Renal Arterial Resistive Index Versus Novel Biomarkers for Early Prediction of Sepsis Associated-acute Kidney Injury

Sepsis Clinical Trial

— RRIBIOSAKI  

Official title:

Renal Arterial Resistive Index Versus Novel Serum and Urinary Biomarkers for Early Prediction of Sepsis Associated-acute Kidney Injury in Critically Ill Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03799159
• Other study ID #: RRIBIOSAKI
• Status: Completed
• Start date: May 15, 2019
• Est. completion date: February 28, 2021

Study information

• Verified date: February 2021
• Source: Alexandria University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Populations at high risk of Sepsis-Associated Acute Kidney Injury (SA-AKI) have been identified. Sources of sepsis, in particular, bloodstream infection, abdominal and genitourinary sepsis, and infective endocarditis, are associated with a higher likelihood of developing AKI. Similar to the poor outcome of patients with sepsis, delayed administration of appropriate antimicrobial therapy was shown to be an independent predictor of the development of AKI. Incremental delays in antimicrobial delivery after the onset of hypotension showed a direct relationship with the development of AKI. The need for sensitive, simple and time-applicable biomarker to predict AKI development after renal insult is urgent.

Serum creatinine (sCr) and urea are used routinely for the diagnosis of AKI. However, these parameters are not accurate for the diagnosis of AKI. Cystatin C. (CysC) is suggested to be a good biomarker because of its constant rate of production, almost filtered by glomeruli (99%), has no significant protein binding and not secreted by renal tubule. Neutrophil gelatinase-associated lipocalin (NGAL) is recently identified and extensively investigated as a most promising early marker of AKI. Urinary NGAL is not only effective in detection of AKI but also its degree of expression might distinguish among AKI, prerenal azotemia and chronic kidney disease, and it is detectable before the accumulation of serum creatinine.

Ultrasonography (US) is used routinely to assess renal morphology. Renal Resistive Index (RRI) is a non-invasive Doppler-measured parameter that is directly correlated with intra-renal arterial resistance. RRI is defined as [(peak systolic velocity - end diastolic velocity)/ peak systolic velocity]. It theoretically ranges from 0 to 1 and it is normally lower than 0.7 with age differences. RRI calculation was found to be useful as an early indicator of the vascular resistance changes and in the determination of the optimal systemic hemodynamics required for renal perfusion.

The aim of this study is to compare the ability of arterial renal resistive index (RRI), serum and urinary neutrophil gelatinase-associated lipocalin (NGAL), Cystatin C (CysC) in early diagnosis and predicting the persistence of acute kidney injury in septic patients.

Description:

All included patients in this study will be assessed for the following:

1. Data Collection

• Complete history taking (age, sex, illness, medications, etc.).

• Complete physical examination (Glasgow coma scale (GCS), temperature, blood pressure, urine output, heart rate, respiratory rate and chest auscultation).

• SOFA score, APACHE II score, and Quick SOFA (qSOFA).

• Routine laboratory investigations and Coagulation profile.

• C-reactive protein (CRP), and Serum lactate.

• Complete sepsis workup (chest x-ray, urine analysis, abdomen and pelvis ultrasound, microbiological cultures) to identify the source of sepsis.

2. Renal Biomarkers

• Serum and urinary samples will be collected directly at time of enrollment (within 2 hours from admission). It will be assayed for serum creatinine, serum neutrophil gelatinase-associated lipocalin (NGAL), urinary NGAL and serum Cystatin C (CysC). Then, it will be repeated at day 3.

3. Ultrasound evaluation of kidneys and renal Doppler

• In each patient, both kidneys will be examined with real-time ultrasound (US) with a 3.75-MHz transducer (ACUSON X 300). Pulsed Doppler US evaluation of the intrarenal arteries will be obtained at the same respective scanning frequencies. The color Doppler functions are set for a study focused on interlobar arteries, that is, the highest gains possible, the use of the lowest filters and a low pulse repetition frequency (PRF) of 1-1.5 kHz that must be preferred while always limiting the aliasing phenomenon.

• The renal resistance index (RRI, [peak systolic frequency shift-minimum diastolic frequency shift]/ peak systolic frequency shift) will be calculated from calibrated software. (26) All measurements will be performed by the same examiner.

• The renal resistive index (RRI) will be measured at time of enrollment (within 2 hours from admission) and 24 hours after admission.

4. Treatment All patients will receive the standard treatment for management of sepsis on the guidelines of SCC (sepsis-3). The protocol of treatment will not be changed during the study time.

5. Follow up - All patients will be followed up using urine output (UOP), serum creatinine, KDIGO (Kidney Disease Improving Global Outcomes) classification, the use of vasopressors and need for renal replacement therapy (RRT).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: February 28, 2021
• Est. primary completion date: February 28, 2021
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult patients (aged above 18 years) recently admitted with sepsis

Exclusion Criteria:

• Pregnant Females

• Patients with renal transplant.

• Patients with End Stage Renal Disease (ESRD).

• Patients with Chronic Kidney Disease (CKD) known with history, laboratory or ultrasonographic evaluation with chronic nephropathic changes.

• Patients with renal artery stenosis.

• Patients with obstructive uropathy.

