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In chronic kidney disease (CKD), reduced clearance of certain solutes principally excreted by the kidney results in their retention in the body fluids. The solutes are end products of endogenous metabolism as well as exogenous substances (eg, drugs). The most commonly measured indicators of renal failure are blood urea nitrogen (BUN) and serum creatinine. The renal clearance of creatinine (as calculated from a 24-hour urine collection) is often used as a surrogate measure of glomerular filtration rate (GFR).

Renal failure may be classified as acute or chronic depending on the rapidity of onset and the subsequent course of azotemia. An analysis of the acute or chronic development of renal failure is important in understanding physiologic adaptations, disease mechanisms, and ultimate therapy. In individual cases, it is often difficult to establish the duration of renal failure. Historical clues such as preceding hypertension or radiologic findings such as small, shrunken kidneys tend to indicate a more chronic process. Acute kidney injury (AKI) may progress to irreversible chronic renal failure. For a discussion of AKI, see Chapter 34.

A new classification has been established by the National Kidney Foundation–Kidney Disease Outcomes Quality Initiative (K/DOQI). This delineates CKD by varying degrees of reduced GFR, either in the presence or absence of structural or functional renal abnormalities (available on the NFK website: This has been useful in studies of the progression of CKD, especially in varying drug regimens to reduce the rate of worsening of GFRs.

There are now numerous online calculators that can estimate a person’s GFR (eGFR) on the basis of the creatinine value, one example of which is available through the National Kidney Foundation ( Although not perfect, these calculations help us to alert patients with subtle renal function impairment in the face of creatinine values within the normal reference ranges.

The incidence of end-stage renal disease (ESRD) reached 378 cases per million population in 2015, after a period of relative stability between 2001 and 2005. This increase can be explained almost entirely by the uptake in incidence of diabetic nephropathy over the same period (Figure 35–1). Particularly affected are older patients (75+ years old) and African-Americans (3.6 times higher than Caucasians; Figures 35–2 and 35–3). The severity and the rapidity of development of uremia are difficult to predict. The use of dialysis and transplantation is expanding rapidly worldwide. As of December 31, 2015, more than 440,000 prevalent ESRD patients in the United States were treated with hemodialysis, with around 49,000 patients treated with peritoneal dialysis. There are approximately 208,000 patients with a functioning kidney transplant.

Figure 35–1.

Incident ESRD patients; rates adjusted for age, gender, and race. (Data from Centers for Disease Control and Prevention. Behavioral Risk Factor Surveillance System.)

Figure 35–2.

Trends in adjusted ESRD incidence rate, ...

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