Rare Kidney Autoimmune Shift Struck an 85-Year-Old Weeks After Vasculitis Remission

When an 85-year-old Japanese woman arrived at hospital with fever and swollen legs, her medical team faced a diagnostic puzzle complicated by her age. She carried a history of cerebral infarction treated with daily aspirin, lived with severe dementia that limited the detail she could provide about her own symptoms, and had a low body weight that would later complicate the interpretation of standard kidney function equations. Laboratory testing revealed a markedly elevated level of myeloperoxidase anti-neutrophil cytoplasmic antibody, or MPO-ANCA, at 206 units per milliliter, alongside mild microscopic hematuria, modest proteinuria, and a strikingly high urinary β2-microglobulin of 21,200 micrograms per liter. That last marker, a low-molecular-weight protein shed by damaged proximal tubular cells, pointed toward prominent tubular injury rather than classic glomerular destruction. Serum anti-glomerular basement membrane antibodies, measured by chemiluminescent enzyme immunoassay, came back below the detection threshold of 2.0 units per milliliter, effectively ruling out the Goodpasture-type antibody that drives one of nephrology’s most aggressive diseases.

Because of her advanced age, severe dementia, antiplatelet therapy, and her family’s explicit preference for non-invasive management, no renal biopsy was performed. The team, led by Hiroki Ito of Tohoku Medical and Pharmaceutical University in Sendai, therefore made a clinical diagnosis of MPO-ANCA-positive ANCA-associated vasculitis, a condition in which autoantibodies directed against neutrophil enzymes trigger inflammation of small blood vessels throughout the body. Given the relatively mild renal presentation and the absence of pulmonary hemorrhage or other life-threatening manifestations, they chose corticosteroid monotherapy with oral prednisolone at 40 milligrams per day, deliberately avoiding cyclophosphamide or rituximab to minimize treatment-related toxicity in such a frail patient. The response appeared favorable. Within six weeks, serum creatinine fell from 0.97 to 0.69 milligrams per deciliter, cystatin C dropped from 2.09 to 1.18 milligrams per liter, urinary β2-microglobulin plummeted to 3,230 micrograms per liter, and hematuria resolved entirely. By late December, with prednisolone tapered to 7.5 milligrams per day, she seemed to be in clinical remission.

One laboratory value, however, refused to cooperate. Despite the apparent clinical quiescence, MPO-ANCA remained persistently elevated at 181 units per milliliter, barely lower than the initial titer. The team interpreted this as residual seropositivity without active vasculitis, a common and often benign finding in treated ANCA-associated vasculitis. In retrospect, the authors now suggest that this persistent antibody elevation during a relatively rapid steroid taper may have signaled subclinical ANCA-mediated inflammation that was incompletely suppressed, quietly continuing to damage the glomerular basement membrane even as overt clinical signs of vasculitis faded. They are careful to emphasize that persistent MPO-ANCA positivity alone does not establish ongoing vasculitic activity, and that the temporal association in this single case cannot be read as proof of causality. Whether a slower glucocorticoid taper or additional immunosuppressive therapy would have prevented what came next remains unknowable from this report.

What came next arrived with brutal speed. In January, while still on 7.5 milligrams of prednisolone daily, the woman suddenly developed marked lower-extremity edema and dyspnea. Her body weight had surged by 9.3 kilograms over roughly seven weeks, from 37.1 kilograms at discharge to 46.4 kilograms at readmission, indicating catastrophic fluid overload. Chest radiography revealed pulmonary edema and bilateral pleural effusions. Laboratory testing confirmed rapidly progressive kidney failure: serum creatinine had exploded from 0.69 to 5.91 milligrams per deciliter, blood urea nitrogen reached 109 milligrams per deciliter, and the creatinine-based estimated glomerular filtration rate collapsed from 60.3 to 5.8 milliliters per minute per 1.73 square meters. Urinalysis showed severe hematuria exceeding 100 red blood cells per high-power field, proteinuria climbing to 2.72 grams per gram of creatinine, and a cast profile including red blood cell, white blood cell, granular, waxy, and epithelial casts, the classic sediment signature of aggressive crescentic glomerulonephritis.

The decisive clue was immunological. Anti-GBM antibodies, negative just 2.5 months earlier using the identical chemiluminescent enzyme immunoassay platform, had surged to 317 units per milliliter. Emergency hemodialysis was initiated via a femoral vein catheter for refractory fluid overload and uremic symptoms. The team treated the clinically diagnosed anti-GBM disease with methylprednisolone pulse therapy at 500 milligrams per day for three days, followed by oral prednisolone at 20 milligrams per day, together with five sessions of plasma exchange. After those five exchanges, the anti-GBM antibody titer had fallen to a nearly undetectable level, and since anuria persisted without any evidence of kidney recovery, no further plasma exchange was performed. Cyclophosphamide and rituximab were deliberately withheld because the patient had developed an active Escherichia coli urinary tract infection, confirmed by positive urine culture, and because her advanced age, severe dementia, and frailty made standard immunosuppression exceptionally dangerous. Despite corticosteroids, plasma exchange, and dialysis, renal function never recovered, and she was transitioned to maintenance hemodialysis.

