Chronic renal failure causes difficult to pinpoint
Q: What causes chronic renal failure (CRF)?
A: Unlike acute renal failure, the cause of CRF usually is difficult to determine. Because of the interdependence of the vascular and tubular components of the nephron, the end-point of irreversible glomerular or tubular damage is the same. A morphologic heterogeneity among nephrons exists in the chronically diseased kidney with the changes ranging from severe atrophy and fibrous scar tissue replacement to marked hypertrophy. The histopathologic changes are not process-specific, and therefore the cause is usually unknown.
Q: What are the clinical signs of CRF?A: CRF develops over a period of weeks, months or years, and its clinical signs are often relatively mild for the magnitude of the azotemia. Unique signs of CRF include a long-standing history of weight loss, polydipsia/polyuria and poor body condition. A non-regenerative anemia is often documented on a CBC, and small and irregularly shaped kidneys can be palpated on physical examination. Renal ultrasonography usually will show diffusely hyperechoic renal cortices with loss of the normal corticomedullary boundary. The increased cortical echogenicity results from replacement of the irreversibly damaged nephrons with fibrous scar tissue. Radiographic studies and ultrasonography also can help identify or rule out potentially treatable causes of CRF, such as bacterial pyelonephritis and renal urolithiasis.
Q: How do the treatment strategies for acute and chronic renal failure differ?
A: The tubular lesions and dysfunction caused by toxic, ischemic and infectious insults can be reversible. The goals of treatment of established acute renal failure (ARF) are to eliminate renal hemodynamic disorders and alleviate water and solute imbalances to "buy time" for nephron repair and compensatory hypertrophy. Conversely, because the nephron damage in CRF usually is irreversible, the goal of treatment is to reduce the renal workload and the clinical signs associated with the decreased renal function. It is also important to attempt to slow down the progressive loss of nephrons in CRF patients.
Q: Why is CRF usually irreversible?
A: Progressive diseases that slowly destroy nephrons allow time for repair of reversibly damaged nephrons as well as hypertrophy of intact nephrons. When renal failure finally occurs, the repaired and hypertrophied nephrons can no longer maintain adequate renal function. Because new nephrons cannot be produced, the functional abnormalities of CRF usually are irreversible and often progressive.
What mechanisms contribute to the progressive decline of renal function observed in many CRF patients?
Proteinuria and systemic hypertension have been associated with increased risk of uremic crises and death, although a direct link to progressive nephron loss has not been established. The soft-tissue mineralization that can occur when the serum calcium x phosphorus product exceeds 50-70 mg/dl has been linked to progressive loss of nephrons in dogs and cats. Ascending urinary tract infections (bacterial pyelonephritis) and renoliths (most commonly calcium oxalate) are additional causes of progressive nephron loss.
Q: Is dietary therapy effective in slowing the progression of CRF?
A: In a controlled, prospective study, dietary modifications were beneficial in minimizing extrarenal manifestations of uremia and mortality rates in dogs with mild/moderate spontaneous CRF. Results were consistent with the hypothesis that the delay in mortality rate was associated, at least in part, with a reduction in disease progression. Similarly, feeding a specifically formulated feline CRF diet, alone or in combination with an enteric phosphate binder, to cats with spontaneous CRF resulted in lower concentrations of parathyroid hormone and phosphorus, as well as increased survival time. These results suggest that dietary therapy and enteric phosphate binders, if appropriate, can improve the quality and quantity of life for our patients.
Q: Is calcitriol indicated as a treatment for CRF?
A: This remains a controversial issue in veterinary medicine. The primary benefit of ultra-low dose calcitriol treatment is lower parathyroid hormone concentrations. Much of the controversy stems from a study in which parathyroidectomized dogs with experimental CRF fared no better than parathyroid-intact CRF dogs. Most experts agree that calcitriol should be supplemented only if parathyroid hormone and phosphorus concentrations remain increased after dietary and enteric phosphate binder treatment has been initiated.