Lifetime progression of IgA nephropathy: a retrospective cohort study with extended long-term follow-up

Abstract

Background: IgA nephropathy (IgAN) exhibits an unpredictable trajectory, creating difficulties in prognostication, monitoring, treatment, and research planning. This study provides a comprehensive depiction of the progression of kidney function throughout the disease course, from diagnosis to a span of 36 years post-diagnosis.

Methods: We utilized a cohort of 400 Norwegian IgAN patients, from diagnosis to the occurrence of death, initiation of kidney replacement therapy (KRT), or the latest follow-up. Recorded proteinuria (n = 2676) and creatinine (n = 8738) measurements were retrieved. Patients were divided into subgroups based on their specific estimated glomerular filtration rate (eGFR) slopes.

Results: Median follow-up was 16 years. During this period, 34% of patients either died or initiated KRT. Among patients who reached endpoint, the median duration from diagnosis to the initiation of KRT or death was 8 years. Notably, 34% of the cohort exhibited a stable disease course, characterized by an eGFR decline of less than 20% between two consecutive measurements. Differences in subsequent disease trajectories among two subgroups with similar eGFR levels at diagnosis could not be accounted for by variations in treatment strategies. Among patients with proteinuria < 1 g/24 h in less than half of the measurements, KRT was five times more prevalent compared to those with more than half of the measurements recording proteinuria < 1 g/24 h (p-value = 0.001).

Conclusions: While a significant proportion of IgAN patients reach kidney failure within their lifetimes, outcomes vary widely. Clinical data at diagnosis offer limited insights into long-term risks. Enhanced risk stratification necessitates data collection at multiple time points.

Keywords: Chronic renal failure; ESKD; Glomerulonephritis; IgA nephropathy; Proteinuria.

Fig. 1

The IgAN disease course. Alluvial diagram describing the disease course for the patients in this cohort, stratified by age and CKD stage at diagnosis, type of disease course and whether they needed kidney replacement therapy. The colors represent CKD stage at diagnosis (G1 = mint, G2 = orange, G3a = purple, G3b = pink, G4 = green, G5 = yellow, unknown = grey). CKD = Chronic kidney disease. RAAS = Renin–angiotensin–aldosterone system

Fig. 2

eGFR throughout the IgAN disease course. A Correlation matrix. Crossed out values reveal correlations that are not statistically significant. B Visual representation of the kidney function throughout the IgAN disease course based on average yearly change in eGFR between first and last measurement. We have divided the patient’s disease courses in seven subgroups based on the average eGFR slopes. The eGFR in each measurement is represented on the x-axis, and the y-axis represents years after diagnostic kidney biopsy. The dark green lines represent a linear model with 95% confidence interval per subgroup. Patients with a light green eGFR slope did not need kidney replacement therapy at the end of follow-up, while those with an orange eGFR slope initiated kidney replacement therapy after the last measurement. C Visual representation of the kidney function throughout the IgAN disease course. The eGFR in each measurement is represented on the x-axis, and the y-axis represents years after diagnostic kidney biopsy. The two main groups of the cohort, patients with a stable (n = 134) or an unstable (n = 261) disease course, have been further divided into several subgroups, based on the patient´s eGFR at the time of diagnosis (Normal: ≥ 90 mL/min/1.73 m²; Mildly decreased: 60–89 mL/min/1.73 m²; Moderately/severely decreased: < 60 mL/min/1.73 m²). Red lines indicate the eGFR slopes of patients who did not need kidney replacement therapy at the end of the follow-up period. Blue lines indicate the eGFR slopes of those who initiated kidney replacement therapy during follow-up, with the last eGFR measurement being the last one before initiation of dialysis or kidney transplantation. The black line in each graph represents eGFR = 15 mL/min/1.73 m². CKD = Chronic kidney disease. eGFR = Estimated glomerular filtration rate. BP = Blood pressure

Fig. 3

Proteinuria throughout the IgAN disease course. A Mean proteinuria (g/24) during follow-up. Orange points equal outliers. Dashed line symbolizes base mean (1.2 g/24 h). ns = Not significant. * = p-value (0.01, 0.05]. ** = p-value (0.001, 0.01]. **** = p-value < 0.001. B Kaplan–Meier plot describing the differences in time from diagnosis until initiation of kidney replacement therapy based on mean proteinuria (g/24 h) during follow-up. Censored cases are marked with a cross. C Kaplan–Meier plot describing the differences in time from diagnosis until initiation of kidney replacement therapy based on the proportion measurements with proteinuria < 1 g/24 h. Censored cases are marked with a cross. KRT = Kidney replacement therapy