Serum Urate Lowering with Allopurinol and Kidney Function in Type 1 Diabetes

Doria, Alessandro; Gałecki, Andrzej T.; Spino, Cathie; Pop‐Busui, Rodica; Cherney, David Z.I.; Lingvay, Ildiko; Parsa, Afshin; Rossing, Peter; Sigal, Ronald J.; Afkarian, Maryam; Aronson, Ronnie; Caramori, M. Luiza; Crandall, Jill P.; Boer, Ian H. de; Elliott, Thomas; Goldfine, Allison B.; Haw, J. Sonya; Hirsch, Irl B.; Karger, Amy B.; Maahs, David M.; McGill, Janet B.; Molitch, Mark E.; Perkins, Bruce A.; Polsky, Sarit; Pragnell, Marlon; Robiner, William N.; Rosas, Sylvia E.; Senior, Peter; Tuttle, Katherine R.; Umpiérrez, Guillermo E.; Wallia, Amisha; Weinstock, Ruth S.; Wu, Chunyi; Mauer, Michael

doi:10.1056/nejmoa1916624

Cited by 275 publications

(213 citation statements)

References 36 publications

Supporting

Mentioning

199

Contrasting

Unclassified

Order By: Relevance

“…Moreover, UA sodium deposited in the renal interstitium impairs renal tubular function. However, a recent double-blind trial failed to show the clinical benefits of serum urate reduction with allopurinol on kidney outcomes among patients with T1DM ( Doria et al, 2020 ). The discrepancy in conclusions between this study with previous studies may be caused by the indirect predictive effect of SUA on kidney dysfunction, which can be ascribed to the association of SUA with other risk factors that are causally related to DN, such as insulin resistance ( Wang et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

The association between serum uric acid and diabetic complications in patients with type 2 diabetes mellitus by gender: a cross-sectional study

Qing-e

Min

et al. 2021

PeerJ

View full text Add to dashboard Cite

Background The relationship between serum uric acid (SUA) and several diabetic complications or co-morbidities remains a matter of debate. The study aims to explore the association between SUA levels and the prevalence of non-alcoholic fatty liver disease (NAFLD), diabetic retinopathy (DR), diabetic nephropathy (DN) and diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes mellitus (T2DM). Methods A total of 2,809 participants (1,784 males and 1,025 females) were included in this cross-sectional study. Clinical characteristics and the prevalence of each of the four diseases were analyzed based on gender-specific quartiles of SUA levels. The Pearson correlation analysis and linear-regression analysis were used to access the correlation between SUA levels and clinical characteristics. Furthermore, a binary logistic regression analysis was carried out to determine whether SUA was an independent risk factor for each of the four complications. Results SUA levels were positively correlated to BMI, BUN, Scr and TG, but negatively associated with eGFR, HDL, FBG, 2h-PG and HbA1c% for the patients with T2DM. The prevalence of NAFLD and DN, but not DR or DPN, were increased with SUA levels from the first to the fourth quartile. Binary logistic regression further disclosed that SUA was an independent risk factor for NAFLD (ORs Male = 1.002, ∗P = 0.0013; ORs Female = 1.002, ∗P = 0.015) and DN (ORs Male = 1.006, ∗P < 0.001; ORs Female = 1.005, ∗P < 0.001), but not for DR and DPN. After adjustment for the confounders, SUA levels were significantly associated with NAFLD within the 3rd (ORs = 1.829, P = 0.004) and 4th quartile (ORs = 2.064, P = 0.001) for women, but not independently associated with SUA for man. On the other hand, our results revealed increased prevalence of DN for SUA quartile 2 (ORs = 3.643, P = 0.039), quartile 3 (ORs = 3.967, P = 0.024) and quartile 4 (ORs = 9.133, P < 0.001) in men; however, SUA quartiles were significantly associated with DN only for quartile 4 (ORs = 4.083, P = 0.042) in women Conclusion For patients with T2DM, elevated SUA concentration is an independent risk factor for the prevalence of NAFLD and DN after adjustment for other indicators, but not DR or DPN.

show abstract

Section: Discussionmentioning

confidence: 99%

The association between serum uric acid and diabetic complications in patients with type 2 diabetes mellitus by gender: a cross-sectional study

