ACE inhibition delays development of terminal renal failure in the presence of severe albuminuria.
The hypertensive fawn-hooded (FHH) rat develops progressive albuminuria (UalbV) and focal glomerulosclerosis (FGS). Early-onset angiotensin-converting enzyme inhibition (ACE-i) completely prevented the development of hypertension, UalbV, and FGS. ACE-i was still effective when the start of treatment was delayed, albeit less than early-onset treatment. In this study, we examined whether more advanced renal damage reduces the efficacy of ACE-i, and, if so, which factors dampen the efficacy. ACE-i was started in 36-week-old FHH rats, and follow-up consisted of regular assessment of systolic blood pressure (SBP) and UalbV. Untreated rats, matched for age, SBP, and UalbV, served as controls. In separate groups, untreated or treated with ACE-i from either week 7 or week 36, glomerular hemodynamics and FGS were determined at week 40. ACE-i normalized SBP and markedly reduced UalbV. The Initial UalbV response to ACE-i was inversely correlated with pretreatment UalbV, but despite control of SBP, UalbV rose again. Eventually, rats died of terminal renal failure. Life expectancy was significantly increased in treated rats. In both untreated and treated rats, there was a significant inverse correlation between baseline UalbV and survival time. However, the gain in survival time decreased when pretreatment UalbV was higher. Late-onset ACE-i reduced glomerular capillary pressure to the same extent as early-onset ACE-i. There was a significant linear correlation between FGS and UalbV. We conclude that in FHH rats with advanced renal damage, ACE-i slows down the progression to terminal renal failure. The outcome is an increased survival time that is inversely correlated with baseline UalbV.
Verseput
G H
GH
Department of Nephrology and Hypertension, Utrecht University, The Netherlands. G.Verseput@knoware.nl
Koomans
H A
HA
Braam
B
B
Weening
J J
JJ
Provoost
A P
AP
D000419:Albuminuria / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D005919:Glomerular Filtration Rate; D006439:Hemodynamics; D007676:Kidney Failure, Chronic / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D008297:Male; D051381:Rats; D012720:Severity of Illness Index; D015996:Survival Rate; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors