Angiotensin-converting enzyme inhibition prevents glomerular-tubule disconnection and atrophy in passive Heymann nephritis, an effect not observed with a calcium antagonist

In proteinuric nephropathies tubular atrophy leads to glomerular-tubule dis connection through an unknown mechanism. Here we studied whether proteinuri a promoted glomerular-tubule disconnection in individual nephrons and wheth er this phenomenon was prevented by an angiotensin-converting enzyme (ACE) inhibitor. Passive Heymann nephritis (PHN) and control rats were studied at 4 and 8 months. Two additional groups of PHN rats received lisinopril (40 mg/L) or a calcium channel blocker (lacidipine, 3 mg/ kg) from day 7 after surgery to 8 months. At sacrifice, kidneys were serially sectioned to ident ify glomerular-tubule abnormalities in individual nephrons and changes in i nterstitial volume. In PHN rats, the time-dependent increase in proteinuria was paralleled by tubular atrophy leading to glomerular-tubule disconnecti on and interstitial volume enlargement. Marked apoptosis was invariably fou nd in atrophic tubules in contrast to the absent or very mild terminal dUTP nick-end Labeling staining in tubules normally connected to glomeruli in P HN animals. Treatment with an ACE inhibitor prevented hypertension, protein uria, the formation of atrophic tubuli, glomerular-tubule disconnection and limited the fractional interstitial volume expansion. Although lacidipine limited hypertension, it did not reduce proteinuria or prevent tubular atro phy and disconnection. Multivariate analysis showed that the appearance of atubular glomeruli and the increase in interstitial volume were better pred icted by proteinuria than blood pressure. This study suggests that ACE inhi bitors effectively prevent glomerular-tubule disconnection possibly by thei r ability of reducing proteinuria, which in turn favors proximal tubular ce ll apoptosis. Agents that only reduced hypertension but not proteinuria do not affect tubular behavior.