HYPERURICEMIA IN CYCLOSPORINE-TREATED PATIENTS - A GFR-RELATED EFFECT

Background. Hyperuricaemia is a well known sideeffect of cyclosporin A (CsA) treatment. The pathogenic mechanisms, however, remain controver sial. There is no convincing evidence that hyperuricaemia is due to Cs A-induced, impaired tubular handling of uric acid. The impact of dimin ished GFR in this particular context has never been investigated. Meth ods. We prospectively studied plasma uric acid, inulin clearances, and fractional clearances of uric acid in two groups of CsA-treated patie nts (bone-marrow transplant patients, n=50; renal transplant patients; , n=32), and one healthy control group without CsA (living related kid ney donors, n=28). Bone-marrow transplant patients were examined befor e transplantation and 6, 12, 18, 24 months after transplantation, rena l transplant patients 1 year after transplantation, and living related kidney donors before and 1 year after unilateral nephrectomy. Results . After 1 year of CsA treatment, hyperuricaemia was found in 36% of bo ne-marrow transplant patients and in 53% of renal transplant patients. Thirty per cent of living related kidney donors were borderline hyper uricaemic 1 year after unilateral nephrectomy. The fractional clearanc e of uric acid, measured serially in bone-marrow transplant patients d id not change significantly over time; it was, however, slightly highe r during CsA treatment than after CsA withdrawal. Moreover, the bone-m arrow transplant patients' fractional clearance of uric acid was not s tatistically different from the renal transplant patients' and the liv ing related kidney donors' (values 1 year after transplantation/unilat eral nephrectomy: bone-marrow transplant patients, 15.3+/-2.3%; renal transplant patients: 11.9+/-0.9%; living related kidney donors, 11.1+/ -0.8%). The GFR at 1 year, measured by inulin clearance, was identical in the CsA-treated groups and slightly higher in the living related k idney donors (bone-marrow transplant patients, 51+/-6 ml/min per 1.73 m(2); renal transplant patients, 49+/-3 ml/min per 1.73 m(2); living r elated kidney donors, 61+/-2 ml/min per 1.73 m(2)). Conclusion. There is no evidence for impaired tubular handling of uric acid, induced by a CsA-specific tubulotoxic effect. Hyperuricaemia in CsA-treated trans plant patients can therefore be attributed to the cyclosporin-associat ed decrease of GFR.