Uric acid and allograft loss from interstitial fibrosis/tubular atrophy: post hoc analysis from the angiotensin II blockade in chronic allograft nephropathy trial.
Hart A, Jackson S, et al.Transplantation 2014; 97(10): 1066-1071.
Aims
To investigate participants of the Angiotensin II Blockade for Chronic Allograft Nephropathy trial (ABCAN) in order to evaluate the link between baseline uric acid and the outcome of doubling of interstitium or end stage renal disease from interstitial fibrosis and tubular atrophy.
Interventions
Patients of the ABCAN trial were randomised to receive either losartan (100mg/d) or placebo.
Participants
153 recipients aged >18 years, with a first or second kidney transplant alone, or in combination with a pancreas transplant.
Outcomes
The outcomes included allograft biopsy (at baseline), uric acid, iothalamate glomerular filtration rate and urine albumin to creatinine measurements.
Follow-up
5 years.
CET Conclusions
In this interesting post-hoc analysis of data from the ABCAN study, the authors explore the effect of elevated baseline uric acid level on outcomes five years following renal transplantation. They demonstrate a significant increase in the odds of the composite endpoint of graft loss due to Interstitial Fibrosis/Tubular Atrophy (IF/TA) or doubling of interstitium, suggesting that high uric acid levels may contribute to chronic allograft nephropathy (CAN). In support of these findings, there was also a significant association between uric acid levels and reduced GFR, although these do not translate to a difference in graft survival. These results are important due to our lack of understanding of CAN and lack of preventative strategies or treatment options. This work brings the potential for a randomised controlled trial of uric acid lowering agents (e.g. allopurinol) as a strategy to slow down the progression of IF/TA and CAN in renal transplant recipients.
Quality notes
Previously assessed in Ibrahim HN. Angiotensin II blockade in kidney transplant recipients. J Am Soc Nephrol 2013; 24: 320.
Trial registration
NCT00067990