Diabetic Kidney Alarm (DKA) Study

NCT03128229 | Completed DMC

• 1 other identifier: 16-1403
• Study Type: observational
• Target: 41
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 1 Diabetes Mellitus; Diabetic Ketoacidosis

Outcome Measures

Primary Outcomes (2)

• Proximal tubular dysfunction

  Change in urine Na, HCO3 and amino acids concentrations

  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

  At DKA (0-8 and 12-24 hours after starting IV insulin)

Secondary Outcomes (3)

• Proposed mediators of tubular dysfunction and injury

  At DKA (0-8 and 12-24 hours after starting IV insulin)

• Proposed mediators of tubular dysfunction and injury

  At DKA (0-8 hours after starting IV insulin)

• Proposed mediators of tubular dysfunction and injury

  At DKA (12-24 hours after starting IV insulin)

Eligibility Criteria

• Age: 3 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Participants (3-18 years) with T1D presenting with DKA will be recruited from the Emergency Department (ED) at Children's Hospital Colorado.

You may qualify if:

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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Thrasher Research Fund: collaborator

Study Sites (1)

Children's Hospital Colorado

Aurora, Colorado, 80238, United States

Location

Related Publications (8)

• Bjornstad P, Johnson RJ, Snell-Bergeon JK, Pyle L, Davis A, Foster N, Cherney DZ, Maahs DM. Albuminuria is associated with greater copeptin concentrations in men with type 1 diabetes: A brief report from the T1D exchange Biobank. J Diabetes Complications. 2017 Feb;31(2):387-389. doi: 10.1016/j.jdiacomp.2016.11.015. Epub 2016 Dec 7.

  PMID: 27979439 BACKGROUND

• Bjornstad P, Maahs DM, Jensen T, Lanaspa MA, Johnson RJ, Rewers M, Snell-Bergeon JK. Elevated copeptin is associated with atherosclerosis and diabetic kidney disease in adults with type 1 diabetes. J Diabetes Complications. 2016 Aug;30(6):1093-6. doi: 10.1016/j.jdiacomp.2016.04.012. Epub 2016 Apr 19.

  PMID: 27141815 BACKGROUND

• Roncal-Jimenez CA, Milagres T, Andres-Hernando A, Kuwabara M, Jensen T, Song Z, Bjornstad P, Garcia GE, Sato Y, Sanchez-Lozada LG, Lanaspa MA, Johnson RJ. Effects of exogenous desmopressin on a model of heat stress nephropathy in mice. Am J Physiol Renal Physiol. 2017 Mar 1;312(3):F418-F426. doi: 10.1152/ajprenal.00495.2016. Epub 2016 Dec 21.

  PMID: 28003190 BACKGROUND

• Bakes K, Haukoos JS, Deakyne SJ, Hopkins E, Easter J, McFann K, Brent A, Rewers A. Effect of Volume of Fluid Resuscitation on Metabolic Normalization in Children Presenting in Diabetic Ketoacidosis: A Randomized Controlled Trial. J Emerg Med. 2016 Apr;50(4):551-9. doi: 10.1016/j.jemermed.2015.12.003. Epub 2016 Jan 25.

  PMID: 26823137 BACKGROUND

• Rewers A, Dong F, Slover RH, Klingensmith GJ, Rewers M. Incidence of diabetic ketoacidosis at diagnosis of type 1 diabetes in Colorado youth, 1998-2012. JAMA. 2015 Apr 21;313(15):1570-2. doi: 10.1001/jama.2015.1414. No abstract available.

  PMID: 25898057 BACKGROUND

• Dabelea D, Rewers A, Stafford JM, Standiford DA, Lawrence JM, Saydah S, Imperatore G, D'Agostino RB Jr, Mayer-Davis EJ, Pihoker C; SEARCH for Diabetes in Youth Study Group. Trends in the prevalence of ketoacidosis at diabetes diagnosis: the SEARCH for diabetes in youth study. Pediatrics. 2014 Apr;133(4):e938-45. doi: 10.1542/peds.2013-2795. Epub 2014 Mar 31.

  PMID: 24685959 BACKGROUND

• Rewers A, Chase HP, Mackenzie T, Walravens P, Roback M, Rewers M, Hamman RF, Klingensmith G. Predictors of acute complications in children with type 1 diabetes. JAMA. 2002 May 15;287(19):2511-8. doi: 10.1001/jama.287.19.2511.

  PMID: 12020331 BACKGROUND

• Bjornstad P, Roncal C, Milagres T, Pyle L, Lanaspa MA, Bishop FK, Snell-Bergeon JK, Johnson RJ, Wadwa RP, Maahs DM. Hyperfiltration and uricosuria in adolescents with type 1 diabetes. Pediatr Nephrol. 2016 May;31(5):787-93. doi: 10.1007/s00467-015-3299-8. Epub 2015 Dec 23.

  PMID: 26701836 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum and urine collection at 0-8h and 12-24h after starting IV insulin, and at 3 month follow-up.

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetic Ketoacidosis

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Ketosis; Acidosis; Acid-Base Imbalance; Diabetes Complications

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2017
• First Posted: April 25, 2017
• Study Start: June 1, 2017
• Primary Completion: December 13, 2019
• Study Completion: December 13, 2019
• Last Updated: January 20, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)