Haubitz Marion, Wittke Stefan, Weissinger Eva M, Walden Michael, Rupprecht Harald D, Floege Jürgen, Haller Hermann, Mischak Harald
Department of Nephrology, Hannover Medical School, Hannover, Germany.
Kidney Int. 2005 Jun;67(6):2313-20. doi: 10.1111/j.1523-1755.2005.00335.x.
IgA nephropathy (IgAN) is the most common chronic glomerular disease in adults. End-stage renal disease (ESRD) develops in about 30% of the patients. Early intervention and consequent therapy may prevent or at least delay the development of ESRD in these patients. Up to now, the diagnosis could only be achieved with a renal biopsy.
The urine of 45 patients with IgAN was collected and screened for protein/polypeptide patterns with a novel high throughput method, capillary electrophoreses on-line coupled to a mass spectrometer (CE-MS). CE-MS allows the fast and accurate evaluation of up to 2000 polypeptides in one urine sample. The results in IgAN were compared to findings in 13 patients with membranous nephropathy (MN) and 57 healthy individuals.
In the patients with IgAN, even when urinary protein excretion was within the normal range of regular tests, the polypeptide pattern in urine differed significantly from that of healthy controls and patients with MN, indicating a specific "IgAN" pattern of polypeptide excretion. Classification regarding discrimination of IgAN from healthy controls and from MN had a sensitivity of 100% and 77%, respectively. Specificity was 90% and 100%, respectively. Compared to patterns established earlier in patients with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), or diabetic nephropathy (DN), sensitivity and specificity were 100%. Treatment of the patients was associated with changes of the pattern, possibly indicating a therapeutic effect.
Proteomic analysis with CE-MS coupling permits fast and accurate identification and differentiation of polypeptide patterns in the urine of patients with IgAN, allowing differentiation from healthy controls and, probably, other renal diseases.
IgA 肾病(IgAN)是成人中最常见的慢性肾小球疾病。约 30%的患者会发展为终末期肾病(ESRD)。早期干预及后续治疗可能预防或至少延缓这些患者 ESRD 的发展。到目前为止,诊断只能通过肾活检来实现。
收集 45 例 IgA 肾病患者的尿液,采用一种新型高通量方法——毛细管电泳在线联用质谱仪(CE-MS)筛查蛋白质/多肽图谱。CE-MS 可在一个尿液样本中快速准确地评估多达 2000 种多肽。将 IgA 肾病患者的结果与 13 例膜性肾病(MN)患者及 57 名健康个体的结果进行比较。
在 IgA 肾病患者中,即使尿蛋白排泄在常规检测的正常范围内,尿液中的多肽图谱与健康对照者及 MN 患者的图谱也有显著差异,表明存在特定的“IgA 肾病”多肽排泄模式。区分 IgA 肾病与健康对照者及 MN 的分类,敏感性分别为 100%和 77%,特异性分别为 90%和 100%。与早期在微小病变肾病(MCD)、局灶节段性肾小球硬化(FSGS)或糖尿病肾病(DN)患者中建立的图谱相比,敏感性和特异性均为 100%。患者的治疗与图谱变化相关,这可能表明有治疗效果。
CE-MS 联用的蛋白质组学分析能够快速准确地识别和区分 IgA 肾病患者尿液中的多肽图谱,从而与健康对照者以及可能的其他肾脏疾病相鉴别。