Long-term mineralocorticoid receptor blockade ameliorates progression of experimental diabetic renal disease

• Published in: Nephrology, dialysis, transplantation Vol. 27; no. 3; pp. 906 - 912
• Main Authors: LIAN, Michael, HEWITSON, Tim D, WIGG, Belinda, SAMUEL, Chrishan S, CHOW, Fiona, BECKER, Gavin J
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.03.2012
• Subjects: Aldosterone - blood; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Associated diseases and complications; Biological and medical sciences; Blood Pressure; Blotting, Western; Collagen Type IV - metabolism; Diabetes Mellitus, Experimental - physiopathology; Diabetes. Impaired glucose tolerance; Diabetic Nephropathies - pathology; Diabetic Nephropathies - prevention & control; Disease Progression; Emergency and intensive care: renal failure. Dialysis management; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Female; Hyperglycemia - metabolism; Hyperglycemia - pathology; Intensive care medicine; Medical sciences; Mineralocorticoid Receptor Antagonists; Rats; Rats, Inbred SHR; Spironolactone - therapeutic use; Time Factors; Transforming Growth Factor beta1 - metabolism; Endocrinopathy; Kidney disease; Urinary system disease; Steroid hormone; Hemodialysis; Mineralocorticoid; Diabetes mellitus; Aldosterone; Extrarenal dialysis; albuminuria; Nephropathy; Adrenal hormone; Fibrosis; Renal failure; diabetic nephropathy
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfr495

The final end point of diabetic renal disease is the accumulation of excess collagen. A number of studies have shown that aldosterone antagonism ameliorates progression of renal fibrosis. This study was designed to examine the effect of the mineralocorticoid receptor blocker eplerenone (EPL) on progression in streptozotocin (STZ)-treated spontaneously hypertensive rats (SHR), an accelerated model of Type I diabetes. STZ-treated SHRs with a blood glucose >18 mmol/L were randomly divided into treatment (100 mg/kg/day EPL) and non-treatment groups. Sham-injected SHR animals were used as a control. Functional parameters were monitored for 16 weeks, with structural parameters assessed at completion. Both hyperglycaemic groups developed progressive albuminuria, but the increase was ameliorated by EPL from Week 12. STZ-SHRs had elevated kidney weight/body weight ratio, glomerular size, glomerular macrophages (ED-1-positive cells), tissue transforming growth factor beta 1 (TGFβ1) concentrations and glomerular collagen IV staining (all P < 0.05 versus control animals). EPL reduced glomerular volume, TGFβ1 expression and glomerular collagen IV without changing glomerular macrophage infiltration. The ability of EPL to ameliorate these functional and structural changes in hyperglycaemic SHRs suggest that EPL has a renoprotective role in diabetic renal disease.