Comparison of efficacy and safety between febuxostat and allopurinol in early post-renal transplant recipients with new onset of hyperuricemia

Abstract

Summary What is known and objective Febuxostat and allopurinol are xanthine oxidase inhibitors for urate‐lowering therapy. The efficacy and safety of febuxostat and allopurinol have been mostly reported in hyperuricemia patients with normal renal function. Here, we aimed to compare the effects of these two drugs in early post‐renal transplant recipients, focusing on evaluating the urate‐lowering effect and recovery of allograft renal function. Methods A retrospective cohort study was performed in early post‐renal transplant recipients with new onset of hyperuricemia receiving febuxostat or allopurinol therapy. Serum uric acid (UA) and estimated glomerular filtration rate (eGFR) were detected on days 3, 7 and 15 and months 1, 3 and 6 after therapy initiation. Liver and blood functions were monitored and other adverse events were recorded. Results and discussion A total of 48 and 33 patients were enrolled in the febuxostat and allopurinol groups, respectively. Significant UA‐lowering effects were observed on day 3 in both groups. Febuxostat caused a more rapid UA decline, starting on day 3 and lasting for 1 month. The most apparent contrast was found in UA level (267.25 ± 93.66 vs 334.18 ± 96.56 μmol/L, P = 0.003) on day 7; 62.5% and 30.3% of patients achieved target UA level in febuxostat and allopurinol groups respectively on day 3 (P = 0.004), but there was no significant difference between two groups from days 15 to months 6. The median times to achieve target UA level were 3 and 5 days in febuxostat and allopurinol groups respectively (P = 0.002). The eGFR levels and recovering rates were gradually upregulated but no significant differences were found between two groups. No abnormities related to febuxostat or allopurinol were observed. What is new and conclusion This is the first comprehensive evaluation of UA‐lowering effects of febuxostat and allopurinol in early post‐renal transplant recipients. Febuxostat caused a marginally quicker serum UA‐lowering effect than allopurinol, but there was no advantage for long‐term use of febuxostat. The drugs had no significant differences in impacting renal allograft function recovery, and both were well tolerated.

Efficacy and safety of febuxostat for treatment of asymptomatic hyperuricemia among kidney transplant patients: A meta‐analysis of observational studies

“…Even though the Egger test for our main primary outcome of eGFR at end of study was not significant ( P > .05), a funnel plot for serum UA of the included studies in this meta‐analysis suggested two studies rendering a large effect estimate that lay outside the pseudo 95% CI (Figure ).…”

“…Sample sizes of the seven studies ranged from 15 to 124 participants. Three studies were conducted in China, two in Japan, one in Korea, and one in Spain . There were three studies that had no control group .…”

“…Seven observational studies with 270 patients treated with febuxostat demonstrated a significantly lower serum UA at end of study compared with baseline (WMD = −2.3 mg/dL [95% CI: −2.7, −1.9]; P < .001, I 2 = 79.5%) (Figure A). Three studies with 160 patients revealed the higher odds of achieving target serum UA < 6 mg/dL within a year among febuxostat compared with allopurinol group (OR = 2.9 [95% CI: 1.4, 6.0]; P = .004, I 2 = 0%) (Figure B). While two studies with 79 patients suggested a higher decline in serum UA among febuxostat compared with allopurinol but it did not reach statistical significance (WMD = −1.0 mg/dL over a year [95% CI: −3.0, 0.9]; P = .32, I 2 = 96.9%), Table .…”

“…One study was conducted among early transplanted kidney patients. Hence, we excluded this study in the analysis of kidney function since it was not stable like other studies.…”

“…Among patients treated with febuxostat, there was no significant difference in hemoglobin (WMD = −0.6 g/dL [95% CI: −3.0, 1.8]; P = .61, I 2 = 96.8%), white blood cells (WMD = −1.42 × 10 9 /L [95% CI: −3.14, 0.31]; P = .31, I 2 = 0%), AST (WMD = −0.5 IU/L [95% CI: −3.4, 2.4]; P = .74, I 2 = 50.7%), ALT (WMD = 0.5 IU/L [95% CI: −1.7, 2.6]; P = .68, I 2 = 15.7%), or trough level of tacrolimus (WMD = 0.4 ng/mL [95% CI: −3.0, 1.0]; P = .36, I 2 = 0%).…”