Dittrich S, Aktuerk D, Seitz S, Mehwald P, Schulte-Mönting J, Schlensak C, Kececioglu D
Department of Congenital Heart Disease/Pediatric Cardiology, Albert-Ludwigs University of Freiburg, Mathildenstrasse 1, D-79106 Freiburg i.Br., Germany.
Eur J Cardiothorac Surg. 2004 Jun;25(6):935-40. doi: 10.1016/j.ejcts.2004.02.008.
To assess the impact of balanced ultrafiltration and peritoneal dialysis (PD) on plasma and urinary cytokines and renal dysfunction after cardiopulmonary bypass (CPB) surgery in newborns and infants.
Twenty-three newborns and infants weighing less than 7 kg and scheduled for operation on congenital malformation were enrolled in this descriptive open clinical study. All patients received conventional ultrafiltration in the CPB rewarming period. Eleven newborns underwent Tenckhoff-catheter implantation in the operation theatre as a routine institutional procedure and received PD after admission to the ICU (the PD [+] group). No PD was used in another 12 patients (the PD [-] group). Interleukins (IL) 6 and 8 were measured four times pre- and post-operatively. Kidney function was assessed by creatinine clearances and urine protein and enzyme analyses.
All patients had an uneventful clinical course. Age (10+/-2 days, PD [+] vs. 96+/-19 days, PD [-]), CPB duration (215+/-23 vs. 143+/-20 min), and degree of hypothermia (26+/-1.3 vs. 31+/-0.1 degrees C) differed significantly between the groups. Age, CPB duration and ultrafiltration influenced post-operative IL-levels in an analysis of variance. While there were few differences immediately after the end of ultrafiltration, post-operative levels of IL-6 and IL-8 were higher and more sustained in the newborns (PD [+]) than in the older infants (PD [-]). The median amount of IL-6 and IL-8 removed by ultrafiltration came to 28 and 59% compared to the amount of IL-6 and IL-8 remaining in the blood at the end of CPB. IL-clearance by ultrafiltration was more than 1000-fold and by PD more than 100-fold as effective as IL-clearance by the kidney. While the kidneys showed an unselective mixed glomerular and tubular pattern of injury, during CPB higher serum IL-concentrations correlated with lower urinary IL-clearances in both study groups.
Ultrafiltration and PD are highly effective in removing proinflammatory cytokines. Impaired kidney function was associated with proinflammatory IL-serum concentrations. Thus, we raise the hypothesis that glomerular-filtered proinflammatory ILs damage the proximal tubular cells of the kidney in newborns and infants, thus contributing to post-operative renal dysfunction. Conversely, we conclude that removing proinflammatory ILs by ultrafiltration and PD acts renoprotectively. A future prospective randomised study could demonstrate whether this can indeed improve clinical outcome.
评估平衡超滤和腹膜透析(PD)对新生儿和婴儿体外循环(CPB)手术后血浆和尿液细胞因子及肾功能障碍的影响。
本描述性开放性临床研究纳入了23例体重小于7kg且计划进行先天性畸形手术的新生儿和婴儿。所有患者在CPB复温期接受常规超滤。11例新生儿在手术室作为常规机构程序进行Tenckhoff导管植入,并在入住重症监护病房(ICU)后接受PD(PD[+]组)。另外12例患者未使用PD(PD[-]组)。术前和术后4次测量白细胞介素(IL)6和8。通过肌酐清除率、尿蛋白和酶分析评估肾功能。
所有患者临床过程平稳。两组之间的年龄(10±2天,PD[+]组对96±19天,PD[-]组)、CPB持续时间(215±23对143±20分钟)和低温程度(26±1.3对31±0.1℃)差异显著。在方差分析中,年龄、CPB持续时间和超滤影响术后IL水平。虽然超滤结束后立即差异不大,但新生儿(PD[+]组)术后IL-6和IL-8水平高于大龄婴儿(PD[-]组)且持续时间更长。与CPB结束时血液中剩余的IL-6和IL-8量相比,超滤去除的IL-6和IL-8中位数分别达到28%和59%。超滤清除IL的效率比肾脏清除IL的效率高1000倍以上,PD清除IL的效率比肾脏高100倍以上。虽然肾脏显示出非选择性的混合性肾小球和肾小管损伤模式,但在CPB期间,两个研究组中较高的血清IL浓度与较低的尿液IL清除率相关。
超滤和PD在去除促炎细胞因子方面非常有效。肾功能受损与促炎IL血清浓度相关。因此,我们提出假说:肾小球滤过的促炎ILs会损害新生儿和婴儿肾脏的近端肾小管细胞,从而导致术后肾功能障碍。相反,我们得出结论:通过超滤和PD去除促炎ILs具有肾脏保护作用。未来的前瞻性随机研究可以证明这是否真的能改善临床结局。