Loss of Renal Mass Exacerbates Renal Damage in a Mouse Model of High‐Renin Hypertension

Abstract

Chronic renal failure is a growing public health problem. Experimental and clinical data suggest that the loss of functional renal mass itself is a major driver for the progression of renal failure. Surprisingly, mice appear to be largely resistant to this pathogenic mechanism. In patients, chronic renal failure usually develops slowly over years, and increased arterial blood pressure and an activated renin‐angiotensin system are common comorbidities of the clinical phenotype. Hence, we formulated the hypothesis that coexistence of both changes over a prolonged period is required to induce sensitivity to a reduction in renal mass in mouse kidneys. To test this, we examined the effects of a moderate reduction in renal mass (unilateral nephrectomy) in SV‐129 renin transgenic mice, which have chronically elevated blood pressure levels subsequent to a genetically clamped high renin. The reduction in renal mass induced albuminuria and histopathological changes (glomerulosclerosis and protein casts) in renin transgenic animals, which were further enhanced when the mice were fed a high‐salt diet. In contrast, fibrosis of the myocardium and aortic wall was not increased in renin‐transgenic compared with control animals. We conclude that loss of renal mass can be an effective pathogenic factor in the development of chronic renal damage in mice. Renin transgenic mice may be a relevant model for chronic renal failure associated with high‐renin hypertension.