About IgAN

Is it time to rethink treatment goals in IgAN?

Several factors should be considered when evaluating patients with IgAN, including^1,2:

• Proteinuria level

• eGFR level

• Hematuria

• MEST-C score

eGFR decline and persistent proteinuria can indicate IgAN progression³

Based on a retrospective study of patients with IgAN enrolled in the UK National Registry of Rare Kidney Diseases:

This retrospective cohort study analyzed data from the UK National Registry of Rare Kidney Diseases on 2439 patients with biopsy-proven IgAN, who met criteria for proteinuria >0.5 g/day or eGFR <60 mL/min/1.73 m². Patients were followed over time (median follow-up: ~5.9 years) to evaluate relationships between baseline and time-averaged proteinuria, eGFR slope, and kidney survival. Multiple patient subgroups (incident, prevalent, and trial-representative cohorts) were assessed to determine how proteinuria over time predicts long-term outcomes. eGFR decline was modeled using linear mixed-effects analyses, and kidney survival was evaluated using Kaplan-Meier and Cox regression methods. Generalizability outside the UK is uncertain.

This was a retrospective longitudinal cohort study using data from 655 adult members of Kaiser Permanente Southern California who were diagnosed with IgAN based on kidney biopsies performed between January 1, 2000 and December 31, 2021. Individuals were followed until the onset of ≥50% eGFR decline, kidney failure, death, disenrollment from the health plan, or the end of the study observation period. The primary end point was the composite of ≥50% eGFR decline, kidney failure, or mortality. At baseline, 70% of patients were on an ACEi or ARB, 0.2% of patients were on a GLP-1, and 0.3% of patients were on an SGLT2i. At baseline, patients had a mean eGFR of 59.9 mL/min/1.73 m² and mean UPCR 2.5 g/g. Cox proportional hazards regression modeling was used to estimate hazard ratios for the eGFR decline/kidney failure with adjustment for potential confounders.

*Median time to event: ~2.7 years.

2025 KDIGO Guidelines treatment goals for patients with IgAN at risk of progressive loss of kidney function include¹:

• Reducing the rate of kidney function loss

• Targeting a proteinuria level of <0.5 g/day, ideally <0.3 g/day (or equivalent)

KDIGO Guidelines recommend a personalized, targeted approach to IgAN due to its heterogeneous presentation and multiple underlying drivers¹

Rapidly declining eGFR and persistent proteinuria despite supportive care may signify the need for a different approach^1,5-7

Meet Fiona: a 34-year-old Asian female diagnosed with primary IgAN and signs of glomerular inflammation⁸

Nephrologist referral and kidney biopsy revealed⁹:

• eGFR (mL/min/1.73 m²): 70

• Proteinuria: 1.8 g/g

• BP (mm Hg): 140/90

• Hematuria +1 on dipstick*

• Evidence of complement activation*

• MEST-C score^†: M1, E1, S1, T0, C1

*Not part of the inclusion criteria for the APPLAUSE trial.^9
†MEST-C scoring helps assess disease severity and may inform clinical evaluation.¹⁰

Fiona is experiencing persistent proteinuria and declining eGFR after multiple treatments

These data are not derived from clinical trials and are for illustrative purposes only.