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

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  1. ASN Kidney Week 2017

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    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. A large remaining potential in lipid-lowering drug treatment in the type 2 diabetes population: A Danish nationwide cohort study

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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.
Publikationsdato2 nov. 2017
Antal sider1
StatusUdgivet - 2 nov. 2017
BegivenhedASN Kidney Week 2017 - Ernest N. Morial Convention Center, New Orleans, USA
Varighed: 31 okt. 20175 nov. 2017


KonferenceASN Kidney Week 2017
LokationErnest N. Morial Convention Center
ByNew Orleans


ASN Kidney Week 2017


New Orleans, USA

Begivenhed: Konference

ID: 52001360