AJP - Renal Physiology, Vol 258, Issue 4 934-F939, Copyright © 1990 by American Physiological Society
Effects of chronic volume expansion and enalapril on chronic cyclosporine nephropathy
D. M. Gillum and L. Truong
Department of Medicine, Baylor College of Medicine, Methodist Hospital, Houston, Texas 77030.
Prolonged treatment with cyclosporine (CS) results in an irreversible renal
lesion consisting of interstitial fibrosis and tubular atrophy, as well as
prominent hyperplasia of the juxtaglomerular apparatus (JGA). Ischemia to
the tubulointerstitial compartment caused by intense CS-mediated renal
vasoconstriction may contribute significantly to the development of this
lesion. To explore the potential role of volume contraction and activation
of the renin-angiotensin system (RAS) in the genesis of this lesion, we
have employed a recently described rodent model of chronic cyclosporine
nephropathy (CCN). Over 28 days of CS therapy, animals received plain
drinking water, 1% saline, or enalapril (ENAL), 50 mg/l in drinking water.
At the end of 28 days, Na+ balance in saline-treated animals was markedly
positive, and plasma volume was increased; however, glomerular filtration
rate (GFR) did not change, and the tubulointerstitial lesion and JGA
hyperplasia as evaluated by morphometric techniques were unaffected.
Enalapril-treated animals were relatively hypotensive with lower GFR than
CS controls. Enalapril conferred no protection against the development of
tubulointerstitial disease and exacerbated the development of JGA
hyperplasia and hyperkalemia. We conclude that volume contraction is not an
important contributor to the reduced GFR, tubulointerstitial lesion, or JGA
hyperplasia associated with long-term CS treatment. Blockade of the RAS
also conferred no protection against the development of tubulointerstitial
disease but resulted in worsening of JGA hyperplasia and hyperkalemia.
