Chapter 045. Azotemia and Urinary Abnormalities (Part 2) pot

Chapter 045. Azotemia and
Urinary Abnormalities
(Part 2)

Assessment of Glomerular Filtration Rate
Monitoring the GFR is important in both the hospital and outpatient
settings, and several different methodologies are available (discussed below). In
most acute clinical circumstances a measured GFR is not available, and the serum
creatinine level is used to estimate the GFR in order to supply appropriate doses of
renally excreted drugs and to follow short-term changes in GFR. Serum creatinine
is the most widely used marker for GFR, and the GFR is related directly to the
urine creatinine excretion and inversely to the serum creatinine (U
Cr
/P
Cr
). The
creatinine clearance is calculated from these measurements for a defined time
period (usually 24 h) and is expressed in mL/min. Based upon this relationship
and some important caveats (discussed below), the GFR will fall in roughly
inverse proportion to the rise in P
Cr
. Failure to account for GFR reductions in drug
dosing can lead to significant morbidity and mortality from drug toxicities (e.g.,
digoxin, aminoglycosides). In the outpatient setting, the serum creatinine is often
used as a surrogate for GFR (although much less accurate; see below). In patients
with chronic progressive renal disease there is an approximately linear relationship
between 1/P
Cr
and time. The slope of this line will remain constant for an
individual patient, and when values are obtained that do not fall on this line, an
investigation for a superimposed acute process (e.g., volume depletion, drug

reaction) should be initiated. It should be emphasized that the signs and symptoms
of uremia will develop at significantly different levels of serum creatinine
depending upon the patient (size, age, and sex), the underlying renal disease,
existence of concurrent diseases, and true GFR. In general, patients do not develop
symptomatic uremia until renal insufficiency is usually quite severe (GFR < 15
mL/min).
A reduced GFR leads to retention of nitrogenous waste products (azotemia)
such as urea and creatinine. Azotemia may result from reduced renal perfusion,
intrinsic renal disease, or postrenal processes (ureteral obstruction; see below and
Fig. 45-1). Precise determination of GFR is problematic as both commonly
measured indices (urea and creatinine) have characteristics that affect their
accuracy as markers of clearance. Urea clearance may significantly underestimate
GFR because of tubule urea reabsorption. Creatinine is derived from muscle
metabolism of creatine, and its generation varies little from day to day. Creatinine
is useful for estimating GFR because it is a small, freely filtered solute. However,
serum creatinine levels can increase acutely from dietary ingestion of cooked
meat, and creatinine can be secreted into the proximal tubule through an organic
cation pathway, leading to overestimation of the GFR. There are many clinical
settings where a creatinine clearance is not available, and decisions concerning
drug dosing must be made based on the serum creatinine. Two formulas are
widely used to estimate GFR: (1) Cockcroft-Gault, which accounts for age and
muscle mass (this value should be multiplied by 0.85 for women, since a lower
fraction of the body weight is composed of muscle):

and (2) MDRD (modification of diet in renal disease):


Approach to the patient with azotemia. WBC, white blood cell; RBC, red
blood cell; GBM, glomerular basement membrane
Although more cumbersome than Cockcroft-Gault, the MDRD equation is

felt to be more accurate, and numerous websites are available for making the
calculation (www.kidney.org/professionals/kdoqi/gfr_calculator.cfm).
The gradual loss of muscle from chronic illness, chronic use of
glucocorticoids, or malnutrition can mask significant changes in GFR with small
or imperceptible changes in serum creatinine concentration. More accurate
determinations of GFR are available using inulin clearance or radionuclide-labeled
markers such as
125
I-iothalamate or EDTA. These methods are highly accurate due
to precise quantitation and the absence of any renal reabsorption/secretion and
should be used to follow GFR in patients in whom creatinine is not likely to be a
reliable indicator (patients with decreased muscle mass secondary to age,
malnutrition, concurrent illnesses). (See also Table 274-2.) Cystatin C is a member
of the cystatin superfamily of cysteine protease inhibitors and is produced at a
relatively constant rate from all nucleated cells. Cystatin C production is not
affected by diet or nutritional status and may provide a more sensitive indicator of
GFR than the plasma creatinine concentration. However, it remains to be validated
in many clinical settings.