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S E C T I O N V I I   Pediatric Critical Care: Renal

Sensitized Recipient
The presence of preformed HLA antibodies is likely to result in
severe antibody-mediated rejection and early allograft loss. Several different assays are available to determine the sensitivity (i.e.,
presence of HLA antibodies) of a potential transplant recipient
to donor HLA antigens. These assays typically test for the presence of HLA antibodies by testing the serum from the recipient
to a panel of HLA antigens or lymphocytes from different donors. Patient sensitization is classically reported as the percent
panel reactive antibody (PRA) and is an estimate of the likelihood of a positive crossmatch to a pool of potential donors. The
PRA is reported as historical (the highest value recorded on previous testing) and as current PRA. Leading causes of the sensitized recipients include blood transfusion, pregnancy, and prior
transplantation.

Surgical Procedure
The transplanted kidney is usually placed in an extraperitoneal
location when possible to allow for easier clinical monitoring and
access to the graft. In an infant or small child, it may be placed
intraperitoneally. Occasionally, native nephrectomy is needed at
the time of transplantation. Indications for nephrectomy include
(1) need for space, such as in the case of polycystic kidney disease,
especially in patients with massively enlarged kidneys; (2) uncontrolled renal-related hypertension; (3) persistent recurrent infections in native kidneys; (4) polyuria; and (5) nephrotic syndrome.
Native nephrectomy is often needed in patients with nephrotic
syndrome, either congenital or acquired. In this case, nephrectomies need to be done at least 3 months before transplantation so
that the nephrotic hypercoagulable physiology corrects in order to
minimize the risk of vascular thrombosis.
The aorta and inferior vena cava are usually used for anastomosis to ensure adequate blood flow, but smaller vessels may be used.
These anastomoses may be difficult in children who have had
previous hemodialysis accesses in the lower extremities. A thorough evaluation of the vasculature is important prior to transplantation. Cold ischemia time refers to the period of cold storage or
machine perfusion. Cold ischemia time of more than 24 hours is
associated with an increased risk of delayed graft function. Surgical teams make every effort to minimize cold ischemia time.

Warm ischemia time refers to the period between circulatory arrest and commencement of cold storage, with a goal of less than
60 minutes.
Serious urologic anomalies are present in many children who
undergo renal transplantation, the most common being posterior
urethral valves and vesicoureteral reflux. Some of these children
have undergone urinary diversion or bladder augmentation as a
consequence of these malformations. In children with significant
bladder abnormalities, urology should be part of the pre- and
postoperative multidisciplinary transplantation team caring for
these patients in order to optimize outcomes.

Multiorgan Transplantation
In general, genetic or anatomic disease that affects both the kidney and one other organ, such as polycystic kidney disease (may
affect both liver and kidney) can serve as an indication for multiorgan transplantation. Each transplantation can be performed simultaneously or at different time points. In some circumstances,
a liver-kidney transplantation can be performed for diseases

resulting from abnormalities in liver function that affect kidney
function. These include primary hyperoxaluria and forms of
atypical hemolytic uremic syndrome in which the disease may
result from deficiency in factor H. Kidney disease following heart
transplantation is rare in pediatric practice, but there have been
cases in which ESRD can require treatment with renal transplantation. Kidney-pancreas transplantation is very rare in children;
however, there are cases in which diabetic nephropathy results in
ESRD in older children and young adults.

Immediate Arrival to the Pediatric Intensive
Care Unit (Boxes 76.1, 76.2, and 76.3)
Initial assessment of patients upon arrival to the pediatric intensive care unit (PICU) includes assessment of routine respiratory
and hemodynamic stability. The majority of children are extubated, with the occasional exception of the youngest recipients
who weigh around 10 kg. Sign out from the anesthesia and OR

team should include details on the intraoperative blood pressures,
central venous pressure (CVP), volume administered, metabolic
correction, urine output, and any bleeding or need for transfusion. The surgeon reports the cold and warm ischemia times and
any surgical concerns. It is at this time that the PICU team, along
with the surgery and nephrology team, establish goals for the next
24 hours; target low and high blood pressure goals for which fluid
• BOX 76.1 Immediate Pediatric Intensive Care

