The prevalence of chronic kidney disease (CKD), generally defined as a long-standing, irreversible impairment of kidney function, is substantially greater than the number of pts with end-stage renal disease (ESRD), now ≥500,000 in the United States. There is a spectrum of disease related to decrements in renal function; clinical and therapeutic issues differ greatly depending on whether the glomerular filtration rate (GFR) reduction is moderate (stage 3 CKD, 30-59 mL/min per 1.73 m2 ) (see Table 48-1 The Classification of Chronic Kidney Disease), severe (stage 4 CKD, 15-29 mL/min per 1.73 m2 ), or “end-stage renal disease” (stage 5 CKD, <15 mL/min per 1.73 m2 ). Dialysis is usually required once GFR <10 mL/min per 1.73 m2 . Common causes of CKD are outlined in Table 142-1 Common Causes of Chronic Renal Failure.
The first step in the differential diagnosis of CKD is establishing its chronicity, i.e., disproving a major acute component. The two most common means of determining disease chronicity are the history and prior laboratory data (if available) and the renal ultrasound, which is used to measure kidney size. In general, kidneys that have shrunk (<10-11.5 cm, depending on body size) are more likely affected by chronic disease. While reasonably specific (few false positives), reduced kidney size is only a moderately sensitive marker for CKD, i.e., there are several relatively common conditions in which kidney disease may be chronic without any reduction in renal size. Diabetic nephropathy, HIV-associated nephropathy, and infiltrative diseases such as multiple myeloma or amyloidosis may in fact be associated with relatively large kidneys despite chronicity. Renal biopsy, although rarely performed in pts with CKD, is a more reliable means of proving chronicity; a predominance of glomerulosclerosis or interstitial fibrosis argues strongly for chronic disease. Hyperphosphatemia, anemia, and other laboratory abnormalities are not reliable indicators in distinguishing acute from chronic disease.
Once chronicity has been established, clues from the physical examination, laboratory panel, and urine sediment evaluation can be used to determine etiology. A detailed history will identify important comorbid conditions, such as diabetes, HIV seropositivity, or peripheral vascular disease. The family history is paramount in the workup of autosomal dominant polycystic kidney disease or hereditary nephritis (Alport's syndrome). An occupational history may reveal exposure to environmental toxins or culprit drugs (including over-the-counter agents, such as analgesics or Chinese herbs).
Physical examination may demonstrate abdominal masses (i.e., polycystic kidneys), diminished pulses or femoral/carotid bruits (i.e., atherosclerotic peripheral vascular disease), or abdominal or femoral bruits (i.e., renovascular disease). The history and examination may also yield important data regarding severity of disease. Excoriations (uremic pruritus), pallor (anemia), muscle wasting, and a nitrogenous fetor are all signs of advanced CKD, as are pericarditis, pleuritis, and asterixis, complications of particular concern that usually prompt the initiation of dialysis.
Serum and urine laboratory findings typically provide additional information useful in determining the etiology and severity of CKD; serial studies determine the pace of progression and/or whether the renal failure is in fact acute. Heavy proteinuria (>3.5 g/d), hypoalbuminemia, hypercholesterolemia, and edema suggest nephrotic syndrome (Chap. 145 Glomerular Diseases). Diabetic nephropathy, membranous nephropathy, focal segmental glomerulosclerosis, minimal change disease, amyloid, and HIV-associated nephropathy are principal causes. Proteinuria may decrease slightly with decreasing GFR, but rarely to normal levels. Hyperkalemia and metabolic acidosis may complicate all forms of CKD eventually, but can be more prominent in pts with interstitial renal diseases. Serum and urine protein electrophoresis, in addition to serum free light chains, should be obtained in all pts >35 years of age with CKD to exclude paraproteinemia-associated renal disease. If underlying glomerulonephritis is suspected, autoimmune disorders such as lupus and infectious etiologies such as hepatitis B and C should be assessed. Serum concentrations of calcium, phosphate, vitamin D, and parathyroid hormone (PTH) should be measured to evaluate metabolic bone disease. Hemoglobin, vitamin B12, folate, and iron studies should be measured to evaluate anemia.
