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/PCr). The creatinine clearance is calculated from...
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Chapter 045. Azotemia and Urinary Abnormalities (Part 2) Chapter 045. Azotemia and Urinary Abnormalities (Part 2) Assessment of Glomerular Filtration Rate Monitoring the GFR is important in both the hospital and outpatientsettings, and several different methodologies are available (discussed below). Inmost acute clinical circumstances a measured GFR is not available, and the serumcreatinine level is used to estimate the GFR in order to supply appropriate doses ofrenally excreted drugs and to follow short-term changes in GFR. Serum creatinineis the most widely used marker for GFR, and the GFR is related directly to theurine creatinine excretion and inversely to the serum creatinine (U Cr/PCr). Thecreatinine clearance is calculated from these measurements for a defined timeperiod (usually 24 h) and is expressed in mL/min. Based upon this relationshipand some important caveats (discussed below), the GFR will fall in roughlyinverse proportion to the rise in PCr. Failure to account for GFR reductions in drugdosing can lead to significant morbidity and mortality from drug toxicities (e.g.,digoxin, aminoglycosides). In the outpatient setting, the serum creatinine is oftenused as a surrogate for GFR (although much less accurate; see below). In patientswith chronic progressive renal disease there is an approximately linear relationshipbetween 1/PCr and time. The slope of this line will remain constant for anindividual patient, and when values are obtained that do not fall on this line, aninvestigation for a superimposed acute process (e.g., volume depletion, drugreaction) should be initiated. It should be emphasized that the signs and symptomsof uremia will develop at significantly different levels of serum creatininedepending upon the patient (size, age, and sex), the underlying renal disease,existence of concurrent diseases, and true GFR. In general, patients do not developsymptomatic uremia until renal insufficiency is usually quite severe (GFR < 15mL/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 andFig. 45-1). Precise determination of GFR is problematic as both commonlymeasured indices (urea and creatinine) have characteristics that affect theiraccuracy as markers of clearance. Urea clearance may significantly underestimateGFR because of tubule urea reabsorption. Creatinine is derived from musclemetabolism of creatine, and its generation varies little from day to day. Creatinineis useful for estimating GFR because it is a small, freely filtered solute. However,serum creatinine levels can increase acutely from dietary ingestion of cookedmeat, and creatinine can be secreted into the proximal tubule through an organiccation pathway, leading to overestimation of the GFR. There are many clinicalsettings where a creatinine clearance is not available, and decisions concerningdrug dosing must be made based on the serum creatinine. Two formulas arewidely used to estimate GFR: (1) Cockcroft-Gault, which accounts for age andmuscle mass (this value should be multiplied by 0.85 for women, since a lowerfraction 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, redblood cell; GBM, glomerular basement membrane Although more cumbersome than Cockcroft-Gault, the MDRD equation isfelt to be more accurate, and numerous websites are available for making thecalculation (www.kidney.org/professionals/kdoqi/gfr_calculator.cfm). The gradual loss of muscle from chronic illness, chronic use ofglucocorticoids, or malnutrition can mask significant changes in GFR with smallor imperceptible changes in serum creatinine concentration. More accuratedeterminations of GFR are available using inulin clearance or radionuclide-labeledmarkers such as 125I-iothalamate or EDTA. These methods are highly accurate dueto precise quantitation and the absence of any renal reabsorption/secretion andshould be used to follow GFR in patients in whom creatinine is not likely to be areliable indicator (patients with decreased muscle mass secondary to age,malnutrition, concurrent illnesses). (See also Table 274-2.) Cystatin C is a memberof the cystatin superfamily of cysteine protease inhibitors and is produced at arelatively constant rate from all nucleated cells. Cystatin C production is notaffected by diet or nutritional status and may provide a more sensitive indicator ofGFR than the plasma creatinine concentration. However, it remains to be validatedin many clinical settings. ...