Rheumatoid arthritis (RA) is a common systemic autoimmune disease that only infrequently causes severe glomerulonephritis. Renal involvement in RA has been documented in approximately 1–5% of patients, usually stemming from medication toxicity (e.g., NSAIDs, gold, penicillamine) or secondary amyloidosis rather than primary vasculitis (1, 2). In contrast, anti-glomerular basement membrane (anti-GBM) disease is an exceptionally rare cause of rapidly progressive glomerulonephritis (annual incidence ~0.6–1.8 cases per million) (3, 4). Without prompt intervention, anti-GBM disease can quickly progress to irreversible end-stage kidney disease (ESKD) and can be potentially fatal. True anti-GBM disease occurring secondary to RA is extraordinarily uncommon—only a handful of cases have been reported—yet when present it poses significant diagnostic and therapeutic challenges.

Here we describe a rare case of anti-GBM disease secondly to a long-standing seropositive RA in a 71-year-old man. Notably, this occurred without typical medication triggers. The presentation was an RPGN that progressed to irreversible kidney failure despite aggressive therapy. We also review the existing literature on RA with anti-GBM disease to explore potential pathogenic links (such as medication-induced immune dysregulation and intrinsic autoimmune propensity) and discuss the complexities of management in this scenario. This case underscores the need for a high index of suspicion for anti-GBM disease in RA patients with unexplained renal signs, as early recognition and intervention are critical for optimizing outcomes.

A 71-year-old male with a 30-year history of poorly controlled seropositive RA was admitted in May 2024 with severe fatigue, anorexia, and oliguria that had progressed over two months. His RA had been characterized by chronic, erosive polyarthritis affecting the hands, wrists, elbows, shoulders, and ankles, leading to significant joint deformities and bilateral elbow contractures.

Past RA treatments included methotrexate (discontinued years prior due to gastrointestinal intolerance), low dose leflunomide (10 mg daily, ongoing), and intermittent use of Tripterygium wilfordii (a Chinese traditional herbal immunosuppressant). He also frequently took NSAIDs for pain management. Despite these therapies, his RA disease activity remained high, with persistent inflammation and deforming joint damage.

Routine laboratory tests five months before admission (December 2023) had already shown early renal abnormalities, specifically: proteinuria (+ on dipstick), gross hematuria (+++), and elevated inflammatory markers (C-reactive protein [CRP] 20.9 mg/L and erythrocyte sedimentation rate [ESR] 79 mm/hour). Unfortunately, these findings were overlooked at the time – they were attributed to a possible urinary tract infection or NSAID use, and no further nephrological evaluation was pursued. The patient did not report any urinary symptoms then, and follow-up was missed amid his ongoing RA issues. This represented a missed opportunity for earlier diagnosis.

By May 2024, the patient’s condition worsened dramatically. He developed marked fatigue, loss of appetite, and his urine output dwindled to <400 mL/day (oliguria). On May 16, 2024, laboratory tests showed a serum creatinine of 1038 µmol/L (baseline ~80 µmol/L in late 2023). Over just a few days, his creatinine spiked further to 1920 µmol/L by May 21. He also exhibited severe uremic symptoms (nausea, confusion) and electrolyte disturbances (potassium 6.3 mmol/L, sodium 125 mmol/L) consistent with AKI. Arterial blood gas revealed metabolic acidosis. He was anemic (hemoglobin 117 g/L, which later dropped further) and had profound hypoalbuminemia (20.9 g/L). Inflammatory markers were extremely elevated (CRP >186 mg/L, ESR >140 mm/hour), and NT-proBNP was >35,000 pg/mL, reflecting fluid overload and possible cardiac strain ( Table 1 ).

A chest computed tomography (CT) scan on admission showed bilateral interstitial infiltrates and fibrosis, suggestive of RA-associated interstitial lung disease (ILD) versus infection (no discrete lobar consolidation was seen). There were no radiological signs of diffuse alveolar hemorrhage (such as widespread ground-glass opacities), and the patient did not report hemoptysis. Given his critical state, we did not perform bronchoscopy; however, the absence of hemoptysis and the pattern of CT changes made anti-GBM disease-related pulmonary hemorrhage unlikely. The interstitial changes were attributed to chronic RA lung involvement, with superimposed pneumonia also considered. Additionally, a renal ultrasound at admission showed no evidence of obstruction (no hydronephrosis), making a post-renal cause of hematuria unlikely. The urinalysis findings (including red blood cell casts) further supported a glomerular source of bleeding rather than a urologic cause.

