NDT Advance Access originally published online on May 25, 2008
Nephrology Dialysis Transplantation 2008 23(10):3103-3110; doi:10.1093/ndt/gfn233
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Myocardial infarction does not further impair renal damage in 5/6 nephrectomized rats
Department of Clinical Pharmacology, Groningen Institute for Drug Evaluation (GUIDE), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Richard P. E. van Dokkum, Department of Clinical Pharmacology, University Medical Center Groningen, PO Box 196, NL-9700 AD, Groningen, The Netherlands. Tel: +31-50-363-2810, Fax: +31-50-363-2812, E-mail: r.p.e.van.dokkum{at}med.umcg.nl
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Abstract |
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Background. Recent observational studies show that reduced renal function is an independent risk factor for the development of cardiovascular disease. Previously, we reported that myocardial infarction (MI) indeed enhanced mild renal function decline in rats after unilateral nephrectomy (NX) and that RAAS intervention inhibited this decline. The effects of an MI on pre-existing severe renal function loss and the effects of RAAS intervention interrupting this hypothesized cardiorenal interaction are however unknown and clinically even more relevant.
Methods. Male Wistar rats underwent MI, sham MI, 5/6NX, or 5/6NX and MI. Six weeks later, the NX rats were treated with an angiotensin-converting enzyme inhibitor (ACEi) or vehicle for 6 weeks.
Results. An MI did not significantly induce more proteinuria (303 ± 46 versus 265 ± 24 mg/24 h) and glomerulosclerosis (40 ± 11 versus 28 ± 4 arbitrary units) in 5/6NX+MI compared to 5/6NX, and ACEi therapy was equally effective in reducing renal damage in these groups. In the 5/6NX+MI group, decreased renal blood flow and creatinine clearance were observed compared to 5/6NX (2.2 ± 0.6 versus 3.6 ± 0.4 ml/min/kg and 2.1 ± 0.3 versus 2.9 ± 0.3 ml/min/kg), which both increased after ACEi to levels comparable found in the group that underwent 5/6NX alone.
Conclusions. MI does not further deteriorate structural renal damage induced by 5/6NX compared with 5/6NX alone. Furthermore, renal haemodynamic impairment occurs after MI, which can be improved applying ACEi therapy. Therefore, we conclude that treatment with ACEi should be optimized in patients with chronic kidney disease after MI to improve renal function.
Keywords: 5/6 nephrectomy; ACEi therapy; cardiorenal interaction; myocardial infarction
Received for publication: 15. 8.07
Accepted in revised form: 4. 4.08