• Abnormally elevated serum creatinine for 3 or more months.
  
• Calculated glomerular filtration rate (GFR) ≤60 mL/minute/1.73 m2 for 3 or more months.
  
• Clinical manifestations of the uremic syndrome in patients with advanced kidney failure.

The National Kidney Foundation–Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) has defined chronic kidney disease (CKD) as (1) kidney damage for 3 or more months, as defined by structural or functional abnormalities of the kidney, with or without decreased GFR, manifested by either pathologic abnormalities or markers of kidney damage, including abnormalities in the composition of the blood or urine or in imaging tests; or (2) GFR ≤60 mL/minute/1.73 m2 for 3 or more months, with or without markers of kidney damage. The NKF-K/DOQI recommends using the equation derived from the Modification of Diet in Renal Disease (MDRD) to estimate GFR from the serum creatinine (eGFR) and has proposed a classification of CKD based on level of eGFR (Table 17–1).

CKD with decreased GFR (stages 2 through 5 of the NKF-K/DOQI classification), also known as chronic renal failure or chronic renal insufficiency in the literature prior to the NKF-K/DOQI classification, is a clinical syndrome that results from progressive decline of the GFR, typically over months to years, and is due to irreversible destruction of nephrons independent of the cause. In stage 2, the only manifestation of CKD may be a persistently decreased eGFR. As the GFR continues to decline (stages 3 and 4), other laboratory abnormalities begin to appear. The uremic syndrome refers to a constellation of symptoms and signs that occurs in patients with advanced kidney failure (typically GFR <10–15 mL/minute/1.73 m2) and reflects generalized organ dysfunction (stage 5). At this stage, kidney replacement therapy with dialysis or transplantation becomes necessary to sustain life. End-stage renal disease (ESRD) is an administrative term based on conditions for payment of health care by the Medicare ESRD program for patients treated by dialysis and/or transplantation in the United States.

It has been estimated that 8.3 million Americans have an eGFR ≤60 mL/minute/1.73 m2. Moreover, in the year 2002 alone, 100,359 patients began kidney replacement therapy and 431,284 were under active care in the United States. The prevalence and incidence rates of treated ESRD were 333 and 1435 cases per million population, respectively. Diabetes mellitus is the most common cause of ESRD, accounting for nearly 45% of cases; systemic hypertension is the second leading cause, and together with diabetes accounts for over two-thirds of the cases of ESRD. African-Americans are more susceptible to ESRD secondary to diabetes or hypertension.

The progressive nephron and GFR loss associated with progressive CKD leads to (1) abnormalities in water, electrolyte, and pH balance, (2) accumulation of waste products that are normally excreted by the kidney, and (3) abnormalities in the production and metabolism of certain hormones (ie, erythropoietin, active vitamin D). Fortunately, as the GFR declines, a number of compensatory mechanisms are activated, of which the most important is glomerular hyperfiltration in the remaining functioning nephrons. Due to this compensatory mechanism, a patient may be totally asymptomatic despite having lost 70% of kidney function. However, glomerular hyperfiltration is associated with the development of glomerulosclerosis in the remaining functioning nephrons, which contributes to further nephron loss. Other factors that contribute to nephron loss include (1) ongoing activity of the primary cause of CKD, (2) proteinuria, (3) development of tubulointerstitial lesions, (4) hyperlipidemia, and (5) acute superimposed renal insults (ie, contrast nephropathy, aminoglycoside toxicity, etc.).

Aggressive glucose and blood pressure control in diabetic and/or hypertensive patients reduces the risk of developing CKD. Screening individuals at high risk for CKD, particularly those with diabetes, hypertension, or a family history of diabetes, hypertension, or kidney disease, allows for early detection and implementation of interventions that prevent or slow the progression of CKD. Appropriate screening tests include a urinalysis, a first morning or a random “spot” urine sample for albumin or protein to creatinine ratio, serum creatinine level for estimation of GFR using an accepted prediction equation, and blood pressure measurement.

Symptoms and Signs

Patients are usually asymptomatic until kidney failure is advanced. When the GFR falls to approximately 10–15 mL/minute, nonspecific symptoms such as general malaise, weakness, insomnia, inability to concentrate, and nausea and vomiting begin to appear. Eventually other symptoms and signs that reflect generalized organ dysfunction develop as part of the uremic syndrome (Table 17–2).