Role of elevated serum uric acid levels at the onset of overt nephropathy in the risk for renal function decline in patients with type 2 diabetes

Tanaka, Kentaro; Hara, Shigeko; Hattori, Masao; Sakai, Ken; Onishi, Yukiko; Yoshida, Yoko; Kawazu, Shoji; Kushiyama, Akifumi

doi:10.1111/jdi.12243

Cited by 33 publications

(31 citation statements)

References 37 publications

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“…In the present study, we demonstrated that higher levels of SUA were associated with declines of eGFR and identify the onset of rapid progression of CKD, furthermore at a cutoff level of > 6.5 mg/dl may link to progression of CKD in T2DM patients. Our results were consistent with previous findings, which registered that hyperuricemia seemed to be an independent risk factor for the development of incident CKD rather associated with overt nephropathy 37 and even in normalbuminuria patients with T2DM. 38 Collectively in the current study we, achieved that T2DM patients with UA ≤ 6.2 mg/dl were, younger, recently diabetic, better glycemic control, normotensive, lesser BMI, comparatively ideal TG/HDL-C, lower prevalence of early and overt nephropathy and preserved GFR.…”

supporting

confidence: 83%

“…Generally, these results appear compatible with other studies which found, SUA concentration was associated with microalbuminuria and increased progression to overt nephropathy in patients with T2DM 36 as well SUA levels, even within the normal range > 6.3 mg/dl can predict the onset of overt nephropathy. 37 Overt nephropathy resulted in an increased risk for declining renal function in T2DM. The role of UA in patients with T2DM is still not well studied, particularly in association with declining renal function.…”

mentioning

confidence: 99%

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Serum uric acid and its association with hypertension, early nephropathy and chronic kidney disease in type 2 diabetic patients

Fouad¹,

Fathy²,

Zidan³

2016

Jornal Brasileiro De Nefrologia

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Ácido úrico sérico e sua associação com hipertensão, nefropatia precoce e doença renal crônica em pacientes diabéticos tipo 2 Introdução: A detecção precoce da nefropatia diabética (ND) é importante. O áci-do úrico sérico (AUS) tem um papel ainda desconhecido no desenvolvimento de ND. Objetivo: Estudar a relação entre AUS e hipertensão, nefropatia precoce e progressão da doença renal crônica (DRC) no diabetes mellitus tipo 2 (DM2). Métodos: O estudo contou com 986 participantes, de acordo com a presença e a duração do diabetes, os pacientes foram classificados em três grupos. O Grupo I incluiu 250 participantes saudá-veis. O Grupo II incluiu 352 pacientes com início de diabetes < 5 anos. O Grupo III incluiu 384 pacientes com o aparecimento de diabetes > 5 anos. Todos os participantes foram submetidos a exame clínico completo, medidas antropométricas, exames laboratoriais -incluindo hemoglobina glicosilada (HbA1C), bem como a razão entre triglicé-rides e lipoproteína de alta densidade (TG/ HDL-C), AUS, razão creatinina/albumina (RCA) urinária, e taxa estimada de filtração glomerular (eTFG). Resultados: A razão AUS, PA, HbA1c, TG/HDL-C e RCA foi significativamente maior no grupo III do que no grupo I, II e em II do que I. A eTFG foi significativamente menor no grupo III do que nos grupos I, II e no II do que no I (p < 0,001). Idade, IMC, PA, HbA1c, razão TG/ HDL-C, RCA, foram positivamente correlacionados com AUS, enquanto que a TFG esteve negativamente correlacionada. O AUS a níveis > 6,1 mg/dl, > 6,2 mg/dl e > 6,5 mg/dl apresentou maior sensibilidade e especificidade para identificar hipertensão, nefropatia precoce e declínio da eTFG, respectivamente. Conclusão: Mesmo elevados níveis de AUS, foi associado ao risco de hipertensão, nefropatia precoce e declínio da eTFG. Além disso, o nível de AUS pode identificar o iní-cio da hipertensão, nefropatia precoce e progressão da DRC em DM2. ResumoPalavras-chave: ácido úrico; diabetes mellitus tipo 2; hipertensão; nefropatias diabéticas. Introduction:Early detection diabetic nephropathy (DN) is important. Whether serum uric acid (SUA) has a role in the development of DN is not known. Objective: To study the relationship between SUA and hypertension, early nephropathy and progression of chronic kidney disease (CKD) in type 2 diabetes mellitus (T2DM). Methods: The total number of the study was 986 participants, according to presence and duration of diabetes were classified into three groups. Group I; including 250 healthy participants. Group II; including 352 with onset of diabetes < 5 years. Group III; including 384, with the onset of diabetes > 5 years. All participants were submitted to complete clinical examination, anthropometric measurements, laboratory investigations, including glycosylated hemoglobin (HbA1C), as well triglycerides to high-density lipoprotein ratios (TG/HDL-C), SUA, urinary albumin/creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). Results: SUA, BP, HbA1c, TG/HDL-C ratio, and ACR levels were significantly higher in group III tha...