Unit Arrival
• Discuss blood pressure target parameters
• Low blood pressure goal that would require fluid bolus
• High blood pressure that would require PRN hypertension medications
• Set target central venous pressure
• Discuss urine output parameters
• Urine output ,1 mL/kg/h or decrease in urine output by 50% from
previous hour
• Gross hematuria
• Fluid management: insensible plus urine replacement
• Anticoagulation plan
• Immunosuppression plan; timing of induction and maintenance immunosuppression medication
• Antibiotic prophylaxis
• Lab monitoring plan
PRN, As needed.

• BOX 76.2 What to Know About Kidney Transplant

Recipients When They Arrive in the
Pediatric Intensive Care Unit
• Etiology of end-stage renal disease
• Is there a risk of recurrent disease? If so, how does that change monitoring after transplantation? Example: Check daily protein/creatinine ratio

for recurrent focal segmental glomerulosclerosis.
• Special urologic considerations, such as vesicostomy, bladder augment,
or Mitrofanoff procedure
• Preemptive transplantation or dialysis before transplantation
• Pretransplantation blood pressures and antihypertensive medication regimen
• Urine output before transplantation
• Living donor or deceased donor
• Cold ischemia and warm ischemia time


CHAPTER 76  Pediatric Renal Transplantation

• BOX 76.3 Causes of Graft Dysfunction
Volume depletion
Acute tubular necrosis
Vascular
• Renal artery stenosis
• Renal vein thrombosis
Urologic
• Urinary obstruction
• Urinary leak
• Nephrotoxicity
• Hyperacute rejection
• Recurrence of primary disease
• Thrombotic microangiopathy

boluses or as needed antihypertensives should be administered.
Target CVP goals are established at this time in addition to goals
for urine output (e.g., call for urine output less than 1 mL/kg per
hour or a decrease in 50% from the previous hour). Awareness of

the child’s pretransplantation blood pressure and antihypertensive
regimens and native urine output is important to help guide posttransplantation management. Anticoagulation management plans
are discussed, with target levels depending on the patient’s thrombosis risk. The immunosuppression plan, with details on the timing of induction and maintenance medication initiation, is reviewed. Renal Doppler ultrasound is performed within the first
hour of arrival to the PICU to confirm graft vascular flow.

Posttransplantation Monitoring
Hemodynamics and Tissue Perfusion
It is important to avoid severe hypertension and hypotension in
the immediate postoperative period. Invasive blood pressure
monitoring via arterial line is often necessary in the first 48 to
72 hours. Blood pressure parameters, both high and low, must be
established upon arrival to the PICU. In general, relatively higher
blood pressures in the immediate postoperative period are tolerated to avoid renal ischemia. It is helpful to be aware of the patient’s pretransplantation blood pressure ranges and antihypertensive medication regimens.
Hypertension due to high fluid intake, steroids, and calcineurin inhibitors is problematic, adding stress on the renal arterial
anastomosis and increasing the risk of hypertensive seizure. However, great caution should be used in the treatment of hypertension in the initial postoperative period. Blood pressures between
the 90th to 95th percentile for age, gender, and height may be
tolerated depending on the clinical situation. The agents of choice
for treatment of hypertension in the immediate postoperative
period include short-acting vasodilators, b-blockers, or calcium
channel blockers. In general, angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists are avoided in the
first few weeks after transplantation, as they may induce renal insufficiency in the setting of diminished effective arterial blood volume.
Diuretics may be helpful if hypervolemia is contributing to hypertension. Awareness of what pretransplantation antihypertensive
medications the patient took is helpful to guide posttransplant
medication choices, especially if the patient’s regimen included
medications such as b-blockers or clonidine, which can be associated with a risk of rebound hypertension when stopped. If continuous infusion is required, PICU providers should use caution with

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nicardipine, as it may inhibit tacrolimus metabolism by cytochrome P450, resulting in overexposure and potential toxicity.7
Hypotension and underperfusion of the adult-sized kidney in

the pediatric patient is equally problematic. The treatment of
choice for hypotension posttransplantation is volume expansion
with crystalloid and/or colloid. If possible, vasopressors are
avoided given the risk of renal vasoconstriction. An adult kidney
in a small child needs a normal to high blood pressure and good
intravascular volume for adequate perfusion. If the child has one
or both native kidneys, be alert to hypotension and dehydration
from polyuria.

