Costacou Tina, Ferrell Robert E, Ellis Demetrius, Orchard Trevor J
Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Diabetes. 2009 Dec;58(12):2904-9. doi: 10.2337/db09-0874. Epub 2009 Aug 31.
Haptoglobin (Hp) binds free Hb, inhibiting Hb-induced oxidative damage. As oxidative stress has been associated with microvascular complications, we evaluated the relationship between Hp genotype and microalbuminuria, macroalbuminuria, end-stage renal disease (ESRD), and early renal function decline in type 1 diabetes.
Participants from the Epidemiology of Diabetes Complications Study with DNA available were studied for the incidence of microalbuminuria (albumin excretion rate [AER] 20-200 microg/min), macroalbuminuria (AER >200 microg/min), ESRD (renal dialysis or transplantation), and renal function decline (a decline > or =30 ml/min per 1.73 m(2) from baseline estimated [by the Cockcroft-Gault equation] glomerular filtration rate [eGFR] in those with baseline eGFR >60 ml/min per 1.73 m(2)).
The proportions with the Hp 2/2, 2/1, and 1/1 genotype were 43.4, 44.4, and 12.1%, respectively. During 18 years of follow-up, the incidence of eGFR decline, microalbuminuria, macroalbuminuria, and ESRD was 42.0, 40.5, 16.7, and 12.2%, respectively. No significant univariate differences were observed by Hp genotype. However, in multivariable Cox models, an approximately twofold increased risk was observed for the Hp 2/2 compared with the Hp 1/1 genotype for eGFR decline (hazard ratio 1.79 [95% CI 1.06-3.00]) and ESRD (2.74 [1.17-6.45]); no significant associations were observed for microalbuminuria or macroalbuminuria.
These data suggest that although Hp genotype is not associated with albuminuria per se, it may be an independent determinant of early renal function decline and progression to ESRD. Understanding these apparent contradictory findings may provide further insight into the pathogenesis of renal disease in type 1 diabetes.
触珠蛋白（Hp）可结合游离血红蛋白（Hb），抑制Hb诱导的氧化损伤。由于氧化应激与微血管并发症相关，我们评估了Hp基因型与1型糖尿病患者微量白蛋白尿、大量白蛋白尿、终末期肾病（ESRD）及早期肾功能下降之间的关系。
对糖尿病并发症流行病学研究中可获取DNA的参与者进行研究，观察微量白蛋白尿（白蛋白排泄率[AER]20 - 200微克/分钟）、大量白蛋白尿（AER > 200微克/分钟）、ESRD（肾透析或移植）及肾功能下降（基线估计肾小球滤过率[eGFR，通过Cockcroft - Gault方程计算] > 60毫升/分钟每1.73平方米者，eGFR较基线下降≥30毫升/分钟每1.73平方米）的发生率。
Hp 2/2、2/1和1/1基因型的比例分别为43.4%、44.4%和12.1%。在18年的随访期间，eGFR下降、微量白蛋白尿、大量白蛋白尿和ESRD的发生率分别为42.0%、40.5%、16.7%和12.2%。按Hp基因型未观察到显著的单变量差异。然而，在多变量Cox模型中，与Hp 1/1基因型相比，Hp 2/2基因型发生eGFR下降（风险比1.79[95%可信区间1.06 - 3.00]）和ESRD（2.74[1.17 - 6.45]）的风险增加约两倍；未观察到与微量白蛋白尿或大量白蛋白尿有显著关联。
这些数据表明，尽管Hp基因型本身与白蛋白尿无关，但它可能是早期肾功能下降和进展至ESRD的独立决定因素。理解这些明显矛盾的发现可能为深入了解1型糖尿病肾病的发病机制提供进一步线索。
