Proteinuria is associated with increased systemic and glomerular water permeability

Abstract

Proteinuria is associated with an increased risk of cardiovascular death. Evidence suggests that proteinuria reflects systemic endothelial dysfunction as well as renal pathology. The Munich Wistar Fromter (MWF) rat strain develops spontaneous proteinuria, permitting study of altered endothelial function under conditions of increased proteinuria. Male MWF rats (15‐24 wks) were significantly proteinuric (MWF:15.0±1.5 n=14 Wistar: 1.8±0.20 n=10, p<0.0001). Hydraulic conductivity (Lp) and effective oncotic pressure (σδπ) were measured in individually perfused microvessels of the mesentery. Male MWF rats had significantly increased Lp (x10−7 cm s−1 cmH20−1) but unchanged σδπ (cmH20) compared with age matched wistar controls (Lp MWF:6.4±1.8 n=7; Wistar: 2.8±0.4 n=15, p<0.05 σδπ MWF:24.6±2.0 n=7; Wistar:23.7±0.9 n=7). Normalised glomerular ultrafiltration coefficient (LpA/Vi) was measured using an oncometric assay. The increase in systemic Lp was mirrored by a significant increase in glomerular LpA/Vi (MWF: 1.5±0.1 min−1mmHg−1 n=58; Wistar: 1.0±0.1 min−1mmHg−1 n=24, p<0.01). These results suggest proteinuria is associated with increased glomerular and systemic water permeability. The mechanistic links require further investigation and may provide insight into the predictive link between proteinuria and increased cardiovascular mortality.Supported by BHF