Nephrol Dial Transplant (2002) 17: 602-607
© 2002 European Renal Association-European Dialysis and Transplant Association
Impaired creatinine secretion after an intravenous creatinine load is an early characteristic of the nephropathy of sickle cell anaemia
1 Renal Service, and 2 Haematology Service, Hospital Universitario, Universidad del Zulia, Medical School and 3 Instituto de Investigaciones Biomédicas (INBIOMED), Maracaibo, Venezuela
Background. The capacity to increase the tubular secretion of creatinine (TScr) after an intravenous creatinine load (stimulated TScr) has been found to be impaired in subclinical reduction of renal mass. We decided to investigate if this response was impaired in sickle cell anaemia (SCA) patients before there was evidence of deterioration of renal function.
Methods. Studies were done in 16 patients with homozygous SCA who had normal or supranormal glomerular filtration rate (GFR) and in 20 normal controls of similar median age (23 years). The tubular stress test (TST) consisted of 30-min clearance periods ([125I]iothalamate and creatinine) done before (baseline) and after (three successive post-stimulation periods) the intravenous infusion of 88.4 µmol (10 mg) of creatinine per kg of body weight.
Results. Baseline studies showed that the SCA patients had higher GFR and lower serum creatinine concentration. After stimulation there were no changes in GFR. In contrast, creatinine clearance increased 2.3 times in normal but not in SCA patients (P<0.001) and the TScr in the first post-stimulation period was 161±83 nmol/kg/min in SCA patients vs 286±93.2 in normal controls (P<0.001). The mean TScr post-stimulation was also reduced in patients with SCA (123±52 nmol/kg/min vs 179±50 in normal controls, P<0.001). Since SCA patients had lower Pcr values, separate analysis was made of post-load clearance periods in which Pcr was comparable in patients and in normal controls (range 177–265 µmol/l or 2–3 mg/dl) and the reduction in TScr was also present in SCA patients in these study periods.
Conclusion. Patients with SCA have impaired response to the TST before there are reductions in glomerular filtration. Therefore, a reduction in the tubular secretory reserve capacity represents an early event in the nephropathy of this condition.
Keywords: creatinine secretion; sickle cell anaemia; tubular stress test
Correspondence and offprint requests to: Dr B. Rodríguez-Iturbe, Apartado Postal 1430, Maracaibo 4001-A, Venezuela. Email: bri{at}iamnet.com