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Kidneys may incur a variety of injuries (Figure 24–1). Although some patients with kidney disease experience signs or symptoms such as hypertension, edema, gross hematuria, or uremia that may lead to its discovery, kidney disease more often is discovered incidentally or when screening individuals at high risk for kidney disease. The initial approach is to assess the cause and severity of kidney disease. In addition to a careful history and physical examination, evaluation includes (1) eGFR to characterize disease severity and, when previous eGFR values are available, discern kidney disease duration and rate of progression, (2) urine studies, and (3) renal imaging (usually ultrasonography). Select cases may warrant renal biopsy, particularly when glomerular disease is suspected.

Figure 24–1.

A: Kidneys may be damaged by a variety of insults/disease states. B: Narrowing the differential diagnosis of kidney disease to a structural compartment can be helpful. AIN, acute interstitial nephritis. (Reproduced with permission from Megan Troxell, MD.)

GLOMERULAR FILTRATION RATE

The primary function of the kidneys is removal of waste products and excess solutes from plasma.

The GFR reflects the amount of plasma ultrafiltered across the glomerular filtration barrier per unit time and serves as the primary metric of kidney function. Daily GFR in normal individuals is variable, ranging from 150–250 L/24 hours or 100–120 mL/min/1.73 m2 of body surface area. Patients with kidney disease usually have decreased GFR; however, a normal or increased GFR (in the case of glomerular hyperfiltration) may also be seen.

GFR can be measured directly using biomarkers (most commonly creatinine) or estimated using validated formulae. Direct measurement is performed by determination of the renal clearance of a plasma substance that is not bound to plasma proteins, is freely filterable across the glomerulus, and is neither secreted nor reabsorbed along the renal tubules; it is defined as:

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where C is the clearance, U and P are the respective urine and plasma concentrations of the substance, and V̇ is volume of urine per unit time (typically mL/min). The gold standard for GFR measurement is by assessment of clearance of exogenously administered inulin; however, in clinical practice, the clearance of endogenous creatinine (termed creatinine clearance) is primarily used. The normal creatinine clearance (Ccr) is approximately 100 mL/min in healthy young women and 120 mL/min in healthy young men. The creatinine clearance declines by an average of 0.8 mL/min/year after age 40 years as part of the aging process. Creatinine is a useful biomarker because it is produced at a relatively constant rate as a byproduct of muscle metabolism, is freely filtered by the glomerulus, and is not reabsorbed by the renal tubules. (A small amount also is actively secreted by the tubules into the urine.) With stable ...

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