Hyperfiltration and uricosuria in adolescents with type 1 diabetes

Abstract

Background Urine uric acid (UUA) has been implicated in the pathogenesis of diabetic nephropathy via its effect on tubular cells. We hypothesized that UUA would be greater in adolescents with type 1 diabetes (T1D) compared to those without. Second, we hypothesized that UUA and fractional uric acid excretion (FeUA) would be greater in adolescents with T1D and hyperfiltration (estimated glomerular filtration rate (eGFR) ≥141 mL/min/1.73m2) compared to those without hyperfiltration Methods Adolescents with (n=239) and without T1D (n=75) had UUA measured and FeUA calculated. Serum creatinine and cystatin C were used to calculate eGFR by the Zappitelli equation. Results Adolescents with T1D had higher eGFR (mean±standard deviation (SD): 120±22 vs. 112±16 mL/min/1.73m2, p=0.0006), lower urine pH (6.2±0.8 vs. 6.5±1.0, p=0.01), higher UUA (37.7±18.6 vs. 32.8±18.1 mg/dL, p=0.049) and FeUA (median, IQR: 6.2 [4.3–8.7] vs. 5.2 [3.6–7.0]%, p=0.02) compared to non-diabetic adolescents. Among adolescents with T1D, those with hyperfiltration had higher FeUA (8.6 [5.2–9.9] vs. 6.0 [4.2–8.3]%, p=0.02) compared to those without hyperfiltration. Conclusions Adolescents with T1D had higher eGFR, higher UUA and more acidic urine than non-diabetic controls, which may increase their risk of UUA crystallization. Adolescents with T1D and hyperfiltration had higher FeUA than those without hyperfiltration. These hypothesis-generating observations may suggest a potential pathophysiologic association between uricosuria and hyperfiltration.

Uric acid in the pathogenesis of metabolic, renal, and cardiovascular diseases: A review

“…Hyperuricosuria in the presence of acidic urine especially in case of low urine volume can result in formation of urate stones [78]. In type 1 DM adolescents, UUA is significantly higher and urine pH is lower compared to non-diabetic controls [79]. DM patients are more prone to develop urate stones [80].…”

Role of bicarbonate supplementation on urine uric acid crystals and diabetic tubulopathy in adults with type 1 diabetes

“…Compared to glomerular injury, tubular injury is more strongly associated with renal function . Whereas the mechanisms underlying diabetic tubulopathy are still incompletely understood, there is growing evidence that a glucosuria mediated increase in urine uric acid (UA) is a major determinant …”

“…2 Whereas the mechanisms underlying diabetic tubulopathy are still incompletely understood, there is growing evidence that a glucosuria mediated increase in urine uric acid (UA) is a major determinant. 3,4 Glucosuria is associated with activation of the polyol pathway and consequent increased fructose concentration. 3 Intracellular fructose is further metabolized, generating UA as a byproduct.…”

“…3 Intracellular fructose is further metabolized, generating UA as a byproduct. 3 Individuals with type 1 diabetes (T1D) have more acidic urine than their non-diabetic peers, 4 which may predispose them to UA crystallization and UA-mediated tubulopathy by inflammation and apoptosis of tubular cells. [5][6][7] In animal studies, inhibition of UA production protects the kidney from tubular injury, suggesting a causal role for UA in the development of diabetic tubulopathy.…”

Hyperuricemia as a potential risk factor for type 2 diabetes and diabetic nephropathy

“…[1][2][3] Elevated serum uric acid has also been reported to predict development of nephropathy in type 1 diabetes. [4][5][6][7] Less is known, however, about the role of serum uric acid in predicting nephropathy in type 2 diabetes.…”