Windt Willemijn A K M, Henning Robert H, Kluppel Alex C A, Xu Ying, de Zeeuw Dick, van Dokkum Richard P E
Department of Clinical Pharmacology, University Medical Center Groningen, PO Box 196, NL-9700 AD, Groningen, The Netherlands.
Nephrol Dial Transplant. 2008 Oct;23(10):3103-10. doi: 10.1093/ndt/gfn233. Epub 2008 May 25.
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.
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.
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.
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.
近期的观察性研究表明，肾功能减退是心血管疾病发生的独立危险因素。此前，我们报道过心肌梗死（MI）确实会加剧单侧肾切除（NX）大鼠的轻度肾功能下降，而肾素 - 血管紧张素 - 醛固酮系统（RAAS）干预可抑制这种下降。然而，MI对已存在的严重肾功能丧失的影响以及RAAS干预中断这种假设的心肾相互作用的效果尚不清楚，且在临床上更具相关性。
雄性Wistar大鼠接受心肌梗死、假心肌梗死、5/6肾切除或5/6肾切除加心肌梗死手术。六周后，对肾切除大鼠用血管紧张素转换酶抑制剂（ACEi）或赋形剂治疗6周。
与5/6肾切除组相比，5/6肾切除加心肌梗死组的MI并未显著诱导更多蛋白尿（303±46对265±24mg/24h）和肾小球硬化（40±11对28±4任意单位），并且ACEi治疗在降低这些组的肾损伤方面同样有效。与5/6肾切除组相比，5/6肾切除加心肌梗死组的肾血流量和肌酐清除率降低（分别为2.2±0.6对3.6±0.4ml/min/kg和2.1±0.3对2.9±0.3ml/min/kg），ACEi治疗后二者均升高至与仅接受5/6肾切除组相当的水平。
与单纯5/6肾切除相比，心肌梗死不会使5/6肾切除所致的肾脏结构损伤进一步恶化。此外，心肌梗死后会出现肾血流动力学损害，应用ACEi治疗可改善这种损害。因此，我们得出结论，心肌梗死后慢性肾病患者应优化ACEi治疗以改善肾功能。
