Using the T2DN rat as a model to determine therapeutic efficacy of Serelaxin (recombinant human relaxin‐2) for Diabetic Nephropathy

Abstract

Recent studies demonstrate renoprotective and antifibrotic effects of relaxin in non‐diabetic kidney disease. To test the hypothesis that relaxin protects against diabetic renal injury, we infused Serelaxin (RLX, 4ug/h, Corthera, s.c. minipump) or vehicle into 10–12 month old male T2DN rats for 3 weeks (n=10/group). An ELISA confirmed delivery of RLX (21±2 ng/mL plasma, nondetectable in control). Baseline protein excretion (142±27 vs 144±39 mg/d) and blood glucose (322±32 vs 296±31 mg/dL) were similar in RLX and untreated T2DN, respectively. After treatment, RLX and control groups showed no significant differences in blood glucose (313±18 vs 288±23 mg/dL), MAP (130±8 vs 118±7 mmHg), or proteinuria (212±48 vs 199±63 mg/d). Masson's trichrome staining of kidney sections revealed significant glomerular and tubulointerstitial injury in both groups, with no remarkable changes following RLX treatment. There were no differences between the RLX and control groups (n=5) in renal blood flow (6.0±1.7 vs 6.9±2.6 mL/min) or glomerular filtration rate (3.2±1.3 vs 3.3±1.2 mL/min). We conclude that the T2DN rat is a suitable model for diabetic nephropathy as it does exhibit progressive proteinuria and renal injury similar to human diabetic nephropathy; however, 3 weeks of RLX treatment is not sufficient to reverse established renal injury present in the T2DN rat. Earlier and/or longer treatment with RLX may be required.