Zwiech Rafal, Kacprzyk Feliks, Szuflet Adam, Nowicki Michał
Klinika Nefrologii, Hipertensjologii i Transplantologii Nerek UM w Lodzi.
Pol Arch Med Wewn. 2005 Apr;113(4):326-33.
Interleukin-1 receptor antagonist (IL-1ra) and tumor necrosis factor soluble receptors (sTNFR) type I and II reducing the activity of IL-1 and TNFalpha may inhibit inflammatory reactions. The aim of the study was to assess whether serum and urine IL-1ra and sTNFR measurements may be useful as the early predicting factors in patients with IgA nephropathy. Twenty seven patients (16 males, 11 females), mean age 41.6 +/- 22.3 years with biopsy-proven IgA nephropathy and nephrotic-range proteinuria were included in this study. Serum concentrations (sIL-1ra, ssTNFR I and II) and urinary excretions (uIL-1ra, usTNFR I and II) of IL-1ra, sTNFR I and II had been measured before the treatment was instituted. After 12 months of therapy with steroids and cyclophosphamide, the patients were divided into two subgroups i.e. R - responders, and NR - nonresponders according to the treatment results. The control groups comprised 8 healthy people. IL-1ra serum concentration and urinary excretion were lower in the patients than in the controls (202 vs 330 ng/ml and 970 vs 1607 ng/mg creatinine respectively; p < 0.05 both). Serum concentrations and urinary excretion rates of sTNFR 1 (5.1 vs 1.7 ng/ml and 4.1 vs 1.1 ng/mg creatinine respectively) and sTNFR II (14.4 vs. 5.0 ng/ml and 8.3 vs. 4.4 ng/mg creatinine respectively) were higher (p < 0.05 each) in the patients than in the controls. The subdivision of patients and their classification according to achieved treatment results showed no statistically significant differences between initial interstitium volume neither concentration of serum total protein, serum creatinine or proteinuria and glomerular filtration rate in R and NR subgroups. Initial IL-1ra serum concentration, its urinary excretion and sTNFR type I and II urinary excretion rates were significantly higher in R than NR (sIL-1ra - 297 vs 167 ng/ml, p < 0.05; uIL-1ra 1360 vs 87 ng/mg Cr, p < 0.01; and ssTNFR I 5.2 vs 2.2 ng/mg Cr, p < 0.05; ssTNF RII14 vs 6 ng/mg Cr, p < 0.05). However, serum concentration and urinary excretion of sTNF R type I and II were significantly higher in R and NR subgroups than in controls (p < 0.05 both), sIL-1ra and uIL-1ra were significantly lower in R and NR than in healthy subjects. The results of evaluations of serum concentration and urinary excretion of IL-1ra showed similar values to control group results only in responders. No statistically significant differences between sIL-1ra or/and uIL-1ra in both R and control groups were found. Increased serum concentration and urinary excretion of IL-1ra correlates with better prognosis for remission of proteinuria and lower risk of deterioration of kidney function. Those assessments may be helpful as a part of initial screening in patients with IgA nephritis and heavy proteinuria. In contrast the evaluation of both serum and urinary TNF RI and II seems to have no predictive value.
白细胞介素-1受体拮抗剂(IL-1ra)以及I型和II型肿瘤坏死因子可溶性受体(sTNFR)可降低IL-1和TNFα的活性,从而可能抑制炎症反应。本研究的目的是评估血清和尿液中IL-1ra和sTNFR的检测是否有助于作为IgA肾病患者的早期预测指标。本研究纳入了27例患者(16例男性,11例女性),平均年龄41.6±22.3岁,经活检证实为IgA肾病且有肾病范围蛋白尿。在开始治疗前检测了IL-1ra、sTNFR I和II的血清浓度(sIL-1ra、ssTNFR I和II)以及尿液排泄量(uIL-1ra、usTNFR I和II)。在用类固醇和环磷酰胺治疗12个月后,根据治疗结果将患者分为两个亚组,即R组(反应者)和NR组(无反应者)。对照组包括8名健康人。患者的IL-1ra血清浓度和尿液排泄量低于对照组(分别为202 vs 330 ng/ml和970 vs 1607 ng/mg肌酐;两者p均<0.05)。患者的sTNFR 1血清浓度和尿液排泄率(分别为5.1 vs 1.7 ng/ml和4.1 vs 1.1 ng/mg肌酐)以及sTNFR II(分别为14.4 vs. 5.0 ng/ml和8.3 vs. 4.4 ng/mg肌酐)高于对照组(各p<0.05)。根据治疗结果对患者进行细分和分类后发现,R组和NR组在初始间质体积、血清总蛋白浓度、血清肌酐或蛋白尿以及肾小球滤过率方面无统计学显著差异。R组的初始IL-1ra血清浓度、其尿液排泄量以及sTNFR I和II的尿液排泄率显著高于NR组(sIL-1ra - 297 vs 167 ng/ml,p<0.05;uIL-1ra 1360 vs 87 ng/mg Cr,p<0.01;ssTNFR I 5.2 vs 2.2 ng/mg Cr,p<0.05;ssTNF RII 14 vs 6 ng/mg Cr,p<0.05)。然而,R组和NR组的sTNF R I和II的血清浓度和尿液排泄量显著高于对照组(两者p<0.05),R组和NR组的sIL-1ra和uIL-1ra显著低于健康受试者。IL-1ra血清浓度和尿液排泄量的评估结果仅在反应者中与对照组结果相似。在R组和对照组中,sIL-1ra或/和uIL-1ra之间未发现统计学显著差异。IL-1ra血清浓度和尿液排泄量增加与蛋白尿缓解的较好预后以及肾功能恶化风险降低相关。这些评估作为IgA肾炎和重度蛋白尿患者初始筛查的一部分可能会有所帮助。相比之下,血清和尿液中TNF RI和II的评估似乎没有预测价值。