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Myocardial Infarction Enhances Progressive Renal Damage in an Experimental Model for Cardio-Renal Interaction

Richard P.E. van Dokkum^*, Wouter B.A. Eijkelkamp^*, Alex C.A. Kluppel^*, Rob H. Henning^*, Harry van Goor, Marin Citgez^*, Willemijn A.K.M. Windt^*, Dirk J. van Veldhuisen, Pieter A. de Graeff^* and Dick de Zeeuw^*

Departments of *Clinical Pharmacology, Pathology, and Cardiology, Groningen University Medical Center, The Netherlands.

Correspondence to Dr. Richard P.E. van Dokkum, Department of Clinical Pharmacology, University Medical Center Groningen, Antonius Deusinglaan 1, NL-9713 AV, Groningen, The Netherlands. Phone: +31 50 363 28 40; Fax: +31 50 363 28 12; E-mail: r.p.e.van.dokkum{at}med.rug.nl

Studied were the effects of myocardial infarction (MI) on mild renal function loss in unilateral nephrectomized (UnX) rats. UnX was performed, followed after 1 wk by a variable MI (UnX + MI; n = 24). Rats with only UnX (n = 15) or MI (n = 9) and double sham animals (CON, n = 15) served as controls. Renal outcome was measured by proteinuria and plasma creatinine. Focal glomerulosclerosis (FGS) incidence was evaluated by renal histology. Cardiac function and systolic BP were measured. A division into small and large infarcts after UnX was made a priori, resulting in two groups, one with a mild MI (<20%; n = 15) and one with a moderate MI (>20%; n = 9). Mild proteinuria up to 55.5 mg/d was observed in the UnX + mild MI group, whereas proteinuria rose significantly higher to 124.5 mg/d in the UnX + moderate MI group. Incidence of FGS was significantly increased in both UnX + MI groups compared with all other groups. The average MI size was 18%, 17%, and 25% in the MI, UnX + mild MI, and UnX + moderate MI group, respectively. LVP in both UnX + MI groups was correlated with proteinuria, indicative of a cardio-renal interaction. Clinically, these data imply that more patients are at risk for cardiovascular events and that after such an event, their chance of more renal function loss increases. Finding the underlying mechanism will enable improved protection for both kidneys and heart.

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Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673