Urinary Heparanase Activity as a Predictor of Acute Kidney Injury in Critically Ill Adults

Across the world, the most common cause of dying in the ICU is a disease called "sepsis". Sepsis is a disease in which the body's protective response to infection becomes too intense, unnecessarily damaging important organs in the body. Kidney damage during sepsis is particularly bad, as a person's chance of survival drops significantly when he or she develops kidney failure. This study plans to learn more about how to detect (and thus prevent) kidney failure early in sepsis. The current tests doctors use only detect kidney failure once it's already happened. We must therefore find better ways of detecting kidney failure earlier, when there is still a chance to protect the kidneys.

In this study, patients will provide a one-time sample of urine. We will check this urine for signs of a protein called "heparanase", which we believe is important in early kidney failure. We will then see if high heparanase activity in urine predicts the risk of developing kidney failure. We will compare results from patients with sepsis with results from patients with trauma, allowing us to determine if heparanase is only important in sepsis kidney failure.

Study Overview

• Status: Completed
• Conditions: Sepsis; Shock; Trauma; Acute Kidney Injury
• Intervention / Treatment: Other: Urine collection

• Study Type: Observational
• Enrollment (Actual): 57

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80204
      • Denver Health Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Critically ill adults admitted to the Denver Health MICU or SICU for either (a) septic shock or (b) major trauma.

Description

Inclusion Criteria:

1. Septic shock or major trauma. Septic shock will be defined by standard criteria including (a) the presence of the systemic inflammatory response syndrome (SIRS), (b) evidence of infection, and (c) treatment with vasopressor medications for > 4 hours despite > 30 ml/kg intravenous crystalloid resuscitation. As a critically-ill comparator group, we will also enroll adult patients admitted (within 24 hours prior to screening) to the Denver Health Surgical ICU with major trauma, as defined by an Injury Severity Score of > 15.

Exclusion Criteria:

Exclusion criteria include anuria, prisoners, absence of a routinely-inserted urine collection device, or gross hematuria. Additionally, patients with known genitourinary malignancy will be excluded, given that cancers are known to overexpress heparanase. Additional exclusion criteria include age < 18 years, and pregnant women.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Septic shock or major trauma; Patients admitted within 24 hours to ICU for septic shock or major trauma (ISS > 15). Septic shock is defined by sepsis with hypotension requiring >4 hours of vasopressor support over previous 24 hours.	Other: Urine collection; Collection of 5 ml urine from urinary collection device (e.g. foley catheter).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute kidney injury	Acute kidney injury will be determined using RIFLE criteria, based upon change in serum creatinine or urine output.	72 hours

Collaborators and Investigators

• Sponsor: Denver Health and Hospital Authority
• Investigators: Principal Investigator: Eric P Schmidt, MD, Denver Health Medical Center

Publications and helpful links

General Publications

• Schmidt EP, Overdier KH, Sun X, Lin L, Liu X, Yang Y, Ammons LA, Hiller TD, Suflita MA, Yu Y, Chen Y, Zhang F, Cothren Burlew C, Edelstein CL, Douglas IS, Linhardt RJ. Urinary Glycosaminoglycans Predict Outcomes in Septic Shock and Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med. 2016 Aug 15;194(4):439-49. doi: 10.1164/rccm.201511-2281OC.

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (ACTUAL): November 1, 2014

Study Registration Dates

• First Submitted: July 12, 2013
• First Submitted That Met QC Criteria: July 12, 2013
• First Posted (ESTIMATE): July 16, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): November 24, 2014
• Last Update Submitted That Met QC Criteria: November 21, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: Shock; Sepsis; Trauma; Acute kidney injury; Heparanase
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Wounds and Injuries; Acute Kidney Injury
• Other Study ID Numbers: COMIRB 13-0425; UL1TR000154 (U.S. NIH Grant/Contract)