Persistent Disease Activity in Patients With Long-Standing Glomerular Disease

Abstract

Introduction: Glomerular diseases are characterized by variable disease activity over many years. We aimed to analyze the relationship between clinical disease activity and duration of glomerular disease.

Methods: Disease activity in adults with chronic minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and IgA nephropathy (IgAN; first diagnostic biopsy >5 years before enrollment; Of Longstanding Disease [OLD] cohort, n = 256) followed at Columbia University Medical Center (CUMC), was compared with disease activity of an internal and external cohort of patients with first diagnostic biopsy <5 years before enrollment drawn from the Cure Glomerulonephropathy Network (CureGN cohort, n = 1182; CUMC-CureGN cohort, n = 362). Disease activity was defined by (i) Kidney Disease: Improving Global Outcomes-recommended threshold criteria for initiation of immunosuppression in primary glomerulonephropathy (GN) and (ii) CureGN's Disease Activity Working Group definitions for activity.

Results: No significant differences were detected among the 3 cohorts in terms of age, sex, serum creatinine, and urinary protein-to-creatinine ratio. For each GN subtype, disease activity in the OLD cohort was comparable with disease activity in the entire CureGN and the CUMC-CureGN cohort. When limiting our comparisons to disease activity in incident CUMC-CureGN patients (first diagnostic biopsy within 6 months of enrollment), OLD patients demonstrated similar activity rates as incident patients.

Conclusion: Disease activity did not differ among patients with shorter versus longer duration of disease. Such survivor patients, with long-term but persistent disease, are potentially highly informative for understanding the clinical course and pathogenesis of GN and may help identify factors mediating more chronic subtypes of disease.

Keywords: IgA nephropathy; focal segmental glomerulosclerosis; glomerular disease; glomerulonephropathy; membranous nephropathy; minimal change disease.

Graphical abstract

Figure 1

Treatment thresholds across disease groups. Treatment threshold cutoff for IgA nephropathy (IgAN) was urinary protein-to-creatinine ratio (UPCR) >1 g/g or 24-hour urine protein >1 g, despite optimal conservative therapy. Treatment threshold cutoff for minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and membranous nephropathy (MN) was UPCR >3.5 g/g or 24-hour urine protein >3.5 g/d (or serum albumin <3.0 g/dl if proteinuria was not available), despite conservative therapy. CUMC, Columbia University Medical Center; CureGN, Cure Glomerulonephropathy Network; KDIGO, Kidney Disease: Improving Global Outcomes; OLD, of longstanding disease.

Figure 2

Disease activity at enrollment/screening according to Cure Glomerulonephropathy Network (CureGN) disease activity criteria. CUMC, Columbia University Medical Center; FSGS, focal segmental glomerulosclerosis; IgAN, IgA nephropathy; MCD, minimal change disease; MN, membranous nephropathy; OLD, of longstanding disease.

Figure 3

Proportions of patients who underwent an additional kidney biopsy across disease groups. CUMC, Columbia University Medical Center; CureGN, Cure Glomerulonephropathy Network; FSGS, focal segmental glomerulosclerosis; IgAN, IgA nephropathy; MCD, minimal change disease; MN, membranous nephropathy; OLD, of longstanding disease.

Figure 4

Serum creatinine over time in of longstanding disease (OLD) and Columbia University Medical Center (CUMC)–Cure Glomerulonephropathy Network (CureGN) cohorts. ^aPoint 0 marks enrollment/screening.