Meenakshi S R, Agarwal Rajni
Assistant Professor, Department of Biochemistry, Malabar Medical College , Calicut, India .
J Clin Diagn Res. 2013 Jul;7(7):1288-90. doi: 10.7860/JCDR/2013/5972.3119. Epub 2013 May 31.
Nitric Oxide (NO), the L-arginine derivative, is tonically synthesised by the endothelium within the kidney and it plays a crucial role in the regulation of the blood pressure and the renal blood flow. NO regulates the renal function through the modulation of the vascular tone and sodium handling. With the progressive development of the renal insufficiency, it remains unclear whether the endogenous NO production is increased or decreased in the kidney. This study was carried out to determine whether there were any changes in the levels of NO and teir correlation with the routine parameters of the renal dysfunction in the patients of Chronic Renal Failure (CRF), as the disease progresses in conjunction with poor renal functions.
Thirty patients with chronic renal disease which was caused by chronic glomerulonephritis and hypertension, who were on Maintenance Haemodialysis (MHD) with serum creatinine levels of > 2.5 mg/dl, were included in this study. Thirty healthy voluntary blood donors were taken as the controls. NO was estimated by a spectrophotometric method by using cadmium reduction. The routine renal function tests, BUN and Creatinine were performed by the standard clinical chemistry procedures.
The serum NO levels were found to be significantly increased (p < 0.01) in the CRF on MHD (98.77 ± 35.40 μmol/l) as compared to the controls (22.03 ± 7.23 μmol/l). The NO output correlated with the serum creatinine (r = 0.8123, p < 0.01) and the urea concentration (r = 0.5166, p = <0.01) in the CRF group.
The NO levels were markedly enhanced in the CRF patients who were on MHD. This was due to the dialysis procedure itself, which led to the stimulation of cytokine induced NO synthase and also due to the platelets which generated more NO due to uraemia. At high concentrations, NO is a cytotoxic molecule which is responsible for the complications of dialysis and it results in Nitrosative Stress in these patients, as it is a highly reactive free radical. Since the no output correlated with the serum creatinine and urea concentrations, a higher no production probably indicated insufficient blood purification, due to the common effect on their elimination pathways via the renal tract. Therefore, the alterations of the renal function, that are reflected in the changes of the creatinine concentration, will be accompanied by the changes in the serum NO. Thus, the determination of the NO levels in the peripheral blood may be useful in the assessment of the dialysis and they can also be used as markers in the follow up and the prognosis in these type of patients.
一氧化氮(NO)是L - 精氨酸的衍生物,由肾脏内皮持续合成,在调节血压和肾血流量中起关键作用。NO通过调节血管张力和钠代谢来调节肾功能。随着肾功能不全的逐渐发展,肾脏内源性NO生成是增加还是减少仍不清楚。本研究旨在确定慢性肾衰竭(CRF)患者在疾病进展且肾功能不佳时,NO水平是否有变化及其与肾功能不全常规参数的相关性。
本研究纳入30例因慢性肾小球肾炎和高血压导致慢性肾病且维持性血液透析(MHD)、血清肌酐水平>2.5mg/dl的患者。选取30名健康自愿献血者作为对照。采用镉还原分光光度法测定NO。通过标准临床化学程序进行常规肾功能检查、血尿素氮(BUN)和肌酐检测。
与对照组(22.03±7.23μmol/l)相比,MHD治疗的CRF患者血清NO水平显著升高(p<0.01)(98.77±35.40μmol/l)。CRF组中NO生成与血清肌酐(r = 0.8123,p<0.01)和尿素浓度(r = 0.5166,p =<0.01)相关。
MHD治疗的CRF患者NO水平显著升高。这是由于透析过程本身导致细胞因子诱导的NO合酶受刺激,也由于尿毒症使血小板产生更多NO。高浓度时,NO是一种细胞毒性分子,导致透析并发症,因其是高反应性自由基,会在这些患者中导致亚硝化应激。由于NO生成与血清肌酐和尿素浓度相关,较高的NO生成可能表明血液净化不足,这是因为它们通过肾脏途径的清除过程存在共同影响。因此,反映在肌酐浓度变化中的肾功能改变将伴有血清NO的变化。所以,测定外周血NO水平可能有助于评估透析,也可作为这类患者随访和预后的标志物。