AJP - Renal Physiology, Vol 256, Issue 1 71-F78, Copyright © 1989 by American Physiological Society
Cyclosporine nephrotoxicity: blood volume, sodium conservation, and renal hemodynamics
P. Devarajan, F. J. Kaskel, L. A. Arbeit and L. C. Moore
Department of Pediatrics, School of Medicine, State University of New York, Stony Brook 11794.
Glomerular filtration rate (GFR) and renal blood flow (RBF) are depressed
by chronic cyclosporine treatment. We examined the hypothesis that
depletion of extracellular or intravascular fluid volume contributes to the
renal vasoconstriction of early cyclosporine nephrotoxicity (CCN). Control
and CCN rats were given 10 mg/kg cyclosporine A or vehicle intramuscularly
daily for 7 days. The effects of extracellular volume expansion, both acute
(AVE, 10% body wt saline) and chronic (CVE, 10% body wt/day saline ip, 10
days including cyclosporine A treatment period), on renal hemodynamics were
measured. In CCN, AVE completely normalized GFR and RBF, whereas CVE
partially prevented the development of CCN. Renal autoregulatory ability
was depressed in CCN but was largely restored by AVE. Intravascular volumes
were measured with Evans blue and 51Cr-labeled red cells. Plasma and red
cell volumes were reduced by 24% in CCN, indicating circulatory
hypovolemia. Acute repletion of the deficit in blood volume by acute
administration of an isoncotic solution (1.8 ml/100 g body wt of 5% albumin
in isotonic saline) restored GFR and RBF to levels similar to those in
control rats. Extracellular fluid volume, estimated as inulin space, was
similar in both CCN and control groups. A metabolic study (7 day) showed
stool Na loss in CCN to be twice that in controls but both groups remained
in sodium balance. We conclude that the renal vasoconstriction produced in
the rat by short-term cyclosporine treatment is, at least in part, prerenal
in origin and related to the development of circulatory hypovolemia.
