Hyperuricemia frequently occurs after kidney transplantation. In a recent review published in Frontiers in Surgery, Chuan Hao, MD, and colleagues from The Second Hospital of Shanxi Medical University in Taiyuan, China, discussed traditional and novel risk factors for hyperuricemia and potential options for management.
According to Dr Hao’s team, management of risk factors for hyperuricemia along with lifestyle interventions are critical to prevent kidney damage caused by hyperuricemia and prolong graft survival in kidney transplant recipients.
Hyperuricemia risk factors
Increased risk for hyperuricemia after kidney transplantation can be due to demographic characteristics, metabolism-related factors, drug use, hypercalcemia, and reduced estimated glomerular filtration rate (eGFR), according to the reviewers. Older adults and male patients are known to be at increased risk. Hyperuricemia is also more likely to occur in obese recipients and those with diabetes mellitus, hypertriglyceridemia, and hypertension.
Calcineurin inhibitors (CNIs) used for immunosuppression, such as tacrolimus and cyclosporin A, can have nephrotoxic effects and lead to reduced uric acid excretion and lower eGFR. In addition, diuretics and other antihypertensive drugs are associated with hyperuricemia.
Hypercalcemia promotes kidney injury and greatly increases the risk of hyperuricemia after kidney transplantation. Long-term use of dialysis, hyperparathyroidism, the presence of pre-transplant hyperuricemia, and lower post-transplant eGFR also contribute to hyperuricemia.
Newer strategies to prevent renal ischemia reperfusion injury and extend graft survival include machine perfusion, exogenous administration of mesenchymal stem cells, and ex vivo preservation using preservation solutions saturated with alternative gases, Dr Hao’s team noted.
Other strategies for reducing the risk of hyperuricemia after kidney transplantation include improving treatment adherence to mitigate metabolism-related factors and, when feasible, discontinuing drugs that increase serum uric acid such as loop and thiazide diuretics and beta-blockers. Since CNIs are highly nephrotoxic, clinicians should consider other drugs for immunosuppression on a case by case basis.
According to the reviewers, clinicians can also consider appropriate use of uric-acid lowering therapies and strategies:
Drugs that reduce uric acid production
- Febuxostat (use with caution in patients with an eGFR less than 30 mL/min/1.73 m2).
- Allopurinol with dose adjustment to prevent allopurinol hypersensitivity syndrome. Administering allopurinol in kidney transplant recipients receiving azathioprine carries a risk for fatal pancytopenia.
Drugs that increase uric acid excretion
- Benzbromarone, a URAT-1 inhibitor, shows efficacy in patients with chronic kidney disease but liver toxicity is a concern.
- Probenecid, an inhibitor of OAT and URAT1, is less potent than benzbromarone. It is not recommended for patients with urolithiasis and an eGFR less than 50 mL/min/1.73 m2 or in patients with an eGFR less than 30 mL/min/1.73 m2.
- Arhalofenate, a novel anti-inflammatory uricosuric agent, inhibits URAT1, OAT4 and OAT10, and reduces the release of interleukin-1β stimulated by monosodium urate crystals.
- Tranilast, an investigational anti-inflammatory drug, interacts with URAT1, GLUT9, OAT4, and OAT1. However, it carries adverse effects such as liver injury, eosinophilic cystitis, eosinophilic polymyositis and immune thrombocytopenia.
Indirect uric acid-lowering treatment
For patients with relevant comorbidities, use of the following drugs can indirectly lower uric acid by increasing renal uric acid excretion: calcium channel inhibitors or losartan for hypertension; glitazones, biguanides and sodium-glucose cotransporter 2 inhibitors (although these agents are not currently approved for kidney transplant recipients) for diabetes mellitus; and fenofibrate or atorvastatin for dyslipidemia.
Zi X, Zhang X, Hao C, Wang Z. Risk factors and management of hyperuricemia after renal transplantation. Front Surg. 2023 Jan 6;9:956213. doi:10.3389/fsurg.2022.956213