis patients should be monitored for any signs
of cervical shortening or dilatation.
B. Fetal Surveillance
Because of the increased risk of stillbirth, fetal sur-
veillance should be started as soon as there is a pos-
sibility of survival outside the mother. Because of the
risk of precipitating labor, other tests should be used in
preference to oxytocin challenge testing.
C. Labor and Delivery
Vaginal delivery should be the goal of management,
and cesarean section should be done only for the usual
obstetric indications rather than for renal disease per
se. When cesarean section is done in peritoneal dialysis
patients, an attempt should be made to use an extra-
peritoneal approach. An attempt to resume peritoneal
dialysis with low-volume exchanges can be made 24
hours after operative delivery. If there is leaking from
the incision, the patient should be switched to hemo-
dialysis for 2 weeks.
D. Management Issues in the Newborn
Infants born to dialysis patients should be observed in
a high-risk setting even if they appear normal. Infants
of dialysis patients are born with blood urea nitrogen
(BUN) and serum creatinine equal to the mother’s, and
following birth they experience an osmotic diuresis that

results in volume contraction and electrolyte disorders
unless there is careful monitoring and replacement of
fluid and electrolytes.
V. DYSPAREUNIA
Some female dialysis patients may experience dys-
pareunia because of estrogen deficiency and resulting
vaginal dryness. Dyspareunia resulting from atrophic
vaginitis from low estrogen levels can be corrected by
intravaginal conjugated estrogens (2–4 g daily) or oral
estrogen progesterone compounds. A daily dose of
0.625 mg of conjugated estrogen and 2.5 mg of med-
roxyprogesterone provides enough estrogen to prevent
dyspareunia. If there is breakthrough bleeding on this
combination, progesterone can be increased to 5 mg.
Women treated with intravaginal estrogens should re-
ceive progesterone as well because there is substantial
systemic absorption.
VI. SEXUAL DYSFUNCTION
Fifty percent of female dialysis patients under the age
of 55 are sexually active (2), and a majority of them
experience some sexual dysfunction. They suffer from
both decreased libido and decreased ability to achieve
orgasm. Treatment with erythropoietin (EPO) appears
to be associated with an improvement in sexual func-
tion, but most of the data collected have been in men
(36). Various reasons for sexual dysfunction have been
proposed, including hyperprolactinemia, gonadal dys-
function, depression, hyperparathyroidism, and change
in body image.
Hyperprolactinemia is seen in 75–90% of female

dialysis patients (37–39). The mean serum prolactin
levels in women with sexual dysfunction are higher
than in patients with normal sexual function. Treatment
of hyperprolactinemia with the dopamine agonist
bromergocriptine has been reported (in limited uncon-
trolled studies) to improve sexual function in both men
and women on dialysis (40). It has not come into wide-
spread use because hemodialysis patients are particu-
larly susceptible to the hypotensive effects of this drug.
There are no reports of its use in CAPD patients or on
the use of other dopamine agonists. Bromocriptine
should be started at a dose of 1.25 mg, and the first
dose should be taken at night. Subsequent doses can
be gradually increased. Doses of 2.5 mg bid should be
adequate to suppress prolactin secretion. When cor-
rectable physical problems cannot be found, dialysis
patients should be referred for sex therapy, as would
patients without renal failure.
VII. HORMONE REPLACEMENT
THERAPY
Holley and colleagues found that only 5% of women
aged 55 or greater at the time of starting dialysis were
receiving hormone replacement therapy. No firm guide-
714 Hou and Grossman
lines for hormone replacement therapy have been de-
veloped in dialysis patients. Hormone replacement
therapy in healthy women slightly increases the risk of
breast cancer while reducing the risk of osteoporosis
and heart disease. It is not known whether the risk of
breast cancer would be higher in dialysis patients than

in healthy women, but the risk of heart disease and
bone disease are clearly increased. In the absence of
specific data, these risks make treatment of postmeno-
pausal women on dialysis with estrogen-progesterone
cycling a reasonable approach. As noted, many women
younger than 55 years of age have estrogen deficiency.
Hormone replacement therapy is the standard of care
for premenopausal women who undergo oophorec-
tomy. Although it is not general practice, there is every
reason to think that dialysis patients who are estrogen
deficient should receive replacement therapy. An ex-
perienced gynecologist may have to try a number of
combinations of these hormones to find a regimen that
does not cause excessive bleeding.
There is limited experience with the use of other
treatments for osteoporosis in dialysis patients. The use
of alendronate in patients with creatinine clearance of
<35 mL is not recommended by the manufacturer be-
cause of lack of experience, not because of known ad-
verse effect. A large portion of the drug is excreted by
the kidneys, and a dose adjustment would be necessary.
The efficacy of alendronate in decreasing steroid-in-
duced osteoporosis has heightened interest in its use in
renal disease, and its use in dialysis patients is now an
area of active investigation (41).
VIII. DYSFUNCTIONAL UTERINE
BLEEDING
A. Incidence
Many women develop amenorrhea when the glomeru-
lar filtration rate falls to less than 10 mL/min. Men-

struation returns in as many as 50% of premenopausal
women once dialysis is started. Over half of women
with end-stage renal disease (ESRD) who menstruate
report hypermenorrhea (2), and 60% have irregular cy-
cles, with similar menstrual abnormalities in hemodi-
alysis and CAPD patients. Dysfunctional uterine bleed-
ing is common and is of concern because it may be an
early sign of endometrial cancer. Blood loss may lead
to severe anemia even in women treated with EPO,
although the introduction of EPO has made the man-
agement of dysfunctional uterine bleeding substantially
easier.
B. Management
1. Screening for Malignancy
Management of dysfunctional uterine bleeding depends
on the woman’s age and on whether menses have
ceased. In women >40 years of age who have had no
menses for one year prior to the bleeding episode, can-
cer risk is high and dilatation and curettage should be
performed. In women >40 years of age whose men-
struation has not ceased for 1 year prior to bleeding,
the cancer risk is moderate. Dilatation and curettage is
not routinely necessary, and performance of several en-
dometrial biopsies is probably sufficient to screen for
malignancy. In women <40 years of age, the cancer
risk is relatively small, and a yearly Pap smear is usu-
ally a sufficient screen for tumor. Women who have
been exposed to immunosuppression either for treat-
ment of their renal disease or for a transplant that has
failed are at increased risk for malignancy.