Fluid and Electrolytes
Small children may require massive volume expansion in order to
maintain adequate perfusion of the adult-sized kidney. It may be
prudent to keep the small child intubated in the early postoperative phase if there are signs of pulmonary edema. Meticulous fluid
and electrolyte management is critical for pediatric patients, as
they often require additional intravascular volume repletion in the
perioperative period to establish diuresis and avoid delayed graft
function. CVP monitoring is used to help assess intravascular
volume status but needs to be evaluated in the context of the
child’s size.
Intravenous fluid management posttransplantation typically
includes insensible fluids (300–400 mL/m2 per day) in addition
to urine output replacement. Urine output is replaced with intravenous (IV) fluid, usually ½ or 0.5% normal saline with dextrose
and water. In some cases, the postoperative diuresis is so large that
hyperglycemia can result when 5% dextrose is used for urine replacement. Urine output is usually replaced milliliter for milliliter
throughout the first 24 hours with a gradual tapering off of IV
urine replacement as the patient’s oral intake increases.
Supplemental loop diuretics or osmotic agents (mannitol) may
be needed to facilitate diuresis in the oliguric patient. Some centers use “renal dose dopamine” (3–5 mg/kg per minute) to enhance renal vasculature dilation, but this is controversial. PICU
practitioners should carefully administer medications associated
with cytokine release (such as polyclonal and monoclonal T-cell

antibodies) in the patient who is volume expanded. Excessive
volume administration may complicate blood pressure management. High-volume diuresis may deplete electrolytes depending
on the type of fluid replacement administered. At time of transplantation, most patients have normal or elevated serum phosphorus levels. In the setting of delayed graft function, phosphate
binders may be necessary to control hyperphosphatemia (e.g.,
calcium acetate). With improved urine output, phosphaturia occurs due to hyperparathyroidism and/or the effect of calcineurin
inhibitors. The goal phosphate level depends on the age of the
patient, with higher acceptable levels in the young growing child.
Oral phosphate supplements include preparations that contain
potassium phosphate or a combination of sodium and potassium
phosphate in either tablet or powder form. The choice of supplement depends on the patient’s serum potassium and palatability.
Hypomagnesemia may occur due to calcineurin inhibitor–
induced renal magnesium wasting. A complication often seen
with oral magnesium–containing preparations is diarrhea. When
this occurs, a dose reduction is necessary. In the patient who has
delayed graft function, avoid magnesium-containing antacids to
prevent the development of hypermagnesemia. Supplemental sodium bicarbonate may be needed in the postoperative period,
especially in those with delayed graft function. Patients who are
undergoing substantial diuresis and receiving high-volume IV


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S E C T I O N V I I   Pediatric Critical Care: Renal

fluid may also need addition of bicarbonate-containing solution
to avoid metabolic acidosis. Glucose management can be problematic, especially in the pediatric patient with type 1 diabetes
mellitus or in the patient on tacrolimus. An insulin drip may be
required to maintain glycemic control. Once on a stable diet,
patients can be switched to subcutaneous administration of longacting insulin with a sliding scale of a short-acting preparation.
Steroids complicate glycemic control and increased doses of insulin may be needed, especially when the patient is on higher doses

of steroids in the first few months after transplantation.
After transplantation, patients who were on peritoneal dialysis
prior to transplantation may have significant peritoneal fluid accumulation, presumably due to peritoneal irritation from longstanding exposure to dextrose-containing dialysate. Intermittent
drainage of the abdomen via the peritoneal catheter may be warranted in the setting of patient discomfort or if there is concern
for increased intraabdominal pressure. However, the need for
peritoneal dialysis posttransplantation is rare.

