Histological and clinical phenotypes of diabetic kidney disease: a baseline analysis of the HEROIC study

Diabetic kidney disease (DKD) is increasingly recognized as a heterogeneous condition. Our understanding of the structure-function relationships underpinning DKD is limited. The East and North London Diabetes Cohort (HEROIC) study aims to identify prognostic markers in a diverse DKD cohort. We present here the baseline clinical phenotype of the cohort, define clusters of DKD and assess the performance of estimated GFR (eGFR) equations including CKD Epi 2021.

Patients with diabetes and CKD were recruited from two tertiary renal units. Renal biopsies were assessed using the Renal Pathology Society scoring system. Ordinal logistic regression was used to assess clinical associations with histological severity and ensemble consensus clustering was used to identify distinct phenotypes. eGFR bias was calculated as measured GFR-eGFR.

In our cohort of 188 DKD patients (9.0% Black, 46.3% South Asian, 14.9% White, and 29.8% other ethnicity), there was an inverse relationship between BMI and glomerular lesion severity (OR 0.93, P = .008), which persists when restricted to type 2 diabetes patients. Ensemble consensus clustering identified five clusters with moderate separation including a phenotype with high rates of vascular disease, a phenotype with advanced DKD and low BMI, and one with a short duration of diabetes and milder glomerular lesions. CKD Epi 2021 overestimated eGFR in South Asian individuals whilst underestimation of eGFR was noted in Black individuals.

We demonstrate clinically distinct clusters of DKD, which may provide hypotheses for 'personalized' approaches to interventions in DKD in future trials. We demonstrate that CKD-Epi 2021 performs poorly in a multi-ethnic DKD population.