The case, published in Frontiers in Nephrology, is remarkable for its timing. A literature review conducted by the authors across PubMed, CiNii Research, J-STAGE, and Ichushi-Web identified only a handful of previously reported cases in which established ANCA-associated vasculitis preceded anti-GBM disease by a distinct clinical interval. Among those published cases, the intervals ranged from 6 months to 9 years, and the patients ranged in age from 23 to 74 years. This patient was simultaneously the oldest and had the shortest interval, with anti-GBM disease emerging a mere 2.5 months after the initial vasculitis diagnosis. The distinction matters because it separates sequential disease from the more familiar simultaneous double-positive phenomenon, in which both autoantibodies are detected at the same time and typically manifest as severe crescentic glomerulonephritis. A recent meta-analysis of 47 studies including 2,830 anti-GBM patients reported a pooled ANCA positivity rate of 27.4 percent, underscoring that ANCA antibodies are relatively common among anti-GBM patients, but most available cohorts address simultaneous rather than sequential detection.

The authors propose two hypothetical mechanisms, both unproven in this patient but grounded in established immunological theory. The first is epitope spreading, a process in which inflammation induced by the primary autoimmune disease disrupts the quaternary structure of the type IV collagen network within the glomerular basement membrane, thereby exposing cryptic epitopes of the α3(IV)NC1 domain that are normally sequestered from the immune system. In ANCA-associated vasculitis, ANCA-activated neutrophils release reactive oxygen species and proteolytic enzymes that may damage the basement membrane and promote exposure of these hidden antigens, allowing secondary anti-GBM autoimmunity to emerge even without overt clinical relapse of the vasculitis. The second mechanism involves age-related changes to the glomerular basement membrane itself. Aging kidneys show basement membrane folding and thickening, altered glycosaminoglycan sulfation, and changes in type IV collagen and laminins, alterations that may lower the threshold for ANCA-mediated injury and facilitate loss of immunological tolerance. A recent review recognizes anti-GBM disease in older individuals as a distinct clinical phenotypic variant and ANCA-associated anti-GBM disease as an overlapping autoimmune syndrome, lending further theoretical weight to both hypotheses.

The initial renal presentation also deserves scrutiny. At vasculitis onset, mild hematuria and proteinuria contrasted sharply with markedly elevated urinary β2-microglobulin and normoglycemic glycosuria, suggesting prominent tubular injury despite limited urinary evidence of glomerular involvement. The authors considered peritubular capillaritis, inflammation of the capillaries surrounding renal tubules, as a possible underlying mechanism, noting that urinary low-molecular-weight protein excretion has been associated with peritubular capillaritis in ANCA-associated vasculitis and that the condition can present with tubulointerstitial injury without substantial glomerular lesions. This tubular-predominant pattern may have masked the severity of the underlying autoimmune process, and without renal histology the team could not confirm whether peritubular capillaritis was indeed present.

The principal limitation of the report is the absence of renal histology, which means neither diagnosis was confirmed by biopsy. Prognostic features such as the percentage of normal glomeruli, an important predictor of kidney recovery even in dialysis-dependent anti-GBM disease, could not be assessed. Although serum anti-GBM antibody assays have high diagnostic accuracy, with a meta-analysis reporting pooled sensitivity of 93 percent and specificity of 97 percent, the initial result below 2.0 units per milliliter cannot completely exclude a very low circulating antibody level. Nevertheless, the subsequent increase from below 2.0 to 317 units per milliliter using the identical assay method, together with severe hematuria, increased proteinuria, and urinary casts, fulfilled the Japanese diagnostic criteria for anti-GBM glomerulonephritis.

Over four years of follow-up, the patient experienced no relapse of either ANCA-associated vasculitis or anti-GBM disease. Anti-GBM antibodies remained negative, while MPO-ANCA persisted weakly positive at approximately 10 to 20 units per milliliter without elevated inflammatory markers or new systemic symptoms. Prednisolone was cautiously tapered to 2.5 milligrams per day within six months of transitioning to maintenance hemodialysis. The authors caution that this favorable course should not be interpreted as evidence supporting routine de-escalation of immunosuppressive therapy in other patients. The central clinical message is straightforward: clinicians should consider prompt anti-GBM antibody testing when a rapid, unexplained decline in kidney function occurs during or after treatment for ANCA-associated vasculitis, because secondary anti-GBM disease can emerge during apparent clinical remission, under maintenance immunosuppression, and with alarming speed in elderly patients whose frailty complicates both diagnosis and treatment.

Subject of Research: Nephrology / Autoimmune Kidney Disease

Article Title: Anti-GBM disease shortly after clinically presumed ANCA-associated vasculitis in an 85-year-old patient: a case report and literature review

Article References: Ito, H., Abe, H., Suzuki, Y., Yano, K., Sato, F., Numahata, T., Ishikawa, R., Endo-Matsumoto, A., Matsumoto, K., Yuki, T., Kamada, A., Hashimoto, H., Anan, G., Ishiyama, K., Hirose, T., & Mori, T. (2026). Anti-GBM disease shortly after clinically presumed ANCA-associated vasculitis in an 85-year-old patient: a case report and literature review. Frontiers in Nephrology, 6, Article 1967122. https://doi.org/10.3389/fneph.2026.1967122

Image Credits: AI Generated

DOI: 10.3389/fneph.2026.1967122

Keywords: Anti-GBM, disease, shortly, clinically, presumed, ANCA-associated, vasculitis, year-old, patient, case, report, literature