Department of Nephrology, Radboud University Nijmegen Medical Centre Nijmegen, Nijmegen, The Netherlands.
Nephrol Dial Transplant. 2011 Nov;26(11):3581-8. doi: 10.1093/ndt/gfr135. Epub 2011 Apr 5.
The variable course of immunoglobulin A nephropathy (IgAN) warrants accurate tools for the prediction of progression. Urinary kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) are markers for the detection of early tubular damage caused by various renal conditions. We evaluated the prognostic value of these markers in patients with IgAN.
We included patients (n = 65, 72% male, age 43 ± 13 years) with biopsy-proven IgAN, who were evaluated for proteinuria. Urinary KIM-1 and NGAL were measured by enzyme-linked immunosorbent assay. We analysed data using Cox regression for the outcome end-stage renal disease (ESRD).
Median serum creatinine was 142 μmol/L and proteinuria 2.2 g/day. During follow-up (median 75 months), 23 patients (35%) developed ESRD. In patients with IgAN median urinary KIM-1 excretion was 1.7 ng/min and NGAL excretion was 47 ng/min, both significantly higher than in healthy controls. KIM-1 and NGAL were correlated with proteinuria (r = 0.40 and 0.34, respectively, P < 0.01) and each other (r = 0.53, P < 0.01) but not with estimated glomerular filtration rate (eGFR). Interestingly, KIM-1 was not significantly correlated with the excretion of α(1)-microglobulin (α(1)m) and β(2)-microglobulin (β(2)m), known markers of tubular injury. Univariate analysis showed that baseline serum creatinine and urinary excretion of total protein, α(1)m, β(2)m, immunoglobulin G, KIM-1 and NGAL were significantly associated with ESRD. By multivariate analysis, serum creatinine and KIM-1 excretion proved to be significant independent predictors of ESRD.
KIM-1 and NGAL excretion are increased in patients with IgAN and correlate with proteinuria but not with eGFR. Baseline serum creatinine and urinary KIM-1, but not proteinuria, are independent predictors of ESRD.
免疫球蛋白 A 肾病(IgAN)的病程多变,因此需要准确的工具来预测疾病进展。尿肾损伤分子-1(KIM-1)和中性粒细胞明胶酶相关脂质运载蛋白(NGAL)是检测各种肾脏疾病引起的早期肾小管损伤的标志物。我们评估了这些标志物在 IgAN 患者中的预后价值。
我们纳入了 65 名(72%为男性,年龄 43±13 岁)经活检证实为 IgAN 的患者,对其蛋白尿进行评估。通过酶联免疫吸附测定法检测尿 KIM-1 和 NGAL。我们使用 Cox 回归分析来分析终末期肾病(ESRD)的结局数据。
中位血清肌酐为 142μmol/L,蛋白尿为 2.2g/天。在中位随访时间 75 个月期间,23 名患者(35%)发展为 ESRD。IgAN 患者的尿 KIM-1 排泄中位数为 1.7ng/min,NGAL 排泄中位数为 47ng/min,均显著高于健康对照组。KIM-1 和 NGAL 与蛋白尿呈正相关(r=0.40 和 0.34,P<0.01),且彼此相关(r=0.53,P<0.01),但与估算肾小球滤过率(eGFR)无关。有趣的是,KIM-1 与肾小管损伤的已知标志物α(1)-微球蛋白(α(1)m)和β(2)-微球蛋白(β(2)m)的排泄无显著相关性。单变量分析显示,基线时血清肌酐和尿总蛋白、α(1)m、β(2)m、免疫球蛋白 G、KIM-1 和 NGAL 的排泄与 ESRD 显著相关。多变量分析显示,血清肌酐和 KIM-1 排泄是 ESRD 的独立显著预测因子。
IgAN 患者的 KIM-1 和 NGAL 排泄增加,与蛋白尿相关,但与 eGFR 无关。基线时的血清肌酐和尿 KIM-1,但不是蛋白尿,是 ESRD 的独立预测因子。