Uric acid and allograft loss from interstitial fibrosis/tubular atrophy: post hoc analysis from the angiotensin II blockade in chronic allograft nephropathy trial

Transplantation. 2014 May 27;97(10):1066-71. doi: 10.1097/01.TP.0000440952.29757.66.

Abstract

Background: Uric acid has been linked to the progression of native kidney disease. Studies evaluating its contribution to allograft function in kidney transplant recipients, among whom hyperuricemia is common, have yielded mixed results.

Methods: We evaluated the association between baseline uric acid and the primary composite outcome of doubling of interstitium or ESRD from interstitial fibrosis and tubular atrophy (IF/TA) in the Angiotensin II Blockade for Chronic Allograft Nephropathy (ABCAN) Trial participants. Subjects underwent uric acid, iothalamte GFR, and urine albumin to creatinine (ACR) measurements annually for 5 years in addition to an allograft biopsy at baseline and 5 years.

Results: Baseline uric acid was 5.57±1.48 mg/dL; male sex, higher BMI, diuretic use, and lower GFR were associated with higher uric acid, whereas older age, less than 3 HLA matches and having a female donor were associated with lower levels. In multivariate analysis adjusting for baseline GFR, uric acid was associated with doubling of interstitium or ESRD from IF/TA (OR 1.83, 95% CI, 1.06-3.17, P=0.03). Over time, a 1 mg/dL increase in time-varying uric acid was associated with a 2.39 mL/min lower final GFR (P<0.001) but not with the secondary outcome of creatinine doubling, ESRD, or death.

Conclusions: These data suggest that uric acid is associated with IF/TA and thus may be a viable target for intervention.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Allografts
  • Angiotensin II / drug effects*
  • Angiotensin II Type 1 Receptor Blockers / administration & dosage*
  • Atrophy
  • Biopsy
  • Chronic Disease
  • Creatinine / urine
  • Disease Progression
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate / drug effects
  • Glomerular Filtration Rate / physiology
  • Graft Rejection / complications
  • Graft Rejection / metabolism*
  • Graft Rejection / prevention & control
  • Humans
  • Hyperuricemia / blood*
  • Hyperuricemia / etiology
  • Kidney Failure, Chronic / surgery
  • Kidney Transplantation*
  • Kidney Tubules / pathology
  • Male
  • Middle Aged
  • Nephritis, Interstitial / drug therapy
  • Nephritis, Interstitial / etiology
  • Nephritis, Interstitial / metabolism*
  • Treatment Outcome
  • Uric Acid / blood*

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin II
  • Uric Acid
  • Creatinine