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Renal handling of uric acid under cyclosporin A treatment
P F Hoyer1, I J Lee, B S Oemar
1Department of Paediatric Nephrology and Metabolic Disorders, Children's Hospital, Hannover, Federal Republic of Germany.
Insights
Cyclosporin A (CyA) treatment increases uric acid reabsorption in the kidneys, leading to higher serum uric acid levels in pediatric transplant patients. This finding highlights a potential cause of hyperuricemia in these individuals.
Area of Science:
- Nephrology
- Pharmacology
- Pediatric Transplant Medicine
Background:
- Cyclosporin A (CyA) is an immunosuppressant commonly used in organ transplantation.
- Understanding the renal handling of uric acid is crucial for managing metabolic complications in transplant recipients.
- Hyperuricemia is a potential adverse effect that requires investigation into its underlying mechanisms.
Purpose of the Study:
- To investigate the renal handling of uric acid in pediatric renal transplant recipients treated with Cyclosporin A (CyA).
- To compare uric acid metabolism in CyA-treated patients with those on azathioprine/prednisolone, chronic renal failure, and healthy controls.
- To determine if CyA influences tubular reabsorption of uric acid.
Main Methods:
- Clearance studies utilizing 24-hour urine collections were performed.
- Patient groups included: 28 pediatric renal transplant recipients on CyA, 19 on azathioprine/prednisolone, 35 with chronic renal failure (CRF), and 10 healthy children (N group).
- Serum uric acid levels, uric acid clearances, and net tubular uric acid reabsorption per mL of glomerular filtration rate were calculated and compared across groups.
Main Results:
- Serum uric acid levels were significantly higher in the CyA group (567 ± 156 μmol/l) compared to AZA (378 ± 98), CRF (415 ± 119), and N (290 ± 68) groups.
- Mean uric acid clearance was lowest in the CyA group (3.9 ± 2.8 ml/min/1.73 m²) compared to AZA (5.6 ± 3.4), CRF (4.0 ± 2.2), and N (8.4 ± 3.7) groups.
- Net tubular uric acid reabsorption per mL GFR was significantly increased in the CyA group (0.53 ± 0.15 μmol/ml) versus AZA (0.34 ± 0.08), CRF (0.29 ± 0.15), and N (0.27 ± 0.07) groups.
Conclusions:
- Cyclosporin A treatment is associated with increased net tubular reabsorption of uric acid in pediatric renal transplant recipients.
- This enhanced reabsorption mechanism likely contributes to the observed hyperuricemia in patients receiving CyA.
- The findings suggest a direct impact of CyA on renal uric acid handling, necessitating monitoring for hyperuricemia.
Abstract:
The renal handling of uric acid during cyclosporin A (CyA) treatment was investigated by clearance studies using 24-h urine collections in 28 paediatric renal transplant recipients (CyA group), and the results were compared with those of 19 renal transplanted children treated with azathioprine and prednisolone (AZA group), 35 children with chronic renal failure (CRF) and 10 children with normal renal function (N group). Serum uric acid levels were significantly higher in the CyA group (567 +/- 156 mumol/l) compared with the AZA group (378 +/- 98), the CRF group (415 +/- 119) and the N group (290 +/- 68). Mean uric acid clearances in each group measured 3.9 +/- 2.8 ml/min per 1.73 m2 (CyA), 5.6 +/- 3.4 (AZA), 4.0 +/- 2.2 (CRF) and 8.4 +/- 3.7 (N). Calculation of the net tubular uric acid reabsorption per millilitre glomerular filtration rate revealed a significantly increased value of 0.53 +/- 0.15 mumol/ml in the CyA group (P less than 0.01) compared with 0.34 +/- 0.08, 0.29 +/- 0.15 and 0.27 +/- 0.07 mumol/l for the AZA, CRF and N groups respectively. We therefore conclude that CyA treatment is associated with an increased net tubular reabsorption of uric acid, which may lead to hyperuricaemia.