Urine Output
Close monitoring of urine output is very important in the immediate posttransplantation period. In general, a Foley catheter is
usually kept in the bladder for the first 5 postoperative days to
avoid stressing the ureterocystostomy and to facilitate hourly assessment of urine output. It is very important to keep the Foley
catheter in place and patent. If the catheter is inadvertently discontinued or is not draining well, immediate evaluation is indicated. In most cases, the Foley catheter will need to be replaced
emergently to keep the bladder decompressed and to prevent
tension in bladder-ureteral junction.
Urine output in the early posttransplantation period can range
from oligoanuria to polyuria and can fluctuate depending on the
clinical situation. It is helpful to be aware of the patient’s pretransplantation urine output in order to help assess the initial urine
output early after transplantation. The first step in addressing low
urine output is to assess the patient’s intravascular volume status
(CVP, blood pressure) in addition to ensuring patency of the
Foley catheter. If the patient is determined to be hypovolemic,
volume expansion with 10 to 20 mL/kg of isotonic saline can be
administered. It is not unusual for children to receive multiple
fluid boluses in the first 24 hours posttransplantation. In contrast,
if the patient is evaluated to be hypervolemic, a dose of IV furosemide can be given. If urine output does not improve with fluid
resuscitation and diuretic challenge, a renal Doppler ultrasound
should be performed to confirm flow to the graft and assess for
obstruction.
Reasons for a decrease in urinary output include volume depletion, urologic complications such as urine leak or obstruction,
vascular thrombosis, calcineurin inhibitor nephrotoxicity, and

rejection. Urine leak or lymphocele is indicated by abdominal
pain, distention, elevated creatinine and blood urea nitrogen
(BUN), and fever. Ureteral stenosis or obstruction is indicated by
decreased urine output/anuria, elevated BUN and creatinine, and
pain over the graft.
Gross hematuria may occur after transplantation due to the
use of anticoagulation. However, there are some serious complications that one needs to keep in mind. The differential diagnosis of
gross hematuria includes renal vein thrombosis, renal artery
thrombosis, infection, ureteral stent related, recurrent disease, and
thrombotic microangiopathy. Timely evaluation with blood work,
urine analysis and microscopy, renal Doppler ultrasound, and
possible biopsy is recommended.

Recovery of Renal Function
Recovery of renal function can be divided into three broad categories:
rapid recovery of graft function, slow, or delayed. Delayed graft
function has a specific definition and refers to the need for dialysis
in the first week posttransplantation. This occurs in less than 10%
of pediatric kidney transplant recipients.3 Indications for dialysis
posttransplantation include electrolyte abnormalities and/or significant fluid overload leading to pulmonary compromise and
hypertension. Caution should be used when initiating dialysis in
the early posttransplantation period to avoid dramatic intravascular
volume depletion that can compromise renal perfusion.

Immunosuppression
Immunosuppression therapy can be divided into induction and
maintenance phases.8 Induction immunosuppression is typically
initiated in the operating room at the time of transplantation. The
goal of induction therapy is to prevent T-cell activation. The
choice of induction therapy is center and patient dependent. Induction agents can be either monoclonal (binding to just one receptor) or polyclonal (binding to several different receptors). The

