Glomerular charge selectivity is impaired in hypertensive nephropathy

Abstract

BACKGROUND: In hypertensive nephropathy the morphological changes and albuminuria seem to start in the inner cortex but the mechanism of proteinuria is unknown. We tested the hypothesis of reduced glomerular charge selectivity in the juxtamedullary cortex of old spontaneously hypertensive rats (SHR) as a cause of proteinuria in rats with hypertensive nephropathy. METHODS: The glomerular charge barrier was evaluated in 80-week-old SHR and age-matched normotensive Wistar-Kyoto rats (WKY) by measuring the glomerular clearance of radiolabelled cationic and anionic chymotrypsinogen (Chym and aChym, MW 25,000) accumulated by the proximal tubular cells in the outer, middle and inner cortex following intravenous injection. The glomerular filtration rates (GFR) in the cortical zones were obtained by aprotinin (MW 6500) and the sieving coefficient (theta) of the protein tracers calculated as their glomerular clearance/GFR. RESULTS: The theta aChym was similar in SHR and WKY except in the inner cortex where it was 35% higher in SHR (0.65+/-0.05) than in WKY (0.48+/-0.03) (P = 0.01). The ratio of theta aChym to theta Chym was increased from 0.55+/-0.06 to 0.77+/-0.05 (P<0.02) in the inner cortex of SHR, whereas theta Chym remained the same in all cortical zones. Finally, the percentage of glomeruli with adsorption droplets in podocytes quantified by light microscopy was higher in the inner than the outer cortex of SHR (P<0.05). CONCLUSIONS: The study supports the theory of a functioning glomerular charge barrier. An increased relative clearance of aChym in the inner cortex of SHR indicates impairment of the charge barrier, which, at least in part, could explain the increased protein excretion in SHR with hypertensive nephropathy.