Kidney Recovery After Acute Kidney Injury - Longitudinal Study

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.

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:

• 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

Exclusion criteria

• Inability to provide informed consent
• Prisoners
• Pregnancy or breast feeding
• Evidence of CKD