monoclonal agents available currently include basiliximab, which
binds to the interleukin-2 (IL-2) receptor (CD25) on activated T
cells, and alemtuzumab, which binds to CD52, expressed on
multiple immune cells. The available polyclonal agent is rabbit
antithymocyte globulin (Thymoglobulin).
Maintenance agents include calcineurin inhibitors, cell synthesis inhibitors, mammalian target of rapamycin inhibitors, and
glucocorticoids. The calcineurin inhibitors cyclosporine A and
tacrolimus block calcineurin-mediated activation of the IL-2
gene. mTOR inhibitors (sirolimus, everolimus) block the activation process of T cells at a later stage through the mTOR pathways. Cell synthesis inhibitors or antimetabolites (mycophenolates, azathioprine) block the progression of the cell synthesis
cycle from G to S phase. Glucocorticoids have multiple intracellular targets, including, but not limited to, IL-2 gene activation
inhibition. An injectable maintenance agent is belatacept, a fusion
protein that blocks the CD28-B7 costimulatory pathway.
It is important to be aware of potential side effects of these
agents that may be seen in the PICU setting. Use of the induction
medication Thymoglobulin can be associated with a release of
cytokines by activated monocytes and lymphocytes and lead to
cytokine release syndrome. Serious cardiopulmonary events may
result. Premedication with corticosteroids, acetaminophen, and/
or an antihistamine may reduce systemic infusion-related reactions in addition to slowing down the infusion rate. Other infusion reaction symptoms, including flulike symptoms (fever, chills,
nausea, muscle/joint pain) may also occur. Calcineurin inhibitors
may be associated with hypertension and neurotoxicity. Close
daily monitoring of levels is important, with special caution
needed for those with a history of seizure disorder to avoid supratherapeutic levels. Nephrotoxicity can be seen in the early posttransplantation period wherein the initiation may be associated
with a decrease in urine output and delay in renal recovery, especially with high levels. In addition, it is important to be aware of
the drugs that interact with immunosuppressive medications.
Macrolide antibiotics (erythromycin, clarithromycin, but less so
azithromycin) and azole antifungal agents (ketoconazole, fluconazole) delay the metabolism of calcineurin inhibitors, such as tacrolimus, by competing for the same enzymatic degradation
pathways, leading to higher drug levels that may become toxic.

CHAPTER 76  Pediatric Renal Transplantation

Conversely, phenytoin may decrease tacrolimus levels. In the early
posttransplantation period, mTOR inhibitors may be associated
with poor wound healing and lymphoceles. Antimetabolites can
lead to diarrhea and nausea, anemia, and leucopenia.

Infection Surveillance and Prevention
The use of perioperative IV antibiotics is program specific, but
many centers use a first-generation cephalosporin for the first 24
to 48 hours in the nonallergic patient.8 In a child, both elevation
and depression of core body temperature may indicate infection.
Close daily attention to the patient’s vital signs and physical examination is critical, including evaluation of wounds, indwelling
catheters, and drains. Lines, drains, and urinary catheters should
be discontinued as soon as medically indicated to avoid risk of
infection. Urine should be cultured, and the sediment examined
routinely as part of posttransplantation management. Workup for
suspected infection in the pediatric patient should include physical examination, cultures (urine, blood, drains, and peritoneal
fluid if indicated), chest radiographs, cytomegalovirus and
Epstein-Barr virus polymerase chain reaction tests and consider
spinal tap if signs or symptoms persist.
In addition, prophylaxis against Pneumocystis jirovecii using
trimethoprim-sulfamethoxazole (TMP/SMZ) is indicated if the
patient is not allergic. Dapsone or pentamidine monthly inhalation can be used if the patient is TMP/SMZ allergic. Oral antifungal prophylaxis usually is given for the first 3 to 6 months after
transplantation, usually in the form of nystatin or clotrimazole
troches. Viral prophylaxis for CMV with ganciclovir or valganciclovir is routinely used in the posttransplantation period. The
dose for ganciclovir is adjusted according to the estimated creatinine
clearance.

Posttransplantation Complications

Acute Kidney Injury
Several factors may be responsible for postischemic acute kidney
injury. These include the age and condition of the donor, specific
recovery procedure, technique of organ preservation, adequacy of
volume replacement during and after surgery, and the cold and
warm ischemia times. Tubular damage may be aggravated by administration of cyclosporine or tacrolimus. There is evidence that
the addition of sirolimus in combination with either cyclosporine
or tacrolimus prolongs renal function recovery.