Related Conditions & MeSH terms

• Acute Kidney Injury
• Sepsis
• Septic Shock
• Toxemia
• Wounds and Injuries

Locations

Country	Name	City	State
Egypt	Alexandria Main University Hospital	Alexandria

Sponsors (1)

Lead Sponsor	Collaborator
Islam Elsayed Mohamed Ahmed

Country where clinical trial is conducted

Egypt, 

References & Publications (13)

Bagshaw SM, George C, Bellomo R; ANZICS Database Management Committee. Early acute kidney injury and sepsis: a multicentre evaluation. Crit Care. 2008;12(2):R47. doi: 10.1186/cc6863. Epub 2008 Apr 10. — View Citation

Bagshaw SM, Lapinsky S, Dial S, Arabi Y, Dodek P, Wood G, Ellis P, Guzman J, Marshall J, Parrillo JE, Skrobik Y, Kumar A; Cooperative Antimicrobial Therapy of Septic Shock (CATSS) Database Research Group. Acute kidney injury in septic shock: clinical outcomes and impact of duration of hypotension prior to initiation of antimicrobial therapy. Intensive Care Med. 2009 May;35(5):871-81. doi: 10.1007/s00134-008-1367-2. Epub 2008 Dec 9. — View Citation

Bagshaw SM, Uchino S, Bellomo R, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Oudemans-van Straaten HM, Ronco C, Kellum JA; Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators. Septic acute kidney injury in critically ill patients: clinical characteristics and outcomes. Clin J Am Soc Nephrol. 2007 May;2(3):431-9. Epub 2007 Mar 21. — View Citation

Bouglé A, Duranteau J. Pathophysiology of sepsis-induced acute kidney injury: the role of global renal blood flow and renal vascular resistance. Contrib Nephrol. 2011;174:89-97. doi: 10.1159/000329243. Epub 2011 Sep 9. Review. — View Citation

Haase-Fielitz A, Bellomo R, Devarajan P, Bennett M, Story D, Matalanis G, Frei U, Dragun D, Haase M. The predictive performance of plasma neutrophil gelatinase-associated lipocalin (NGAL) increases with grade of acute kidney injury. Nephrol Dial Transplant. 2009 Nov;24(11):3349-54. doi: 10.1093/ndt/gfp234. Epub 2009 May 27. — View Citation

Merrikhi A, Gheissari A, Mousazadeh H. Urine and serum neutrophil gelatinase-associated lipocalin cut-off point for the prediction of acute kidney injury. Adv Biomed Res. 2014 Jan 27;3:66. doi: 10.4103/2277-9175.125847. eCollection 2014. — View Citation

Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, Ruff SM, Zahedi K, Shao M, Bean J, Mori K, Barasch J, Devarajan P. Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet. 2005 Apr 2-8;365(9466):1231-8. — View Citation

Mori K, Lee HT, Rapoport D, Drexler IR, Foster K, Yang J, Schmidt-Ott KM, Chen X, Li JY, Weiss S, Mishra J, Cheema FH, Markowitz G, Suganami T, Sawai K, Mukoyama M, Kunis C, D'Agati V, Devarajan P, Barasch J. Endocytic delivery of lipocalin-siderophore-iron complex rescues the kidney from ischemia-reperfusion injury. J Clin Invest. 2005 Mar;115(3):610-21. — View Citation

Nickolas TL, O'Rourke MJ, Yang J, Sise ME, Canetta PA, Barasch N, Buchen C, Khan F, Mori K, Giglio J, Devarajan P, Barasch J. Sensitivity and specificity of a single emergency department measurement of urinary neutrophil gelatinase-associated lipocalin for diagnosing acute kidney injury. Ann Intern Med. 2008 Jun 3;148(11):810-9. — View Citation

Schnell D, Darmon M. Renal Doppler to assess renal perfusion in the critically ill: a reappraisal. Intensive Care Med. 2012 Nov;38(11):1751-60. doi: 10.1007/s00134-012-2692-z. Epub 2012 Sep 22. Review. — View Citation

Schnell D, Deruddre S, Harrois A, Pottecher J, Cosson C, Adoui N, Benhamou D, Vicaut E, Azoulay E, Duranteau J. Renal resistive index better predicts the occurrence of acute kidney injury than cystatin C. Shock. 2012 Dec;38(6):592-7. doi: 10.1097/SHK.0b013e318271a39c. — View Citation

Zhang Z, Lu B, Sheng X, Jin N. Cystatin C in prediction of acute kidney injury: a systemic review and meta-analysis. Am J Kidney Dis. 2011 Sep;58(3):356-65. doi: 10.1053/j.ajkd.2011.02.389. Epub 2011 May 20. Review. Erratum in: Am J Kidney Dis. 2012 Apr;59(4):590-2. — View Citation

Zwiers AJ, de Wildt SN, van Rosmalen J, de Rijke YB, Buijs EA, Tibboel D, Cransberg K. Urinary neutrophil gelatinase-associated lipocalin identifies critically ill young children with acute kidney injury following intensive care admission: a prospective cohort study. Crit Care. 2015 Apr 21;19:181. doi: 10.1186/s13054-015-0910-0. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Acute Kidney Injury	AKI is defined according to KDIGO (Kidney Disease Improving Global Outcomes)	7 days from inclusion
Primary	Transient Acute Kidney Injury	Transient AKI is defined as AKI with a cause of renal hypoperfusion and recovery within 3 days after inclusion. Recovery from AKI is defined as urine output normalization and/or serum creatinine decrease by 50% and/or serum creatinine normalization to its measured or estimated baseline level.	7 days from inclusion
Primary	Persistent Acute Kidney Injury	Persistent AKI is defined as persistent serum creatinine rise or oliguria after 3 days.	7 days from inclusion
Secondary	Mortality	All cause 28-days mortality	28 days from inclusion