Kidney Recovery After Acute Kidney Injury - Longitudinal Study (KRAKIL)

The endothelin (ET) system is an active target in human Acute Kidney Injury (AKI).

Our primary hypothesis is that the circulating blood concentration of ET will be higher in patients with AKI than in matched controls.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Diseases; Acute Kidney Injury
• Intervention / Treatment: Other: Blood and urine sampling

Detailed Description

Acute kidney injury (AKI) is a major health problem being both common and costly. It affects ~20% of hospital inpatients and consumes ~1% of the annual NHS budget. AKI occurs following a diverse range of insults, commonly ischaemia-reperfusion injury (IRI) but also sepsis and drug toxicity. Therapies for AKI are currently supportive and short-term mortality remains high, with ~2 million deaths per year worldwide. In those who survive an episode of AKI, 30% are left with chronic kidney disease (CKD). The remaining 70% that recover full renal function are at ~28-fold increased risk of ultimately developing CKD. This risk is even greater in elderly patients. Importantly, CKD is strongly and independently associated with incident cardiovascular disease (CVD), and together these exert a global socioeconomic burden.

The recognition that AKI and CKD are linked is recent and the molecular pathways that control the transition from acute injury to chronic disease are not well defined. Currently, there are no specific treatments that reduce the risk of progressing to CKD after AKI. Thus, there is an unmet need for therapies that will prevent the transition from AKI to CKD and reduce the cardiovascular burden associated with both. Our preliminary investigations (not yet published) in humans and mice suggest that AKI causes sustained activation of the endothelin (ET) system to the long-term detriment of renal and systemic haemodynamic function. These pilot data form the basis of our project that seeks to determine whether the ET system is active in patients with AKI and, thus, represents a potential target for therapeutic intervention.

• Study Type: Observational
• Enrollment (Actual): 100

Contacts and Locations

Study Locations

• United Kingdom
  • Edinburgh, United Kingdom
    • NHS Lothian

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

(i) Adult aged 16 or over; (ii) Ability to provide informed consent; (iii) Diagnosis of AKI

Description

Inclusion Criteria:

(i) Adult aged 16 or over; (ii) Ability to provide informed consent; (iii) Diagnosis of AKI determined as:

• Previous (within 3 years) eGFR >45 mL/min/1.73m2 OR no history of kidney disease if no recent (within 3 years) blood results available AND
• Elevated creatinine over 1.5 x previous result OR over 150 μmol/L if no previous value AND
• Increasing creatinine >= 27μmol/L above index value within 48 hours

The control group (N=50) inclusion criteria are:

(i) Adult aged 16 or over; (ii) Ability to provide informed consent; (iii) Admitted to hospital without AKI: (eGFR > 60)

This group will be recruited contemporaneously with, and matched to, AKI participants by:

1. Age (± 5 years)
2. Sex
3. AKI aetiology (ischaemic, infected, nephrotoxic) 4 (i) History of diabetes or not AND/OR (ii) History of cardiovascular disease or not

Exclusion Criteria:

1. Inability to provide informed consent
2. Prisoners
3. Pregnancy or breast feeding
4. Evidence of CKD

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Case; (i) Adult aged 16 or over; (ii) Ability to provide informed consent; (iii) Diagnosis of AKI determined as: Previous (within 3 years) eGFR >45 mL/min/1.73m2 OR no history of kidney disease if no recent (within 3 years) blood results available AND; Elevated creatinine over 1.5 x previous result OR over 150 μmol/L if no previous value AND; Increasing creatinine >= 27μmol/L above index value within 48 hours	Other: Blood and urine sampling; Retinal OCT is a novel, non-invasive method for cross-sectionally imaging the eye's retina and choroid; Other Names: retinal opticla coherence tomography
Control; (i) Adult aged 16 or over; (ii) Ability to provide informed consent; (iii) Admitted to hospital without AKI: (eGFR > 60). This group will be recruited contemporaneously with, and matched to, AKI participants by: Age (± 5 years); Sex; AKI aetiology (ischaemic, infected, nephrotoxic) 4 (i) History of diabetes or not AND/OR (ii) History of cardiovascular disease or not	Other: Blood and urine sampling; Retinal OCT is a novel, non-invasive method for cross-sectionally imaging the eye's retina and choroid; Other Names: retinal opticla coherence tomography

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To primary outcome aims to measure whether circulating ET is higher in patients with AKI than in matched controls.	as above	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The secondary outcome aims to measure differences in urine ET between patients with AKI and matched controls AKI patients that do not fully recover renal function within 90 days will have the highest concentrations of blood and urine ET.	as above	3 YEARS

Collaborators and Investigators

• Sponsor: NHS Lothian
• Collaborators: University of Edinburgh

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2020
• Primary Completion (Actual): November 1, 2023
• Study Completion (Actual): November 1, 2023

Study Registration Dates

• First Submitted: March 3, 2020
• First Submitted That Met QC Criteria: September 10, 2020
• First Posted (Actual): September 16, 2020

Study Record Updates

• Last Update Posted (Actual): November 15, 2023
• Last Update Submitted That Met QC Criteria: November 14, 2023
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Renal Insufficiency; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Wounds and Injuries; Acute Kidney Injury
• Other Study ID Numbers: ss; MR/S01053X/1 (Other Grant/Funding Number: Medical Research Council)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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