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Observations From a Cohort Study

Joanne Thompson, MB, MRCP; Marvin Reid, MB,BS, PhD; Ian Hambleton, PhD, BA, MSc; Graham R. Serjeant, MD, FRCP

Arch Intern Med. 2007;167(7):701-708.

Background  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.

Methods  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.

Results  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 µg/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 µmol/L) in men and 0.77 mg/dL (68 µmol/L) in women. In addition, creatinine clearance measurements were consistently greater than GFR in subjects with SS disease.

Conclusions  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.

Author Affiliations: MRC Laboratories (Drs Thompson, Hambleton, and Serjeant), now incorporated as the Sickle Cell Unit (Dr Reid), Tropical Medicine Research Institute, University of the West Indies, Kingston, Jamaica; Chronic Disease Research Centre (Dr Hambleton), Tropical Medicine Research Institute, University of the West Indies, Barbados; and the Sickle Cell Trust (Dr Serjeant), Kingston.

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