The culprit toxin(s) responsible for the uremic syndrome remain elusive. The serum creatinine (Cr) is the most common laboratory surrogate of renal function. GFR can be estimated using serum Cr-based equations derived from the Modification of Diet in Renal Disease Study. This “eGFR” is now reported with serum Cr by most clinical laboratories in the United States and is the basis for the National Kidney Foundation classification of CKD (see Table 48-1 The Classification of Chronic Kidney Disease). In pts with low muscle mass, resulting in lesser generation of creatinine, creatinine-based measurement of GFR (“eGFR”) may yield an overestimate of the actual GFR; measurement of cystatin-C may yield a more helpful, accurate estimate of eGFR under these circumstances.
Uremic symptoms tend to develop with serum Cr >530-710 µmol/L (>6-8 mg/dL) or CrCl<10 mL/min, although these values vary widely. Uremia is thus a clinical diagnosis made in pts with CKD. Symptoms of advanced uremia include anorexia, weight loss, dyspnea, fatigue, pruritus, sleep and taste disturbance, and confusion and other forms of encephalopathy. Key findings on physical examination include hypertension, jugular venous distention, pericardial and/or pleural friction rub, muscle wasting, asterixis, excoriations, and ecchymoses. Pts may suffer from excessive bleeding due to uremic platelet dysfunction. Laboratory abnormalities may include hyperkalemia, hyperphosphatemia, metabolic acidosis, hypocalcemia, hyperuricemia, anemia, and hypoalbuminemia. Most of these abnormalities eventually resolve with initiation of dialysis or renal transplantation (Chaps. 143 Dialysis and 144 Renal Transplantation) or with appropriate drug therapies (see next).
| TREATMENT | ||
Chronic Kidney Disease and UremiaHypertension complicates many forms of CKD and warrants aggressive treatment to reduce the risk of stroke and potentially to slow the progression of CKD (see below). Volume overload contributes to hypertension in many cases, and potent diuretic agents are frequently required. Anemia can be ameliorated with recombinant human erythropoietin (rHuEPO); current practice is to target a hemoglobin concentration of 90-115 g/L. Iron deficiency and/or other causes of anemia can reduce the response to rHuEPO and should be investigated if present. Iron supplementation is often required; many pts require parenteral iron therapy, since intestinal iron absorption is reduced in CKD. Hyperphosphatemia can be controlled with judicious restriction of dietary phosphorus and the use of postprandial phosphate binders, either calcium-based salts (calcium carbonate or acetate) or nonabsorbed agents (e.g., sevelamer). Hyperkalemia should be controlled with dietary potassium restriction or with potassium binders such as sodium zirconium cyclosilicate (ZS-9) or patiromer; the potassium binder kayexalate has been associated with colonic necrosis and is no longer recommended for chronic management of hyperkalemia. Dialysis should be considered if the potassium is >6 mmol/L on repeated occasions, despite these measures. Dialysis may also be necessary to manage diuretic-resistant hypervolemia. It is also advisable to begin dialysis if severe anorexia, weight loss, and/or hypoalbuminemia develop, as it has been definitively shown that outcomes for dialysis pts with malnutrition are particularly poor. SLOWING PROGRESSION OF RENAL DISEASEProspective clinical trials have explored the roles of blood pressure control and dietary protein restriction on the rate of progression of renal failure. Control of hypertension is of benefit, although angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) may exert unique beneficial effects, most likely due to their effects on intrarenal hemodynamics. The effects of ACE inhibitors and ARBs are most pronounced in pts with diabetic nephropathy and in those without diabetes but with significant proteinuria (>1 g/d). Diuretics and other antihypertensive agents are often required, in addition to ACE inhibitors and ARBs, to optimize hypertension control and attenuate disease progression; diuretics may also help control serum [K+ ]. |