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ACE blockers in chronic renal insufficiency of cats
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Chronic renal insufficiency is a common problem in older cats. Many of them live for years with few clinical signs while others will progress more rapidly. This update discusses also new therapeutic options which might slow the progression of the disease: ACE blockers.
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Conventional monitoring of the affected cats has included periodic blood chemistries and complete blood cell counts assessing for: progression of azotemia, alterations in electrolyte and acid-base balance, changes in the calcium and phosphorous levels and progression of non-regenerative anemia.
Long-term management of these cases is typically aimed at correcting electrolyte and acid-base abnormalities, supplementing water soluble vitamins, alleviating gastrointestinal side effects and controlling serum phosphorous levels. In more severe cases, daily subcutaneous fluids are administered to provide diuresis and in some more severely anemic patients, erythropoietin therapy may be considered.
Recently, the importance of monitoring and controlling systemic blood pressure has become more widely accepted.
Despite the large number of cats with chronic renal insufficiency, predicting the survival time can be difficult. Definitive, clinically obtainable, risk factors for progression of renal insufficiency have not been widely established in the cat. Furthermore, management of the disease has changed very little in the past decade. Recent abstracts from the 2003 ACVIM Forum (#103,104,106 and 228) have attempted to address these issues.
In humans, proteinuria is an independent risk factor for the progression of chronic renal insufficiency and is related to survival times in patients with renal failure. In addition, angiotensin converting enzyme (ACE) inhibitors have been shown to reduce proteinuria and increase survival time. There are several mechanisms, by which ACE inhibitors may reduce proteinuria, including: reduction in the size of the glomerular capillary endothelial cell pores, improvement in lipoprotein metabolism, decrease in intraglomerular pressures and reduction of glomerular cell proliferation.
Recently, the importance of proteinuria in cats and the ability to minimize proteinuria has become an area of interest for veterinary researchers. One study (Influence of Proteinuria on Survival Times in Cats with Chronic Renal Insufficiency; D. Gunn-Moore) looked at 193 cats with chronic renal insufficiency. The cats were randomized to receive benazepril (0.5-1 mg/kg once daily) or a placebo for up to three years. Cats treated with benazepril had lower urine protein:creatinine (UPC) and higher plasma protein levels as compared to the placebo group. Although, mean survival times were not significantly different between the two groups, the benazepril treated group did have higher survival rates.
Another study (Relation of Survival Time and Urinary Protein Excretion in Cats with Renal Failure and/or Hypertension; HM Syme) compared normal cats to those with chronic renal disease in various parameters (age, systolic blood pressure, plasma creatinine concentration, urine protein concentration, UPC). Urine protein:creatinine appeared to be a significant predictor of survival time. Median survival time for cats with UPC < 0.43 was 766 days while median survival time for cats with UPC > 0.43 was only 281 days. Interestingly, systolic blood pressure was not predictive of survival time.
Proteinuria appears to be a risk factor for progression of chronic renal disease in cats and also appears to be associated with reduced survival times. Benazepril, an ACE inhibitor, appears to lower UPC and in doing so may increase survival times and slow progression of renal disease in cats.
Periodic assessment of urine including a urine protein:creatinine ratio should be performed in all cats with chronic renal insufficiency. In addition, benazepril therapy should be considered along with the more conventional therapeutic regimens.
Further investigation is required to determine whether reducing proteinuria with ACE inhibitors will slow the progression of renal disease and ultimately improve survival times. Potential side effects associated with long-term benazepril therapy in cats with chronic renal disease, will also need to be addressed.
Source: DVM Newsmagazine Dember 1, 2003. www.newsmagazine.com/dvm/
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