ARID Main Study
Research type
Research Study
Full title
DEFINING THE LONG TERM CONSEQUENCES OF ACUTE KIDNEY INJURY: THE AKI RISK IN DERBY (ARID) STUDY
IRAS ID
115656
Contact name
Nick Selby
Contact email
Sponsor organisation
University Hospitals of Derby and Burton NHS Foundation Trust
Research summary
Sumary of results
The AKI Risk in Derby (ARID) study was a prospective matched parallel-group cohort study designed to investigate the long-term consequences of acute kidney injury (AKI). Participants were recruited from Royal Derby Hospital between 2013 and 2016. Individuals who experi-enced AKI during a non-elective hospital admission were matched 1:1 with hospitalised con-trols without AKI according to age, diabetes status, and baseline kidney function. The primary objective was to determine the association between AKI and long-term adverse renal and cardiovascular outcomes. Secondary objectives included investigation of biomarker profiles associated with post-AKI recovery, chronic kidney disease (CKD) progression, frailty, and mortality. A total of 1,125 participants were recruited, with 866 successfully matched participants included in the principal analyses. Conduct of the Study The study was conducted in accordance with Good Clinical Practice and applicable UK regula-tory requirements. Participants underwent longitudinal follow-up including assessment of kidney function, cardiovascular outcomes, hospitalisation, and mortality. Blood and urine samples were collected for biomarker analyses. Recruitment and follow-up were completed as planned. No major safety concerns or significant breaches requiring regulatory escalation occurred during the study. Main Findings The principal findings demonstrated that AKI is associated with significantly increased long-term risks of mortality, CKD progression, heart failure, and cardiovascular events compared with matched hospitalised controls without AKI. These findings were independent of baseline kidney function and comorbidity burden. The primary outcomes were published in Kidney International, demonstrating that AKI survivors had substantially worse long-term renal and cardiovascular outcomes over follow-up compared with matched controls. Subsequent biomarker analyses arising from ARID identified important associations between post-AKI biomarker profiles and future adverse outcomes. In particular, soluble tumour necro-sis factor receptor-1 (sTNFR1), soluble tumour necrosis factor receptor-2 (sTNFR2), and cystatin C measured during recovery from AKI were associated with subsequent CKD progression, heart failure, and mortality risk. These studies supported the potential role of biomarker-based risk stratification following AKI. Additional analyses evaluating cystatin C and creatinine-derived estimated glomerular filtration rate (eGFR) demonstrated that cystatin C-based eGFR identified substantially more participants with impaired kidney function after AKI compared with creatinine-based assessment alone. The discrepancy between creatinine- and cystatin C-derived kidney function estimates, expressed as the creatinine muscle index (CMI), was independently associated with long-term mortality risk, suggesting a relationship between post-AKI frailty/sarcopenia and adverse outcomes. Publications and Dissemination Key publications arising from the study include: • https://www.kidney-international.org/article/S0085-2538(23)00564-1/fulltext • https://www.ajkd.org/article/S0272-6386(22)00871-X/abstract • https://www.ajkd.org/article/S0272-6386(21)00891-X/abstract • Findings have also been disseminated through national and international nephrology conferences and academic collaborations. Conclusion The ARID study has provided important evidence demonstrating that AKI is associated with substantial long-term adverse renal and cardiovascular consequences. The study has also con-tributed to improved understanding of biomarker-based risk stratification and the limitations of creatinine-based kidney function assessment following AKI. Follow-on research that arises from this is now underway to determine improved post-AKI follow-up and management, and how best to assess kidney function and recovery.REC name
East Midlands - Derby Research Ethics Committee
REC reference
12/EM/0441
Date of REC Opinion
21 Dec 2012
REC opinion
Further Information Favourable Opinion