Primary Glomerular Diseases in the Elderly: Clinical Features, Treatment Patterns, and Outcomes in the CureGN Cohort.

Abstract

Key points: Elderly onset primary glomerular diseases are characterized by decreased GFR and a higher comorbidity burden compared with younger adult subgroups. Histologic features of nephrosclerosis become more prevalent with advancing age. Excess morbidity, mortality and, possibly, underlying biologic differences, shape outcomes in elderly onset primary glomerular diseases.

Background: Primary glomerular diseases (PGDs) are not uncommon in elderly patients, where age-related histologic changes, frailty, and multimorbidity overlap with disease-specific drivers of damage. Evidence on the impact of older age at onset on PGD presentation and outcomes remains heterogeneous. This retrospective multicenter study assessed the impact of older age at diagnosis on the clinical-histologic presentation, treatment, and outcome of PGDs.

Methods: Adults with biopsy-proven minimal change disease, FSGS, membranous nephropathy, and IgA nephropathy/vasculitis with nephritis enrolled in Cure Glomerulonephropathy between 2014 and 2023 with available kidney function data were stratified by age at diagnosis into three age groups: young adults (18-39 years), middle-aged adults (40-64 years), and elderly patients (≥65 years). Clinical-histologic features and treatment patterns were compared across age groups, with a focus on elderly patients. Evaluated outcomes included all-cause mortality and a composite kidney outcome (>40% eGFR decline or kidney failure). Cox regression and Fine-Gray models were fitted to evaluate the impact of age on the composite kidney outcome.

Results: Among 1562 adults, 211 were aged ≥65 years at diagnosis. Elderly patients exhibited a higher comorbidity burden and lower eGFR at enrollment (55 [34-75] versus 84 [50-115] in young adults and 65 [43-91] ml/min in middle-aged adults, P < 0.001). In 704 biopsies with an available Cure Glomerulopathy Pathology Classification, nephrosclerosis features-particularly arteriosclerosis-increased with advancing age, whereas disease-specific features were similar across age groups. Elderly patients more often received conservative or steroid-sparing regimens. A 5-year excess mortality of 7%-14% compared with young adults was observed in the elderly patients. In adjusted models, older age was independently protective for the composite kidney outcome (subdistribution hazard ratios 0.65-0.79).

Conclusions: Aging adds comorbidity and histologic chronicity without altering PGDs phenotype; excess mortality and, possibly, underlying biologic differences shape outcomes in elderly onset PGDs.