Efficacy and Safety of Finerenone in a Patient with IgA Nephropathy Complicated by Neurosyphilis: A Case Report

IgA Nephropathy (IgAN) is one of the most common forms of glomerulonephritis, yet treatment options remain limited for patients who cannot tolerate immunosuppressive therapy. The management becomes particularly challenging in the context of active infection, such as syphilis, where immunosuppression poses significant risks. Finerenone, a novel non-steroidal Mineralocorticoid Receptor Antagonist (MRA), presents a promising non-immunosuppressive strategy to reduce proteinuria and slow the progression of Chronic Kidney Disease (CKD). We report the case of a 35-year-old woman with biopsy-proven IgAN (Oxford classification M0E0S0T0-C0) and persistent proteinuria, despite treatment with sacubitril-valsartan, dapagliflozin, hydroxychloroquine, and prednisone. Further immunosuppression was limited by complications including urinary tract infection and blurred vision. The patient was subsequently diagnosed with neurosyphilis based on neurological manifestations and cerebrospinal fluid findings. Given the contraindication to enhanced immunosuppression, finerenone was initiated as an add-on therapy. After titration to a daily dose of 20 mg, her proteinuria significantly decreased to below 100 mg/24h, without inducing hyperkalemia or reducing glomerular filtration rate. The treatment was well-tolerated, and no drug interactions were observed with concurrent penicillin therapy for syphilis. This case illustrates that finerenone may serve as an effective and safe adjunctive treatment for reducing proteinuria in IgAN, especially in complex clinical scenarios where standard immunosuppressive therapies are contraindicated or poorly tolerated-such as in the presence of an active concurrent infection.

IgAN: Immunoglobulin A Nephropathy; MRA: Mineralocorticoid Receptor Antagonist; CKD: Chronic Kidney Disease; ACEi: Angiotensin-Converting Enzyme inhibitor; ARB: Angiotensin Receptor Blocker; SGLT2i: Sodium-Glucose Cotransporter-2 Inhibitor; RPR: Rapid Plasma Reagin; TPPA: Treponema Pallidum Particle Agglutination; eGFR: Estimated Glomerular Filtration Rate; PASM: Periodic Acid–Silver Methenamine; HE: Hematoxylin and Eosin

IgA Nephropathy (IgAN) remains the most prevalent primary glomerulonephritis worldwide and a leading cause of end-stage renal disease, particularly in East Asia [1-5]. The pathogenesis of IgAN is multifaceted, with the "four-hit" hypothesis providing a framework that culminates in glomerular inflammation and fibrosis [3,4]. Current treatment strategies, including Angiotensin-Converting Enzyme inhibitors/Angiotensin Receptor Blockers (ACEi/ARB), Sodium-Glucose cotransporter-2 inhibitors (SGLT2i), and immunosuppressive agents, aim to reduce proteinuria and slow disease progression3. However, a significant number of patients exhibit suboptimal responses or experience adverse effects, such as increased infection risk with immunosuppressants.

The management dilemma intensifies when IgAN coexists with an active infection, creating a therapeutic conflict between suppressing the immune system and controlling the pathogen. Herein, we report a challenging case of a young woman with IgAN and persistently high proteinuria, who was subsequently diagnosed with neurosyphilis. The inability to optimize immunosuppressive therapy led to the introduction of finerenone, a selective non-steroidal MRA4. This case highlights the potential role of finerenone as a valuable therapeutic option in managing complex IgAN cases, offering robust antiproteinuric and antifibrotic effects without compromising immunosuppression.

A 35-year-old female patient was admitted to our hospital due to “recurrent hematuria and proteinuria for six months”. The patient first presented with hematuria and proteinuria during a routine physical examination six months ago. Laboratory findings at that time included: urinary red blood cells 1200/μL, dysmorphic red blood cells 70%, urinary microalbumin 300 mg/L, and serum creatinine 65 μmol/L. She reported no edema of the lower limbs, no gross hematuria, no photosensitivity, no bone pain, no malar rash, no recurrent fever or painless oral ulcers, and no petechiae or ecchymosis. She did not seek medical attention or receive any treatment at that time. On November 24, 2022, a 24-hour urinary protein quantification result was 2712 mg, and she was admitted to our department for further diagnostic evaluation.

Physical examination on admission revealed: blood pressure 100/60 mmHg, no eyelid edema, no costovertebral tenderness, and no lower extremity edema. Laboratory tests showed: white blood cell count 11.75 × 10^⁹/L, Hemoglobin (HGB) 99 g/L, Albumin (ALB) 31.7 g/L, urea 10.72 mmol/L, creatinine 70 μmol/L, uric acid 355 μmol/L, and a negative antinuclear antibody test.A renal biopsy was performed and confirmed Immunoglobulin A Nephropathy (IgAN) under light microscopy, with histology revealing mild mesangial hypercellularity and global sclerosis in 3 out of 13 glomeruli, classified as M0E0S0T0-C0 according to the Oxford classification.

Initial management included sacubitril-valsartan, dapagliflozin, and hydroxychloroquine. However, by mid-December 2022, her proteinuria had increased to 3057 mg/24h. She also developed asymptomatic bacteriuria, prompting discontinuation of dapagliflozin and a course of levofloxacin. Due to persistent high-grade proteinuria into early 2023, oral prednisone was initiated at 30 mg/day in January. Although a subsequent reduction in proteinuria to 1011 mg/24h was observed, hydroxychloroquine was discontinued owing to blurred vision. Proteinuria remained variable around 1000–1200 mg/24h in the following months.

