---
title: "Liver–kidney crosstalk in primary biliary cholangitis: article summary and missing details"
id: "frontiers-in-immunology-15-liver-kidney-crosstalk-in-primary-biliary-cholangitis-insights-into-the"
canonical_url: "https://medichelpline.com/clinical-feed/frontiers-in-immunology-15-liver-kidney-crosstalk-in-primary-biliary-cholangitis-insights-into-the"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "Frontiers in Immunology"
source_url: "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1845113"
published_at: "2026-07-30T00:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Liver–kidney crosstalk in primary biliary cholangitis: article summary and missing details
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/frontiers-in-immunology-15-liver-kidney-crosstalk-in-primary-biliary-cholangitis-insights-into-the
- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** Frontiers in Immunology
- **Source URL:** [Original Journal Publication](https://www.frontiersin.org/articles/10.3389/fimmu.2026.1845113)
- **Published At:** 2026-07-30T00:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- The provided source page is from **Frontiers in Immunology** and cites an article titled “Liver–kidney crosstalk in primary biliary cholangitis: insights into the mechanisms of renal involvement.” - The accessible content on the source URL is navigation, journal sections, and site information; the body text of the article and its scientific details were not included in the provided source. - No study methods, results, mechanistic data, patient characteristics, biomarkers, histology, experimental models, or clinical recommendations were reported in the supplied content. - Because the primary article text is missing from the source, no factual claims about specific **mechanisms**, pathways, or prevalence of renal involvement in **primary biliary cholangitis** can be extracted or summarized. - The source does identify the journal and likely subject area (autoimmune and inflammatory disorders within immunology), but it does not include authorship, abstract, figures, tables, or references. - Readers seeking clinically relevant details—such as proposed mechanisms of **liver–kidney crosstalk**, diagnostic criteria for renal involvement, or implications for management—will need to consult the full article; those elements were not reported in the provided material. - The summary below organizes expected sections and lists the types of data and analysis that are absent from the supplied source but would be essential for clinical interpretation and guideline translation.
## Clinical Analysis & Structured Key Points
Frontiers | Liver–kidney crosstalk in primary biliary cholangitis: insights into the mechanisms of renal involvement REVIEW article Front. Immunol. , 30 July 2026 Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1845113 Published in Frontiers in Immunology Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders 7 impact factor 11.3 citescore Part of a Research Topic Cholestatic Liver Diseases: From Bench to Bedside Submission open 1251 views 1 articles Editor & Reviewers Edited by M R Mario Romeo Reviewed by T A Theodoros Androutsakos B L Bin Liu Outline Figures and Tables Figure 1 View in article Table 1 Clinical features and treatment strategies in primary biliary cirrhosis patients with membranous nephropathy. View in article REVIEW article Front. Immunol. , 30 July 2026 Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1845113 Liver–kidney crosstalk in primary biliary cholangitis: insights into the mechanisms of renal involvement Z F Zhaoyang Fan 1,2 S J Siqi Jia 2 Y W Yi Wei 2 X F Xiaohong Fan 3 X L Xiangling Li 1 * L W Li Wang 2 * 1. Department of Nephrology, Affiliated Hospital of Shandong Second Medical University, School of Clinical Medicine, Shandong Second Medical University, Weifang, China 2. Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China 3. Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China See more Article metrics View details Abstract Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic liver disease primarily affecting the intrahepatic small bile ducts. Although PBC is mainly a hepatobiliary disease, renal abnormalities have been reported in a subset of patients and should be regarded as uncommon but clinically relevant extrahepatic manifestations. Reported glomerular lesions in patients with PBC include membranous nephropathy, immunoglobulin A nephropathy, crescentic glomerulonephritis, and minimal change disease, although most evidence is derived from case reports and small series. Tubulointerstitial involvement has also been described, most commonly as distal renal tubular acidosis in reported cases and less commonly as Fanconi syndrome; these conditions may reflect immune-mediated tubular dysfunction in selected patients. In addition, metabolic disturbances secondary to cholestasis and tubular injury may increase the risk of nephrolithiasis and nephrocalcinosis, whereas advanced cirrhosis can precipitate hepatorenal syndrome. Limited reports further suggest that cholestatic nephropathy and drug-related nephrotoxicity may contribute to renal impairment in selected patients. From a mechanistic perspective, immune complex deposition, T-cell–mediated inflammation, mitochondrial dysfunction, cholestatic/metabolic disturbances, and gut microbiota dysbiosis have been proposed as potential contributors, but direct causal evidence remains limited. Given the heterogeneity and potential clinical significance of renal manifestations in PBC, early detection, thorough nephrological assessment, and individualized therapeutic strategies are essential. 1 Introduction Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic liver disease characterized by non-suppurative, progressive destruction of the intrahepatic small bile ducts. The fundamental pathological process involves immune-mediated injury to biliary epithelial cells, leading to persistent cholestasis, progressive fibrosis, and ultimately cirrhosis ( 1 ). PBC predominantly affects middle-aged and elderly women. Ursodeoxycholic acid (UDCA) remains the first-line therapy; however, approximately one-third of patients exhibit an inadequate biochemical response, which is associated with continued disease progression and a markedly increased risk of hepatic decompensation and liver-related mortality ( 2 , 3 ). The epidemiological burden of PBC has increased in recent decades, with recent studies reporting rising prevalence worldwide despite geographical heterogeneity ( 4 ). Although the precise pathogenesis of PBC remains incompletely understood, current evidence supports a multifactorial etiology involving genetic susceptibility, immune dysregulation, environmental triggers, and alterations in the intestinal microenvironment ( 5 , 6 ). Clinically, patients commonly present with pruritus and fatigue, accompanied by biochemical abnormalities related to cholestasis. With advancing disease, features of portal hypertension and cirrhosis may develop ( 6 – 8 ). Traditionally, PBC has been regarded as an organ-specific autoimmune disease confined to the intrahepatic bile ducts. However, accumulating evidence suggests that PBC represents a systemic autoimmune disorder with extrahepatic involvement affecting multiple organ systems, including the respiratory, gastrointestinal, urinary, and hematologic systems. Reported extrahepatic manifestations include pulmonary arterial hypertension, interstitial lung disease, hemolytic anemia, and renal impairment ( 1 , 9 – 11 ). Renal involvement is well recognized in systemic autoimmune diseases, including systemic lupus erythematosus (SLE), Sjögren disease (SjD; formerly known as Sjögren syndrome), systemic sclerosis, and antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV); however, it remains less well characterized and underrecognized in PBC. PBC also frequently coexists with other autoimmune diseases, among which SjD is one of the most common comorbidities. A systematic review and meta-analysis reported that the prevalence of SjD in patients with PBC varied widely across studies, with a pooled estimate of approximately 35% ( 12 ). This comorbidity is clinically relevant because renal involvement is a recognized manifestation of SjD. A recent multicenter retrospective study of 1, 058 patients with PBC reported a baseline prevalence of chronic kidney disease of 10% and a cumulative incidence of 7% during follow-up ( 13 ). Despite this emerging cohort-based evidence, the current literature on PBC-associated renal involvement remains limited, consisting largely of case reports and small retrospective studies, and standardized diagnostic and therapeutic approaches have not yet been established. Accordingly, this review aims to comprehensively summarize the clinical features, potential pathophysiological mechanisms, and management