2. Bloody Peritoneal Dialysate
Menstruation, ovulation, or uterine bleeding from any
cause can result in bloody peritoneal fluid in peritoneal
dialysis patients. There is no specific management, and
treatment is rarely necessary unless there is profuse
bleeding. In rare cases, frank hemoperitoneum may oc-
cur, requiring suppression of ovulation (42). An aseptic
peritonitis picture during menstruation or ovulation has
also been reported (43).
3. Anticoagulation
The lowest possible dosage of heparin should be used
to perform hemodialysis when a woman is menstruat-
ing. Heparin-free techniques and citrate anticoagulation
also are available.
4. Hormone Therapy
Recent advances in therapy have facilitated the man-
agement of dysfunctional uterine bleeding in women
with end-stage renal disease.
Oral contraceptives remain the safest therapy and
the first-line treatment, although they should not be
used if hypertension control is a problem or if there is
a history of deep vein thrombosis. There are theoretical
benefits of using estrogen-progesterone combinations
to prevent uterine cancer and osteoporosis.
Medroxyprogesterone acetate (Depo-Provera) can be
given in a dose of 100 mg IM once a week for 4 weeks
and then once a month. Because many dialysis patients
have a platelet dysfunction, IM injections may result in
Problems of Women on Dialysis 715
hematoma formation. Moreover, the half-life of IM

medroxyprogesterone acetate is unpredictable. Medrox-
yprogesterone acetate is best reserved for patients with
chronic hypermenorrhea who do not respond to oral
hormonal therapy. In women whose hypermenorrhea
does not respond to oral contraceptives or progestins,
gonadotropin-releasing hormone agonists can be used.
The dosage is 7.5 mg of long-acting leuprolide acetate
IM, monthly. This drug is extremely expensive. There
is one report of ovarian hyperstimulation in a patient
on chronic dialysis who received two doses of leu-
prolide acetate (44). It has been postulated that women
with ESRD may be at risk for this complication be-
cause of decreased excretion of the gonadotropin-re-
leasing hormone agonists. The use of leuprolide should
be undertaken by a gynecologist familiar with the prob-
lems of patients with end-stage renal disease.
In the case of acute excessive blood loss, high-dose
estrogen therapy can be used, giving 25 mg of conju-
gated estrogens IV every 6 hours. Bleeding usually
subsides within 12 hours.
In setting of acute blood loss when bleeding time is
prolonged, DDAVP can be used as it is in with other
bleeding problems, in a dosage of 0.3 pg/kg in 50 mL
of saline given every 4–8 hours for three to four doses.
5. Nonhormonal Treatments
a. Laser Ablation
The neodymium (Nd):YAG laser now offers a safe and
effective alternative to hysterectomy. With this tech-
nique, the endometrial lining is ablated by vaporizing
all three of its layers. Patients are pretreated with either

danazol 200 mg four times daily for 4–6 weeks or with
gonadotropin-releasing hormone agonists. The tech-
nique requires a surgeon trained and experienced in
operative hysteroscopy and the use of the Nd:YAG la-
ser. The procedure leads to permanent infertility.
b. Hysterectomy
For postmenopausal women with significant dysfunc-
tional uterine bleeding, hysterectomy is a possible ap-
proach. The proposed operation should be carefully
discussed with the patient, and concomitant medical
problems and the risks of surgery should be taken into
consideration. With the advent of endometrial ablation
with laser, hysterectomy will now probably be reserved
for women who have bleeding secondary to uterine fi-
broids or to other uterine or pelvic pathology that in
itself warrants the surgery. Hysterectomy should be
done only as a life-saving procedure in a premenopau-
sal woman who is a candidate for renal transplantation,
because the latter will frequently restore fertility.
6. Gynecological Neoplasms
a. Benign
Uterine fibroids, or leiomyomata, are extremely com-
mon, occurring in approximately 25% of women over
the age of 30. There is no information about their fre-
quency in chronic renal failure. In dialysis patients
without serious comorbidities, the management of uter-
ine fibroids is similar to the approach in women with-
out renal failure.
b. Incidence of Malignant Tumors
Although it was previously believed that the incidence

of endometrial carcinoma is increased in female dial-
ysis patients, several recent studies suggest that breast,
endometrial, and ovarian cancers are not increased in
this population.
c. Screening
Guidelines for breast cancer screening are given similar
to those given for the general population. Pap smears
should be done yearly to screen for cervical cancer in
dialysis patients. Women who have had immunosup-
pressive therapy, because of either previous transplan-
tation or underlying renal disease, or women with
AIDS should have PAP smears every 6 months because
of the increased incidence of cervical cancer in these
populations. Endometrial cancer usually presents as
dysfunctional uterine bleeding, the investigation and
management of which have been discussed above.
Ovarian cancer usually presents with vague abdominal
symptoms and later as an ovarian mass. Abdominal dis-
comfort, nausea, and weight loss induced by ovarian
cancer may initially be misinterpreted as symptoms of
uremia or underdialysis. In patients on peritoneal di-
alysis, ovarian cancer may present as bloody peritoneal
fluid, an abnormal peritoneal cell count, or a change in
the color of the fluid. A high index of suspicion is nec-
essary to detect ovarian cancer at an early and poten-
tially curable stage.
IX. DIAGNOSTIC TESTS FOR
GYNECOLOGICAL DISEASE IN
DIALYSIS PATIENTS
A. Computed Tomography

