Glomerular charge selectivity is impaired in hypertensive nephropathy

• Published in: Nephrology, dialysis, transplantation dialysis, transplantation, 2004-05, Vol.19 (5), p.1083-1091
• Main Authors: Christiansen, Rolf E. F., Tenstad, Olav, Leh, Sabine, Iversen, Bjarne M.
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Associated diseases and complications; Biological and medical sciences; Chymotrypsinogen - pharmacokinetics; Diabetes. Impaired glucose tolerance; Disease Models, Animal; Emergency and intensive care: renal failure. Dialysis management; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; glomerular charge selectivity; Glomerular Filtration Rate; Glomerulonephritis; Hypertension, Renal - pathology; Hypertension, Renal - physiopathology; hypertensive nephropathy; Intensive care medicine; Kidney Cortex - pathology; Kidney Cortex - physiology; Kidney Cortex - physiopathology; Kidney Glomerulus - pathology; Kidney Glomerulus - physiology; Male; Medical sciences; Metabolic Clearance Rate; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; proteinuria; Rats; Rats, Inbred SHR; Rats, Inbred WKY
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfh101

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 (θ) of the protein tracers calculated as their glomerular clearance/GFR. Results. The θ 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 θ aChym to θ Chym was increased from 0.55±0.06 to 0.77±0.05 (P