Kidney Recovery After Acute Kidney Injury - Longitudinal Study

Study Overview
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Brief Summary
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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
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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.

Official Title
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Kidney Recovery After Acute Kidney Injury - Longitudinal Study

Conditions
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Acute Kidney Injury, Chronic Kidney Diseases

Intervention / Treatment
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* Other: Blood and urine sampling


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Case<br>(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<br>* Retinal OCT is a novel, non-invasive method for cross-sectionally imaging the eye's retina and choroid<br>* Other names: retinal opticla coherence tomography;|
| Control<br>(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<br>* Retinal OCT is a novel, non-invasive method for cross-sectionally imaging the eye's retina and choroid<br>* Other names: retinal opticla coherence tomography;|

What is the study measuring?
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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 |