Diabetic Kidney Alarm (DKA) Study

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.

Inclusion criteria

• New onset T1D and known T1D
• DKA (mild, moderate and severe DKA eligible)
• 3-17 years of age
• Toilet trained
• Boys and girls
• All ethnicities
• Initial presentation to Children's Hospital Colorado (CHCO) Main ED

Exclusion criteria

• Non-T1D etiology
• History of chronic kidney disease (eGFR <60ml/min/1.73m2) or dialysis dependent
• History of tubulopathy (e.g. Fanconi syndrome)
• Currently menstruating
• Patient visiting Colorado with plan to establish diabetes care outside of Colorado
• On ACE-inhibitors or angiotensin II-receptor blockers (ARB)
• On sodium-glucose co-transporter 2 inhibitors (SGLT2 inhibitors)