HEROIC: a 5-year observational cohort study aimed at identifying novel factors that drive diabetic kidney disease: rationale and study protocol

Abstract

Introduction: Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease worldwide and a major cause of premature mortality in diabetes mellitus (DM). While improvements in care have reduced the incidence of kidney disease among those with DM, the increasing prevalence of DM means that the number of patients worldwide with DKD is increasing. Improved understanding of the biology of DKD and identification of novel therapeutic targets may lead to new treatments. A major challenge to progress has been the heterogeneity of the DKD phenotype and renal progression. To investigate the heterogeneity of DKD we have set up The East and North London Diabetes Cohort (HEROIC) Study, a secondary care-based, multiethnic observational study of patients with biopsy-proven DKD. Our primary objective is to identify histological features of DKD associated with kidney endpoints in a cohort of patients diagnosed with type 1 and type 2 DM, proteinuria and kidney impairment.

Methods and analysis: HEROIC is a longitudinal observational study that aims to recruit 500 patients with DKD at high-risk of renal and cardiovascular events. Demographic, clinical and laboratory data will be collected and assessed annually for 5 years. Renal biopsy tissue will be collected and archived at recruitment. Blood and urine samples will be collected at baseline and during annual follow-up visits. Measured glomerular filtration rate (GFR), echocardiography, retinal optical coherence tomography angiography and kidney and cardiac MRI will be performed at baseline and twice more during follow-up. The study is 90% powered to detect an association between key histological and imaging parameters and a composite of death, renal replacement therapy or a 30% decline in estimated GFR.

Ethics and dissemination: Ethical approval has been obtained from the Bloomsbury Research Ethics Committee (REC 18-LO-1921). Any patient identifiable data will be stored on a password-protected National Health Services N3 network with full audit trail. Anonymised imaging data will be stored in a ISO27001-certificated data warehouse.Results will be reported through peer-reviewed manuscripts and conferences and disseminated to participants, patients and the public using web-based and social media engagement tools as well as through public events.

Keywords: cohort study; diabetic Kidney disease; histopathology; magnetic resonance imaging.

Figure 1

White/non-white population (Asian, black, mixed race and other) of London (left) and deaths due to diabetes (SMR; right, based on 2833 male deaths due to diabetes based on data from the office for national statistics). Camden (C); City and Hackney (H); Enfield (E); Haringey (R); Islington (I); Newham (N) and Tower Hamlets (T). Images reproduced from: http://www.theguardian.com/graphic/0,5812,1395103,00.html and https://www.ucl.ac.uk/ineqcities/atlas/cities/london/disease-specific-mortality/diabetes-mellitus. SMR, standardised mortality ratio.

Figure 2

Flow chart of study design that consists of referral, screening and consent of patients with moderate or high risk of renal progression (defined as those with heavy proteinuria uACR >30 mg/mmol, and/or a ≥5 mL/year decline in eGFR calculated across at least three measurements across ≥6 months prior to study enrolment). Screening and enrolment of patients with moderate or high-risk DKD confirmed on renal biopsy. Participants will be followed up annually for up to 5 years. ACR, albumin to creatinine ratio; CKD, chronic kidney disease; DKD, diabetic kidney disease; eGFR, estimated glomerular filtration rate; HEROIC, The East and North London Diabetes Cohort; uACR, urinary ACR.