A. Symptoms and Signs: The symptoms of chronic renal failure are nonspecific. Manifestations include fatigue, weakness, malaise, and lassitude. Gastrointestinal complaints such as anorexia, nausea, vomiting, a metallic taste in the mouth, and hiccup are common initially. Neuromuscular problems are also common and include decreased ability to concentrate, insomnia, irritability, restless legs, and twitching. As uremia progresses, decreased libido and menstrual irregularities, pruritus, chest pain from pericarditis, easy bruisability, and paresthesias can develop.

On physical examination, the individual may have a sallow complexion and appear chronically ill. The skin may be yellow-brown, with ecchymoses and petechiae. Cardiovascular findings may include hypertension, cardiomegaly, edema, and a pericardial friction rub. Mental status changes may be present and include confusion, stupor, and coma if uremia is severe. Myoclonus and asterixis can be noted as well.

In any patient with renal failure, it is important to eliminate all possible reversible causes, which can result in a more rapid deterioration of renal function than previously observed. It is often helpful to plot the inverse of serum creatinine (1/Scr) versus time to determine if the slope of the line representing progressive loss of renal function has declined. In all individuals with progressive renal failure, urinary tract infections, obstruction, extracellular fluid volume depletion, nephrotoxins, hypertension, congestive heart failure, and pericarditis should be excluded. Any one of these factors can worsen the underlying chronic renal failure.

B. Laboratory Findings: The diagnosis of renal failure is made by documenting elevations of the BUN and serum creatinine concentrations. Further evaluation is then necessary to differentiate between acute and chronic renal failure. Evidence from old records documenting previously elevated BUN and serum creatinine helps to establish a diagnosis of chronic renal failure. Anemia, metabolic acidosis, hyperphosphatemia, and hypocalcemia occur in both acute and chronic renal failure.

C. Imaging: The finding of small kidneys bilaterally (< 10 cm) by ultrasonography supports a diagnosis of chronic renal failure, though normal or even large kidneys can be seen with chronic renal failure caused by adult polycystic kidney disease, diabetic nephropathy, multiple myeloma, amyloidosis, and obstructive uropathy. Radiographic evidence of renal osteodystrophy is another helpful finding, since x-ray changes of secondary hyperparathyroidism do not appear unless parathyroid hormone levels have been elevated for at least 1 year. Evidence for subperiosteal reabsorption along the radial sides of the digital bones of the hand confirms hyperparathyroidism.

A number of management options are appropriate that may reduce the rate of progression of chronic renal failure as well as the symptoms and long-term complications.

A. Hyperkalemia: Potassium balance is generally intact until the GFR is less than 10 mL/min. However, some individuals may be placed at risk for hyperkalemia before the onset of end-stage renal disease. Low-salt diets with ingestion of salt substitutes (which contain potassium chloride) and administration of drugs that either interfere with renal potassium excretion (triamterene, amiloride, spironolactone, ACE inhibitors, NSAIDs) or block cellular potassium uptake (beta-blockers) can produce hyperkalemia at higher levels of GFR. The presence of hyporeninemic hypoaldosteronism, seen in many patients with chronic renal failure, renders patients more susceptible to hyperkalemia.

Early therapy involves the use of calcium chloride, glucose, insulin, and bicarbonate. Long-standing hyperkalemia is best treated by dietary potassium restriction and, when necessary, sodium polystyrene sulfonate, an orally administered ion exchange resin. The usual dose is 15–30 g once a day in juice or sorbitol.

B. Acid-Base Disorders: Most metabolic acidosis in renal failure is due to inability of damaged kidneys to excrete the 1 meq/kg/d of acid generated by metabolism of dietary proteins. Though patients with chronic renal failure are in positive hydrogen ion balance, the arterial blood pH is maintained at 7.25–7.35 and the serum bicarbonate concentration rarely falls below 15 meq/L. The excess hydrogen ions are buffered by the large calcium carbonate stores in bone that may contribute to uremic osteodystrophy. Generally, maintaining the serum HCO3– concentration at 18–20 meq/L is recommended. Sodium bicarbonate can be given as 650 mg tablets three times a day and titrated as needed. Calcium carbonate may also be used, since it addresses both hypocalcemia and the acidosis. Modest dietary restriction of protein is recommended to decrease the daily metabolic acid load.

Many patients with chronic renal failure start dialysis when the serum creatinine is approximately 10 mg/dL (or BUN 100 mg/dL); patients with diabetic nephropathy often seem to require dialysis somewhat earlier. When possible, an arteriovenous fistula should be placed several weeks before the anticipated initiation of hemodialysis. This allows maturation of the fistula and a higher blood flow through the dialyzer.

1. Hemodialysis–Most patients will require hemodialysis three times weekly. The procedure takes 3–4 hours depending on the type of membranes used, the size of the patient, and other factors.

Home hemodialysis has the advantage that it can be performed at the patient's convenience. Patients receiving home hemodialysis must become much more knowledgeable about their treatment than patients treated in a center. Many believe that home dialysis patients do better for this reason, but selection bias obviously plays a role. A major disadvantage of home hemodialysis is that a helper must be available, and training is required.

2. Peritoneal dialysis–While the percentage of patients receiving home hemodialysis has declined over the past 10 years, the number of patients receiving continuous ambulatory peritoneal dialysis has greatly increased. Peritoneal dialysis is performed by the patient, and the continual nature of the dialysis leads to better clearance of poorly dialyzable compounds, especially phosphate. This in turn results in less dietary restriction for these patients. Similarly, continuous dialysis is not associated with symptom swings observed in hemodialysis.

When it was first introduced, it was hoped that the cost of continuous ambulatory peritoneal dialysis would be much less than that of hemodialysis. While the equipment costs are indeed less, the total cost of care of these patients is not. Peritonitis remains a major complication of peritoneal dialysis, and its treatment (which sometimes requires hospitalization) is expensive. When vascular access for hemodialysis is technically difficult, such as in small children and in some diabetic patients, continuous ambulatory peritoneal dialysis is a reasonable alternative. Patients who have been treated with both modalities usually prefer peritoneal dialysis.

C. Kidney Transplantation: In most patients who develop chronic renal failure, consideration should be given to kidney transplantation. About two-thirds of kidney transplants performed in the United States come from cadaveric donors and the remainder from living related donors. Posttransplant immunosuppression with corticosteroids, azathioprine, and cyclosporine—singly or in combination—are regularly required in cadaveric kidney transplants and generally in living related donor transplants as well, though the number of drugs and the duration of administration depend upon the degree of HLA matching. The 2-year kidney graft survival rate for living related donor transplantations is 85%; the 2-year graft survival rate for cadaveric donor transplantations is 70%.