Hyperuricaemia is a mediator of endothelial dysfunction and inflammation in renal allograft recipients

Hyperuricaemia is common in renal transplant recipients treated with calcineurine inhibitors. Experimental studies suggest that uric acid induces glomerular hypertension, microvascular disease and renal interstitial fibrosis Hyperuricaemia is also an independent risk factor of cardiovascular complications. The mechanism by which uric acid injures renal allograft and cardiovascular system is still unclear. The aim of this study was to assess the influence of serum uric acid level on biomarkers of endothelial dysfunction and inflammation in renal allograft recipients. The study involved 78 adult renal transplant recipients (aged 19-70 years) with stable graft function (creatinine 0.7-1.4 mg/dl). The patients were transplanted between 2003 and 2006. Exclusion criteria were: abnormal renal function, proteinuria, diabetes mellitus, BMI above 30 and inflammation. The immunosuppressive protocol consisted of CsA or tacrolimus and azathioprine or mycophenolate mofetil and prednisone. The patients were divided into 2 groups: I - 48 patients with hyperuricaemia (uric acid 7.72±1.33 mg/dl) and II - 30 patients with normal uric acid level 5.48±0.92 mg/dl (control group). Markers of endothelial function and inflammation were assessed in both groups: plasma resistin level, CD146 and sVCAM-1. No significant differences were found in demographic data between both groups of patients with and without hyperuricaemia, such as age, gender, cause of renal failure, the number of HLA mismatches, DGF and number of episodes of acute rejection. The examined biomarkers were elevated in patients with hyperuricaemia. Resistin level was higher in hyperuricemic patients than in the control group (7.15±2.42 ng/ml vs. 6.29±2.76 ng/ml), and was higher in women (7.83 ng/ml) than in men (6.58 ng/ml). Also sVCAM-1 was significantly higher in hyperuricemic patients (1126±371ng/ml) when compared to patients with normal uric acid level (955±269 ng/ml) P<0.03. Resistin level correlated significantly with sVCAM-1 (P<0.01). CD146 was elevated in patients with hyperuricaemia (389.7±150 ug/ml). Hyperuricaemia mediates endothelial dysfunction and inflammation and may contribute to chronic allograft injury and cardiovascular events in renal allograft recipients.

Keywords: Kidney Transplantation