Serum uric acid and progression of diabetic nephropathy in type 1 diabetes

Pilemann-Lyberg, Sascha; Lindhardt, Morten; Persson, Frederik; Andersen, Steen; Rossing, Peter

doi:10.1016/j.jdiacomp.2018.02.002

Cited by 9 publications

(8 citation statements)

References 23 publications

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“…Liu et al (7) demonstrated no independent association between uric acid in the upper quartiles and rapid renal progression (eGFR slope below 26 mL/min/1.73 m 2 /year) or increased risk for commencing renal replacement therapy in patients with stage 3-5 chronic kidney disease with and without diabetes. We have previously demonstrated that uric acid in the highest quartile was associated with a GFR decline of below 25 mL/min/1.73 m 2 /year in the adjusted model in patients with type 1 diabetes (6). We also found that uric acid interacted with both albuminuria and GFR, so that uric acid, albuminuria, and eGFR were no longer predictors on their own (6).…”

Section: Discussionmentioning

confidence: 69%

“…We have previously demonstrated that uric acid in the highest quartile was associated with a GFR decline of below 25 mL/min/1.73 m 2 /year in the adjusted model in patients with type 1 diabetes (6). We also found that uric acid interacted with both albuminuria and GFR, so that uric acid, albuminuria, and eGFR were no longer predictors on their own (6). In the current study, we also demonstrated that an increase of uric acid, expressed as HR per doubling of uric acid, was significantly associated with a steeper yearly decline in eGFR after adjustment for traditional risk factors.…”

Section: Discussionmentioning

confidence: 88%

“…Studies have shown that elevated uric acid levels independently predict the incidence and development of chronic kidney disease both in patients without diabetes and in patients with diabetes (2)(3)(4). However, other studies have not been able to confirm these findings (5)(6)(7).…”

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confidence: 99%

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Uric Acid Is an Independent Risk Factor for Decline in Kidney Function, Cardiovascular Events, and Mortality in Patients With Type 1 Diabetes

et al. 2019

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Previous studies have provided inconclusive results on the role of uric acid (UA) in risk prediction. Here we aimed to improve the power and precision of the predictive value of UA for the risk of decline in kidney function, cardiovascular events (CVEs), and mortality in patients with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODSPlasma UA was measured in 670 patients with T1D and various degrees of albuminuria, ranging from normoalbuminuria to macroalbuminuria. Associations of UA with an estimated glomerular filtration rate (eGFR) decline of ‡30%, CVEs, and mortality were analyzed. The median follow-up time was 5.3 years [interquartile range (IQR) 2.7-6.2 years] for a decline in eGFR of ‡30%, 5.8 years (2.5-6.4 years) for progression in albuminuria status, 5.1 years (4.7-5.6 years) for CVE, and 6.2 years (5.8-6.7 years) for mortality. Both univariable and multivariable associations of UA with relevant outcomes and variables were reported. Hazard ratios (HRs) were calculated per doubling of the UA level. RESULTSA doubling in UA level was associated with a higher risk of decline in eGFR of ‡30% (n = 89) (HR 3.18 [IQR 1.71-5.93]; P < 0.001), CVE (n = 94) ; P = 0.011), and mortality (n = 58) (HR 2.58 [IQR 1.12-5.90]; P = 0.025) in adjusted analyses. Adding UA to the adjusted model including conventional risk factors improved the relative integrated discrimination index by 12.6% for a decline in eGFR of ‡30% (P < 0.001), 6.5% for CVE (P = 0.010), and 11.8% (P = 0.003) for mortality. A doubling in UA level was also associated with a steeper decline in eGFR (P < 0.0026) and a steeper increase in urine albumin-to-creatinine ratio (P < 0.0027) in adjusted analysis. CONCLUSIONSIn individuals with T1D, a higher UA level is associated with a higher risk of decline in kidney function, CVE, and mortality, independently of other risk factors. Our results suggest that UA has a promising role in risk stratification among individuals with T1D.

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Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 88%

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Uric Acid Is an Independent Risk Factor for Decline in Kidney Function, Cardiovascular Events, and Mortality in Patients With Type 1 Diabetes

et al. 2019

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“…Moreover, as one Mendelian randomization study suggests that SU is a causal risk factor for CKD in the general population ( 38 ), it might be that SU plays a role only in the processes leading to nondiabetic renal disease rather than in pure diabetic nephropathy. Furthermore, the authors of a post hoc analysis in diabetic nephropathy with mean follow-up of 3 years concluded that urate was weakly associated with decline in the glomerular filtration rate (GFR) in patients with type 1 diabetes with overt nephropathy ( 39 ). Evidence showed urate may facilitate the development and progression of CKD in people with diabetes ( 40 – 42 ).…”

Section: Discussionmentioning

confidence: 99%

Hyperuricemia Predisposes to the Onset of Diabetes via Promoting Pancreatic β-Cell Death in Uricase-Deficient Male Mice

