Altered organic anion and osmolyte content and excretion in rat
polycystic kidney disease: an nmr study.
Ogborn, Malcolm R., Sanjay Sareen, Jonathan Prychitko, Richard Buist,
James Peeling.
Department of Pediatrics and Child Health, Department of Radiology,
Department of Pharmacology and Therapeutics, University of Manitoba,
Winnipeg, Manitoba, Canada
APStracts 3:0182F, 1996.
Polycystic kidney disease (PKD) is the fourth most common cause of
endstage renal disease and the most common potentially lethal
inherited disease in man. Early identification of carriers of
dominant PKD in the absence of genetic markers is problematic in both
man and the Han:SPRD-cy /+ rat, a model of PKD that shares many
features of human disease. We undertook a proton magnetic resonance
imaging (MRI) study of young Han:SPRD-cy/+ and unaffected Han:SPRD
-+/+ animals to determine if carrier status could be identified based
upon image appearance or signal characteristics. Affected animals
demonstrated significant prolongation of T1 and T2 in both cystic
renal cortex and non cystic renal medulla. Both of these measurements
correlated significantly with whole kidney section tubular luminal
space measurements, a correlate of water space, in the renal cortex
but only T1 in renal medulla showed a relationship to tubular luminal
volume measured throughout the kidney. Urine and perchloric acid
kidney extracts were studied using proton nuclear magnetic resonance
(1H-NMR) spectroscopy to test the hypothesis that imaging differences
implied specific urinary and tissue biochemical differences between
affected and normal animals. 1H-NMR spectra of urine from cy/+
animals showed significantly increased excretion of alanine, citrate,
succinate and 2-oxoglutarate but not methylamine compounds compared
with +/+ animals. 1H-NMR spectra of aqueous perchloric acid kidney
extracts confirmed reduced concentrations of the above ions and
others involved in the citric acid cycle, as well the osmolytes
betaine, taurine and glycerophosphocholine. PKD in the Han:SPRD-cy/+
rat is associated with distinct early MRI changes and alterations in
urinary and tissue levels of organic anions and osmolytes.
Received 13 November 1995; accepted in final form 26 September
1996.
APS Manuscript Number F382-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996