Bergmann Shayla, Zheng Deyi, Barredo Julio, Abboud Miguel R, Jaffa Ayad A
Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
J Pediatr Hematol Oncol. 2006 Mar;28(3):147-53. doi: 10.1097/01.mph.0000203722.91189.9d.
Although improvements in the management of sickle cell disease (SCD) have increased patient survival into adulthood, morbidity and mortality from end-organ damage remain major concerns. One of the most serious complications of SCD is renal failure, affecting about 20% of patients. The clinical manifestations of sickle cell nephropathy (SCN) involve changes in glomerular ultrastructure, albuminuria, and a progressive decline in glomerular hemodynamics. The mechanisms or factors that promote SCN are not fully elucidated. In the present study, the role of renal kallikrein as a risk marker for promoting SCN was explored in a cross-sectional study.
We measured the urinary excretion rate of active kallikrein in 73 children with sickle cell anemia (hemoglobin SS, SC, or S thalassemia) and in 30 control healthy African American children. The findings demonstrated that a significant difference in the excretion rate of log kallikrein in male versus female patients with SCD, P<0.0078 was observed. In children with SCD, cross-sectional analysis revealed a positive and significant correlation between the excretion rate of active kallikrein and log albumin excretion rate (AER), P<0.0088. Regression analysis also determined that the excretion rate of active kallikrein negatively correlates with hemoglobin in children with SCD, P<0.0096. In addition, an inverse relationship between log AER and hemoglobin was observed in male patients with SCD, P<0.0143. In children with SCD, cross-sectional analysis revealed a positive and significant correlation between log AER and age, suggesting age as a risk marker for AER in SCD. In multivariate regression analysis, our findings demonstrate a strong association between log AER and age and log kallikrein in children with SCD. About 20% of the variability in log AER in SCD patients is influenced by age and 6% is influenced by log kallikrein, P<0.0001 and P<0.02, respectively.
These findings provide the first evidence that the excretion rate of active kallikrein is positively and independently correlated with log AER in children with SCD, and suggest that kallikrein could be a marker for progressive nephropathy. Longitudinal studies are essential to address this issue.
尽管镰状细胞病（SCD）管理方面的改善已使患者存活至成年，但终末器官损害导致的发病率和死亡率仍是主要关注点。SCD最严重的并发症之一是肾衰竭，约20%的患者受其影响。镰状细胞肾病（SCN）的临床表现包括肾小球超微结构改变、蛋白尿以及肾小球血流动力学的逐渐下降。促进SCN的机制或因素尚未完全阐明。在本横断面研究中，探讨了肾激肽释放酶作为促进SCN的风险标志物的作用。
我们测量了73例镰状细胞贫血患儿（血红蛋白SS、SC或S地中海贫血）和30例对照健康非裔美国儿童的活性激肽释放酶尿排泄率。研究结果表明，SCD男性和女性患者的对数激肽释放酶排泄率存在显著差异，P<0.0078。在SCD患儿中，横断面分析显示活性激肽释放酶排泄率与对数白蛋白排泄率（AER）呈正相关且具有显著性，P<0.0088。回归分析还确定，SCD患儿中活性激肽释放酶排泄率与血红蛋白呈负相关，P<0.0096。此外，在SCD男性患者中观察到对数AER与血红蛋白呈负相关，P<0.0143。在SCD患儿中，横断面分析显示对数AER与年龄呈正相关且具有显著性，提示年龄是SCD中AER的一个风险标志物。在多变量回归分析中，我们的研究结果表明，SCD患儿的对数AER与年龄和对数激肽释放酶之间存在强关联。SCD患者对数AER约20%的变异性受年龄影响，6%受对数激肽释放酶影响，P分别<0.0001和P<0.02。
这些发现首次证明，SCD患儿中活性激肽释放酶排泄率与对数AER呈正相关且独立相关，并提示激肽释放酶可能是进行性肾病的一个标志物。纵向研究对于解决这一问题至关重要。