Vascular Complications
Vascular thrombosis of the renal artery or vein is the third most
common cause of graft failure in children receiving renal transplants. The main risk for thrombosis is an extremely young donor
or recipient. Other risk factors include hypercoagulability (such as
that due to chronic nephrotic syndrome) and venous malformation in the recipient, pretransplantation peritoneal dialysis, a hypotensive episode during or after surgery, the presence of multiple
arteries, and bench surgery of graft vessels. Although vascular
thrombosis is usually observed within the first few days following
transplantation, it can be seen as late as 3 weeks posttransplantation. Careful hemodynamic monitoring of CVP is critical to ensure adequate allograft perfusion. Venous thrombosis of the
transplant is indicated by decreased urine output, graft swelling
and tenderness, and proteinuria.

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Screening for inherited and acquired thrombophilic risk factors,
especially if there is a family history or previous episode of thrombosis, should be considered. Screening is currently available for
protein C, S, or antithrombin III deficiency, factor V Leiden, prothrombin gene mutations, and the presence of antiphospholipid
antibodies. Prophylactic therapy with heparin, low-molecularweight heparin, and/or aspirin to prevent thrombosis for those with
an increased risk of thrombophilia has been successful in preventing
graft loss. In some centers, low-molecular-weight heparin is used
prophylactically in all pediatric renal transplantation recipients.
Renal artery stenosis is indicated by elevated blood pressure

and bruit over the transplant upon auscultation. Conservative
management in the setting of noncritical stenosis is observed.
Maximization of blood pressure control with serial imaging using
renal Doppler ultrasound is used in conjunction with monitoring
of renal function. However, if stenosis is severe, thrombosis may
occur.

Urologic Complications
Early posttransplantation urologic complications are relatively
common in pediatric kidney transplant recipients. Urinary leak
may occur due to ureteral necrosis, bladder injury, or obstruction.
Urinary tract obstruction is most often due to clots in the urinary
tract, postoperative edema, or surgical complication. It is detected
as hydronephrosis by renal ultrasonography. Many centers place
ureteral stents as a measure to reduce these complications.

Rejection
Advances in immunosuppression have led to remarkable decreases
in acute rejection rates. Rejection categorization is subdivided by
its onset posttransplantation: hyperacute, accelerated, and acute.8
Hyperacute and accelerated acute rejection result from preformed
host anti-HLA antibodies that bind to vascular endothelial cells of
the graft, resulting in activation of the complement cascade and
endothelial injury. Neutrophils, macrophages, and platelets are
attracted to the antibody binding site and cause further cellular
damage. Platelet aggregation on the damaged endothelium leads
to fibrin deposition and vascular thrombosis. There are also reports of hyperacute rejection associated with antiendothelial antibodies, which are not detected with standard crossmatch methods
using donor lymphocytes. Hyperacute rejection occurs within the
first minutes following transplantation, while accelerated acute
rejection occurs within 3 to 5 days posttransplantation. Hyperacute and accelerated acute rejection are rare due to advances in

crossmatching assessment. Clinically, patients present with oligoanuria and fever and graft tenderness. Diagnosis is by allograft
biopsy and assessment for donor-specific antibodies. Treatment is
not usually successful. Early acute rejection may be seen in the first
week but is very rare. However, it should be suspected in the setting of delayed return of renal function or an acute deterioration
in allograft function, generally detected by an elevation in the
serum creatinine level. The two principal histologic forms of rejection are acute cellular rejection and acute antibody-mediated rejection. Acute cellular rejection is characterized by infiltration of
the allograft by lymphocytes and other inflammatory cells. Acute
antibody-mediated rejection is diagnosed by morphologic evidence of acute tissue injury, circulating donor-specific alloantibodies, and immunologic evidence of an antibody-mediated
process (such as C4d deposition in the allograft). Cellular infiltrates may not be present.


