Thompson Joanne, Reid Marvin, Hambleton Ian, Serjeant Graham R
MRC Laboratories/Sickle Cell Unit, Tropical Medicine Research Institute, University of the West Indies, Kingston, Jamaica.
Arch Intern Med. 2007 Apr 9;167(7):701-8. doi: 10.1001/archinte.167.7.701.
The glomerular filtration rate (GFR) in homozygous sickle cell (SS) disease is supranormal in childhood but falls steeply with age, often culminating in renal failure. The risk factors underlying these observations are unclear. We therefore sought to investigate the relationships between blood pressure, renal hemodynamics, and urinary albumin excretion in subjects with SS disease and matched controls with a normal AA genotype (hereinafter, controls) as a prelude to intervention studies.
Serum creatinine level, GFR, effective renal plasma flow, blood pressure, and urinary albumin and creatinine excretion rates were measured in Jamaican individuals with SS disease aged 18 to 23 years and in controls followed from birth in a cohort study.
Compared with controls, subjects with SS disease showed lower blood pressure and normal or supranormal GFR and effective renal plasma flow. Urinary albumin excretion exceeded 20 microg/min in 26% of subjects with SS disease and correlated positively with GFR and systolic blood pressure and negatively with hematocrit. A higher GFR and increased tubular secretion of creatinine combined to lower serum creatinine levels in patients with SS disease, giving an upper limit of the reference range of 0.90 mg/dL (80 micromol/L) in men and 0.77 mg/dL (68 micromol/L) in women. In addition, creatinine clearance measurements were consistently greater than GFR in subjects with SS disease.
The GFR remained within reference range or elevated in patients with SS disease aged 18 to 23 years. The higher GFR in patients with albuminuria was consistent with the hypothesis that high glomerular flows cause renal damage. Lower serum creatinine levels characterize patients with SS disease, and a revised clinical definition based on serum creatinine level alone is proposed.
纯合子镰状细胞（SS）病患者的肾小球滤过率（GFR）在儿童期高于正常水平，但随年龄增长急剧下降，常最终导致肾衰竭。这些观察结果背后的危险因素尚不清楚。因此，我们试图研究SS病患者与匹配的正常AA基因型对照者（以下简称对照者）的血压、肾血流动力学和尿白蛋白排泄之间的关系，作为干预研究的前奏。
在一项队列研究中，对18至23岁的牙买加SS病患者以及从出生就开始随访的对照者测量血清肌酐水平、GFR、有效肾血浆流量、血压以及尿白蛋白和肌酐排泄率。
与对照者相比，SS病患者血压较低，GFR和有效肾血浆流量正常或高于正常水平。26%的SS病患者尿白蛋白排泄超过20微克/分钟，且与GFR、收缩压呈正相关，与血细胞比容呈负相关。SS病患者较高的GFR和肌酐肾小管分泌增加共同导致血清肌酐水平降低；男性参考范围上限为0.90毫克/分升（80微摩尔/升），女性为0.77毫克/分升（68微摩尔/升）。此外，SS病患者的肌酐清除率测量值始终大于GFR。
18至23岁的SS病患者GFR仍在参考范围内或升高。蛋白尿患者较高的GFR与高肾小球血流导致肾损伤的假说一致。血清肌酐水平较低是SS病患者的特征，因此提出仅基于血清肌酐水平的修订临床定义。
