Plasma uric acid effects on glomerular haemodynamic profile of patients with uncomplicated Type 1 diabetes mellitus

Škrtić, Marko; Yang, Gary K.; Lai, Vesta; Scholey, James W.; Yip, Paul; Perkins, Bruce A.; Cherney, David Z.I.

doi:10.1111/dme.13051

Cited by 20 publications

(33 citation statements)

References 30 publications

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“…In the current cohort, significantly higher PUA levels were observed in adolescent HC compared with T1D, which is consistent with previous observations in young adults and in adolescents (7,8,22). Increased urinary glucose excretion is thought to be the key mechanism responsible for PUA lowering in patients with diabetes due to a stimulatory effect of urinary glucose on the GLUT9 isoform 2 transporter on the apical membrane of the proximal tubule, which increases uric acid excretion in in vitro studies (23).…”

Section: Discussionsupporting

confidence: 91%

“…Even in normoalbuminuric patients with T1D, Krolewski et al (25) reported that mildly elevated PUA is an independent predictor of early eGFR loss. We also recently showed that higher PUA levels within the normal range are associated with lower GFR and effective renal plasma flow and higher renal vascular resistance in an adult T1D cohort without any complications (7,8). Consistent with the previous body of work in adults, the association between higher PUA and lower eGFR was present in our even earlier adolescent cohort of otherwise healthy T1D patients.…”

Section: Discussionsupporting

confidence: 90%

“…However, the persistent association between higher PUA and lower eGFR in T1D adolescents with normofiltration suggests that hyperfiltration might not be the only factor driving this association. Thus, higher PUA may be linked with lower eGFR through renal vasoconstriction resulting in ischemia (8,26), but this seems unlikely in a pediatric cohort.…”

Section: Discussionmentioning

confidence: 99%

“…This may be due to a decrease in uric acid reabsorption mediated by high concentrations of glucose in the tubular lumen (7). Despite lower PUA levels in adults with T1D, PUA negatively correlates with estimated glomerular filtration rate (eGFR) and effective renal plasma flow (7,8). The association between higher PUA with lower glomerular filtration rate and effective renal plasma flow may be on the basis of PUA-mediated renal vasoconstriction (7,8).…”

mentioning

confidence: 99%

“…Despite lower PUA levels in adults with T1D, PUA negatively correlates with estimated glomerular filtration rate (eGFR) and effective renal plasma flow (7,8). The association between higher PUA with lower glomerular filtration rate and effective renal plasma flow may be on the basis of PUA-mediated renal vasoconstriction (7,8). PUA levels have not yet been characterized in an even earlier, subclinical disease population, such as in adolescent patients with T1D.…”

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confidence: 99%

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Association Between Plasma Uric Acid Levels and Cardiorenal Function in Adolescents With Type 1 Diabetes

et al. 2016

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OBJECTIVE The relationship between plasma uric acid (PUA) and renal and cardiovascular parameters in adolescents with type 1 diabetes (T1D) is not well understood. Our aims in this exploratory analysis were to study the association between PUA and estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (ACR), blood pressure, endothelial function, and arterial stiffness in T1D adolescents. These associations were also studied in healthy control (HC) subjects. RESEARCH DESIGN AND METHODS We studied 188 T1D subjects recruited to the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT) and 65 HC subjects. Baseline PUA, eGFR cystatin C , ACR, blood pressure, flow-mediated dilation (FMD), and carotid-femoral pulse wave velocity (PWV) were measured. RESULTS PUA was lower in T1D vs. HC subjects (242 6 55 vs. 306 6 74 mmol/L, respectively ; P < 0.0001). Higher PUA was inversely associated with eGFR in T1D subjects (r = 20.48, P < 0.0001) even after correction for baseline clinical demographic characteristics. PUA was not associated with ACR in T1D after adjustment for potential confounders such as eGFR. For cardiovascular parameters, PUA levels did not associate with systolic blood pressure, FMD, or PWV in T1D or HC subjects. CONCLUSIONS Even within the physiological range, PUA levels were significantly lower in T1D adolescent patients compared with HC subjects. There was an inverse relationship between PUA and eGFR in T1D, likely reflecting an increase in clearance. There were no associations observed with ACR, blood pressure, arterial stiffness, or endothelial function. Thus, in contrast with adults, PUA may not yet be associated with cardiorenal abnormalities in adolescents with T1D. Recent evidence from animal and human models suggests that plasma uric acid (PUA) levels are associated with multiple key pathways implicated in the pathogen-esis of type 1 diabetes (T1D) complications, such as metabolic abnormalities (insulin resistance and hyperglycemia), cardiovascular disease (hypertension, endothelial dysfunction, arterial stiffness, and cardiac diastolic dysfunction), and kidney dysfunc-tion (1). In healthy adult men and women, PUA is positively associated with activation of proinflammatory pathways and activation of the renin-angiotensin-aldosterone

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Association Between Plasma Uric Acid Levels and Cardiorenal Function in Adolescents With Type 1 Diabetes

et al. 2016

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Diabetic Nephropathy in Children and Adolescents

Bjornstad

2018

Diabetic Nephropathy

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The correlation between serum uric acid and diabetic kidney disease in adult-onset type 1 diabetes patients in China

et al. 2023

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Background/aim To assess the correlation between serum uric acid (UA) level and diabetic kidney disease among adult-onset Type 1 diabetes mellitus (T1DM) patients in China. Methods A total of 184 patients with adult-onset T1DM between January 2014 and December 2016 were recruited, with demographics and medical data collected. Comparisons were performed between according to different serum UA gender-specific quartiles. Relationship between serum UA level with urinary ACR and eGFR was also assessed. Results Median urinary ACR and eGFR were 21.55 [10.79, 45.02] mg/g and 113.86 [88.43, 143.61] ml/min/1.73 m2, respectively. The median UA was 257.4 (208.2–334.8) μmol/L. Participants with higher serum UA levels had higher urinary ACR and lower eGFR than those with lower UA (P < 0.05). Higher serum UA level was significantly associated with higher urinary ACR in Spearman's correlational analysis (P = 0.006) and multiple stepwise regression analysis (P = 0.013). The association between serum UA and urinary ACR was not linear, but showed a curve correlation, which also showed in the sensitivity analysis. Serum UA in the upper gender-specific quartile, was associated with lower eGFR (P < 0.001) and showed an independent negative correlation with eGFR in multiple stepwise regression analysis (P < 0.001). Conclusions The serum UA level was negatively correlated with eGFR and had a curve correlation with urinary ACR in adult-onset T1DM patients of China.

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Plasma uric acid effects on glomerular haemodynamic profile of patients with uncomplicated Type 1 diabetes mellitus

Cited by 20 publications

References 30 publications

Association Between Plasma Uric Acid Levels and Cardiorenal Function in Adolescents With Type 1 Diabetes

Association Between Plasma Uric Acid Levels and Cardiorenal Function in Adolescents With Type 1 Diabetes

Diabetic Nephropathy in Children and Adolescents

The correlation between serum uric acid and diabetic kidney disease in adult-onset type 1 diabetes patients in China

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