Transplant Evidence Alert

The Transplant Evidence Alert provides a monthly overview of the 10 most important new clinical trials in organ transplantation, selected and reviewed by the Peter Morris Centre for Evidence in Transplantation (Oxford University).

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Effect of allopurinol drug use on GFR and proteinuria in patients with renal transplant recipients (ADOPTR study)

Transpl Immunol. 2022 Jun;72:101560 doi: 10.1016/j.trim.2022.101560.
Abstract
BACKGROUND:

Hyperuricemia has been associated with the development of hypertension, cardiovascular, and renal disease. However, there is no data about the effect of lowering uric acid level on renal functions and proteinuria in renal transplant recipients. This study aimed to investigate the effect of allopurinol treatment on renal functions in renal transplant recipients (RTR).

METHODS:

A total of 245 patients with renal transplantation were included in this randomized, placebo-controlled study. Patients were randomized to receive either placebo (121 patients) or 300 mg/day allopurinol (124 patients). We have examined uric acid, urinary protein creatinin ratio, MDRD (the modification of diet in renal diseases) and CRP (C-reactive protein) before and 24 weeks after treatment in both group.

RESULTS:

In the allopurinol group, the mean serum uric acid levels, eGFR (estimated glomerular filtration rate), and creatinine urinary albumin creatinin ratio (UACR) significantly improved (p < 0.001). Also uric acid level was positively correlated with the UACR (r = 0,645 p < 0.001) and negatively correlated with MDRD (r = -0,387 p < 0.05) in allopurinol treatment group. A statistically significant increase in CRP level was observed (p < 0,05) in plasebo group. Multivariate regression analysis showed that uric acid was positively correlated with UACR (r = 0,473, β = 0.021, p = 0.002) and negatively correlated with MDRD (r = -0554 β = 0.016, P = 0.001) in allopurinol treatment RTR.

CONCLUSION:

Urate, a salt of uric acid, is lowered by allopurinol treatment resulting in improved eGFR and decreased proteinuria, when compared to the placebo group. Therefore, we suggest that allopurinol therapy should be part of the management of kidney transplant patients with normal kidney function. Long-term follow-up studies will be useful in revealing the effect of uric acid management on kidney functions and proteinuria.

CET Conclusion
Reviewer: Mr John O'Callaghan, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: This is a study of a simple intervention in renal transplant recipients but there are significant questions about the methodology. Renal transplant recipients were randomised to receive either 300mg allopurinol once daily, or placebo, with 6 months follow up. Unfortunately, there is no description of the method of randomisation, so this cannot be assessed. Also, there is no description of how the placebo was designed or administered and whether there was sufficient blinding of patients or investigators. There is no power calculation, nor declaration which was the primary outcome set in advance of the study commencing. The study found that taking allopurinol daily for 24 weeks, was associated with a significant reduction in plasma uric acid level, as one might expect. It was also associated with improved urine albumin:creatinine ratio, serum creatinine and eGFR. Despite these apparently significant results, it is not clear that the study was truly randomised, or placebo controlled, and hence questions will remain about the potential for systematic bias affecting the results.
Methodological quality
Jadad score 1
Allocation concealment NO
Data analysis PER PROTOCOL
Study Details
Aims: The aim of this study was to examine the effect of using allopurinol on renal functions in kidney transplant patients.
Interventions: Participants were randomly assigned to receive either allopurinol or placebo.
Participants: 245 renal transplant recipients.
Outcomes: The main outcomes were the assessment of uric acid, urinary protein creatinin ratio, the modification of diet in renal diseases (MDRD) and C-reactive protein (CRP).
Follow Up: 24 weeks
Metadata
Funding: Funding not described
Publication type: Randomized Controlled Trial, Randomised Controlled Trial
Organ: Kidney
Language: English
Author email: drahmetziya@hotmail.com
MeSH terms: Allopurinol; C-Reactive Protein; Glomerular Filtration Rate; Humans; Kidney; Kidney Diseases; Kidney Transplantation; Proteinuria; Treatment Outcome; Uric Acid; 268B43MJ25 (Uric Acid); 63CZ7GJN5I (Allopurinol); 9007-41-4 (C-Reactive Protein)