Diabetic Kidney Alarm (DKA) Study

Type 1 Diabetes Mellitus Clinical Trial

— DKA  

Official title:

Diabetic Kidney Alarm (DKA) Study - Tubulopathy in Diabetic Ketoacidosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03128229
• Other study ID #: 16-1403
• Status: Completed
• Start date: June 1, 2017
• Est. completion date: December 13, 2019

Study information

• Verified date: January 2022
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: December 13, 2019
• Est. primary completion date: December 13, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 18 Years

Eligibility

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)

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 1
• Diabetic Ketoacidosis
• Ketosis
• Type 1 Diabetes Mellitus

Locations

Country	Name	City	State
United States	Children's Hospital Colorado	Aurora	Colorado

Sponsors (2)

Lead Sponsor	Collaborator
University of Colorado, Denver	Thrasher Research Fund

Country where clinical trial is conducted

United States, 

References & Publications (8)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proximal tubular dysfunction	Change in urine Na, HCO3 and amino acids concentrations	At DKA (0-8 and 12-24 hours after starting IV insulin)
Primary	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	Proposed mediators of tubular dysfunction and injury	Change in urine uric acid and serum fructose.	At DKA (0-8 and 12-24 hours after starting IV insulin)
Secondary	Proposed mediators of tubular dysfunction and injury	Presence of urine uric acid crystals by polarized microscopy	At DKA (0-8 hours after starting IV insulin)
Secondary	Proposed mediators of tubular dysfunction and injury	Presence of urine uric acid crystals by polarized microscopy	At DKA (12-24 hours after starting IV insulin)