Diabetic Kidney Alarm (DKA) Study - Tubulopathy in Diabetic Ketoacidosis
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Enrollment
- 41
- Locations
- 1
- Primary Endpoint
- Proximal tubular injury
Study Overview
Brief Summary
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.
Detailed Description
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 Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 3 Years to 18 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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)
Outcomes
Primary Outcomes
Proximal tubular injury
Time Frame: At DKA (0-8 and 12-24 hours after starting IV insulin)
Change in urine and serum NGAL, KIM-1 and MMP9 concentrations
Proximal tubular dysfunction
Time Frame: At DKA (0-8 and 12-24 hours after starting IV insulin)
Change in urine Na, HCO3 and amino acids concentrations
Secondary Outcomes
- Proposed mediators of tubular dysfunction and injury(At DKA (12-24 hours after starting IV insulin))