Kidney Recovery After Acute Kidney Injury - Longitudinal Study

NCT ID: NCT04551391

Last Updated: 2023-11-15

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-01-07
• Study Completion Date: 2023-11-01

Brief Summary

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.

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.

Conditions

Acute Kidney Injury; Chronic Kidney Diseases

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

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

Blood and urine sampling

Intervention Type: OTHER

Retinal OCT is a novel, non-invasive method for cross-sectionally imaging the eye's retina and choroid

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:

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

Blood and urine sampling

Intervention Type: OTHER

Retinal OCT is a novel, non-invasive method for cross-sectionally imaging the eye's retina and choroid

Interventions

Blood and urine sampling

Retinal OCT is a novel, non-invasive method for cross-sectionally imaging the eye's retina and choroid

Intervention Type: OTHER

Other Intervention Names

retinal opticla coherence tomography

Eligibility Criteria

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

(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

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Edinburgh

OTHER

Sponsor Role: collaborator

NHS Lothian

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

NHS Lothian

Edinburgh, , United Kingdom

Countries

United Kingdom

Other Identifiers

MR/S01053X/1

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

ss

Identifier Type: -

Identifier Source: org_study_id