strategies of renal involvement in PBC. Through this review, we aim to enhance clinicians’ awareness of renal involvement in patients with PBC and to provide a reference framework for future research in this field ( Figure 1 ). Figure 1 Spectrum and pathophysiological mechanisms of renal involvement in primary biliary cholangitis. Conceptual model of reported renal manifestations in primary biliary cholangitis (PBC). Immune dysregulation and cholestatic/metabolic disturbances may contribute to renal abnormalities in selected patients. Autoantibodies (e.g., AMA), cytokines, and immune complexes contribute to glomerular injury, leading to membranous nephropathy (MN) and IgA nephropathy (IgAN). Immune-mediated tubular damage may impair H + secretion and result in renal tubular acidosis (RTA). In parallel, elevated bile acids, gut microbiota dysbiosis, and increased galactose-deficient IgA1 may be associated with immune activation and mesangial deposition, although direct causal links in PBC remain to be established. Metabolic alterations, including reduced vitamin D and calcium levels, along with bile acid–mediated toxicity and drug-induced injury, further exacerbate renal damage. 2 Reported renal manifestations in PBC 2.1 Glomerular diseases The kidneys receive approximately 20–25% of cardiac output, reflecting their high perfusion state. The glomerulus consists of a dense capillary network exposed to high blood flow and filtration pressure, making it particularly susceptible to the deposition of circulating immune complexes. Its physiological features—namely high perfusion, high filtration capacity, propensity for immune complex trapping, and amplification of inflammatory cascades—facilitate the retention of circulating immune complexes and autoantibodies, thereby initiating localized inflammatory responses ( 14 ). Moreover, the glomerular filtration barrier is a highly specialized and delicate trilaminar structure consisting of fenestrated endothelial cells, the glomerular basement membrane (GBM), and podocytes. Disruption of either its charge-selective properties or structural integrity enhances the deposition and persistence of immune mediators. The GBM and mesangial matrix are enriched with diverse autoantigenic components, providing additional targets for autoantibody binding and immune complex formation ( 15 ). Therefore, in the setting of systemic autoimmunity, the glomerulus is often one of the most commonly and prominently affected renal structures. Lupus nephritis (LN) represents a prototypical immune complex–mediated glomerular disease, in which immune complex deposition activates complement and promotes glomerular inflammation ( 16 ). In contrast, ANCA-associated vasculitis is characterized by pauci-immune necrotizing and crescentic glomerulonephritis driven by ANCA-activated neutrophils ( 17 ). Taken together, as a key target organ in systemic immune dysregulation, the glomerulus is highly vulnerable to injury across a spectrum of autoimmune diseases. Based on the available case reports and small series, the most frequently reported glomerular lesions in patients with PBC appear to be membranous nephropathy (MN), followed by IgA nephropathy (IgAN) and other less common forms of glomerular injury. The following sections summarize these patterns and discuss their possible clinical and immunopathological significance. 2.1.1 Membranous nephropathy 2.1.1.1 Clinical evidence Among glomerular lesions reported in patients with PBC, MN appears to be the most frequently described pattern in the available literature. However, current evidence remains limited to case reports and small retrospective series. A review of the available literature identified 12 reported cases of PBC complicated by MN, with clinical characteristics summarized in Table 1 . Among these patients, five initially presented with edema accompanied by abnormal liver biochemistry. Three were first diagnosed with PBC based on abnormal liver enzyme levels and positive autoantibodies and subsequently developed bilateral lower extremity edema and MN-related manifestations during follow-up. The original reports did not clearly describe the sequence of onset between PBC and renal disease in the remaining four patients ( 18 – 24 ). Table 1 Source article Age (year) /sex PLA2R Cr (μmol/L) 24hUP (g) Treatment of glomerulone-phritis At last follow-up Cr (μmol/L) 24hUP (g) Bian, Sainan et al. ( 18 ) 50/F – 54 3.6 