Clinical Presentation, Pathological Spectrum, and Outcomes of Alcoholic Cirrhosis-Related Immunoglobulin A Nephropathy

Abstract

Introduction: Immunoglobulin A nephropathy (IgAN) associated with cirrhosis is frequent but often overlooked because it is largely considered silent. Until now, little has been known about their presentation and outcomes.

Methods: We conducted a retrospective multicenter study on patients with kidney biopsy-proven cirrhosis-related IgAN (cirrhosis-IgAN), diagnosed between 2009 and 2022. We mixed them up with 83 primary IgAN (pIgAN) diagnosed during the same period, using a partitioning clustering approach, to determine common clinicopathological profiles.

Results: All the 46 patients with cirrhosis-IgAN had an excessive alcoholic consumption. Clinical presentation was severe with acute kidney injury (AKI) in 79%; alternative causes of AKI was found in 62% of cases. Three clinicopathological clusters were identified as follows: the first one represented chronic involvement, the second one could be assimilated to mild disease, and the third one corresponded to a membranoproliferative glomerulonephritis (MPGN) pattern and was associated with heavy proteinuria and intrinsic AKI (without alternative causes). Whereas the first 2 clusters were equally distributed between pIgAN and cirrhosis-IgAN, the third was more frequent in patients with cirrhosis. The cumulative mortality rate in cirrhosis-IgAN was 26% and 46% at 1-year and 3-years, respectively. Steroid exposure and moderate or severe AKI were associated with higher mortality and steroid exposure was associated with the occurrence of severe infection.

Conclusion: Our results suggest that high AKI incidence is related to extrinsic causes in most cases but can also be driven by IgA-dominant MPGN in a subset of patients. Steroid use was associated with infectious disease and mortality. Further studies are needed to clarify the role of immunosuppressive treatment in cirrhosis-IgAN patients.

Keywords: IgA nephropathy; cirrhosis; liver disease.

Graphical abstract

Figure 1

Distribution of the histological variables according to the Oxford classification for cirrhosis-related IgAN and primary IgAN. Kidney biopsy samples with <8 glomeruli were excluded from the analysis. C score, crescent; E score, endocapillary hypercellularity; IgAN, IgA nephropathy; M score, mesangial hypercellularity; S score, segmental glomerulosclerosis; T score tubular atrophy.

Figure 2

Unsupervised analysis of IgAN (primary IgAN and Cirrhosis-IgAN). (a) Partitional clustering using a k-mean algorithm (k = 3) on our 46 cases of cirrhosis-related IgAN mix-up with 83 biopsy-proved primary IgAN nephropathy diagnosed in the same period. The variables included in the analysis were qualitative variables: mesangial hypercellularity (M1), endocapillary hypercellularity (E1), focal segmental glomerulosclerosis (S1), crescent, interstitial fibrosis >25% (T), interstitial infiltrate, presence of ischemic glomeruli, arteriolar hyalinosis (ah), fibro-intimal thickening (FI_thick), thrombotic microangiopathy (TMA), double contour, acute tubular necrosis (ATN), IgA parietal deposit (parietal) and intrinsic AKI occurrence (without confounding factor); along with clinical quantitative variable: uPCR and preexisting eGFR. (b) Visualization of the K-means center values for the 3 identified clusters across the variables, enabling to annotate them as chronic involvement (cluster 1), mild disease (cluster 2), and MPGN-like pattern (cluster 3) respectively. (c) Frequency of each cluster within the primary IgAN and cirrhosis-related IgAN. (d) Frequency of each cluster in cirrhosis-related IgAN according to the history of decompensated cirrhosis or not. IgAN, IgA nephropathy; MPGN, membranoproliferative glomerulonephritis; uPCR, urinary protein-to-creatinine ratio.

Figure 3

Kaplan-Meier curves of survival (a) and severe infection-free (b) according to the cluster group, steroid use, moderate to severe AKI (ICA stage 2 or 3), history of decompensated cirrhosis or not. The x-axis represents time in days. ICA, International Club of Ascites.