Abstract: TH-PO496

The Effect of Uric Acid-Lowering via Allopurinol on Markers of Kidney Function and Damage in Stage III CKD

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 305 CKD: Clinical Trials and Tubulointerstitial Disorders

Authors

  • Perrenoud, Loni J., University of Colorado, Aurora, Colorado, United States
  • Andrews, Emily, University of Colorado Denver, Aurora, Colorado, United States
  • You, Zhiying, UC Denver, Aurora, Colorado, United States
  • Chonchol, Michel, University of Colorado, Aurora, Colorado, United States
  • Johnson, Richard J., University of Colorado Denver, Aurora, Colorado, United States
  • Jalal, Diana I., University of Colorado Denver Health Science Center, Aurora, Colorado, United States
Background

Hyperuricemia associates with kidney disease progression and pilot data suggest that lowering serum uric acid may slow kidney disease progression. It remains unknown if lowering serum uric acid levels improves markers of kidney damage in CKD.

Methods

Post-hoc analysis of a double-blind randomized placebo-controlled clinical study utilizing allopurinol to lower serum uric acid in 80 subjects with stage III CKD. The following markers of kidney damage were evaluated: urinary albumin/creatinine ratio (ACR), urinary neutrophil gelatinase-associated lipocalin (NGAL), urinary kidney injury molecule-1 (KIM-1), and urinary transforming growth factor (TGF)-β1. Urinary NGAL, KIM-1, and TGF-β1 were normalized to urinary creatinine. The Wilcoxon Two-Sample Test was applied.

Results

No significant differences existed between both groups at baseline. Specifically, serum uric acid levels, CKD-EPI estimated glomerular filtration rate (eGFR), and urinary ACR were similar in the placebo and allopruinol groups. After 12 weeks, allopurinol lowered serum uric acid significantly. CKD-EPI eGFR increased by 1.79 (8.08) mL/min/1.72m2 with allopurinol group vs declined by 0.83 (5.2) mL/min/1.72m2 in the placebo arm, but this did not achieve statistical significance (p=0.07). There was no significant difference between study groups regarding changes in serum cystatin C, cystatin C-eGFR, urinary ACR, or urinary NGAL, KIM-1, or TGF-β1 (Table).

Conclusion

Allopurinol significantly lowers serum uric acid levels in adults with stage III CKD and may increase CKD-EPI eGFR. The mechanism behind the increased eGFR is unclear as uric acid-lowering was not associated with significant change in markers of kidney damage.

Changes in markers of kidney function and kidney damage from baseline to the end of study visit (week 12)
VariablePlacebo
(n=41)
Allopurinol
(n=39)
P value
Serum uric acid (mg/dL)0.05±1.54-3.24±1.35<0.0001
CKD EPI eGFR (mL/min/1.73m^2)-0.83±5.21.79±8.080.07
Cystatin C (mg/L)0.01±0.180.02±0.320.83
Cystatin C- eGFR (mL/min)-0.18±5.440.32±6.100.93
Urinary ACR (mg/g)-64(-3064, 52)-0.20(-213, 414)0.17
Urinary NGAL/Creatinine (ng/mL)-68.9(-406, 165)-123.3(-609, 207)0.72
Urinary KIM-1/Creatinine (pg/mL)4767(-19842, 20016)3876(-17818, 36270)0.49
Urinary TGF-β1/Creatinine (pg/mL)0(-1253, 1857)454(-675, 1996)0.59

Values are expressed as means ± SD or median (IQR)

Funding

  • NIDDK Support