Troponin Excretion in Urine in Patients With and Without Chronic Kidney Disease

In this study, in order to better understand the mechanism of troponin clearance and the reason for elevated troponin levels in patients with CKD, we aim to evaluate quantitatively the excretion of troponin in the urine in patients with and without CKD, and with and without myocardial injury. We will compare urinary troponin levels with blood troponin levels in these patients. In addition, we will compare the levels of hs-cTnT and hs-cTnI in the patients' sera and urine.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Diseases; Acute Myocardial Infarction
• Intervention / Treatment: Diagnostic test: Blood and urine sampling

Detailed Description

The study population will be screened at the internal wards, the nephrology ward and clinic, and the intensive cardiac care unit (ICCU) of Soroka Medical Center. It will include patients who suffer from AMI, patients with CKD with and without any cardiac disease and patients with no known renal or cardiac disease.

The following information and measurements will be collected:

Demographics - age, sex, weight, height. Past medical history - specifically regarding renal and cardiac diseases and procedures.

Measured variables in blood serum - troponin T, troponin I, creatinine, total protein, albumin, myoglobin Measured variables in urine - troponin T, troponin I, creatinine, total protein, albumin, microalbumin, β2-microglobulin Calculations - GFR (according to MDRD equation), troponin correction to creatinine (gr troponin per gr creatinine), troponin excretion ( ), urine albumin/creatinine ratio, urine protein/creatinine ratio.

• Study Type: Observational
• Enrollment (Actual): 131

Contacts and Locations

Study Locations

• Israel
  • Be'er Sheva, Israel
    • Soroka Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The study population will be screened at the internal wards, the nephrology ward and clinic, and the intensive cardiac care unit (ICCU) of Soroka Medical Center. It will include patients who suffer from AMI, patients with CKD with and without any cardiac disease and patients with no known renal or cardiac disease. The study population will be enrolled according to the above inclusion and exclusion criteria.

Description

Inclusion Criteria:

1. Patients who are able to give informed consent.
2. Age ≥ 18

Exclusion Criteria:

1. Pregnant women
2. Patients after kidney transplantation.
3. Patients after heart transplantation.
4. Anuric patients.

Study Plan

How is the study designed?

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group 1 - Healthy subjects without any evidence of cardiac o; Inclusion criteria: Normal serum troponin (below the 99th percentile); GFR 60ml/min; Proteinuria <1gr/gr creatinine Blood and urine samples will be collected for troponin and other measures.	Diagnostic test: Blood and urine sampling; Blood tests - hs-cTnT, hs-cTnI, complete metabolic panel including urea, creatinine, albumin and myoglobin; Urine tests - hs-cTnT, hs-cTnI, urea, creatinine, albumin, total protein, β2-microglobulin.
Group 2 - Subjects with acute myocardial infarction and norm; Inclusion criteria: At least one measurements of serum troponin above the 99th percentile, with either a rise or fall in cardiac troponin levels.; GFR 60ml/min/1.73m2 Blood and urine samples will be collected for troponin and other measures.	Diagnostic test: Blood and urine sampling; Blood tests - hs-cTnT, hs-cTnI, complete metabolic panel including urea, creatinine, albumin and myoglobin; Urine tests - hs-cTnT, hs-cTnI, urea, creatinine, albumin, total protein, β2-microglobulin.
Group 3 - Subjects with acute myocardial infarction and decr; Inclusion criteria - Group 3a: At least one measurements of serum troponin above the 99th percentile, with either a rise or fall in cardiac troponin levels.; 30 GFR <60ml/min/1.73m2Inclusion criteria - Group 3b:; At least one measurements of serum troponin above the 99th percentile, with either a rise or fall in cardiac troponin levels.; GFR <30ml/min/1.73m2 Blood and urine samples will be collected for troponin and other measures.	Diagnostic test: Blood and urine sampling; Blood tests - hs-cTnT, hs-cTnI, complete metabolic panel including urea, creatinine, albumin and myoglobin; Urine tests - hs-cTnT, hs-cTnI, urea, creatinine, albumin, total protein, β2-microglobulin.
Group 4 - Subjects with decreased GFR but without any eviden; Inclusion criteria - Group 4a: Normal serum troponin (below the 99th percentile); No known past medical history of any cardiac disease and/or procedure.; 30 GFR <60ml/min/1.73m2Inclusion criteria - Group 4b:; Normal serum troponin (below the 99th percentile); No known past medical history of any cardiac disease and/or procedure.; GFR <30ml/min/1.73m2 Blood and urine samples will be collected for troponin and other measures.	Diagnostic test: Blood and urine sampling; Blood tests - hs-cTnT, hs-cTnI, complete metabolic panel including urea, creatinine, albumin and myoglobin; Urine tests - hs-cTnT, hs-cTnI, urea, creatinine, albumin, total protein, β2-microglobulin.
Group 5 - Subjects with chronic myocardial injury and normal; Inclusion criteria: At least one measurements of serum troponin above the 99th percentile, with neither a rise nor fall in cardiac troponin levels.; GFR 60ml/min/1.73m2 Blood and urine samples will be collected for troponin and other measures.	Diagnostic test: Blood and urine sampling; Blood tests - hs-cTnT, hs-cTnI, complete metabolic panel including urea, creatinine, albumin and myoglobin; Urine tests - hs-cTnT, hs-cTnI, urea, creatinine, albumin, total protein, β2-microglobulin.
Group 6 - patients on RRT; Inclusion criteria: a. Patients who are dependent on renal replacement therapy, including hemodialysis, peritoneal or hemodiafiltration. Blood and urine samples will be collected for troponin and other measures.	Diagnostic test: Blood and urine sampling; Blood tests - hs-cTnT, hs-cTnI, complete metabolic panel including urea, creatinine, albumin and myoglobin; Urine tests - hs-cTnT, hs-cTnI, urea, creatinine, albumin, total protein, β2-microglobulin.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Troponin T in blood vs. urine	Quantitative measurements of hs-cTnT in blood and urine	1 year
Troponin I in blood vs. urine	Quantitative measurements of hs-cTnI in blood and urine	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Troponin excretion in urine compared to creatinine	Comparing urine troponin levels to urine creatinine, albumin, β2-microglobulin	1 year
Troponin excretion in urine compared to albumin	Comparing urine troponin levels to urine albumin	1 year
Troponin excretion in urine compared to β2-microglobulin	Comparing urine troponin levels to urine β2-microglobulin	1 year

