Title: The impact of obesity on recovery from acute kidney injury: the Ob-AKI feasibility study
Funder: Health Education England

Abstract: A rapid deterioration in urine output or kidney filtration rate is defined as acute kidney injury (AKI), and it occurs in over 5% of hospital admission in the UK. AKI is associated with high in-hospital mortality and an increased mortality rate in AKI survivors. Furthermore, emerging data indicates that AKI increases the risk for developing chronic kidney disease (CKD), resulting in an irreversible, and often progressive decline in kidney function.There is a tremendous research effort focusing on interventions to stop or slow progression of CKD, not least due to the high costs of renal replacement therapy and the reduced quality of life in those with kidney failure. Yet there remains a gap in the evidence surrounding our understanding of the long-term effects of AKI, particularly the risk factors for developing CKD. Obesity is both a risk factor for developing AKI in hospitalised patients, and for the development and progression of CKD, even after accounting for diabetes and hypertension. Yet, the effect of obesity on the risk for developing CKD after an episode of AKI has not been studied. As obesity is associated with both an increased risk, and greater severity of AKI, it is predicted that obesity may slow the rate of recovery from AKI. Additionally, it is hypothesised that AKI in obese patients may increase the risk of development of CKD in the longer term. The proposed research will begin to address this gap in the evidence through a feasibility study to explore the relationship between obesity (and associated cardiovascular disease risk factors:- metabolic syndrome, diabetes and hypertension), the degree of recovery of AKI, and the likelihood of future development of CKD. The feasibility study will focus on demonstrating the capacity for recruitment and retention of hospitalised patients with an identified episode of AKI, and determining the degree of recovery from AKI and progression to CKD in obese and non-obese participants with AKI, to inform the development of a future nested case-control study. 100 patients will be identified by an electronic alert system for AKI during their hospital admission, and recruited and consented whilst an inpatient with AKI or just after discharge. Baseline data collection including measured height, weight, waist circumference, blood pressure, baseline kidney function, blood and urine samples, AKI staging and reason for hospitalisation, co-morbidities and dietary assessment (interview and questionnaire) will occur within 4 weeks. Follow up data collection of blood pressure, blood and urine samples will occur at hospital study visits 3, 6, and 12 months after the episode of AKI. Rates of recruitment, retention and completion of data collection will be described. The prevalence of AKI in obese and non-obese participants will be defined. The incidence of CKD or CKD progression after AKI in obese and non-obese participants will be described and the effect size calculated, to inform the future planned nested case-control study. One of the major outputs of the training award will be to generate grant income to fund the future, longer-term, observational study, once feasibility has been established. Potentially, patients will benefit within 5 years from optimal placement of weight loss interventions immediately post AKI, to prevent progression to CKD if an association between obesity and progression of AKI to CKD is identified. We are optimally placed to extend this research to identify the patient benefit as we have an established structured, multidisciplinary renal weight management programme in place and lead the London Renal Obesity Network. Our team is in a position to deliver a clinical intervention study targeting the period immediately post AKI in obese patients, to determine if progression to CKD decreases.

Lay abstract: One in every 20 people hospitalised experience acute kidney injury (AKI) when the kidneys stop working. Recovery from the more common mild-to-moderate forms of AKI was previously thought to have no long-term effects. Newer research shows that people who have AKI are more likely to develop permanent kidney damage, or chronic kidney disease (CKD). Obesity increases the risk for AKI, but it's not known if obesity changes the risk for future CKD. The relationship between obesity, recovery from AKI, and later, CKD will be studied in 100 participants over 1 year to determine if a larger study is possible.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: RENAL AND UROGENITAL