Open Collections

Abstract

Patients with Glomerulonephritis (GN) may be at increased risk of developing de novo malignancies due to a combination of chronic immune system activation, tissue inflammation, immunosuppression use and as a consequence of the progression to end stage kidney disease (ESKD). However, there are limited epidemiologic data to accurately quantify cancer risk in GN and to determine the contributions of traditional and GN-specific risk factors including estimated glomerular filtration rate (eGFR), proteinuria and immunosuppressive therapies. This thesis intends to bridge these gaps. Chapter 1 introduces GN, its background, epidemiology, and the hypothesized relationship with cancer. Chapter 2 presents a narrative review summarizing existing observational studies and highlighting their limitations and methodological challenges. In Chapter 3, we assembled one of the largest cohorts of biopsy-proven GN patients by linking provincial GN registry with the Cancer Registry and other administrative databases spanning twenty years to conduct robust investigation of cancer risk and its associated factors in patients with GN. We showed that patients with GN have a substantially increased risk of cancer compared to the general population. This excessive risk was mostly observed for lymphoma, colorectal, kidney, and lung cancers, and was present both before and after the onset of ESKD, particularly among patients younger than 40 years. In Chapters 4 and 5, we found that cancer risk accumulates gradually with ongoing kidney dysfunction rather than being triggered solely by the onset of ESKD. To study the effect of immunosuppression on cancer risk in patients with GN, we used a data-driven approach to identify the most etiologically relevant exposure metrics for each immunosuppressive agent in relation to cancer risk. High cumulative exposure over years to immunosuppressive therapies, including antimetabolites, corticosteroids, and cyclophosphamide, was associated with increased cancer risk. The dosing thresholds linked to increased risk could be readily reached with conventional treatment protocols. Findings of this thesis highlight that while immunosuppression remains central to GN management, treatment decisions should involve shared decision-making, with a preference for low-dose agents that are not associated with increased cancer risk when possible, and careful reassessment as cumulative doses approach identified thresholds.