Hyperuricaemia in cyclosporin-treated patients: GFR-related effect.
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).


CONCLUSIONS
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.
Zürcher
R M
RM
Department of Medicine, University Hospital Basel, Switzerland.
Bock
H A
HA
Thiel
G
G
D016026:Bone Marrow Transplantation / Q000276:immunology; D016572:Cyclosporine / Q000009:adverse effects*; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006084:Graft Rejection / Q000097:blood / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007444:Inulin / Q000378:metabolism; D016030:Kidney Transplantation / Q000276:immunology; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism; D011446:Prospective Studies; D014527:Uric Acid / Q000097:blood*
D007166:Immunosuppressive Agents; D014527:Uric Acid; D016572:Cyclosporine; D007444:Inulin