Qing-e

Min

et al. 2021

PeerJ

View full text Add to dashboard Cite

show abstract

“…The PERL (Preventing Early Renal Loss in Diabetes) trial investigators showed that the use of allopurinol in middle-aged patients with early-stage diabetic nephropathy due to long-standing type 1 diabetes on background renin-angiotensin system-inhibiting treatment did not reduce the rate of renal function decline compared with placebo. 151 Similarly, CKD-FIX (Controlled Trial of Slowing of Kidney Disease Progression from the Inhibition of Xanthine Oxidase) concluded that allopurinol treatment does not prevent renal function deterioration in patients with stage 3-4 chronic kidney disease and a high risk of progression to end-stage renal disease. 152 Interestingly, hyperuricemia was not an inclusion criterion in either of these 2 trials, yet most patients in both studies had baseline serum urate levels above the normality threshold (6.1 AE 1.5 mg/dl in PERL and 8.2 AE 1.8 mg/dl in CKD-FIX).…”

Section: Treatmentmentioning

confidence: 99%

Hyperuricemia as a trigger of immune response in hypertension and chronic kidney disease

Ponticelli

Podestà

Moroni

2020

Kidney International

117

View full text Add to dashboard Cite

“…However, there is large heterogeneity in study designs, endpoints, and baseline characteristics making it very difficult to compare the results of multiple trials and to draw firm conclusions. For example, a recent study in patients with type 1 diabetes and early-to-moderate diabetes kidney disease found that there were no clinically meaningful benefits of ULT on renal outcomes [ 73 •]. Another recent trial randomized patients with stage 3 or 4 kidney disease, with no history of gout, to allopurinol or placebo and reported that ULT did not slow the decline in eGFR when compared with the placebo group at week 104 [ 74 ••].…”

Section: Introductionmentioning

confidence: 99%

“…Notwithstanding, there is still compelling evidence that links CKD to uric acid, which has an injurious impact on renal function. In this regard, a “two-hit” mechanism has been proposed involving activation of the renin-angiotensin system and inhibition of nitric oxide synthesis, leading to a small increase in blood pressure, and involvement of the inflammasome and subsequent secretion of proinflammatory cytokines [ 73 •]. In such a mechanism, ULT in patients with CKD and hyperuricemia with or without deposition has the potential to slow or delay the progression of CKD and may be considered unless there are clear contraindications to ULT.…”

Section: Introductionmentioning

confidence: 99%

Management of Hyperuricemia in Patients with Chronic Kidney Disease: a Focus on Renal Protection

2020

View full text Add to dashboard Cite

Purpose of Review In chronic kidney disease (CKD), plasma uric acid levels are increased because of the decrease in glomerular filtration rate. However, in addition to CKD, hyperuricemia is frequently associated with a number of other conditions such as hypertension, type 2 diabetes, obesity, and heart failure, overweight, and cardiovascular disease. Recent Findings It is now becoming increasingly clear that, in many clinical conditions, elevated levels of uric acid have a much greater role beyond just causing gout. The present review will summarize current knowledge on the relation between hyperuricemia, CKD, and existing comorbidities, as well as the mechanisms of uric acid–related renal damage. In addition, the role and evidence for urate-lowering therapy in prevention and cardiovascular protection in CKD patients is discussed with a focus on allopurinol and febuxostat. To date, several clinical studies have provided evidence that urate-lowering therapy may help to prevent and delay the decline of renal function in patients with CKD. Summary Use of a xanthine oxidase inhibitor should be considered in patients who are at high renal risk and/or with declining renal function in the presence of hyperuricemia with and without deposition, although additional studies are warranted to define treatment targets. Notwithstanding, the possibility to delay deterioration of renal function in patients with CKD merits consideration.

show abstract

Serum Urate Lowering with Allopurinol and Kidney Function in Type 1 Diabetes

Cited by 275 publications

References 36 publications

The association between serum uric acid and diabetic complications in patients with type 2 diabetes mellitus by gender: a cross-sectional study

The association between serum uric acid and diabetic complications in patients with type 2 diabetes mellitus by gender: a cross-sectional study

Hyperuricemia as a trigger of immune response in hypertension and chronic kidney disease

Management of Hyperuricemia in Patients with Chronic Kidney Disease: a Focus on Renal Protection

Contact Info

Product

Resources

About