Intravenous contrast infusion, if needed to perform a
CT scan or angiography, is not contraindicated in a
716 Hou and Grossman
dialysis patient. Although the administration of contrast
involves increasing intravascular volume and osmolal-
ity, immediate dialysis following the study can be per-
formed if deemed necessary. A patient on peritoneal
dialysis requiring an abdominal CT scan can present
for the examination with dialysis fluid in the abdomen.
B. Pelvic and Abdominal Ultrasonography
The patient on peritoneal dialysis with a suspected pel-
vic or ovarian lesion should undergo ultrasound scan-
ning of the involved area. In those instances where pel-
vic pathological changes cannot be visualized without
distending the bladder, the latter can be filled via a
Foley catheter. Hyponatremia will result from mis-
guided attempts by ultrasound personnel to fill the
bladder by having the patient drink water.
C. Transvaginal Ultrasound
Pelvic abnormalities can be delineated more clearly us-
ing transvaginal ultrasound because of the proximity of
the probe to the pelvic organs and the relatively thin
vaginal vault, which enables the use of higher sound
frequencies and therefore higher resolution. On the
other hand, the transabdominal probe will give a more
panoramic view of the pelvis, showing the interrela-
tionship of the major anatomic structures in the pelvic
organs and their pathology. The transvaginal probe is
able to furnish a more focused image of the organ of
interest but permits effective imaging to no more than

7–10 cm in depth. The transvaginal ultrasound study
is best done while the bladder is empty. Since many
patients on dialysis are not able to fill their bladders
unless a Foley catheter is placed and fluid instilled into
the bladder, it makes sense to first perform a trans-
vaginal ultrasound if the pelvic pathology is suspected
and proceed to transabdominal pelvic sonogram if the
information needed cannot be obtained with the trans-
vaginal approach. CAPD patients should have the ab-
domen full for transabdominal ultrasound and empty
for transvaginal ultrasound.
X. MANAGEMENT
The management of gynecological cancers and non-
malignant tumors in women with chronic renal failure
includes surgical excisions and chemotherapy.
A. Surgery
The general approach to performing surgery in dialysis
patients is discussed elsewhere. There are several ad-
ditional points that pertain specifically to gynecological
procedures. In patients with peritoneal catheters under-
going pelvic or abdominal operations, the catheter can
be left in place unless there is bacterial contamination
of the peritoneal cavity. When there is a low but mea-
surable risk of peritoneal contamination as in a vaginal
hysterectomy, 1.0 g of vancomycin hydrochloride and
1.0 g of cefoxitin can be administered prophylactically,
IV, just prior to surgery. If the patient is known to be
colonized with Pseudomonas, tobramycin 2.0 mg/kg
IV should be added to the prophylactic regimen. Post-
operatively, the catheter is irrigated with 500 mL of

peritoneal dialysis solution three times daily to main-
tain patency. Irrigations are decreased to once daily
when the fluid is no longer bloody. The patient can be
maintained on hemodialysis for 10 days to 2 weeks
before the peritoneal catheter is used again.
B. Chemotherapy
Use of chemotherapeutic agents in dialysis patients is
discussed elsewhere. Chemotherapeutic agents have
been given via the intraperitoneal route in patients with
normal renal function who have intraabdominal tumors
and occasionally in peritoneal dialysis patients. Intra-
peritoneal installation of chemotherapeutic agents re-
sults in local concentrations of drugs 10–20 times
higher than systemic levels as well as high portal vein
concentrations. Drugs that have been used intraperito-
neally include 5-fluorouracil (5 FU), cisplatinum, cy-
tarabine, and doxorubicin. 5-FU and doxyrubicin can
be given in the usual doses intraperitoneally, but the
dose of cisplatinum should still be reduced to 25% of
the usual dose.
C. Transplantation After Curative Resection
of Gynecological Neoplasms
Because immunosuppression increases the risk of tu-
mor, most transplant centers wait 2–5 years before
transplanting a patient who has had a malignancy. Early
stages of cervical cancer do not contraindicate trans-
plantation, but transplantation after treatment, thought
to be curative, of other tumors must be individualized
according to prognosis.
XI. GYNECOLOGICAL INFECTIONS

Female dialysis patients are subject to the same infec-
tions that occur in women without renal disease. Some
changes in treatment are required because of the effect
of renal failure and dialysis on drug metabolism.
Problems of Women on Dialysis 717
Candida albicans is the most common cause of vul-
vovaginitis. Treatment is not affected by either renal
failure of dialysis. Similarly, the treatment of nonspe-
cific vaginitis is not changed. Metronidazole should be
taken after dialysis. There have been rare cases of fun-
gal peritonitis with torulopsis resulting from vaginal
infections in peritoneal dialysis patients.
A. Chlamydia and Mycoplasma
These organisms are often the cause of nonspecific vag-
initis that does not respond to metronidazole therapy.
In addition, they are major causes of infertility and pel-
vic inflammatory disease. Treatment is to administer
doxycycline 100 mg daily for 14 days. Other tetracy-
clines should be avoided in dialysis patients. Alterna-
tive regimens include a single 1 g dose of azithromy-
cin, ofloxacin 150 mg daily for 7 days, or erythromycin
500 mg po qid for 14 days. Only ofloxacin and doxy-
cycline also treat gonorrhea. Sexual partners should
also be treated.
B. Genital Herpes
Oral acyclovir has been shown to shorten the intensity
and duration of first-time infections with genital herpes.
Acyclovir is normally excreted by the kidney and is
dialyzable. When herpetic infection is severe enough
to warrant use of acyclovir, the drug should be given

