A retrospective study of CKDu progression in Sri Lanka: analysis of kidney biopsies and association with risk factors

Background Chronic kidney disease of uncertain aetiology (CKDu) is a regionally prevalent tropical disease whose pathogenesis is still unclear. Although kidney biopsies can help to characterize the disease, it is unclear whether histological analysis can also be used to make a prognosis. Methods This retrospective study investigated kidney biopsy findings and progression factors in a 230 CKDu patients in Sri Lanka, with detailed follow-up of 62 participants for 4.2 ± 2.1 years. Results Participants were predominantly male farmers (93.3%), and 87.0% reported agrochemical exposure. Histology showed a wide range of tubulointerstitial injury. Most specimens exhibited tubular atrophy (90.9%), interstitial fibrosis (75.2%), and glomerulosclerosis (92.1%) to varying degrees. Unsupervised hierarchical clustering of eight activity and chronicity variables identified three groups: (1) mild chronic changes with minimal inflammation, (2) pronounced inflammation with chronic changes, and (3) chronic changes with low grade inflammation. Estimated glomerular filtration rate correlated negatively with seven histologic parameters. Baseline eGFR was significantly higher in cluster 1 than in clusters 2 and 3. In the follow up cohort, tubulitis and glomerulosclerosis were associated with faster eGFR decline and predicted progression. Progression was not explained by differences in reported risk exposures. Conclusion This large-scale biopsy study revealed that patients with CKDu could be categorised into three subgroups based on their histological changes, with significantly different eGFR values observed between these subgroups. Tubulitis was associated with faster decline in kidney function in the follow-up subcohort. Further research is needed to determine whether the identified clusters represent different stages of the disease or different progression.