Induction of albuminuria and kidney damage in SHR by transfer of chromosome 8 from Munich Wistar Frömter rats.

ABSTRACT

Inbred Munich Wistar Frömter [MWF/FubRkb (RGD724569), MWF] rats develop progressive albuminuria with age that is under polygenetic influence. We previously identified a major albuminuria quantitative trait locus (QTL) on rat chromosome (RNO)8 in MWF. To test the independent role of QTL(s) for albuminuria development on RNO8, we generated a consomic SHR-Chr 8(MWF)/Rkb (SHR-8(MWF)) strain by transferring RNO8 from MWF into the albuminuria-resistant background of the spontaneously hypertensive rat [SHR/FubRkb (RGD631696; SHR)]. Young male MWF, SHR, and SHR-8(MWF) were sham-operated or unilaterally nephrectomized (Nx) at 6 wk and followed up to 24 wk of age, respectively. Systolic blood pressure was significantly lower in SHR-8(MWF) Sham compared with SHR Sham (-19.4 mmHg, P = 0.03) at 24 wk. In contrast, transfer of MWF-RNO8 into SHR induced a significant elevation of urinary albumin excretion (UAE) between weeks 12 and 24 in SHR-8(MWF) compared with SHR Sham animals (P < 0.0001, respectively). Nx resulted in a significant increase in UAE in both strains during follow-up (P < 0.0001, respectively), with significant higher values in SHR-8(MWF) compared with SHR (P < 0.005, respectively). Renal structural changes as determined by glomerulosclerosis (GSI) and tubulointerstitial damage index (TDI) were significantly higher in consomic animals either at Sham (TDI) or Nx (GSI) conditions (P < 0.05, respectively). These data confirm the independent role of MWF QTL(s) on RNO8 for both albuminuria and structural kidney damage. Moreover, this study shows for the first time the induction of albuminuria by transferring one or more albuminuria QTL into a resistant recipient background in a consomic rat strain.