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Kidney Disease

The Merck Manual Professional Edition><
"Chronic kidney disease (CKD) is long-standing, progressive deterioration of renal function. Symptoms develop slowly and include anorexia, nausea, vomiting, stomatitis, dysgeusia, nocturia, lassitude, fatigue, pruritus, decreased mental acuity, muscle twitches and cramps, water retention, undernutrition, peripheral neuropathies, and seizures. Diagnosis is based on laboratory testing of renal function, sometimes followed by renal biopsy. Treatment is primarily directed at the underlying condition but includes fluid and electrolyte management, erythropoietin for anemia, and often dialysis or transplantation.

CKD may result from any cause of renal dysfunction of sufficient magnitude (see Table 1: Major Causes of Chronic Kidney DiseaseTables). The most common cause in the US is diabetic nephropathy (see Diabetic nephropathy), followed by hypertensive nephroangiosclerosis and various primary and secondary glomerulopathies. Metabolic syndrome (see Metabolic Syndrome), in which hypertension and type 2 diabetes are present, is a large and growing cause of renal damage.

Pathophysiology CKD can be roughly categorized as diminished renal reserve, renal insufficiency, or renal failure (end-stage renal disease). Initially, as renal tissue loses function, there are few abnormalities because the remaining tissue increases its performance (renal functional adaptation); a loss of 75% of renal tissue causes a fall in GFR to only 50% of normal.

Decreased renal function interferes with the kidneys' ability to maintain fluid and electrolyte homeostasis. Changes proceed predictably, but considerable overlap and individual variation exist. The ability to concentrate urine declines early and is followed by decreases in ability to excrete phosphate, acid, and K. When renal failure is advanced (GFR ≤ 10 mL/min/1.73 m2), the ability to dilute urine is lost; thus urine osmolality is usually fixed close to that of plasma (300 to 320 mOsm/kg), and urinary volume does not respond readily to variations in water intake.

Plasma concentrations of creatinine and urea (which are highly dependent on glomerular filtration) begin a hyperbolic rise as GFR diminishes. These changes are minimal early on. When the GFR falls below 10 mL/min/1.73 m2 (normal = 100 mL/min/1.73 m2), their levels increase rapidly and are usually associated with systemic manifestations (uremia). Urea and creatinine are not major contributors to the uremic symptoms; they are markers for many other substances (some not yet well defined) that cause the symptoms."

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