in a reduced dosage of 200 mg po bid, with the doses
scheduled in such a way that one is normally given
after a dialysis session.
C. Gonorrhea
In many locations, ceftriaxone has become the initial
drug of choice because of the increased incidence of
penicillin-resistant gonococci. The one-time 250 mg
IM dosage is not changed for dialysis patients. Treat-
ment with penicillin follows usual dosage regimens.
Probenecid, included in the usual regimen to retard re-
nal excretion of penicillin, need not be given when
treating dialysis patients. If the patient is allergic to
penicillin, doxycycline in the usual dosage can be ad-
ministered. Therapy of resistant strains should be
guided by local information, and sensitivity results.
D. Syphilis
The treatment of syphilis is unchanged in the dialysis
patient. Staff should be aware that secondary syphilis
is highly contagious through blood contact. Dialysis
machines should be cleaned with formaldehyde or so-
dium hypochlorite solution after use in a patient with
secondary syphilis.
E. Human Papillomavirus
Human papillomavirus (HPV) infection has become
one of the most common sexually transmitted diseases
in the United States. Patients may present with venereal
warts or with an abnormal Pap smear. There is no dif-
ference in therapy of this infection for dialysis patients.
Women with HPV infections can be referred for trans-
plantation but should be aware of the risk of aggrava-

tion of the disease following transplant. (Treatment of
sexually transmitted hepatitis and HIV is discussed
elsewhere in this volume.)
XII. CONCLUSION
With the improved survival of women treated with di-
alysis, our care of them should address obstetric and
gynecological problems. When pregnancy occurs, it re-
quires extreme vigilance to minimize the risk to the
mother and careful management to increase the likeli-
hood of a successful outcome. With increased under-
standing of the causes of infertility in women with re-
nal failure and development of management strategies
that result in healthy mothers and infants, we may
reach the point of actively helping these women at-
tempt pregnancy. Management of hormonal abnormal-
ities, estrogen-replacement therapy, and common gy-
necological problems, including dysfunctional uterine
bleeding, tumors, and infection, needs to be incorpo-
rated into our treatment of these women.
REFERENCES
1. Perez RJ, Lipner H, Abdulla N, Cicotto S, Abrams M.
Menstrual dysfunction of patients undergoing hemodi-
alysis. Obstet Gynecol 1978; 51:552–555.
2. Holley JL, Schmidt RJ, Bender FH, Dumler F, Schiff
M. Gynecologic and reproductive issues in women on
dialysis. Am J Kidney Disease 1997; 29:685–690.
3. Souqiyyeh MZ, Huraib SO, Saleh AGM, Aswad S.
Pregnancy in chronic hemodialysis patients in the King-
dom of Saudi Arabia. Am J Kidney Disease 1992; 19:
235–238.

4. Okundaye IB, Abrinko P, Hou SH. A registry for preg-
nancy in dialysis patients. Am J Kidney Dis 1998; 31:
766–773.
718 Hou and Grossman
5. Bagon JA, Martens J, Van Roost G, Vernaeve H, De
Muylder X. Pregnancy and dialysis Am J Kidney Dis
1998; 31:756–765.
6. Registration Committee of the European Dialysis and
Transplant Association. Successful pregnancies in
women treated by dialysis and kidney transplantation.
Br J Obstet Gynecol 1980; 87:839–845.
7. Hou SH. Pregnancy in women on haemodialysis and
peritoneal dialysis. Baillie`re’s Clin Obstet Gynaecol
1994; 8:481–500.
8. Schwartz A, Post KG, Keller F, Molzhan M. Value of
human chorionic gonadotropin measurements in blood
as a pregnancy test in women on maintenance hemo-
dialysis. Nephron 1985; 39:341–343.
9. Hanssens M, Keirse MJNC, Vankelecom F, Van Assche
FA. Fetal and neonatal effects of angiotensin converting
enzyme inhibitors during pregnancy. Obstet Gynecol
1991; 78:128–135.
10. Briggs GG, Freeman RK, Yaffe SJ, eds. Drugs in Preg-
nancy and Lactation. Baltimore: Williams and Wilkins,
1994.
11. Cockburn J, Moar VA, Ounsted MK, Good FJ, Redman
CWG. Final report of study on hypertension during
pregnancy: the effects of specific treatment on growth
and development of the children. Lancet 1982; 1:647–
649.

12. Gladstone GW, Hordof A, Gersony WM. Propranolol
administration during pregnancy: effects on the fetus.
Pediatrics 1975; 86:962–964.
13. Pruyn SC, Phelan JP, Buchanan GC. Long term pro-
pranolol therapy in pregnancy: maternal and fetal out-
come. Am J Obstet Gynecol 1979; 135:485–489.
14. Cottle MKW, Van Petten GR, van Muyden P. Maternal
and fetal cardiovascular indices during fetal hypoxia
due to cord compression in chronically cannulated
sheep. Am J Obstet Gynecol 1983; 146:678–685.
15. Plouin PF, Breart G, Maillard F, Relier JP, Breart G,
Papiernik E, the Labetalol Methyl Dopa Study Group.
Comparison of antihypertensive efficacy and perinatal
safety of labetalol and methyldopa in the treatment of
hypertension in pregnancy: a randomized controlled
trial. Br J Obstet Gynecol 1988; 95:868–876.
16. Horvath JS, Phippard A, Korda A, Henderson-Smart
DJ, Child A, Tiller DJ. Clonidine hydrochloride-a safe
and effective antihypertensive agent in pregnancy. Ob-
stet Gynecol 1985; 66:634–638.
17. Waisman GD, Davis N, Davey DA, et al. Magnesium
plus nifedipine: Potentiation of hypotensive effect in
preeclampsia? Am J Obstet Gynecol 1988; 159:308–
309.
18. Dynder SW, Cardwell MS. Neuromuscular blockade
with magnesium sulfate and nifedipine. Am J Obstet
Gynecol 1988; 161:35–36.
19. Kaler SG, Patrinos ME, Lambert GH, Myers TF, Karl-
man R, Anderson CL. Hypertrichosis and congenital
anomalies associated with maternal use of minoxidil.