Prednisone 53 0.7 Bian, Sainan et al. ( 18 ) 65/F – 114 13.4 Prednisone, CTX 58 0.56 Bian, Sainan et al. ( 18 ) 49/F + 48 6.9 ARB 49 0.2 Bian, Sainan et al. ( 18 ) 52/F + 176 8.3 Prednisone, CTX, Rituximab 264 7.0 Lei, Xiwen et al. ( 19 ) 53/M + / 8.2 Methylprednisolone, Rituximab / 3.2 Sakamaki, Yusuke et al. ( 20 ) 76/M / 88.4 10.1 CsA 88.4 0.68 Zimmermann, Jonas et al. ( 21 ) 39/M – 79.6 7.3 Prednisone, CsA 114.9 2.0 Sato, Shuzo et al. ( 22 ) 40/M / 57.5 4.45 ARB / 4.0 Hong, Xia et al. ( 23 ) 54/M + 64.5 5.11 Prednisone, AZA 102 2.6 Dauvergne, Maxime et al. ( 24 ) 55/F – 58.7 1.6 Prednisone, MMF / / Dauvergne, Maxime et al. ( 24 ) 66/M – 480 11 Prednisone, AZA / / Dauvergne, Maxime et al. ( 24 ) 64/M + 70 3 Prednisone / / Clinical features and treatment strategies in primary biliary cirrhosis patients with membranous nephropathy. F, female; M, male; PLA2R, phospholipase A2 receptor; Cr, creatinine; 24hUP, 24-h urine protein; CTX, cyclophosphamide; ARB, angiotensin receptor blocker; CsA, cyclosporine A, AZA, azathioprine; MMF, mycophenolate mofetil. 2.1.1.2 Pathological/diagnostic features MN is an immune-mediated glomerular disease characterized by subepithelial immune complex deposition along the GBM. Its pathogenesis primarily involves complement activation and podocyte injury, resulting in disruption of the glomerular filtration barrier and diffuse thickening of the GBM. Histopathologically, MN is characterized by thickened glomerular capillary walls with “spike” formation on silver staining, granular deposition of IgG and complement components along the capillary loops on immunofluorescence, and subepithelial electron-dense deposits observed on electron microscopy ( 25 ). In 2009, Beck et al. identified podocyte-expressed PLA2R as a major target antigen in adult MN. Circulating autoantibodies against PLA2R were subsequently detected in the serum of affected patients, establishing PLA2R as a central antigen in the pathogenesis of primary MN ( 26 ). These observations raise an important question: does MN in the context of PBC represent idiopathic MN that coincidentally occurs in patients with PBC, or does it constitute a secondary manifestation driven by the underlying immune dysregulation of PBC? To address this issue, particular attention should be directed toward the expression of anti-phospholipase A2 receptor (PLA2R) antibodies and the immunopathological features of affected patients. 2.1.1.3 Possible mechanisms 2.1.1.3.1 PLA2R antibody–positive MN The immune response in PLA2R-associated MN is characterized predominantly by IgG4 autoantibodies targeting PLA2R on the podocyte surface. Binding of these antibodies results in in situ immune complex formation beneath the podocyte layer and activation of the complement cascade—particularly the assembly of the C5b-9 membrane attack complex. This leads to podocyte injury, cytoskeletal disruption, and increased glomerular permeability, ultimately manifesting as proteinuria and nephrotic syndrome ( 27 ). In recent years, several additional target antigens have been identified in MN, including neural epidermal growth factor-like 1 protein (NELL1), protocadherin 7 (PCDH7), and exostosin 1/2 (EXT1/EXT2). These antigens are predominantly localized to podocytes or the GBM and similarly result in subepithelial immune complex deposition. Currently, there is no direct evidence demonstrating that these antigens specifically target hepatocytes or biliary epithelial cells. Notably, EXT1/EXT2-associated MN is frequently observed in patients with systemic autoimmune diseases such as SjD and SLE, suggesting a potential link to systemic immune dysregulation ( 28 , 29 ). Although future studies may clarify possible associations between these novel antigens and autoimmune liver diseases, including PBC, definitive mechanistic and clinical evidence is currently lacking. Therefore, in patients with PBC who are positive for anti-PLA2R antibodies, MN is more likely to represent a coincidental overlap with primary (idiopathic) MN rather than a direct secondary manifestation of PBC-related immune abnormalities. 