In May 2023, the patient was readmitted with new-onset generalized myalgia. Laboratory evaluation revealed microcytic anemia with a hemoglobin level of 99 g/L. Notably, serological testing returned strongly positive for syphilis, with a Rapid Plasma Reagin (RPR) titer of 1:32 and a positive Treponema Pallidum Particle Agglutination (TPPA) assay. By October 2023, she developed additional neurological symptoms including dizziness, gait instability, and a limb rash. Cerebrospinal fluid analysis confirmed neurosyphilis, showing pleocytosis (113.0 × 10^⁶/L WBCs), elevated protein (569.3 mg/L), and a positive CSF-TPPA. Treatment with intravenous penicillin G was promptly initiated.

Given the confirmed neurosyphilis and contraindication for intensified immunosuppression, the treatment strategy was adjusted. Finerenone was introduced and titrated to 20 mg daily as an add-on agent, alongside olmesartan and low-dose prednisone, forming a multi-target regimen aimed at controlling proteinuria without increasing infection risk. This combination led to a sustained reduction in proteinuria without episodes of hyperkalemia or deterioration in renal function. Detailed follow-up data were shown in figures 1-4.

Figure 1: Pathological picture of kidney tissue of the patient (original magnifi cation ×400).

Figure 2: Fluctuation curve of proteinuria in the patient.

Figure 3: Fluctuation curve of eGFR in the patient.

Figure 4: Fluctuation curve of serum potassium concentration in the patient.

The management of Immunoglobulin A Nephropathy (IgAN) remains a considerable clinical challenge, particularly in cases refractory to conventional treatment or when complicated by severe comorbidities that contraindicate standard immunosuppressive regimens. The present case of a young woman with steroid-resistant IgAN who subsequently developed neurosyphilis illustrates a complex therapeutic dilemma increasingly encountered in clinical nephrology. Her course underscores the critical need for individualized, non-immunosuppressive strategies and offers valuable insight into the evolving paradigm of precision medicine in glomerular diseases.

A central feature of this case is the concomitant presence of an immune-mediated glomerulopathy and a severe opportunistic infection, which presented a serious treatment conflict. The temporal association between the initiation of prednisone in early 2023 and the emergence of symptomatic neurosyphilis in October suggests that immunosuppressive therapy may have facilitated the reactivation and dissemination of *Treponema pallidum*. This observation highlights the importance of thorough screening for latent infections prior to initiating immunosuppression. At the same time, systemic inflammation induced by syphilis may have aggravated underlying IgA-mediated glomerular injury, creating a vicious cycle. In such high-risk scenarios, a treatment strategy that provides renal protection without exacerbating infection risk is essential.

In this context, the introduction of finerenone proved to be a pivotal therapeutic decision. Its efficacy can be mechanistically interpreted within the “four-hit” hypothesis of IgAN pathogenesis. Unlike conventional agents that target upstream immune activation, finerenone acts by selectively blocking mineralocorticoid receptors on podocytes and mesangial cells-key mediators in the final common pathway of glomerular inflammation and fibrosis. By attenuating MR overactivation, finerenone suppresses pro-fibrotic and pro-inflammatory cytokines such as TGF-β, PAI-1, IL-6, and TNF-α. This direct mode of action likely contributed to the marked and sustained reduction in proteinuria observed in our patient, affording significant renal protection without compromising antimicrobial immunity.

Furthermore, this case underscores several advantages of finerenone over established drug classes. Although SGLT2 inhibitors such as dapagliflozin offer renal benefits, their association with genitourinary infections-which led to its discontinuation in this patient-limits their use in infection-prone individuals. Similarly, corticosteroids and conventional immunosuppressants carry well-documented risks of infections and metabolic complications, which were already evident in this case with the development of neurosyphilis and hydroxychloroquine-related blurred vision. Additionally, unlike traditional steroidal MRAs (e.g., spironolactone), which are limited by off-target hormonal effects, finerenone’s non-steroidal structure confers high receptor selectivity and a more favorable safety profile, supporting its long-term use across diverse patient populations.

In conclusion, this case demonstrates that finerenone can serve as an effective and safe antiproteinuric agent in the management of IgAN, especially in complex clinical settings where standard immunosuppressive therapies are contraindicated. It exemplifies a targeted, mechanism-based approach that aligns with the principles of precision nephrology. Further clinical studies are warranted to validate its role in the treatment algorithm of IgA nephropathy, particularly among high-risk patients with concurrent infections or contraindications to immunosuppression.

This case highlights the considerable challenge of managing immunoglobulin A nephropathy in the presence of concurrent active infection, where conventional immunosuppressive therapies are often contraindicated. The successful use of finerenone in this context demonstrates its potential as an effective and well-tolerated antiproteinuric agent that can provide meaningful renal protection without increasing the risk of infectious complications.

All data associated with this study are present in the paper.

Written informed consents for publication of the clinical details were obtained from the patients or their first-degree relatives.

The authors declare that they have no conflicts of interest.

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