COVID-19 survivors and kidney disease: The long term effects on kidney function, and health outcomes for people with pre-existing chronic kidney disease - a study using electronic health records

Research question What is the long-term impact of COVID-19 on renal function, and on health outcomes among people with pre-existing chronic kidney disease (CKD)?

Background: COVID-19 hospitalisation is associated with acute kidney injury (AKI) but long-term effects on kidney function remain unknown.

Outside of COVID-19, AKI is a risk factor for CKD, with potential complications including increased mortality, cardiovascular disease, and end-stage renal disease (ESRD).

Given the volume of detailed digitised records, the UK is well placed to conduct studies to determine the long-term impact of COVID-19 including important and costly, but relatively rare, outcomes like ESRD.

Aims and objectives: To investigate the impact of COVID-19 on renal function by comparing those who survived with matched population controls, for risk of: 30% reduction in renal function ESRD Hospital admissions with AKI To investigate the impact of COVID-19 on people with baseline CKD, by comparing those who survived with matched population controls, for risk of: Death Hospitalisation ESRD Cardiovascular events Thromboembolic events Anaemia Increased frailty To develop a clinically-accessible, externally-validated risk prediction model for renal impairment and ESRD amongst COVID-19 survivors.

Methods: I aim to conduct this work in the OpenSAFELY platform if continued access is mandated.

If not, I will use linked primary and secondary care electronic records from the UK Clinical Practice Research Datalink (CPRD).

There will be two study cohorts: Study A: adults with confirmed/suspected COVID-19 matched 1:4 to controls by age, sex, and general practice Study B: adults with baseline CKD with confirmed/suspected COVID-19 matched 1:2 to controls by age, sex, and CKD stage After comparing the distribution of covariables between matched cohorts, using Cox regression, I will obtain adjusted hazard ratio estimates for outcomes (listed in objectives), with stratification by age, sex, ethnicity, CKD stage and diabetes.

I will perform a series of sensitivity analyses. I will replicate my analysis for Study B using a Swedish data source to assess for international generalisability.

Using the Study A cohort, I will develop routinely-applicable prognostic prediction models for 2-year risk of 30% reduction in renal function, and ESRD.

I will quantify predictive performance of these models using internal validation methods within CPRD, before external validation studies using data from an alternative UK data source, and from Sweden.

Timelines for delivery: 03/2021 - Obtain approvals for data access 03/2022 - PhD upgrading assessment 12/2022 - Publication 1: Impact of COVID-19 on renal function 04/2023 - Publication 2: COVID-19 outcomes in CKD in UK 11/2023 - Publication 3: Prognostic prediction model for decline in renal function 02/2024 - Publication 4: COVID-19 outcomes in CKD in Sweden 12/2024 - Thesis submission From 2022 onwards, I will deliver national/international presentations at conferences annually.

Anticipated impact and dissemination: Given the scale and international significance of the study, I aim to publish results in high-impact peer-reviewed scientific journals and disseminate my findings to policy makers, healthcare commissioners, and charities. I will meet with my patient and public advisory panel at regular intervals. .