Study of clinical and histopathological factors predicting rapid progression in biopsy-proven type 2 diabetic kidney disease

Introduction: Rapid progression of diabetic kidney disease (DKD) is a significant concern, particularly in developing countries. It remains uncertain whether histopathological parameters, in addition to clinical factors, can predict DKD progression. Objectives: To evaluate renal histopathological and clinical parameters in predicting rapid progression to end-stage kidney disease (ESKD) in type 2 diabetes mellitus (Type 2 DM) patients with biopsy-proven DKD. Patients and Methods: This was an observational retrospective study that included 49 biopsy-proven DKD from January 2018 to December 2022. Those with less than six months of follow-up and CKD stage 5 were excluded. The outcomes studied were rapid progression and progression to ESKD. Patients were categorized into rapid progressors and non-progressors based on the estimated glomerular filtration (eGFR) decline of > or <10 mL/min/1.73 m2 /year, respectively. The association of histopathological factors and clinical parameters with rapid progression and independent risk factors for progression to ESKD were analysed using SPSS 22. Results: In a median follow-up of 1.6 years, 57% were rapid progressors, and 42.9% were non-progressors, with a median eGFR decline of 21 mL/min/1.73 m2 /year and 5 mL/min/1.73 m2 /year, respectively. Among histopathological factors, global glomerular sclerosis (class 4) predicted rapid progression (P= 0.03), since among clinical factors, hypertension (89.3%) elevated hemoglobin A1c (HbA1c) (9.6%), and massive proteinuria (75.1%) were significant parameters associated with rapid progression (P<0.05). In Cox regression analysis, the progression to ESKD was independently associated with global glomerular sclerosis (HR 1.1, CI 1.0-1.4, P=0.04) and massive proteinuria (HR 1.6, CI 1.0-2.1, P=0.01) Conclusion: In our cohort, hypertension, high HbA1c, severe proteinuria, and global glomerular sclerosis (Class 4) were associated with rapid progression. Severe proteinuria and global glomerular sclerosis were independent risk factors for progression to ESKD. This highlights the need for large prospective studies in identifying the factors predicting rapid progressors in DKD; therefore, timely intervention can be considered.