CHRONIC RENAL FAILURE

Chronic renal failure implies an irreversible and significant reduction in renal function that persists for a minimum of three months. The list of etiologies is excessive; however, common etiologies include diabetic nephropathy, hypertensive nephropathy, postinfectious nephropathy, and nephropathy secondary to systemic diseases such as connective tissue diseases or the vasculitides. Worldwide, Bergers disease (IgA nephropathy) is the most common cause. Once an underlying insult occurs to the kidney, renal function often continues to decline over months or years until remaining renal function is inadequate to maintain life. At this point, dialysis (either hemodialysis or continuous ambulatory peritoneal dialysis) or renal transplantation is necessary to maintain life and to prevent many of the symptoms of uremia from occurring. Symptoms of uremia often manifest when the GFR has decreased to less than 10 ml/min. Cardiovascular disease is a common result of chronic kidney disease.  Characteristic lab abnormalities include elevated BUN and creatinine levels. The serum phosphorus and magnesium levels increase; whereas, the serum calcium is characteristically low. Metabolic acidosis is common and manifests as a low serum bicarbonate level. The inability of the damaged kidneys to produce erythropoietin results in a normocytic anemia.  Parathyroid hormone (PTH) levels increase progressively whereas vitamin D levels are low and difficult to elevate despite aggressive therapy.

Initial evaluation should include a CBC, serum electrolytes( including phosphorous and magnesium), glucose, parathyroid hormone level, vitamin D levels, a renal ultrasound, urinalysis with microscopic sediment examination, and collection of either a 24-hour urine sample for protein and creatinine or calculation of the protein/creatinine ratio of a random urine sample.  The various forms of dialysis should be explained to the patient so that a decision may be made if and when dialysis becomes necessary, or if transplantation is a consideration, then appropriate screening to determine a donor should be undertaken.

To slow the progression of kidney disease, underlying factors such as hypertension and diabetes mellitus should be managed appropriately.  ACEI's or ARB's are considered first line antihypertensive agents especially if patients manifest microalbuminuria or proteinuria.  Blood pressures should be maintained below 130/80 mm Hg. Thiazides should be discontinued and replaced by loop diuretics once the GFR is less than 30 mL/min. Antiplatelet therapy is appropriate due to the high risk for cardiovascular events. High dose vitamin D supplementation should be instituted to normalize serum 1,25-dihydroxyvitamin D levels and to help maintain adequate calcium levels.

Erythropoietin (50-100 units/kg IV or SQ three times/week) and FeSO4 (325 mg PO TID) are often effective at improving anemia. Concomitant iron therapy should be given to maintain ferritin levels above 100 ng/mL and a transferrin saturation above 20%. Calcium carbonate (1-2 grams PO with meals) and dietary phosphorus restriction are effective prophylaxis against hyperphosphatemia. Calcium carbonate and vitamin D supplementation are used to treat the hypocalcemia associated with chronic renal failure. Secondary hyperparathyroidism may be treated with high dose vitamin D or vitamin D analogues (calcitriol or paricalcitriol). Oral sodium bicarbonate (650 mg tablet PO QD-TID) is administered to patients with renal failure induced acidosis and is titrated to increase the serum bicarbonate to approximately 20 mEq/L. Since atherosclerosis is a common complication, statin therapy should be initiated.

There are various degrees of renal impairment, which are based on the GFR. The different stages of renal impairment are as follows:

Stage I      GFR greater than 80% with single kidney, evidence of renal disease on radiographic studies or diseases associated with progressive renal impairment 

Stage II     GFR  between 60% and 80% with single kidney, evidence of renal disease on radiographic studies or disease associated with progressive renal impairment 

Stage III   GFR between 30% and 60% 

Stage IV   GFR between 15% and 30%

Stage V     GFR less than 15%