Hyperuricaemia in cyclosporin-treated patients: GFR-related effect

Abstract

Background: Hyperuricaemia is a well known side-effect of cyclosporin A (CsA) treatment. The pathogenic mechanisms, however, remain controversial. There is no convincing evidence that hyperuricaemia is due to CsA-induced, impaired tubular handling of uric acid. The impact of diminished GFR in this particular context has never been investigated.

Methods: We prospectively studied plasma uric acid, inulin clearances, and fractional clearances of uric acid in two groups of CsA-treated patients (bone-marrow transplant patients, n = 50; renal transplant patients, n = 32), and one healthy control group without CsA (living related kidney donors, n = 28). Bone-marrow transplant patients were examined before transplantation and 6, 12, 18, 24 months after transplantation, renal 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 bone-marrow transplant patients and in 53% of renal transplant patients. Thirty per cent of living related kidney donors were borderline hyperuricaemic 1 year after unilateral nephrectomy. The fractional clearance of uric acid, measured serially in bone-marrow transplant patients did not change significantly over time; it was, however, slightly higher during CsA treatment than after CsA withdrawal. Moreover, the bone-marrow transplant patients' fractional clearance of uric acid was not statistically different from the renal transplant patients' and the living related kidney donors' (values 1 year after transplantation/unilateral 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 kidney donors (bone-marrow transplant patients, 51 +/- 6 ml/min per 1.73 m2; renal transplant patients, 49 +/- 3 ml/min per 1.73 m2; living related kidney donors, 61 +/- 2 ml/min per 1.73 m2).

Conclusion: There is no evidence for impaired tubular handling of uric acid, induced by a CsA-specific tubulotoxic effect. Hyperuricaemia in CsA-treated transplant patients can therefore be attributed to the cyclosporin-associated decrease of GFR.