Pediatrics 1987; 79:434–436.
20. Bhorat IE, Naidoo DP, Rout CC, Moodley J. Malignant
ventricular arrhythmias in eclampsia: a comparison of
labetolol with dihydralazine. Am J Obstet Gynecol
1993; 168:1292–1296.
21. Sibai BM. Drug therapy: treatment of hypertension in
pregnant women. N Engl J Med 1996; 335:257–265.
22. Hedstrom S, Martens MG. Antibiotics in pregnancy.
Clin Obstet Gynecol 1993; 36:886–892.
23. Jacobi P, Ohel G, Szylman P, Levit A, Lewin M, Paldi
E. Continuous ambulatory peritoneal dialysis as the pri-
mary approach in the management of severe renal in-
sufficiency in pregnancy. Obstet Gynecol 1992; 79:
808–810.
24. Gadallah MF, Ahmad B, Karubian F, Campese VM.
Pregnancy in patients on chronic ambulatory peritoneal
dialysis. Am J Kidney Dis 1992; 20:407–410.
25. Tison A, Lozowy C, Benjamin A, Usher R, Pritchard
S. Successful pregnancy complicated by peritonitis in
a 35-year-old CAPD patient. Perit Dial Int 1996; 16:
S489–S491.
26. Hou SH, Orlowski J, Pahl M, Ambrose S, Hussey M,
Wong D. Pregnancy in women with end stage renal
disease: treatment of anemia and premature labor. Am
J Dis Kidney 1993; 21:16–22.
27. Redrow M, Cherem L, Elliot J, Mangalat J, Mishler RE,
Bennet WM, Lutz M, Sigala J, Byrnes J, Phillipe M,
Hou S, Schon D. Dialysis in the management of preg-
nant patients with renal insufficiency. Medicine 1988;
67:199–208.

28. Roma˜o JE, Luders C, Kahhale S, Pascoal IJF, Abensur
H, Sabbaga E, Zugaib M, Marcondes M. Pregnancy in
women on chronic dialysis. Nephron 1998; 78:416–
422.
29. Ginsberg JS, Kowalchuk G, Hirsh J, Brill-Edwards P,
Burrows R. Heparin therapy during pregnancy. Arch
Intern Med 1989; 149:2233–2236.
30. Lester GL: Cholecalciferol and placental calcium trans-
fer. Fed Proc 1986; 2524–2527.
31. Marx SJ, Swart EG, Hamstra AJ, DeLuca HF. Normal
intrauterine development of the fetus of a woman re-
ceiving extraordinarily high doses of 1,25, dihydroxy-
vitamin D
3
. J Clin Endocrinol Metab 1980; 51:1138–
1142.
32. Brookhyser J, Wiggins K. Medical nutrition therapy in
pregnancy and kidney disease. Adv Ren Replacement
Ther 1998; 5:53–63.
33. Czeizel AE, Duda´s I. Prevention of the first occurrence
of neural tube defects by periconceptional vitamin sup-
plementation. N Engl J Med 1992; 327:1832–1835.
34. Pitkin RM and Committee on Nutritional Status During
Pregnancy and Lactation, Institute of Medicine, Na-
tional Academy of Sciences, eds. Nutrition During
Pregnancy, Washington, DC: National Academy Press,
1990.
35. Hussey MJ, Pombar X. Obstetric care for renal allograft
recipients or for women treated with hemodialysis or
Problems of Women on Dialysis 719

peritoneal dialysis during pregnancy. Adv Ren Replace-
ment Ther 1998; 5:3–13.
36. Bommer J, Kugel M, Schwobel B, Ritz E, Barth HP,
Seelig R. Improved sexual function during recombinant
human erythropoietin therapy. Nephrol Dial Transplant
1990; 5:204–207.
37. Lim VS, Kathpalia SC, Frohman LA. Hyperprolacti-
nemia and impaired pituitary response to suppression
and stimulation in chronic renal failure: reversal after
transplantation. J Clin Endocrin Metab 1979; 48:101–
107.
38. Hou SH, Grossman S, Molitch ME. Hyperprolactine-
mia in patients with renal insufficiency and chronic re-
nal failure requiring hemodialysis or continuous am-
bulatory peritoneal dialysis. Am J Kidney Dis 1985; 6:
245–249.
39. Gomez F, De La Cueva R, Wauters JP, Lemarchand-
Be´raud T. Endocrine abnormalities in patients under-
going long-term dialysis. Am J Med 1980; 68:522–530.
40. Muir JW, Besser GM, Edwards CRW, Rees LH, Cattell,
Ackrill P, Baker LRI. Bromocriptine improves reduced
libido and potency in men receiving maintenance he-
modialysis. Clin Nephrol 1983; 26:308–314.
41. Saag KG, Emkey R, Schnitzer TJ, Brown JP, Hawkins
F, Goemaere S, Thamsborg G, Liberman UA, Delmas
PD, Malice MP, Czachur M, Daifotis AG, Glucocorti-
coid-Induced Osteoporosis Study Group. Alendronate
for the prevention and treatment of glucocorticoid-in-
duced osteoporosis. N Engl J Med 1998; 339:292–299.
42. Harnett JD, et al. Recurrent hemoperitoneum in women

receiving continuous ambulatory peritoneal dialysis.
Ann Intern Med 1987; 107:341.
43. Poole CL, et al. Aseptic peritonitis associated with men-
struation and ovulation in a peritoneal dialysis patient.
In Khanna R, et al., eds. Advances in Continuous Am-
bulatory Peritoneal Dialysis. Toronto: Peritoneal Dial-
ysis Bulletin, 1987.
44. Hampton HL, Whitworth NS, Cowan BD. Gonadotro-
pin-releasing hormone agonist (leuprolide acetate) in-
duced ovarian hyperstimulation syndrome in a woman
undergoing intermittent hemodialysis. Fertil Steril
1991; 55:429.
45. Nakamura Y, Yoshimura Y. Treatment of uterine her-
onyomias in premenopausal women with gonadotropin-
releasing hormone agonists. In Pitkin RM and Scott JR,
ed. Clinical Obstetrics and Gynecology 36: 9/93.
721
41
Complications During Plasma Exchange
Andre´ A. Kaplan
University of Connecticut Health Center, Farmington, Connecticut
I. TECHNIQUES
A. Standard Plasmapheresis
Automated plasma exchange was originally performed
with centrifugation devices used in blood blanking pro-
cedures. These devices offer the advantage of allowing
for selective cell removal (cytapheresis) (1). Plasma
exchange can also be performed with a highly perme-
able filter and standard dialysis equipment, a technique
often referred to as membrane plasma separation

