Key result
Mineralocorticoid-resistant rats show ~100% reduction in glomerular damage vs controls following 5/6 nephrectomy.
Why the study?
The role of aldosterone in mediating renal injury after renal mass reduction was unclear, and Wistar-Furth rats resistant to mineralocorticoids were used to investigate this.
Does mineralocorticoid resistance in Wistar-Furth rats prevent progressive renal injury following 5/6 nephrectomy compared to control Wistar rats?
Does mineralocorticoid resistance in Wistar-Furth rats prevent progressive renal injury following 5/6 nephrectomy compared to control Wistar rats?
Absolute Event Rate: 0% vs 42%
p-value: p=<0.01
Mineralocorticoid-resistant Wistar-Furth rats are protected from renal injury following 5/6 nephrectomy, supporting the hypothesis that aldosterone mediates progressive renal damage after renal mass reduction.
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Supports aldosterone's role in post-nephrectomy renal progression in rats; hypothesis-generating for mineralocorticoid antagonism in human CKD.
The Wistar-Furth rat, an inbred strain resistant to actions of mineralocorticoids, was used to study the concept that mineralocorticoids contribute to progressive renal injury. It was postulated that if chronic nephropathy depends on aldosterone and if Wistar-Furth rats are resistant to aldosterone, remnant nephropathy would be attenuated in Wistar-Furth rats. Wistar-Furth rats and control Wistar rats were subjected to 5/6 nephrectomy or a sham procedure and then followed for 4 wk. Renal ablation resulted in hypertension at 4 wk in both strains (164+/-5 [Wistar-Furth] versus 184+/-7 [Wistar] mm Hg mean arterial pressure), with sham animals remaining normotensive (134+/-6 mm Hg). Renal damage in response to 5/6 nephrectomy was greatly decreased in Wistar-Furth rats compared with Wistar rats. Albuminuria was markedly less in Wistar-Furth rats (12.7+/-4.2 [Wistar-Furth] versus 97.4+/-22.6 [Wistar] mg/d per 100 g body wt, P<0.01). Glomerular damage, consisting of mesangial proliferation, mesangial lysis, and segmental necrosis, was observed in 42% of glomeruli from Wistar rats but in 0% of glomeruli from Wistar-Furth rats (P<0.01). To address the possibility that higher BP in partially nephrectomized Wistar rats mediated the greater renal damage, the study was repeated, with Wistar rats (not Wistar-Furth rats) being treated with a hydralazine-reserpine-hydrochlorothiazide regimen. Although this antihypertensive regimen equalized BP (conscious systolic) (144+/-8 mm Hg [Wistar] versus 157+/-7 mm Hg [Wistar-Furth] at 4 wk), albuminuria remained more than 10-fold greater in Wistar rats. In summary, renal damage upon 5/6 nephrectomy was markedly reduced in Wistar-Furth rats, a finding not attributable to reduced systemic BP. Since Wistar-Furth rats have been shown previously to be resistant to the actions of mineralocorticoids, the data from the present study support the hypothesis that aldosterone mediates, at least in part, the renal injury attendant to renal mass reduction.
Fitzgibbon et al. (1999) studied Remnant nephropathy. Wistar-Furth rat strain (mineralocorticoid resistance) vs. Wistar rat strain was evaluated on Glomerular damage (mesangial proliferation, mesangial lysis, and segmental necrosis) (p=<0.01). Following 5/6 nephrectomy, mineralocorticoid-resistant Wistar-Furth rats developed significantly less glomerular damage (0% vs 42%, P<0.01) than control Wistar rats.
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