Abstract: TH-PO494

The Effect of Uric Acid Lowering on Albuminuria and Renal Function in Type 1 Diabetes: A Randomized Clinical Trial

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 305 CKD: Clinical Trials and Tubulointerstitial Disorders

Authors

  • Pilemann-lyberg, Sascha, Steno Diabetes Center Copenhagen, Gentofte, Denmark
  • Persson, Frederik, Steno Diabetes Center, Gentofte, Denmark
  • Frystyk, Jan, Aarhus University, Aarhus, Denmark
  • Rossing, Peter, Steno Diabetes Center Copenhagen, Gentofte, Denmark
Background

Epidemiological studies indicate that uric acid (UA) is a risk factor for development and progression of CKD. Whether UA lowering with allopurinol changes urinary albumin excretion rate (UAER) or GFR in patients with type 1 diabetes (T1D) suffering from diabetic nephropathy is not known.

Methods

We conducted a randomized, placebo-controlled, double-blinded, cross-over trial enrolling patients with T1D and a plasma uric acid ≥ 4.4 mg/dL, persistent albuminuria (urinary albumin creatinine ration) ≥30 mg/g and an eGFR ≥ 40 ml/min/1.73m2 on stable RAS blocking intervention. The participants were randomized to: (1) Allopurinol (400 mg daily) + standard therapy; or (2) placebo + standard therapy for 60 days. Participants underwent a 4 week washout period prior to cross-over. Primary end-point was change in UAER (3*24h collections), secondary endpoint was change in GFR (51Cr-EDTA-plasma clearance) measured at the end of each treatment period. The effect of UA lowering was tested using a paired t-test, after testing for carryover effects.

Results

We enrolled 30 patients, blood pressure 133(3)/75(2) mmHg and HbA1c 67(3) mmol/mol. UA decreased to 3.6 (1.2) mg/dl with allopurinol compared to 5.8 (1.5) with placebo (p<0.001). The 24h UAER (geometric mean (IQR)) was 221 ( 131-367) mg/24h after treatment with allopurinol and 228 (151-344) mg/24h with placebo (p=0.83). Mean (SD) GFR (51Cr-EDTA) was 74 (20) ml/min/1.73m2 after allopurinol treatment compared with 73 (20) ml/min/1.73m2 after placebo (p=0.51). Glycemic control 24h-blood pressure and RAS blockade was stable. We found no significant association (p=0.45) between uric acid and UAER. In an unadjusted linear model, UA was significantly associated with the level of GFR (51Cr-EDTA) in the placebo treatment period (R2=0.2, p=0.017).

Conclusion

Short term UA lowering by allopurinol did not improve UAER or GFR in patients with T1D and nephropathy. The clinical significance of long-term UA lowering is currently investigated in a large multicentre clinical trial (the PERL Study), investigating the effect of 3 years of allopurinol treatment on albuminuria and slopes of measured GFR.

Funding

  • Private Foundation Support