Uric acid and allograft loss from interstitial fibrosis/tubular atrophy

Post hoc analysis from the angiotensin II blockade in chronic allograft nephropathy trial

Allyson Hart, Scott Jackson, Bert L Kasiske, Michael Mauer, Behzad Najafian, Arthur J Matas, Richard S Spong, Hassan N. Ibrahim

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1066-1071
Number of pages6
JournalTransplantation
Volume97
Issue number10
DOIs
StatePublished - May 27 2014

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Uric Acid
Angiotensin II
Atrophy
Allografts
Fibrosis
Chronic Kidney Failure
Creatinine
Hyperuricemia
Kidney Diseases
Diuretics
Albumins
Multivariate Analysis
Tissue Donors
Urine
Kidney
Biopsy

Keywords

  • Albuminuria
  • Glomerular filtration rate
  • Interstitial fibrosis
  • Kidney transplant
  • Uric acid

Cite this

Uric acid and allograft loss from interstitial fibrosis/tubular atrophy : Post hoc analysis from the angiotensin II blockade in chronic allograft nephropathy trial. / Hart, Allyson; Jackson, Scott; Kasiske, Bert L; Mauer, Michael; Najafian, Behzad; Matas, Arthur J; Spong, Richard S; Ibrahim, Hassan N.

In: Transplantation, Vol. 97, No. 10, 27.05.2014, p. 1066-1071.

Research output: Contribution to journalArticle

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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.",
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AU - Jackson, Scott

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AU - Mauer, Michael

AU - Najafian, Behzad

AU - Matas, Arthur J

AU - Spong, Richard S

AU - Ibrahim, Hassan N.

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