Diabetic Kidney Alarm (DKA) Study
Diabetic Kidney Alarm (DKA) Study
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.
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)