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

NHS Lothian

Status: Completed

Conditions: Chronic Kidney Diseases; Acute Kidney Injury

Treatments: Other: Blood and urine sampling

Study type: Observational

Funder types: Other

Identifiers

NCT04551391

MR/S01053X/1 (Other Grant/Funding Number)

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Details and patient eligibility

About

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.

Full 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.

Enrollment: 100 patients

Sex: All

Ages: 16+ years old

Volunteers: No Healthy Volunteers

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

Trial design

100 participants in 2 patient groups

Case

Description:

(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

Treatment:

Other: Blood and urine sampling

Control

Description:

(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

Treatment:

Other: Blood and urine sampling