(MPS) (2). A detailed review of the available removal
systems has been provided by Sowada et al. (3).
Centrifugal systems utilize G forces to separate the
plasma into its different components. Separation of the
plasma can be either intermittent or continuous. In the
intermittent system, whole blood is collected into a re-
ceptacle (bowl) and centrifuged down to its plasma and
cellular components. After separation, the cellular com-
ponents are resuspended in an appropriate amount of
replacement solution (e.g., albumin, fresh frozen
plasma) and subsequently returned to the patient.
Newer devices utilize a continuous flow system in
which the whole blood is processed in an ongoing, on-
line manner.
Separation of plasma from the blood’s cellular com-
ponents can also be accomplished by filtration through
a highly permeable membrane. This methodology sep-
arates the blood into its cellular and noncellular com-
ponents by subjecting it to sieving through a membrane
whose pores allow the plasma proteins to pass but that
retain the larger cellular elements within the blood
path. Configuration of the semi-permeable membrane
can be in a layered flat plate design (3), rolled in a tube
(4), or in bundles of hollow fibers (2). The hollow fiber
configuration can be used with standard dialysis equip-
ment with the filter connected to the blood pump and
pressure monitoring system while the dialysis machine
is utilized in its ‘‘isolated’’ ultrafiltration mode, which
bypasses the dialysate proportioning system.
B. Selective Plasmapheresis

Many imaginative techniques have been designed to
selectively remove a particular pathogenic substance
from the plasma, allowing the majority of the plasma
to be returned to the patient, thus minimizing the risks
of depletion coagulopathy and hypogammaglobuline-
mia (Table 1) (5).
Cascade filtration or double filtration plasmapheresis
is a selective method of plasma fractionation in which
the whole plasma separated from the cellular compo-
nents is refiltered through a secondary filter with a
smaller pore size in order to separate out the larger,
unwanted molecules (6). This type of selective removal
will limit the amount of replacement fluid required by
allowing most of the smaller molecules, such as albu-
min (60,000 daltons), to return to the patient. This
methodology has been used to selectively remove the
relatively large
␤
-lipoproteins (approximately 1 million
daltons), IgM (900,000 daltons), cryoglobulins, and im-
mune complexes.
Cryofiltration is a technique in which the removed
plasma is subjected to cooling, causing certain patho-
genic substances to aggregate, thus increasing their
overall size and allowing for efficient secondary filtra-
722 Kaplan
Table 1 Plasmapheresis Techniques
Standard Plasmapheresis
Centrifugation
Plasma exchange

Cytapheresis
Filtration
Membrane plasma separation
Selective Plasmapheresis
Cascade filtration
Cryofiltration
Lipid apheresis
LDL immunoadsorption
Dextran binding
HELP system
Immunoadsorption
Protein A
Polymyxin B
Others
tion (7). The process can be used to selectively remove
cyroglobulins and immune complexes.
Selective lipid-removal techniques are employed for
the treatment of hypercholesterolemia and can limit the
loss of non–lipid-containing plasma proteins and the
desirable high-density lipoprotein (HDL) cholesterol.
Of these, three have undergone extensive clinical trials.
One is an immunoadsorbant system in which plasma is
perfused over sepharose beads coated with antibodies
against low-density lipoprotein (LDL) (8). Another is
a dextran sulfate system by which negatively charged
dextran molecules are covalently bound to the posi-
tively charged apoprotein B lipoproteins (9), and a third
is known as the HELP system and involves the extra-
corporeal precipitation of LDL lipoproteins by nega-
tively charged heparin (10).

C. Immunoadsorbant Techniques
There are several commercially available systems for
selective immunoadsorption of a variety of targets.
These systems may be designed for nonselective ad-
sorption of immunoglobulins, such as those employing
protein A, or for more selective targets, such as those
mentioned above for the specific immunoadsorption of
LDL cholesterol.
Protein A is a 42,000 dalton protein released from
certain strains of Staphylococcus aureus, which can be
used for the ex vivo adsorption of three of the four
classes of IgG (1, 2, and 4). Binding occurs at a par-
ticular site on the heavy chain of the immunoglobulin,
leaving binding sites for complement and antigens un-
affected (11). These devices may work by immuno-
modulation, with activation of immune modulators, or
by net removal of immunoglobulin.
Selective adsorption of endotoxin can be accom-
plished by filters impregnated with polymyxin B, an
antibiotic that has the particular propensity to bind en-
dotoxin fragments (12).
D. Anticoagulation
Regardless of the technique employed, therapeutic
plasma exchange (TPE) will normally require some
form of anticoagulation in order to avoid clotting
within the extracorporeal circuit. For centrifugal tech-
niques, this is often provided by citrate infusions,
which bind ionized calcium in the extracorporeal cir-
cuit such that the coagulation cascade is impeded. The
ionized calcium level returns towards its original level

as the blood is returned to the intravascular compart-
ment where there are substantial stores of ionized cal-
cium and where the citrate will be metabolized to bi-
carbonate. Rapid infusions of citrate may exceed the
patient’s capability to metabolize citrate and may lead
to hypocalcemia and alkalosis (see below). Membrane
plasma separation, using plasma-permeable filters,
commonly employs heparin anticoagulation in a man-
ner analogous to that used for hemodialysis.
II. COMPLICATIONS OF TPE
Several reviews have outlined the potential risks of
TPE (13–15), but there have been only a few large
series that allow the clinician to assess the incidence
of these complications (16–24). Reports from these
nine series, involving more than 15,000 TPE treat-
ments, reveal that the most common complications are
citrate-induced parethesias, muscle cramps, and urti-
caria (Table 2) (23). Serious complications are reported
at a rate of 0.025–0.2% and include life-threatening
anaphylactoid reactions, which are most commonly as-
sociated with the use of plasma-containing replacement
fluids (e.g., fresh frozen plasma, purified protein frac-
tion) (25). The overall incidence of death is 0.05%, but
some of these ‘‘treatment-associated’’ deaths were in
patients with severe preexisting conditions, and the
TPE treatment per se may not have been the precipi-
tating factor.
A. Citrate-Induced Hypocalcemia
During TPE, citrate may be infused either as the anti-
coagulant or in the fresh frozen plasma (FFP) admin-

