The overarching goals of this study are to determine whether tubular dysfunction (elevated urine sodium, bicarbonate and amino acids) and injury (elevated kidney injury molecule 1 \[KIM-1\], neutrophil gelatinase-associated lipocalin \[NGAL\] and matrix metallopeptidase 9 \[MMP9\]) exist in diabetic ketoacidosis (age 3-18), whether it is reversible and whether it is related to uricosuria and copeptin. The investigators propose to study a cohort of youth (ages 3-18, n=40) with T1D who have serum and urine collection at DKA diagnosis and 3-month follow-up.
Every year over 86,000 children (0-14 years) worldwide are diagnosed with type 1 diabetes (T1D) translating to a lifetime of exposure and risk for early death from cardiovascular disease (CVD) and diabetic kidney disease (DKD). DKD, which manifests in children and adolescents, remains the leading cause of renal failure and dialysis in the Western world (4). While diabetic glomerulopathy has received significant attention from researchers, determinants of tubular injury in diabetes are less well examined. Compared to glomerular injury, tubular injury is known to associate better with renal function. The majority of youth diagnosed with T1D in the US present with diabetic ketoacidosis (DKA), a condition associated with risks factors for tubular injury including dehydration, metabolic acidosis and acute glycemia. It is unknown whether DKA is associated with tubular injury. The investigators published the first report showing that youth with established T1D have more acidic urine and higher fractional excretion of uric acid (FeUA) than their non-diabetic peers, which may predispose to UUA-mediated tubulopathy. Furthermore, T1D is associated with vasopressin overactivity, and the investigators reported strong relationships between serum copeptin, a reliable surrogate marker for vasopressin, and DKD in T1D. The overarching goals of this study are to determine whether tubular dysfunction (elevated urine sodium, bicarbonate and amino acids) and injury (elevated KIM-1, NGAL and MMP9) exist in DKA, whether it is reversible and whether it is related to uricosuria and copeptin. The investigators propose to study a cohort of youth (ages 3-18, n=40) with T1D who have serum and urine collection at DKA diagnosis and 3-month follow-up.
Study Type
OBSERVATIONAL
Enrollment
41
Children's Hospital Colorado
Aurora, Colorado, United States
Proximal tubular dysfunction
Change in urine Na, HCO3 and amino acids concentrations
Time frame: At DKA (0-8 and 12-24 hours after starting IV insulin)
Proximal tubular injury
Change in urine and serum NGAL, KIM-1 and MMP9 concentrations
Time frame: At DKA (0-8 and 12-24 hours after starting IV insulin)
Proposed mediators of tubular dysfunction and injury
Change in urine uric acid and serum fructose.
Time frame: At DKA (0-8 and 12-24 hours after starting IV insulin)
Proposed mediators of tubular dysfunction and injury
Presence of urine uric acid crystals by polarized microscopy
Time frame: At DKA (0-8 hours after starting IV insulin)
Proposed mediators of tubular dysfunction and injury
Presence of urine uric acid crystals by polarized microscopy
Time frame: At DKA (12-24 hours after starting IV insulin)
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