Lü¹,

He²,

Cui³

et al. 2020

Diabetes

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Clinical studies have shown a link between hyperuricemia (HU) and diabetes, while the exact effect of soluble serum urate on glucose metabolism remains elusive. This study aims to characterize the glucose metabolic phenotypes and investigate the underlying molecular mechanisms using a novel spontaneous HU mouse model in which the uricase ( Uox ) gene is absent. In an attempt to study the role of HU in glycometabolism, we implemented external stimulation on Uox knockout (KO) and wild-type (WT) males with a high-fat diet (HFD) and/or injections of multiple low-dose streptozotocin (MLD-STZ) to provoke the potential role of urate. Notably, while Uox- KO mice developed glucose intolerance in the basal condition, no mice spontaneously developed diabetes, even with aging. HFD-fed Uox- KO mice manifested similar insulin sensitivity compared with WT controls. HU augmented the existing glycometabolism abnormality induced by MLD-STZ and eventually led to diabetes, as evidenced by the increased random glucose. Reduced β-cell masses and increased terminal deoxynucleotidyl TUNEL-positive β-cells suggested that HU-mediated diabetes was cell death dependent. However, urate-lowering therapy (ULT) cannot ameliorate the diabetes incidence or reverse β-cell apoptosis with significance. ULT displayed a significant therapeutic effect of HU-crystal–associated kidney injury and tubulointerstitial damage in diabetes. Moreover, we present transcriptomic analysis of isolated islets, using Uox -KO versus WT mice and streptozotocin-induced diabetic WT (STZ-WT) versus diabetic Uox -KO (STZ-KO) mice. Shared differentially expressed genes of HU primacy revealed Stk17β is a possible target gene in HU-related β-cell death. Together, this study suggests that HU accelerates but does not cause diabetes by inhibiting islet β-cell survival.

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“…SUA independently amplifies the likelihood of new-onset kidney disease [6]. SUA has been linked with reduced GFR and augments the possibility of early progressive DKD in DM [7]. The impact of microinflammation on renal vascular function leads to endothelial damage provoked by SUA, suggesting that SUA affecting renal diseases may be conciliated by inflammatory response.…”

Section: Introductionmentioning

confidence: 99%

Effects of Hyperuricemia on Beta-Cell Function, Renal Function, and Lipid Panels of Patients with Diabetic Kidney Disease: A Gender-Based Retrospective Study

Rajkarnikar

Bhattarai

2020

Dubai Diabetes Endocrinol J

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Objective: Serum uric acid (SUA) has been linked with development and progression of diabetic kidney disease (DKD). In this study, we intend to compare the effects of hyperuricemia (HUA) on beta-cell function, renal function, and lipid panels of patients with DKD. Methods: A total of 492 patients with DKD were included for data collection and analysis. Males and females have different standard SUA levels; thus, we analyzed these 2 groups separately. Normouricemia (NUA) for men (n = 253) was ≤428 μmol/L and for women (n = 83) was ≤357 μmol/L, whereas HUA for men (n = 94) was >428 μmol/L and for women (n = 62) was >357 μmol/L. Clinical characteristics of patients were analyzed based on gender-specific NUA and HUA. The Spearman rank correlation test was used to evaluate the correlation between SUA and other clinical variables. Finally, stepwise multinomial logistic regression test was performed to identify the factors that are independently associated with HUA. Results: A total of 492 patients were included in this study. The regression analysis showed that there was a significant association between HUA and decreased estimated glomerular filtration rate (eGFR) in both male and female patients (odds ratio (OR) [95% confidence interval (CI)] = 4.73 [2.19–10.24], p value ≤0.01 in male patients and OR [95% CI] = 3.07 [], p value = 0.04 in female patients). FBG, 2hPBG, and HbA1c were negatively correlated with SUA in male patients (r = −0.182, p value ≤0.01; r = −0.168, p value ≤0.01; and r = −0.187, p value ≤0.01, respectively), whereas fasting insulin was positively correlated in male patients (r = 0.131, p value = 0.023) and female patients (r = 0.192, p value = 0.041). The atherogenic index of plasma was significantly high in patients with HUA (OR [95% CI] = 5.75 [2.32–14.23], p value ≤0.01 in male patients and OR [95% CI] = 8.37 [1.96–35.78], p value ≤0.01 in female patients). Other indices of lipid profile such as lipoprotein combine index, atherosclerosis index, and triglyceride/high-density lipoprotein ratio were also independently associated with HUA in both male and female patients. Conclusion: SUA can affect various clinical parameters in patients with DKD. There is a significant association between HUA and decline in eGFR in both male and female patients. HUA is also associated with dyslipidemia in DKD, increasing the risk of cardiac complications and mortality.

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Serum uric acid and progression of diabetic nephropathy in type 1 diabetes

Cited by 9 publications

References 23 publications

Uric Acid Is an Independent Risk Factor for Decline in Kidney Function, Cardiovascular Events, and Mortality in Patients With Type 1 Diabetes

Uric Acid Is an Independent Risk Factor for Decline in Kidney Function, Cardiovascular Events, and Mortality in Patients With Type 1 Diabetes

Hyperuricemia Predisposes to the Onset of Diabetes via Promoting Pancreatic β-Cell Death in Uricase-Deficient Male Mice

Effects of Hyperuricemia on Beta-Cell Function, Renal Function, and Lipid Panels of Patients with Diabetic Kidney Disease: A Gender-Based Retrospective Study

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