Abstract
Abstract Background and Aims IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide. The clinical course is heterogeneous. As such, determining which patients to treat with immunosuppression (IS) is often the key decision in management. Here, we present a 20-year retrospective study from a single centre with the following aims: to describe the epidemiology of our cohort, to assess outcomes (such as progression to end-stage kidney disease [ESKD] requiring renal replacement therapy [RRT] and mortality), and to determine the effect of IS. Method We collected all cases of IgAN from our biopsy database between January 2000 and December 2019. After exclusion, the total number for analysis was 401 patients. We collected demographic data for each patient, along with creatinine and proteinuria values over time, MEST-C histological scores, progression to ESKD, mortality, use of renin-angiotensin system blockade (RAS) blockade and IS treatment. CKD progression in the overall cohort was computed using the rate of change of estimated glomerular filtration rate [eGFR] (delta eGFR) from baseline to study end point, with the linear regression slope generated using all available eGFR measurements. Similarly, the rate of change of urine protein creatinine ratio [uPCR] (delta uPCR) from baseline to study endpoint was calculated using linear regression from serial uPCR measurements. Results Median age of the cohort was 45.0 years, with 69.6% male and 87.5% were Caucasian. Baseline laboratory values (median) included: creatinine 142µmol/L, eGFR 46.7ml/min/1.73 m2, uPCR 183mg/mmol. The median rate of decline of eGFR was -1.31ml/min/1.73 m2/yr and median change in uPCR was -4.46mg/mmol/yr. RAS blockade was used in 79.6% and IS in 20.4%. Progression to ESKD requiring RRT was seen in 29.7% and mortality in 19.7%. Median follow up duration was 51 months. Cox regression analysis revealed several factors associated with mortality, including increasing age, non-Caucasian ethnicity, diabetes, hypertension, cardiovascular disease, systolic blood pressure, creatinine, uPCR, ACEi/ARB use, and E and T score on biopsy. Several factors were associated with need for RRT including hypertension, various histological markers, creatinine, uPCR and ACEi/ ARB use. IS was not found to be a factor associated with all-cause mortality or RRT. Those treated with IS (table 1) had a higher uPCR (301.5mg/mol vs 141mg/mmol, p<0.001), were more likely to have a C score (37.7% vs 10.8%, p <0.001) or total MEST score >2 (42% vs 29.1%, p = 0.041). They showed greater reduction in proteinuria over time (−16.8mg/mmol/year vs −2.64mg/mmol/year, p = 0.003), but no difference in eGFR decline (−1.18 vs −1.32ml/min/1.7 3m2/yr, p = 0.703). Conclusion This is one of the largest retrospective observational studies assessing clinical and histological characteristics, along with outcomes, for IgAN. This provides important real-world data which will be useful for clinicians, particularly as the IgAN landscape changes with the introduction of novel therapies. Whilst IS was associated with a greater proteinuria reduction over time, this did not translate into an amelioration of eGFR decline. The study received grant support from CSL Vifor.
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