RESUMEN
RATIONALE & OBJECTIVE: Atypical anti-glomerular basement membrane (GBM) nephritis is characterized by a bright linear immunoglobulin staining along the GBM by immunofluorescence without a diffuse crescentic glomerulonephritis nor serum anti-GBM antibodies by conventional enzyme-linked immunosorbent assay (ELISA). We characterized a series of patients with atypical anti-GBM disease. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: Patients identified by the French Nephropathology Group as having atypical anti-GBM nephritis between 2003 and 2022. FINDINGS: Among 38 potential cases, 25 were included, of whom 14 (56%) were female and 23 (92%) had hematuria. The median serum creatinine at diagnosis was 150 (IQR, 102-203) µmol/L and median urine protein-creatinine ratio (UPCR) was 2.4 (IQR, 1.3-5.2) g/g. Nine patients (36%) had endocapillary proliferative glomerulonephritis (GN), 4 (16%) had mesangial proliferative GN, 4 (16%) had membranoproliferative GN, 2 (8%) had pure and focal crescentic GN, 1 (4%) had focal segmental glomerulosclerosis, and 5 had glomeruli that were unremarkable on histopathology. Nine patients (36%) had crescents, involving a median of 9% of glomeruli. Bright linear staining for IgG was seen in 22 cases (88%) and for IgA in 3 cases (12%). The 9 patients (38%) who had a monotypic staining pattern tended to be older with less proteinuria and rarely had crescents. Kidney survival rate at 1 year was 83% and did not appear to be associated with the light chain restriction. LIMITATIONS: Retrospective case series with a limited number of biopsies including electron microscopy. CONCLUSIONS: Compared with typical anti-GBM disease, atypical anti-GBM nephritis frequently presents with an endocapillary or mesangial proliferative glomerulonephritis pattern and appears to have a slower disease progression. Further studies are needed to fully characterize its pathophysiology and associated clinical outcomes. PLAIN-LANGUAGE SUMMARY: Atypical anti-glomerular basement membrane (GBM) nephritis is characterized histologically by bright linear immunoglobulin staining along the GBM without diffuse crescentic glomerulonephritis or circulating anti-GBM antibodies. We report a case series of 25 atypical cases of anti-GBM nephritis in collaboration with the French Nephropathology Group. Compared with typical anti-GBM disease, we observed a slower disease progression. Patients frequently presented with heavy proteinuria and commonly had evidence of endocapillary or mesangial proliferative glomerulonephritis. About half of the patients displayed a monotypic immune staining pattern; they tended to be older, with less proteinuria, and commonly without glomerular crescents in biopsy specimens. No concomitant circulating monoclonal gammopathy was detected. Further studies are needed to fully characterize its pathophysiology and associated clinical outcomes.
Asunto(s)
Enfermedad por Anticuerpos Antimembrana Basal Glomerular , Humanos , Femenino , Masculino , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/diagnóstico , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/patología , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/inmunología , Adulto , Persona de Mediana Edad , Francia/epidemiología , Estudios Retrospectivos , Anciano , Membrana Basal Glomerular/patología , Membrana Basal Glomerular/inmunología , Membrana Basal Glomerular/ultraestructura , AutoanticuerposAsunto(s)
Cadenas Ligeras de Inmunoglobulina , Enfermedades Renales , Humanos , Estudios Retrospectivos , Masculino , Femenino , Anciano , Cadenas Ligeras de Inmunoglobulina/metabolismo , Persona de Mediana Edad , Enfermedades Renales/patología , Enfermedades Renales/etiología , Enfermedades Renales/diagnóstico , Mieloma Múltiple/patología , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/mortalidad , Anciano de 80 o más AñosRESUMEN
Amyloidosis is a complex group of rare disorders characterized by the deposition of misfolded proteins in the extracellular space of various tissues and organs, leading to progressive organ dysfunction. The kidneys constitute a very common site affected, most notably by immunoglobulin-mediated (light chain, heavy chain, and light and heavy chain amyloidosis), but other types that include serum amyloid A (AA) amyloidosis and leukocyte chemotactic factor 2 amyloidosis, along with mutant proteins in several hereditary forms of amyloidosis such as transthyretin, fibrinogen α-chain, gelsolin, lysozyme, and apolipoproteins AI/AII/AIV/CII/CIII amyloidosis have been incriminated as well. The clinical presentation is variable and can range from minimal proteinuria for leukocyte chemotactic factor 2 amyloidosis to a full-blown nephrotic syndrome for AA amyloidosis. Clinical correlation, genetic analysis, and adequate tissue typing through a kidney biopsy are essential to make the correct diagnosis, especially when a family history of amyloidosis is absent. Except for AA and transthyretin amyloidosis, the treatment is usually purely supportive. Kidney transplantation is an acceptable form of treatment for end-stage kidney disease in all types of non-Ig-mediated renal amyloidosis.
Asunto(s)
Amiloidosis , Humanos , Amiloidosis/diagnóstico , Amiloidosis/genética , Amiloidosis/inmunología , Amiloidosis/metabolismo , Enfermedades Renales/diagnóstico , Enfermedades Renales/patología , Enfermedades Renales/genética , Enfermedades Renales/etiología , Enfermedades Renales/metabolismo , Trasplante de Riñón , Riñón/patología , Riñón/metabolismo , Riñón/inmunología , Proteína Amiloide A SéricaRESUMEN
Introduction: Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are related podocytopathies with distinct kidney outcomes. Surprisingly, elevated urinary activation fragments have been found in FSGS despite little complement deposition on immunofluorescence (IF) staining. Whether complement activation distinguishes FSGS from MCD, participating in the development of segmental lesions, remains unknown. Methods: We performed an observational study in patients with MCD and FSGS, and proteinuria ≥1 g/g of creatinine. We included both primary and secondary or unknown causes. We compared urinary fragments of terminal pathway activation, sC5b9, and C5a expressed as creatinine ratios, between MCD and FSGS. Results: Patients with FSGS (n = 41) had a serum albumin of 31±10 g/l and proteinuria of 5.1 (2.6-9.1) g/g at sampling, whereas those with MCD (n = 15) had a lower serum albumin (22 ± 9 g/l; P = 0.002), and a proteinuria of 3.8 (1.9-7.7) g/g (P = 0.40). Urinary sC5b9 and C5a were 8.7 (1.7-52.3) and 1.26 (0.45-1.84) µg/mmol of creatinine, respectively in patients with FSGS; compared to 0.8 (0.0-1.5) and 0.06 (0.01-0.15) µg/mmol of creatinine in MCD (P < 0.001), respectively. We found no association between urinary complement fragments and age, estimated glomerular filtration rate (eGFR), or chronic kidney lesions. When analyzing samples with proteinuria ≥ 3 g/g, the c-statistics for urinary sC5b9 and C5a were 0.96 and 1.00, respectively, in differentiating FSGS from MCD. Conclusion: We found no urinary complement activation fragments in MCD, in comparison to FSGS, despite similar levels of proteinuria. This suggests a role for complement activation in the pathogenesis of FSGS and provides an additional tool for distinguishing these 2 entities.