Saraf Santosh L, Zhang Xu, Kanias Tamir, Lash James P, Molokie Robert E, Oza Bharvi, Lai Catherine, Rowe Julie H, Gowhari Michel, Hassan Johara, Desimone Joseph, Machado Roberto F, Gladwin Mark T, Little Jane A, Gordeuk Victor R
Section of Hematology-Oncology, Department of Medicine, Comprehensive Sickle Cell Center, University of Illinois at Chicago, Chicago, IL, USA.
Br J Haematol. 2014 Mar;164(5):729-39. doi: 10.1111/bjh.12690. Epub 2013 Dec 12.
To evaluate the association between haemoglobinuria and chronic kidney disease (CKD) in sickle cell anaemia (SCA), we analysed 356 adult haemoglobin SS or Sβ(o) thalassaemia patients from the University of Illinois at Chicago (UIC) and 439 from the multi-centre Walk-Treatment of Pulmonary Hypertension and Sickle Cell Disease with Sildenafil Therapy (Walk-PHaSST) cohort. CKD was classified according to National Kidney Foundation Kidney Disease Outcomes Quality Initiatives guidelines. Haemoglobinuria, defined as positive haem on urine dipstick with absent red blood cells on microscopy, was confirmed by enzyme-linked immunosorbent assay in a subset of patients. The prevalence of CKD was 58% in the UIC cohort and 54% in the Walk-PHaSST cohort, and haemoglobinuria was observed in 36% and 20% of the patients, respectively. Pathway analysis in both cohorts indicated an independent association of lactate dehydrogenase with haemoglobinuria and, in turn, independent associations of haemoglobinuria and age with CKD (P < 0·0001). After a median of 32 months of follow-up in the UIC cohort, haemoglobinuria was associated with progression of CKD [halving of estimated glomerular filtration rate or requirement for dialysis; Hazard ratio (HR) 13·9, 95% confidence interval (CI) 1·7-113·2, P = 0·0012] and increasing albuminuria (HR 3·1, 95% CI: 1·3-7·7; logrank P = 0·0035). In conclusion haemoglobinuria is common in SCA and is associated with CKD, consistent with a role for intravascular haemolysis in the pathogenesis of renal dysfunction in SCA.
为评估镰状细胞贫血（SCA）患者中血红蛋白尿与慢性肾脏病（CKD）之间的关联，我们分析了来自伊利诺伊大学芝加哥分校（UIC）的356例成年血红蛋白SS型或Sβ（o）地中海贫血患者以及多中心西地那非治疗肺动脉高压和镰状细胞病（Walk-PHaSST）队列中的439例患者。CKD根据美国国家肾脏基金会肾脏病预后质量倡议指南进行分类。血红蛋白尿定义为尿试纸潜血阳性且显微镜检查无红细胞，部分患者通过酶联免疫吸附测定法进行确诊。UIC队列中CKD的患病率为58%，Walk-PHaSST队列中为54%，血红蛋白尿分别在36%和20%的患者中观察到。两个队列的通路分析均表明乳酸脱氢酶与血红蛋白尿独立相关，进而血红蛋白尿和年龄与CKD独立相关（P < 0.0001）。在UIC队列中位随访32个月后，血红蛋白尿与CKD进展相关[估计肾小球滤过率减半或需要透析；风险比（HR）13.9，95%置信区间（CI）1.7 - 113.2，P = 0.0012]以及蛋白尿增加（HR 3.1，95% CI：1.3 - 7.7；对数秩检验P = 0.0035）。总之，血红蛋白尿在SCA中常见且与CKD相关，这与血管内溶血在SCA肾功能障碍发病机制中的作用一致。