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Urinary Tract Infection
Urinary tract infection (UTI) is the most common bacterial infection in both adult and pediatric kidney transplant recipients.8
UTIs will develop in 20% to 40% in the first year posttransplantation and 40% to 60% by 3 years posttransplantation. UTI is
not only a cause of morbidity but is also associated with higher
rates of graft loss and patient death. The urogenital tract is the
most common entry point for systemic sepsis. Numerous risk factors have been identified for UTIs posttransplantation. Urologic
anomalies such as neurogenic bladder, urinary tract obstruction,
vesicoureteral reflux, bladder augmentation, and clean intermittent catheterization have all been associated with an increased risk
of UTIs posttransplantation. Foreign bodies, such as ureteral
stents, have also been associated with increased UTIs posttransplantation.
The organisms implicated are usually the same as in immunocompetent individuals, such as Escherichia coli and Klebsiella species. A higher percentage of UTIs in transplant patients is due to
unusual organisms, such as Pseudomonas species. Clinical symptoms may include fever, dysuria, graft tenderness, and cloudy
urine. In some patients, symptoms may be masked due to immunosuppression. A rise in serum creatinine may occur and can
mimic acute rejection. UTIs can also precipitate acute rejection.
The diagnosis of UTI is usually made by urine culture, though

patients on TMP/SMZ prophylaxis for pneumocystis may not
demonstrate positive cultures. Initially, the antimicrobial prescribed should cover the common gram-negative organisms. Once
the organism is known, the most specific and cost-effective antimicrobial can be prescribed. Treatment route and total duration
are determined by the severity of infection, recipient age, and
other risk factors.

Other Infections
Other bacterial infections—such as wound infections, line sepsis,
and pneumonia—are seen with significant frequency in kidney
transplant recipients. Wound infections and line sepsis are commonly due to gram-positive staphylococcus and streptococcus.
Pneumonia can be due to multiple etiologies (bacterial, viral, or
fungal), but bacterial pathogens are responsible for approximately
44% of cases. The treatment of these infections is generally no
different from standard treatment in immunocompetent hosts,
though duration of therapy may be longer.
Kidney transplant recipients are at increased risk for oral and
esophageal infections due to Candida species. The use of oral

clotrimazole troches or nystatin provides effective prophylaxis
without systemic absorption and, hence, without concerns for
side effects. Although data regarding the duration of prophylaxis
are not available, prophylaxis should be continued until patients
are on stable maintenance immunosuppression.

Recurrence of Primary Renal Disease
It is important to recognize the clinical presentation and natural
history of diseases that recur after renal transplantation. In most
pediatric series, recurrence of primary disease is responsible for
renal allograft failure in 5% to 15% of cases. Among the glomerular diseases that may recur in the graft and can present in the
early posttransplantation period, the most frequent is FSGS.9,10

Focal Segmental Glomerulosclerosis
Steroid-resistant idiopathic nephrotic syndrome due to primary
FSGS accounts for 10% of cases of ESRD in childhood.9,10 The
overall risk of recurrence of nephrotic syndrome after transplantation is estimated to be about 30%. FSGS is the most frequent
cause of graft loss due to recurrent disease. The risk of recurrence
with FSGS is greater in children than adults. In children, recurrence is more frequent when the disease begins after the age of
6 years and there is a rapid progression to ESRD. In most series,
the disease recurs in one-half of patients when the duration of
disease has been shorter than 3 years. The histopathologic pattern
observed in the first biopsy of the original disease is also an important predictive factor of disease recurrence. As an example,
recurrence occurs in 50% to 80% of patients in whom the initial
biopsy reveals diffuse mesangial proliferation (suggestive of more
rapidly progressive disease) but in only 25% of patients with
minimal-change disease. Patients with FSGS due to mutations in
genes encoding podocyte proteins appear to have a very low risk
of recurring disease after renal transplantation. Recurrence of
FSGS enhances the risk of allograft loss and is associated with an
increased incidence of delayed graft function and acute rejection.
Recurrence most often occurs within the first few days after transplantation. Close daily monitoring of urine protein excretion is
important for the early detection of possible disease recurrence. In
patients with a first graft lost to recurrent disease, the recurrence
rate is approximately 80% in a subsequent graft. Treatment remains controversial and may include plasmapheresis, rituximab,
angiotensin-converting enzyme inhibitors, or angiotensin receptor
blockers depending on the timing of recurrence.
The full reference list for this chapter is available atExpertConsult.com.