Complications During Plasma Exchange 723
Table 2 Complications of Plasmapheresis
Centrifugal system
Borberg (16)
Aufeuvre
et al. (17)
Ziselman
et al. (18)
Fabre
et al. (19)
Rossi
et al. (20)
Membrane-based system
Sprenger
et al. (21)
Samtleben
et al. (22)
Mokrzycki
et al. (23)
Both
Sutton
et. al. (24)
No. of treatments 205 3,086 1,389 578 926 306 120 699 5,235
Adverse reactions 13% 22% 1.6% 25% 17.3% 4.2% 17.5% 9.7% 12%
Mild 0% 4.8% 0.4* 7.6% 0 5 5.4% 9%
Moderate 11.2% 16.4% 0.6%
23%
}
6.5% 4.2 12.5% 2.4% 3%
Severe 2% 0.6% 0.5% 1.5% 3.1% 0 0 0.7% 0.5%

Deaths 0 0.1% 0.1% 0 0 0 0 0 0
Symptoms
Urticaria 12% 0.7% 8.3% 2.4% 3.7%
Paresthesias 1.5% 9% 2.4% 5% 1.7%
Muscle cramps 0.4%
2.5%
}
Dizziness 15.8%
Headaches 1% 5% 0.3% 1.2%
Nausea 0.1% 0.2% 1% 0.6% 1.5%
Hypotension 0.4% 0.5% 1.6% 2% 4.2% 1.4% 2.3%
Chest pain 0.03% 0.1% 1.3% 0.2%
Dysrhythmia 0.2% 0.7% 0.1% 0.1%
Anaphylactoid reactions 0.05% 0.03% 0.7% 0.5%
Rigors 8.8% 1.1%
Hyperthermia 1.0% 5.3% 0.7%
Bronchospasm 0.4% 0.1%
Seizure 0.03% 0.4%
Respiratory arrest/
Pulmonary edema
0.3% 0.2%
Myocardial ischemia 0.1%
Shock/MI 1.5% 0.1% 0.1%
Metabolic alkalosis 0.03%
DIC 0.03%
CNS ischemia 0.03% 0.1%
Other 0.3% 0.8% 0.8%
Hepatitis 0.7%
Hemorrhage 0.2%
Hypoxemia 0.1%

Pulmonary embolism 0.1%
Access related
Thrombosis/hemorrhage 0.7% 0.02%
Infection 0.3%
Pneumothorax 0.1%
Mechanical 0.4% 1.2% 4% 1.5% 0.08%
MI = Myocardial infarction; DIC = disseminated intravascular coagulation; CNS = central nervous system.
Source: Adapted from Ref. 23.
724 Kaplan
Table 3 Percent Decrease in
Serum Levels of Coagulation
Factors After a Single
Plasma Exchange
Factor Percent
Fibrinogen 20
Prothrombin 40
Factor V 42
Factor VII 47
Factor VIII 50
Factor IX 57
Factor X 32
AT-III 42
Source: Modified from Ref. 33.
istered as the replacement fluid. Symptoms of citrate-
induced hypocalcemia represent one of the most
common complications and can occur in up to 9% of
treatments (23). The incidence is highest in those treat-
ments utilizing FFP as the replacement fluid, since this
preparation is approximately 15% citrate by volume.
Most often the patient will complain of perioral or dis-

tal extremity tingling or paresthesias. If severe, citrate-
induced hypocalcemia may be associated with prolon-
gation of the QT interval on electrocardiogram, thus
increasing the risk of cardiac arrhythmia (26,27).
Widely used protocols suggest that citrate toxicity
can be reasonably well controlled with the oral admin-
istration of calcium tablets during the procedure, re-
serving intravenous calcium replacement only for those
who develop symptoms. Another conservative ap-
proach involves decreasing the rate of plasma exchange
and decreasing the citrate to blood ratio and supple-
menting with heparin (24,28,29). Others have found
that prophylactic replacement of intravenous calcium
can significantly reduce the incidence of citrate-
induced paresthesias (23,30,31). In an in-depth review
of the topic, Hester et al. concluded that the incidence
of citrate-induced hypocalcemic symptoms could be re-
duced if the citrate-infusion rate was limited to between
1.0 and 1.8 mg/kg/min (26). If symptoms occurred de-
spite this limitation, they recommended an infusion of
10 mL of 10% calcium gluconate infused over 15
minutes approximately halfway through the procedure.
Kinetic studies have demonstrated that increases in
parathyroid hormone provide an endogenous compen-
satory response to calcium removal during TPE (28),
but patients receiving multiple treatments with albumin
replacement may experience a significant loss of cal-
cium amounting to approximately 150 mg per treat-
ment (31). In contrast, with supplementation calcium
balance can be positive.

