A full-house pattern at immunofluorescence in kidney biopsies is usually associated with lupus nephritis. The cases that do not meet criteria for diagnosis of systemic lupus erythematosus (SLE) and have no secondary causes are classified as idiopathic full house (non-Lupus) nephropathy (iFH-N), which is a poorly defined entity. We aimed to evaluate the clinical presentation, renal outcome and development of SLE in the long term. We carried out a retrospective observational study from 2012 to 2022 on patients with iFH-N, i.e. having a full-house pattern at immunofluorescence, but not meeting the criteria for the diagnosis of SLE and without a secondary cause. Of 2210 patients, 91 presented with full-house pattern at immunofluorescence: 84 had the criteria for SLE diagnosis, 2 had secondary causes, 5 were idiopathic. iFH-N cases were all young females with histological pattern of membranous nephropathy and impaired kidney function, at presentation two had a nephrotic syndrome, three a nephrotic range proteinuria. Mean serum creatinine was 2.1 mg/dl (SD± 0.47), mean eGFR 35.2 ml/min/1.73m2 (SD±11), mean proteinuria 7.1 gr/24h (SD±3.2). Four had negative antinuclear antibodies; none had anti-dsDNA, anti-extractable nuclear antigens, antiphospholipid antibodies; three had low C3 levels. All received aggressive immunosuppression (IS), including steroids, cyclophosphamide, mycophenolate mofetil or Intensified B Cell Depletion Protocol. Mean follow-up was 7.4 year (SD ± 2.4). Four patients (80%) developed end stage renal disease, three within 24 months, one patient chronic kidney disease stage 4. One subject developed SLE after two years. All patients with iFH-N had similar clinical presentation, appeared to be refractory to aggressive IS, and had poor renal outcome.

Non-lupus full-house nephropathy describes a pattern of "full-house" immunofluorescence on renal biopsy in the absence of clinical or serologic markers for systemic lupus erythematosus. It is a rare disease with a broad range of etiologies, including idiopathic, secondary, or a prodrome of systemic lupus erythematosus. Current treatment options are lacking, with mixed results in the literature for varied immunosuppressive regimens. Rituximab, a selective anti-CD20 B-cell monoclonal antibody, has shown success in immune-complex mediated glomerular diseases but has not been commonly used or studied in non-lupus full-house nephropathy. Here, we present a case of non-lupus full-house nephropathy that was refractory to first-line immunosuppressants, in which two rounds of rituximab treatment achieved a positive response. This case emphasizes the need for systemic analysis of rituximab use in non-lupus full-house nephropathy, particularly given its mixed etiologies and presentations.

Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease. Lupus nephritis (LN) is a major risk factor for mortality in SLE, and glomerular "full-house" immunofluorescence staining is a well-known characteristic of LN. However, some cases of non-lupus glomerulonephritis can also present with a "full-house" immunofluorescence pattern. We recently encountered a patient with full-house nephropathy (FHN) during adalimumab administration for Crohn's disease. IgA nephropathy or idiopathic FHN was diagnosed, and treatment with steroids was started, after which there was improvement in proteinuria. The prognosis of FHN has been reported to be poor; therefore, aggressive treatment is required for such patients.

Full-house immunofluorescence in combination with various histopathologic lesions in the renal biopsies of patients without overt systemic lupus erythematosus (SLE) poses a diagnostic challenge. In this setting, the biopsy findings are sometimes termed non-lupus 'full-house nephropathy' (FHN). It is presently unknown whether idiopathic non-lupus FHN is clinicopathologically and prognostically distinct from lupus FHN. We included non-lupus FHN patients and lupus FHN controls (four or more American College of Rheumatology or Systemic Lupus International Collaborating Clinics criteria) who were biopsied between 1968 and 2014 at the Leiden University Medical Centre. Non-lupus FHN patients were studied for progression to SLE and/or the presence of other conditions with FHN. The clinicopathologic characteristics and prognosis of idiopathic non-lupus FHN patients were compared with those of lupus FHN patients. Of 149 included patients, 32 had non-lupus FHN. During the median follow-up of 20 years, no non-lupus FHN patients developed SLE. In all, 20 non-lupus FHN patients had idiopathic non-lupus FHN, and in 12 patients, secondary non-lupus FHN was considered due to membranous nephropathy (anti-PLA2R-positive, n  = 1; cancer-associated, n  = 3), IgA nephropathy ( n  = 4), infection-related glomerulonephritis ( n  = 2) or anti-neutrophil cytoplasmic antibody-associated glomerulonephritis ( n  = 2). Idiopathic non-lupus FHN patients were more often male (P   <   0.001) than lupus FHN patients and their renal biopsies more often showed a mesangial (P   =   0.04) or membranous pattern of injury (P   =   0.02) and less intense C1q staining (P   =   0.002). Clinically, they presented with lower-range erythrocyturia (P   =   0.04), more proteinuria (P   <   0.01) and less complement consumption in the classical pathway (P   <   0.001) than lupus FHN patients. By multivariable Cox regression analysis of patients with a lupus nephritis class III/IV pattern of injury, idiopathic non-lupus FHN compared with lupus FHN was an independent risk factor for end-stage renal disease [hazard ratio 5.31 (95% confidence interval 1.47-19.24)]. Our results show that the clinical recognition of idiopathic non-lupus FHN as a diagnostic category is critical.