On admission, the patient was in critical condition. He was hypotensive (BP 85/50 mmHg) and tachypneic, with signs of fluid overload (marked bilateral leg edema) and uremic encephalopathy (asterixis and confusion). He had basal crackles on lung auscultation (consistent with fluid/inflammatory infiltrates), but no frank pulmonary hemorrhage. Joint exam showed active synovitis in multiple joints, consistent with an ongoing RA flare (he had painful swelling in the wrists, knees, and ankles despite his advanced joint deformities).

Emergency hemodialysis was initiated on admission to manage AKI and metabolic derangements. Empiric broad-spectrum antibiotics were started (meropenem) for possible sepsis. We also obtained extensive immunological tests given the unexplained RPGN. Strikingly, results revealed a very high titer of circulating anti-GBM antibodies (655.5 Chemiluminescence Units; normal <20 CU). Anti-neutrophil cytoplasmic antibodies (ANCA) were negative. RA serologies remained strongly positive (anti-CCP >500 U/mL, rheumatoid factor 92.9 IU/mL), reflecting active disease. Given the combination of oliguric RPGN and a high anti-GBM antibody titer, a diagnosis of anti-GBM disease was made. No renal biopsy was performed – the patient was hemodynamically unstable and coagulopathic, and he (and his family) did not consent to an invasive biopsy. We acknowledge that lacking histology is a limitation; however, the clinical presentation and serology were considered confirmatory in this emergency setting.

Microbiological studies aided in clarifying the lung findings: sputum cultures grew Stenotrophomonas maltophilia (a multi-drug-resistant Gram-negative organism) at heavy growth, and fungal cultures grew Candida species. These results indicated a severe hospital-acquired pneumonia with fungal co-infection. The patient was started on targeted antimicrobial therapy (intravenous trimethoprim-sulfamethoxazole for S. maltophilia, which also served as Pneumocystis jirovecii prophylaxis, and an echinocandin antifungal for Candida coverage). We also implemented prophylactic measures appropriate for his immunosuppressed state – for example, trimethoprim-sulfamethoxazole was continued prophylactically to prevent Pneumocystis pneumonia and other opportunistic infections, and fluconazole was given to prevent fungal thrush. Infection control was a major ongoing concern throughout his treatment.

A multidisciplinary team (nephrology, rheumatology, pulmonology, intensive care) coordinated the next steps. We initiated plasmapheresis on hospital day 2, given the classic indication for anti-GBM disease. He underwent a total of eight plasmapheresis sessions (replacing plasma with albumin) over the next two weeks. Concurrently, we started high-dose corticosteroids (initially IV methylprednisolone 40 mg daily, then tapering to oral prednisone 40 mg/day after one week). For additional immunosuppression, we carefully introduced cyclophosphamide – however, considering the patient’s advanced age and active infections, we used a cautious low-dose regimen (50 mg every other day orally) instead of the standard high-dose protocol. This adjusted dosing was chosen to balance treating the anti-GBM disease with avoiding further immunocompromise.

Remarkably, after about 6 plasmapheresis sessions, the patient’s anti-GBM antibody titer dropped from 655.5 CU to 84.9 CU. After the full 8 plasmapheresis (by early June 2024), the titer further declined to 55 CU (just above the upper limit of normal). Given this near normalization of anti-GBM antibody levels and economic concern, plasmapheresis was concluded after the eighth exchange to minimize additional immunosuppressive exposure and infection risk in this elderly patient. (At follow-up visits in July, August, and September 2024, his anti-GBM antibody titers further decreased to 36.6, 12.6, and 6.7 CU, respectively, as shown in Table 1 and Figure 1 ). This serological response indicated that our therapy was successful in removing circulating autoantibodies. Clinically, the patient’s pulmonary status improved: follow-up chest imaging in June showed resolution of the pneumonia infiltrates, although the underlying interstitial lung fibrosis had progressed (likely due to RA-ILD). Importantly, he never developed any signs of alveolar hemorrhage during hospitalization, suggesting our timely interventions may have averted the pulmonary manifestations of anti-GBM disease.

