Abstract P118: The Complexity of the Albuminuria Development in Salt-sensitive Hypertension

Abstract

Hypertension is one of the most prevalent diseases worldwide, and is a major risk factor for developing albuminuria, renal failure and cardiovascular diseases. The goal of this study was to investigate the mechanisms leading to albuminuria in the kidney of a canonical rat model of hypertension, the Dahl salt-sensitive (SS) rat. To determine the relative contributions of the glomerulus and proximal tubule (PT) to albuminuria, we applied intravital two-photon-based imaging to investigate complex changes in renal function that occur during salt-induced hypertension. Following a high salt (HS) diet, SS rats exhibited elevated blood pressure, accompanied by increased glomerular sieving of albumin (GSC alb =0.0686) and decreased serum albumin (-Δ0.54 g/dL), which corresponded to increased daily filtered albumin up to 3.7 vs 0.8 g at normal diet. Pathologically, hypertensive animals had significant tubular damage as indicated by increased prevalence of granular casts (+Δ2.20 casts/image), dilation/expansion and necrosis of PT epithelial cells, increased vascular injury (+Δ0.61 leakage/image), and progressive inflammation. HS diet significantly reduced total PT uptake of albumin, which also coincided with reduced transcellular transport of albumin back into circulation. Collectively, these results indicate that both the glomerulus and the proximal tubule contribute to albuminuria and dual treatment of glomerular filtration and albumin reabsorption may represent an effective treatment of salt-sensitive hypertension.