Rare Association between Minimal Change Disease and Primary Biliary Cholangitis: Case Report

Primary biliary cholangitis (PBC) is an autoimmune progressive cholestatic liver disease characterized by circulating anti-mitochondrial antibodies (AMAs) [1]. Autoimmune disorders such as systemic lupus erythematosus, rheumatoid arthritis, and Sjogren’s syndrome have been concomitantly observed in patients with PBC. Though quite rare, PBC has been associated with a wide variety of renal disorders including distal tubular acidosis, membranous nephropathy, microscopic polyangiitis, and tubulointerstitial nephritis [2]. Glomerular diseases have an even rarer association with PBC, such as minimal change disease (MCD), which has been sparsely described in prior literature. Here we present a case of biopsy-proven MCD in a patient with PBC treated with a course of steroids and achieving complete recovery.

Hispanic 70-year-old female with a recent diagnosis of PBC presented with new-onset shortness of breath and anasarca: no recent COVID-19 exposure or vaccination received. One month prior, she was evaluated for elevated alkaline phosphatase (ALP) and abnormal liver function (LFTs) including AST/ALT and bilirubin. Medical workup was notable for an elevated antinuclear antibody titer (ANA) of 1:1,280 and AMA titer of 1:160 resulting in a clinical diagnosis of PBC without a need for liver biopsy. During her hospitalization, serum creatinine was at near baseline 1.01 mg/dL (prior level 0.9 mg/dL, normal reference range 0.6–1.1 mg/dL), urine protein/creatinine ratio was 12.95 mg/g (prior level 7.46 mg/g, normal reference range <0.2 mg/mg), and serum albumin was 1.7 g/dL (normal reference range 3.5–5.4 g/dL). Kidney ultrasound 1 year prior was completely unremarkable, and repeat ultrasound demonstrated left renal pole AV fistula without steal phenomenon. Nephrotic workup was unrevealing and subsequently a kidney biopsy was pursued. Kidney biopsy demonstrated extensive foot process effacement consistent with MCD (shown in Fig. 1). Given the patient’s worsening renal function and persistent anasarca, the patient was started on prednisone 60 mg with tapering regimen; diuretic, angiotensin-converting enzyme inhibitor, and a low sodium diet were prescribed. At 1-month follow-up, the patient had complete resolution of nephrotic symptoms, and repeat urine protein/creatinine was 8.05 mg/g with normalized LFTs.

PBC is an autoimmune disorder characterized by progressive destruction of intrahepatic bile ducts leading to cholestasis and evidently long-term consequences of cirrhosis and portal hypertension. MCD is characterized with selective proteinuria and hypoalbuminemia that occurs in the absence of cellular glomerular infiltrates or immunoglobulin deposits. Generally known as the most common cause of pediatric idiopathic nephrotic syndrome, approximately 70–90% of cases, it has only been seen in 10–15% of adults. Even more, the association between PBC and MCD has been rarely studied as shown with the current limited amount of literature, which calls forth to the importance of recognizing the important relationship between the two diseases.

The first association between PBC and glomerular disease was demonstrated with Rai et al. [3] who first noted the association between PBC and diffuse glomerulonephritis. Study at the time demonstrated extensive IgG deposition along the basement. Since then, multiple groups have demonstrated other case reports between PBC and glomerulonephritis, especially with a possible underlying genetic cause [1]. However, only a handful of cases have reported the association between PBC and nephrotic syndrome [4]. Lai et al. [2] present a single case of MCD in a PBC highlighting the disparity of discussion in literature for this association (Table 1).

We present a case of MCD in a patient with clinically diagnosed PBC. Our patient presented with typical signs and symptoms associated with nephrotic syndrome, such as new onset of shortness of breath and anasarca. Notable in medical workup includes a severely elevated ANA titer of 1:1,280 as well as an elevated AMA titer of 1:160, resulting in a clinical diagnosis without need for further biopsy. Current evidence has demonstrated an ANA titer greater than 1:500 is clinically significant for an underlying autoimmune disorder and a positive AMA titer has a high sensitivity and specificity for diagnosing PBC [5]. Biopsy pursued due to an unrevealing possible cause of patient’s nephrotic syndrome, which demonstrated extensive foot process effacement without immunoglobulin deposits, consistent with MCD (Fig. 1). It is thought that MCD is caused by an aberrant immune response by T-cell dysregulation [6]; thus, given the coexistence of both PBC and MCD, it is safe to postulate PBC as the underlying autoimmune cause. Perhaps the combined autoimmune nature of PBC and immune-mediated pathology of MCD is what makes the clinical course response to steroids. Even more, current KDIGO guidelines recommendations include oral glucocorticoid treatment for MCD followed by steroid taper 2 weeks after complete remission (max steroid course length is 16 weeks). For patients with contraindications to steroids or frequent relapses, alternative immunosuppressants such as cyclophosphamide, calcineurin inhibitors, mycophenolate mofetil, and rituximab can be considered [7]. Recent studies have demonstrated the use of antinephrin autoantibodies as a reliable marker for MCD or nephrotic syndrome. Thus, patients treated with B-cell therapy such as rituximab have led to clinical remission due to its autoantibody-depleting mechanism. However, antinephrin autoantibodies are not routinely available in commercial laboratories [8]. In conclusion, we demonstrate a case of biopsy-proven MCD in a patient with clinically diagnosed PBC, treated successfully with a steroid course and achieving complete recovery. Based upon prior literature [2], it has been noted for subsequent episodes of infrequent relapses, requiring patients to be placed back on a steroid taper [7]. For example, it has been noted that AKI with high-grade proteinuria is a relatively common phenomenon and approximately 10–20% of adults with MCD may become steroid resistant. It also has been noted on repeat kidney biopsies that focal segmental glomerular sclerosis is present, which is associated with a worse prognosis, highlighting the importance of routine follow-up despite resolution of primary episode. In summary, establishing the relationship between PBC and MCD has been limited in prior literature, and our goal is to bring forth this rare association, which may help dictate future treatment courses. Review of a larger case series for further in-dept insights is recommended. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000545015).

We would like to thank all our colleagues who helped us in the management of this case.

Written informed consent was obtained from the patient for publication of the details of her medical case and any accompanying images. Ethical approval is not required for this study in accordance with local or national guidelines.

The authors have no conflicts of interest to declare.

This study was not supported by any sponsor or funder.

Neeraj Sharma (N.S.) developed the concept of the case report. Heidi Duong (H.D.) and Bahman Moghadam (B.M.) participated in the clinical care of the patient. Tachaporn Sangwattanarat (T.S.) wrote the first draft of the manuscript. N.S., H.D., and B.M. critically reviewed the manuscript. N.S. and H.D. revised the manuscript based on reviewer’s feedback. N.S., H.D., B.M., and T.S. read and approved the final manuscript.

The data that support the findings of this study are not publicly available due to privacy reasons but are available from the corresponding author upon reasonable request.