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Hyperuricaemia in cyclosporin-treated patients: GFR-related effect
R M Zürcher1, H A Bock, G Thiel
1Department of Medicine, University Hospital Basel, Switzerland.
Insights
Cyclosporin A (CsA) treatment can cause hyperuricaemia. This study found no evidence of impaired uric acid handling by the kidneys. Hyperuricaemia in CsA patients is linked to reduced glomerular filtration rate (GFR).
Area of Science:
- Nephrology
- Pharmacology
- Transplantation Medicine
Background:
- Hyperuricaemia is a known side effect of cyclosporin A (CsA) treatment.
- The exact mechanisms causing hyperuricaemia during CsA therapy are not fully understood.
- Previous research has not conclusively linked hyperuricaemia to impaired tubular handling of uric acid or investigated the role of reduced glomerular filtration rate (GFR).
Purpose of the Study:
- To investigate the pathogenic mechanisms of hyperuricaemia in patients treated with CsA.
- To determine if CsA-induced hyperuricaemia is due to impaired tubular handling of uric acid or diminished GFR.
- To assess the impact of CsA on uric acid handling and GFR in transplant recipients.
Main Methods:
- Prospective study of plasma uric acid, inulin clearances (GFR), and fractional uric acid clearances.
- Involved two groups of CsA-treated patients: bone-marrow transplant (n=50) and renal transplant (n=32).
- Included a control group of healthy living related kidney donors (n=28) without CsA exposure.
Main Results:
- Hyperuricaemia was observed in 36% of bone-marrow transplant and 53% of renal transplant patients after 1 year of CsA.
- Fractional clearance of uric acid did not significantly change over time in bone-marrow transplant patients and was not statistically different across groups.
- GFR, measured by inulin clearance, was similar in CsA-treated groups and lower than in healthy controls.
Conclusions:
- The study found no evidence of CsA-induced tubulotoxicity impairing uric acid handling.
- Hyperuricaemia in CsA-treated transplant patients is primarily attributed to a CsA-associated decrease in GFR.
- These findings suggest that reduced kidney function, rather than direct tubular effects, is the main driver of hyperuricaemia in CsA therapy.
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.