Collaborators and Investigators

• Sponsor: Soroka University Medical Center
• Investigators: Study Chair: Yosef Haviv, MD, Soroka UMC, Nephrology Department, Director

Publications and helpful links

General Publications

• Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, White HD; Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth Universal Definition of Myocardial Infarction (2018). Glob Heart. 2018 Dec;13(4):305-338. doi: 10.1016/j.gheart.2018.08.004. Epub 2018 Aug 25. No abstract available.
• Twerenbold R, Wildi K, Jaeger C, Gimenez MR, Reiter M, Reichlin T, Walukiewicz A, Gugala M, Krivoshei L, Marti N, Moreno Weidmann Z, Hillinger P, Puelacher C, Rentsch K, Honegger U, Schumacher C, Zurbriggen F, Freese M, Stelzig C, Campodarve I, Bassetti S, Osswald S, Mueller C. Optimal Cutoff Levels of More Sensitive Cardiac Troponin Assays for the Early Diagnosis of Myocardial Infarction in Patients With Renal Dysfunction. Circulation. 2015 Jun 9;131(23):2041-50. doi: 10.1161/CIRCULATIONAHA.114.014245. Epub 2015 May 6.
• Freda BJ, Tang WH, Van Lente F, Peacock WF, Francis GS. Cardiac troponins in renal insufficiency: review and clinical implications. J Am Coll Cardiol. 2002 Dec 18;40(12):2065-71. doi: 10.1016/s0735-1097(02)02608-6.
• Kanderian AS, Francis GS. Cardiac troponins and chronic kidney disease. Kidney Int. 2006 Apr;69(7):1112-4. doi: 10.1038/sj.ki.5000174.
• Ziebig R, Lun A, Hocher B, Priem F, Altermann C, Asmus G, Kern H, Krause R, Lorenz B, Mobes R, Sinha P. Renal elimination of troponin T and troponin I. Clin Chem. 2003 Jul;49(7):1191-3. doi: 10.1373/49.7.1191. No abstract available.
• Petra, P., Tomo, S., Ingrid, P., Jurica, V., Andrea, R., & Sonja, P. Urine Concentrations of High-Sensitivity Cardiac Troponin I in Healthy Adults - Preliminary Reference Intervals. Acta Med Croatica , 461-465, 2018
• Petra, P., Tomo, S., Ingrid, P., Ana, S., Matija, B., & Sonja, P. Urine High-Sensitive Troponin I Measuring in Patients with Hypertension. Signa Vitae , 13(SUPPL 3): 62-64, 2017
• Friden V, Starnberg K, Muslimovic A, Ricksten SE, Bjurman C, Forsgard N, Wickman A, Hammarsten O. Clearance of cardiac troponin T with and without kidney function. Clin Biochem. 2017 Jun;50(9):468-474. doi: 10.1016/j.clinbiochem.2017.02.007. Epub 2017 Feb 11.
• Dubin RF, Li Y, He J, Jaar BG, Kallem R, Lash JP, Makos G, Rosas SE, Soliman EZ, Townsend RR, Yang W, Go AS, Keane M, Defilippi C, Mishra R, Wolf M, Shlipak MG; CRIC Study Investigators. Predictors of high sensitivity cardiac troponin T in chronic kidney disease patients: a cross-sectional study in the chronic renal insufficiency cohort (CRIC). BMC Nephrol. 2013 Oct 22;14:229. doi: 10.1186/1471-2369-14-229.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2020
• Primary Completion (Actual): December 31, 2023
• Study Completion (Actual): December 31, 2023

Study Registration Dates

• First Submitted: December 23, 2019
• First Submitted That Met QC Criteria: December 23, 2019
• First Posted (Actual): December 26, 2019

Study Record Updates

• Last Update Posted (Actual): January 17, 2024
• Last Update Submitted That Met QC Criteria: January 13, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Myocardial Infarction; Infarction; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: 0234-19-SOR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No