Uhl et al. described a case of severe citrate toxicity
when the citrate infusion line became disengaged from
its rotary pump allowing a massive infusion of citrate
into the patient (32). Seven minutes into the procedure,
the patient developed signs and symptoms suggesting
severe hypocalcemia, including muscle spasms, chest
pain, and hypotension. Ionized calcium level was 0.64
mmol/L (normal range, 1.18–1.38 mmol/L).
B. Coagulation Abnormalities
1. ‘‘Depletion’’ Coagulopathy
Albumin solutions used for replacement fluid are de-
void of clotting factors, and a TPE treatment with al-
bumin as the replacement fluid will result in a depletion
of all coagulation factors, including fibrinogen and an-
tithrombin III (AT-III) (25,33,34). After a single plasma
exchange, the serum levels of most of these factors will
be decreased by approximately 40–60% (Table 3). Se-
rum levels of these factors rebound in a biphasic man-
ner, characterized by a rapid initial increase in the first
4 hours after treatment, followed by a slower increase
over the next few days (23). This dual rate of recovery
represents two phenomena: a reequilibration of extra-
vascular stores with the intravascular compartment and
a resynthesis of new clotting factors. Twenty-four hours
after treatment, fibrinogen levels are 50% and AT-III
levels are 85% of initial levels, while both factors may
require 48–72 hours for complete recovery (23). Pro-
thrombin time (PT) increases 30% and partial throm-
boplastin time (PTT) doubles immediately after a one
plasma volume exchange (31,35). Partial thromboplas-

tin time and thrombin time are back to normal range 4
hours postpheresis, while prothrombin time normalizes
in 24 hours (25).
When multiple treatments are performed over a
short period (three or more treatments per week), the
depletion in clotting factors is more pronounced and
may require several days for spontaneous recovery
(33–35). Under these conditions, the risks of hemor-
rhage can be minimized by substituting between 500
and 1000 mL (2–4 units) of FFP as the replacement
fluid towards the end of the procedure. This approach
is most helpful in patients who are immediately post-
surgery (e.g., thymectomy for myasthenia gravis), who
have had a recent renal biopsy (e.g., glomerulonephri-
tis), who have active hemoptysis (Goodpasture’s syn-
drome or Wegener’s granulomatosis), or in whom there
is a desire for the immediate removal of a large-bore
intravascular catheter.
Complications During Plasma Exchange 725
2. Thrombocytopenia
Thrombocytopenia may result from a loss of platelets
in the discarded plasma, as a result of thrombosis
within the plasma filter, as a consequence of heparin-
induced antiplatelet antibodies, or as a result of a mild
dilutional effect by the infusion of 5% albumin solu-
tion, which is relatively hyperoncotic compared to the
removed plasma (36). With the older centrifugal ma-
chines such as the Haemonetics V-50 (Haemonetics,
Braintree, MA), inefficient separation of the different
plasmatic components resulted in platelet losses with

the discarded plasma, and these treatments have been
associated with decreases in platelet counts of up to
50%. The newer centrifugal devices provide more ef-
ficient separation of the plasmatic components and a
more modest loss of platelets. Membrane plasma sep-
aration (MPS) can result in a 15% decrease in platelet
count, possibly related to partial thrombosis within the
filter (1,25,31,37). Because heparin is more commonly
used as the anticoagulant, heparin-induced antiplatelet
antibodies are also more likely to occur with MPS.
3. Anemia
Posttreatment decreases in hematocrit may result from
hemorrhage associated with the vascular access, from
substantial clotting in the extracorporeal circuit, or
from treatment-related hemolysis. Initiation of treat-
ment with a membrane plasma separator is often as-
sociated with a minimal amount of plasma tinting,
which is rarely a cause for significant blood loss and
can be quantified by measuring the free hemoglobin
levels in the collected plasma. In most cases, plasma
tinting lasts for only a few seconds; if persistent, the
blood flow should be slowed in order to lower the
transmembrane pressure. Hemolysis can also occur in
centrifugal systems as a result of hypotonic priming
solutions. Even in the absence of any extracorporeal
losses or hemolysis, hematocrits may decrease by 10%
after each treatment, a phenomenon that may be due
to intravascular expansion related to the use of rela-
tively hyperoncotic replacement fluids (5% albumin)
(31,36,38).

4. Thrombosis
TPE treatments using albumin replacement will cause
a relative depletion of all coagulation factors, including
inhibitors of coagulation such as AT-III. In one report,
two episodes of thrombosis were associated with a
postpheresis depletion of AT-III and this deficiency
may have resulted in a hypercoaguable state (39).
Thrombosis has also been associated with the pro-
longed use of indwelling vascular catheters (23). Pul-
monary embolism, cerebral ischemia, and myocardial
infarction have been reported to occur in association
with TPE, but the incidence is rare (0.06–0.14%)
(18,40). An association with low levels of AT-III is
speculative, especially since these patients will also
have a concomitant depletion of ‘‘pro’’ coagulant fac-
tors (see above).
C. Infections
Aside from the infections related to indwelling vascular
catheters, the risk of infection associated with TPE can
be divided into two broad categories: those that may
be the result of a posttreatment depletion of immuno-
globulins, a situation most likely to occur when the
replacement fluid is mostly albumin, and those that oc-
cur as a result of viral transmission from the replace-
ment fluid, most likely to occur when the replacement
fluid is fresh frozen plasma.
1. Postpheresis Infection
TPE using albumin as the replacement fluid will result
in a predictable decline in levels of immunoglobulins
and complement and may predispose patients to high

rates of infection. One plasma volume exchange will
result in a 60% reduction in serum immunoglobulin
levels and a net 20% reduction in total body immu-
noglobulin stores (31,36). Multiple treatments over
short periods, especially when associated with immu-
nosuppressive agents, will yield more substantive de-
creases in immunoglobulin levels that may persist for
several weeks (41,42). Although concentrations of C3
and C4 may be reduced by a series of daily treatments,
because of rapid resynthesis (short half-lives), levels of
these proteins rebound within several days. CH50 can
be predictably lowered to about 40% of its initial value
immediately after a given treatment but rebound to pre-
treatment values occurs within one day, and even re-
petitive daily treatments have a minimal effect on this
parameter (41). Therapeutic plasma exchange with FFP
replacement would not be expected to deplete immu-
noglobulin or complement levels.
The incidence of infection in patients undergoing
TPE varies widely. Wing et al. compared the incidence
of infection in patients with rapidly progressive
glomerulonephritis (RPGN) who received standard
therapy (steroids and cytotoxic agents) with or without
plasma exchange (43). The apheresis-treated group had
a higher occurrence of infection, but some of the con-