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 46-1. ).
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. 140. Dialysis and 141. Renal Transplantation) or with appropriate drug therapies (see below).
Treatment: Chronic Kidney Disease and Uremia Hypertension 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 90-110 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. Dialysis should be considered if the potassium is >6 mmol/L on repeated occasions. If these conditions cannot be conservatively controlled, dialysis should be instituted (Chap. 140. Dialysis). 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 DISEASE Prospective 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+]. |
For a more detailed discussion, see Bargman JM, Skorecki K: Chronic Kidney Disease, Chap. 335, p. 1811, in HPIM-19. |