Despite clearing the anti-GBM antibodies from the circulation, the renal damage was already irreversible at presentation. The patient remained dialysis-dependent; his urine output did not recover (consistent with advanced RPGN and essentially complete ESKD by the time therapy began). We continued intermittent hemodialysis three times per week as chronic renal replacement therapy.

By mid-June, as the acute phase of the anti-GBM disease stabilized, we faced active RA issues. With steroid tapering (we reduced prednisone to 20 mg/day by late June), the patient developed a flare of his arthritis – swelling and pain recurred in multiple joints (particularly knees and shoulders). Considering his refractory RA and contraindications to some other therapies, we started tocilizumab, an IL-6 receptor inhibitor, for its efficacy in RA and relative safety in infection-prone patients. After obtaining clearance from the infectious disease team, tocilizumab 8 mg/kg IV was administered (with doses planned every 4 weeks). This led to a notable improvement in his joint symptoms and inflammatory markers over the next month. We also administered local therapy (intra-articular steroid injections to his shoulders and knees) to provide additional relief during the flare.

During the course of treatment, we were vigilant about prophylaxis and monitoring for opportunistic infections. Despite these efforts, the patient’s recovery was complicated by several serious infections due to his prolonged immunosuppression: in July 2024 he tested positive for COVID-19 (with moderate pneumonia), and shortly thereafter he developed reactivation of cytomegalovirus (CMV) (confirmed by PCR, with CMV viremia and hepatitis). He was treated with supportive care and antivirals (remdesivir for COVID-19, then ganciclovir for CMV). Cyclophosphamide was promptly discontinued by this time (after ~6 weeks of therapy) to help immune recovery, and we managed him with low-dose prednisone plus tocilizumab for RA thereafter. The patient initially recovered from both COVID-19 and CMV infections by August 2024, thanks to aggressive antimicrobial therapy and supportive ICU care.

Unfortunately, on 3 January 2025, approximately eight months after the anti-GBM diagnosis, the patient suffered a new episode of severe pneumonia (unrelated to COVID-19, likely bacterial). Despite broad-spectrum antibiotics and maximal supportive therapy, his condition deteriorated rapidly, and he passed away in the hospital due to respiratory failure. The cause of death was determined to be overwhelming pneumonia on a background of immunosuppression and end-stage renal disease.

This case timeline is visually summarized in Figure 1 . It underscores how an initial oversight of renal warning signs led to a cascade of critical illness. Despite timely use of plasmapheresis and immunosuppression once diagnosed (which potentially prevented pulmonary hemorrhage), the delay resulted in permanent dialysis dependence and set the stage for fatal infectious complications. Earlier recognition and intervention might have altered the outcome, highlighting a crucial lesson for clinicians managing complex patients with autoimmune diseases.

The coexistence of RA and anti-GBM disease is exceedingly rare. Through our updated review, we identified eight previously reported RA with anti-GBM cases worldwide (six full reports and two conference abstracts). We conducted a search of PubMed, Embase, and Web of Science, together with forward/backward citation tracking and other open resources (e.g., CrossRef/Google Scholar), from inception to September 2025, which identified 292 records (PubMed n = 32; Embase n = 200; Web of Science n = 59; other resources n = 1). After removing 26 duplicates, 266 records were screened; eleven reports underwent full-text assessment, one was excluded because the biopsy confirmed fibrillary GN with negative anti-GBM serology, and ten studies were included, as shown in Figure 2 . Each reported case displayed unique features, underscoring substantial heterogeneity in this overlap (5–14). Our patient adds another documented instance to this limited body of evidence and highlights several points that may refine clinical understanding.

In summary, this case underscores several key lessons. Clinicians caring for patients with rheumatoid arthritis should maintain a high level of vigilance for anti-GBM disease when otherwise unexplained hematuria or proteinuria is encountered. Once the diagnosis is established, plasmapheresis and immunosuppression need to be initiated as early as possible to maximize the chance of preserving renal function. At the same time, the coexistence of RA and anti-GBM disease demands an individualized approach that carefully balances the need for effective immunosuppression with the heightened risk of infection. Close collaboration between nephrology, rheumatology, and infectious disease specialists is essential to achieve optimal outcomes in such complex cases.