2.1.1.3.2 PLA2R antibody–negative MN In contrast, PLA2R-negative MN occurring in patients with PBC may be more plausibly associated with systemic immune dysregulation, although current evidence is insufficient to establish a direct causal relationship with PBC. The characteristic hepatic pathology of PBC includes portal tract infiltration by activated T lymphocytes and upregulation of T-cell surface markers, indicating that T-cell–mediated immune responses and cytokine release are central drivers of disease progression.In reported cases of MN overlapping with anti-GBM disease, renal biopsy demonstrated multifocal lymphocytic and mononuclear cell infiltration, reflecting active intrarenal inflammation. Such inflammatory infiltrates may amplify glomerular injury by establishing a pro-inflammatory microenvironment and releasing multiple cytokines. T-cell–mediated cellular immunity may therefore contribute to the initiation or propagation of glomerular damage in this context. Additionally, PBC is frequently associated with elevated serum IgM levels. It has been hypothesized that circulating immune components—such as IgM or anti-mitochondrial antibody subtype M2 (AMA-M2)—may deposit along the GBM, contributing to or exacerbating MN-like lesions. Previous case reports have described granular IgM deposition along glomerular capillary walls accompanied by subepithelial electron-dense deposits on electron microscopy ( 30 , 31 ). Among the 11 patients who underwent renal biopsy in the reviewed cases, two exhibited IgM deposition in addition to IgG and C3. These findings raise the possibility that IgM-mediated immune deposition within the GBM may contribute to MN-like lesions in selected patients with PBC, although this mechanism remains speculative. 2.1.1.4 Management Management of MN generally depends on the severity of proteinuria, renal function, anti-PLA2R antibody status, and risk of progression. Standard therapeutic strategies for MN include glucocorticoids combined with cyclophosphamide (CTX), calcineurin inhibitors such as cyclosporine (CsA), and B-cell–depleting agents including rituximab. In the reviewed cases, the majority of patients (9/12, 75%) received corticosteroid therapy, with several undergoing combination immunosuppressive treatment involving CTX, CsA, or rituximab for induction of remission. Based on available follow-up data, all patients demonstrated improvement in proteinuria, achieving either complete or partial remission of renal involvement. For patients diagnosed with both PBC and MN, optimal clinical management requires careful differentiation between primary and secondary MN. Renal biopsy combined with serological testing—particularly assessment of anti-PLA2R antibodies—is essential for clarifying the underlying pathogenic mechanism. Accurate classification enables individualized therapeutic decision-making and may improve renal and hepatic outcomes. Overall, MN is the most frequently reported glomerular lesion in PBC, but available evidence is insufficient to determine whether this association is causal or coincidental in most patients. 2.1.2 IgA nephropathy 2.1.2.1 Clinical evidence Reports of PBC complicated by IgAN remain exceedingly scarce and are limited to isolated case descriptions. The following discussion is based on two published cases ( 32 , 33 ). Both patients were middle-aged or elderly women with concurrent PBC and IgAN, and both had additional autoimmune comorbidities, such as rheumatoid arthritis. Renal biopsy in each case confirmed mesangial IgA deposition. Notably, one patient also exhibited IgM-positive plasma cell–associated tubulointerstitial nephritis (IgM + PC-TIN), suggesting that renal involvement in PBC may extend beyond the glomerulus to include tubulointerstitial compartments, thereby producing heterogeneous and complex clinical phenotypes. 2.1.2.2 Pathological/diagnostic features The central pathogenic mechanism of IgAN involves the mesangial deposition of immune complexes containing galactose-deficient IgA1 (Gd-IgA1), which subsequently trigger localized inflammatory and proliferative responses within the glomerulus ( 34 ). Histopathologically, light microscopy typically demonstrates diffuse mesangial hypercellularity and mesangial matrix expansion, which may present in diffuse or focal segmental patterns. Immunofluorescence microscopy constitutes the diagnostic hallmark, revealing granular or clumped mesangial deposits of IgA—often IgA-dominant—frequently accompanied by complement component C3 deposition ( 35 ). These pathological features remain essential for confirming IgAN in patients with PBC who present with hematuria, proteinuria, or impaired renal function. 2.1.2.3 Possible mechanisms Despite involving distinct
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