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supporting

confidence: 83%

mentioning

confidence: 99%

Serum uric acid and its association with hypertension, early nephropathy and chronic kidney disease in type 2 diabetic patients

Fouad¹,

Fathy²,

Zidan³

2016

Jornal Brasileiro De Nefrologia

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“…Recent studies have shown that elevated SUA levels may be associated with the faster progression of diabetic kidney disease [28][29][30]. The present data indicate that these past findings may be applicable to early stage diabetic nephropathy.…”

Section: Discussionsupporting

confidence: 64%

Uric acid-lowering and renoprotective effects of topiroxostat, a selective xanthine oxidoreductase inhibitor, in patients with diabetic nephropathy and hyperuricemia: a randomized, double-blind, placebo-controlled, parallel-group study (UPWARD study)

et al. 2018

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Background Hyperuricemia is supposed to be an independent risk factor for kidney dysfunction in diabetic patients. We attempted to examine the uric acid-lowering effect and the renoprotective effect of topiroxostat, a selective xanthine oxidoreductase inhibitor, in patients with diabetic nephropathy and hyperuricemia in this pilot study. Methods The study design was randomized, double-blind, placebo-controlled, parallel-group study. A total of 65 patients with hyperuricemia and diabetic nephropathy with microalbuminuria were enrolled and assigned to either the topiroxostat group or the placebo group. Topiroxostat (stepwise dosing from 40 to 160 mg/day) or matching placebo was administered BID for 28 weeks. The primary endpoint was a change in the urinary albumin-to-creatinine ratio in the first-morning-void urine sample. Secondary endpoints were changes in the estimated glomerular filtration rate and the serum uric acid level. Results At 28 weeks, there was no significant difference in the percent change from baseline in the urinary albumin-tocreatinine ratio between the two groups (topiroxostat: 0 vs. placebo: 17%, p = 0.3206), but the changes in the estimated glomerular filtration rate (− 0.2 vs. − 4.0 mL/min/1.73 m 2 , p = 0.0303) and the serum uric acid level (− 2.94 vs. − 0.20 mg/ dL, p < 0.0001) were significantly different between the topiroxostat and placebo groups. Gouty arthritis occurred in 1 patient in the placebo group and no patients in the topiroxostat group. Conclusion These findings support that diabetic nephropathy combined with hyperuricemia may be associated with kidney dysfunctions. Topiroxostat provides strict control of the serum uric acid level preventing decline of eGFR in these patients.

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“…SUA is known to be associated with disease progression in the early stage of diabetic nephropathy [17,58] . We found that the progression of renal dysfunction in patients with type 2 diabetic overt nephropathy with an SUA concentration of ≥ 6.3 mg/dL carries a poor prognosis, even though their SUA range is considered high-normal [59] . Our data shows the association between UA and disease progression is independent of diabetic control in multivariate analysis.…”

Section: Nephropathymentioning

confidence: 98%

“…Through inhibition of XDH/XO activity, cytokine-induced neudependent risk factor for renal dysfunction, even after adjustments for confounding factors. Furthermore, even high-normal SUA levels accelerated renal dysfunction in T2DM patients [17,[59][60][61][62] . UA is lowered in diabetes mellitus (DM) due to hyperfiltration [50] , but decreased UA excretion during renal dysfunction raises SUA levels.…”

Section: Atherosclerosis and Xdh/xo In Monocytes/macrophagesmentioning

confidence: 99%

Linking uric acid metabolism to diabetic complications

Kushiyama

Tanaka

Hara

et al. 2014

WJD

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Hyperuricemia have been thought to be caused by the ingestion of large amounts of purines, and prevention or treatment of hyperuricemia has intended to prevent gout. Xanthine dehydrogenase/xanthine oxidase (XDH/ XO) is rate-limiting enzyme of uric acid generation, and allopurinol was developed as a uric acid (UA) generation inhibitor in the 1950s and has been routinely used for gout prevention since then. Serum UA levels are an important risk factor of disease progression for various diseases, including those related to lifestyle. Recently, other UA generation inhibitors such as febuxostat and topiroxostat were launched. The emergence of these novel medications has promoted new research in the field. Lifestyle-related diseases, such as metabolic syndrome or type 2 diabetes mellitus, often have a common pathological foundation. As such, hyperuricemia is often present among these patients. Many in vitro and animal studies have implicated inflammation and oxidative stress in UA metabolism and vascular injury because XDH/XO act as one of the major source of reactive oxygen species Many studies on UA levels and associated diseases implicate involvement of UA generation in disease onset and/or progression. Interventional studies for UA generation, not UA excretion revealed XDH/XO can be the therapeutic target for vascular injury and renal dysfunction. In this review, the relationship between UA metabolism and diabetic complications is highlighted.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Uric acid; Xanthine dehydrogenase/xanthine oxidase; Diabetes mellitus; Diabetic complications; Xanthine oxidase inhibitor; Metabolism Core tip: Uric acid (UA) is derived from essential metabolism, and UA metabolism is becoming a novel risk and interventional factor of lifestyle-related diseases in this obesity-prone era. The relationship between UA metabolism and diabetic complications is highlighted in this review and supposed molecular mechanisms are mentioned.Kushiyama A, Tanaka K, Hara S, Kawazu S. Linking uric acid metabolism to diabetic complications. World J Diabetes 2014; 5(6): 787-795 Available from:

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Role of elevated serum uric acid levels at the onset of overt nephropathy in the risk for renal function decline in patients with type 2 diabetes

Cited by 33 publications

References 37 publications

Serum uric acid and its association with hypertension, early nephropathy and chronic kidney disease in type 2 diabetic patients

Serum uric acid and its association with hypertension, early nephropathy and chronic kidney disease in type 2 diabetic patients

Uric acid-lowering and renoprotective effects of topiroxostat, a selective xanthine oxidoreductase inhibitor, in patients with diabetic nephropathy and hyperuricemia: a randomized, double-blind, placebo-controlled, parallel-group study (UPWARD study)

Linking uric acid metabolism to diabetic complications

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