Prolonging life and kidney function (Proceedings) - Veterinary Healthcare


Prolonging life and kidney function (Proceedings)


Control of proteinuria

The detection of proteinuria is a diagnostic index in cats with CRF. Based on the theories of glomerular hypertension that occur in "super nephrons" of the adapted kidney, protein gaining access to tubular fluid and the mesangium is also a creator of further renal injury. The magnitude of proteinuria is a function of the integrity of the glomerular barrier, GFR, tubular reabsorptive capacity, and effects from elevated systemic and intraglomerular blood pressure.

Cats with CRF increased their risk for death or euthanasia when the UPC was 0.2 to 0.4 compared to <0.2 and was further increased in cats with UPC of >0.4. The prognosis for survival is influenced by the UPC despite what has traditionally been thought to be low-level proteinuria. The effect of treatments that lower proteinuria on survival have not been specifically studied.

Since even low-level proteinuria is a risk factor to not survive in cats, it is prudent to consider treatments that lower the amount of proteinuria in those with CKD and CRF. Benazepril has been shown in two recent clinical studies to reduce the UPC in cats with CRF. Cats treated with benazepril in one study did not progress from IRIS stage 2 or 3 to the next stage as rapidly as those treated with placebo but over 6 months. Despite reduction in proteinuria in CKD cats with initial UPC > 1.0 that were treated with benazepril in another study, a significant increase in survival time was not found over placebo.

In a study of dogs with naturally occurring CRF, the relative risks for the development of uremic crises and death were approximately 3 times higher in dogs with urinary protein to creatinine ratios (UPC) ≥ 1.0, compared with dogs with UPC < 1.0. Relative risk of adverse outcome was approximately 1.5 times higher for every 1-unit increment in the UPC. Renal function decreased more severely in dogs with initial UPC ≥ 1.0, compared with CRF dogs with UPC < 1.0.

Hormone replacement: Erythropoietin

Recombinant human erythropoietin (rhEPO) has been used to successfully correct nonregenerative anemia in CKD cats. Treated animals demonstrate resolution of anemia, weight gain, improved appetite, improved haircoat, increased alertness, and increased activity. Therapy may be started in symptomatic cats with PCV values < 20% if clinical signs of anemia are present and problematic. The starting dosage is 100 U/kg administered subcutaneously 3 times per week. Iron deficiency is avoided by monitoring serum iron and total iron binding capacity and providing oral supplementation with ferrous sulfate (5 to 50 mg per cat per day). When the lower end of the target PCV range (30-40%) is reached, frequency of administration is reduced to twice a week. Depending upon the severity of anemia, it may require 3-4 weeks for the PCV to enter the target range. Although initially effective in correcting the anemia of CRF, use of rhEPO is associated with antibody formation in up to 50% of treated dogs and cats after 1 to 3 months of treatment. The resulting anemia can be more severe than that present before treatment because the induced antibodies can cross-react with the animal's native EPO. The canine EPO gene has been isolated, and recombinant canine EPO has been used to stimulate erythropoiesis in normal dogs and in those with naturally occurring CRF. It is not as effective when used in dogs that have developed red cell aplasia from previous treatment with rhEPO. Feline recombinant EPO also has been produced, but unfortunately unexplained red cell aplasia developed in some treated cats. Other adverse effects have been observed during administration of rhEPO to dogs and cats including vomiting, seizures, hypertension, uveitis, and hypersensitivity-like mucocutaneous reaction.


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