Increases in intraglomerular hydrostatic pressure and up-regulation of the renin-angiotensin-aldosterone system (Figure 1) are beneficial short-term adaptive mechanisms that promote flow across the glomerular filtration barrier and slow the accumulation of uremic toxins in people and animals with kidney disease.1-3 However, persistently increased plasma angiotensin II and aldosterone concentrations and intraglomerular hypertension contribute to the long-term progression of kidney disease by worsening proteinuria and promoting the interstitial fibrosis and mesangial cell proliferation typical of "end-stage kidneys."3-5
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Increased urine protein excretion is the hallmark clinicopathologic abnormality in dogs with protein-losing nephropathies. After the exclusion of preglomerular and postglomerular causes of increased urine protein excretion, such as immunoglobulin-producing neoplasms, hemoglobinuria, renal tubular disease, and any cause of lower urinary tract inflammation (e.g. bacterial infections or urolithiasis), glomerular disease can be presumptively diagnosed if the urine protein:creatinine ratio (UPC) is persistently > 0.5.
1. The renin-angiotensin-aldosterone system and sites of action of antiproteinuric drugs administered to dogs with glomerular disease.
Pharmacologic inhibition of the renin-angiotensin-aldosterone system delays the development of azotemia and prolongs the survival of both people and dogs with glomerulopathies.6-9 Treatment with antiproteinuric drugs is recommended when the UPC ratio is > 2.010; however, the preferred drug class, dosage, and monitoring scheme remain unclear. In this article, I summarize the published support for administering angiotensin-converting enzyme (ACE) inhibitors and angiotensin II-receptor blockers (ARBs) and suggest an evidence-based treatment protocol.
Click here to download an algorithm on administering ACE inhibitors and ARBs to treat proteinuria in dogs with glomerular disease.