There is currently no one-size-fits-all definition of Full House Nephropathy (FHN). The immunofluorescence (IF) Full-House pattern at biopsy is characterized by the concomitant presence of all immunoglobulins and complement fractions. This pattern is almost always present in Lupus Nephritis (LN). Because of this, despite in 1982 Jones and Magil [1] described this pattern in 5 patients without systemic signs, it has been synonymous with LN and/or Systemic Lupus Erythematosus (SLE) for a long time. Gianviti et al. [2], described that isolated FHN could be the first presentation of LN or SLE, at least in some percentage of cases. However, other case reports/series showed that these forms had very different evolutions and outcomes and that only a minority developed an SLE or LN during the follow-up [3]. The idea that this form could be a distinct condition started to rise until Wen and Chen [4] reported the first systematic description of this new clinicopathological entity. Currently, one possible definition of FHN is the simultaneous presence at IF of IgA, IgG, IgM, C1q, and C3 in different renal structures (capillary, mesangium, interstitium) in the absence of diagnostic criteria for SLE (EULAR/ACR and SLICC) and positivity for ANA and/or ds-DNA antibodies [3]. The prevalence of FHN with this definition in the different case series is about 15-25% of the total cases of FHN [4-6].

However, it is becoming evident that FHN is an umbrella definition. In effect, besides the 10% of FHN that may develop an SLE during the follow-up, as Ruggiero et al. [7] demonstrated, the remaining cases have a very heterogeneous histological and clinical picture. Cases of FHN have been described as secondary to infections (syphilis, hepatitis B) [5, 8], systemic inflammatory diseases (Crhon Disease) [9], or other glomerulonephritis with significant immunological activation at onset. Rijnink et al. [5] and Wani et al. [6], in their case series, described how, based on some histological and clinical features, an important percentage of non-lupus FHN was attributable to membranous nephropathy, IgA nephropathy, membranoproliferative glomerulonephritis, ANCA associated glomerulonephritis, and C1q nephropathy. In addition, Rijnink et al. [5] described 60% of cases as “idiopathic,” speculating about a possible distinct disease that could share some pathogenesis aspects with lupus FHN.

Regarding the outcome of FHN, there are very variable data, depending on the definitions, the treatment, and the intensity of the same that have been used. In fact, in studies where the histological picture of FHN was considered “seronegative lupus,” receiving a lupus-like treatment scheme, the prognosis was excellent, with a partial and complete remission rate of 92.9% and 76.2% of the patients, respectively [7]. On the other hand, in studies where treatment was conservative or with a low dose of immunosuppression, the prognosis of both “secondary” and “idiopathic” forms was poor, with a percentage of ESKD or ESKD/death of approximately 50-60% [5].
From these data, it is clear that finding a more homogeneous and shared definition/classification of FHN is essential to orient the treatment in a more precise way.

References:
1. Jones E, Magil A. Nonsystemic mesangiopathic glomerulonephritis with “full house” immunofluorescence. Pathological and clinical observation in five patients. Am J Clin Pathol 1982;78(1):29–34.
2. Gianviti A, Barsotti P, Barbera V, Faraggiana T, Rizzoni G. Delayed onset of systemic lupus erythematosus in patients with "full-house" nephropathy. Pediatr Nephrol. 1999 Oct;13(8):683-7.
3. Uzzo M, Kronbichler A, Alberici F, Bajema I. Non-Lupus Full House Nephropathy. Clin J Am Soc Nephrol. 2024 Mar 26. doi: 10.2215/CJN.0000000000000438. Epub ahead of print. PMID: 38527995.
4. Wen YK, Chen ML. Clinicopathological study of originally non-lupus "full-house" nephropathy. Ren Fail. 2010;32(9):1025-30.
5. Rijnink EC, Teng YK, Kraaij T, Wolterbeek R, Bruijn JA, Bajema IM. Idiopathic non-lupus full-house nephropathy is associated with poor renal outcome. Nephrol Dial Transplant. 2017 Apr 1;32(4):654-662.
6. Wani AS, Zahir Z, Gupta A, Agrawal V. Clinicopathological Pattern of Non-lupus Full House Nephropathy. Indian J Nephrol. 2020 Sep-Oct;30(5):301-306.
7. Ruggiero B, Vivarelli M, Gianviti A, Pecoraro C, Peruzzi L, Benetti E, Ventura G, Pennesi M, Murer L, Coppo R, Emma F. Outcome of childhood-onset full-house nephropathy. Nephrol Dial Transplant. 2017 Jul 1;32(7):1194-1204.
8. Fan SL, Landgren A, Ruderman I. Syphilis as the great mimicker: A case of full-house pattern membranous nephropathy. Nephrology (Carlton). 2024 Jan;29(1):18-20.
9. Uedono H, Tsuda A, Ueno N, Natsuki Y, Nakaya R, Nishide K, Machiba Y, Fujimoto K, Nakatani S, Mori K, Emoto M. Seronegative Full-house Nephropathy with Crohn's Disease. Intern Med. 2022 Dec 1;61(23):3553-3558.

We would like to propose a study based on the ERKReg registry in which we will analyze the clinical data of pediatric and adult patients with FHN. This sudy aims to improve our understanding of this heterogenous clinical and pathological entity. We will describe the prevalence, features, treatment, and outcome of this large cohort of European patients with FHN, trying to identify prognostic and therapeutic subgroups in FHN.

The patient population will be all subjects with FHN present in the ERKReg registry or newly diagnosed subjects with a first renal biopsy with a full-house histological picture: immunofluorescence >1+ for IgA, IgG, IgM, C3, and C1q in 2 or more renal structure (capillary, mesangium, interstitium); with no diagnostic European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) and Systemic Lupus International Collaborating Clinics (SLICC) criteria and negativity for ANA or dsDNA. Currently, the number of patients in the registry is around 60. To further expand the cohort, a survey will be launched through ERKNet, ERA, ESPN and the Ped Neph mailing list to collect as large a cohort as possible.

Data Sources: ERKReg and surveys

Data Elements:
Clinical, laboratory, and histological parameters will be analyzed. Onset data will be gender, age, ethnicity, anthropometric data, symptoms according to EULAR/ACR, renal function tests, protein profile, and immune profile (immunoglobulins, complement, autoantibodies).
Biopsy data: type of histological lesions and degree of activity or chronicity, immunofluorescence with possible prevalence or codominance of one parameter over another, electron microscopy parameters (tubuloreticular inclusions and localization of immune-complex deposits). Type and scheme of treatment at onset. Data at follow-up will be anthropometric, renal function and immunological parameters, treatment schedule, hemodialysis/plasmapheresis, any second biopsies, and treatment complications.

The work will analyze clinical and laboratory data at disease onset and during follow-up (annually) to establish possible diagnostic predictive factors and, eventually, a possible disease classification. Once identified, the subgroups will be studied for the different treatments and outcomes. These subgroups will be compared with the treatment and outcome of lupus nephritis. Then, we will try to establish a model that allows us to identify the parameters that define each disease subgroup from the onset and establish the correct treatment scheme, to avoid possible over- or under-treatment.