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Glomerular visceral epithelial cells (i.e., podocytes) are an essential component of the tripartite glomerular filtration barrier. Healthy podocytes are terminally differentiated cells with limited replicative capacity; however, inappropriate cell cycle reentry can be induced in podocytes by various injurious stimuli. In this issue of the JCI, Yamaguchi et al. report on a somatic mosaic gain-of-function mutation in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic α subunit (p110α, encoded by PIK3CA). The study reveals that activating mutations of p110α can drive podocyte proliferation in PIK3CA-related overgrowth syndrome (PROS). They also showed that selective, small-molecule inhibitors of p110 may be useful for the treatment of proliferative glomerulonephritis.
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Fosfatidilinositol 3-Quinasa Clase I , Fosfatidilinositol 3-Quinasas , Podocitos , Humanos , Podocitos/patología , Podocitos/metabolismo , Animales , Fosfatidilinositol 3-Quinasa Clase I/genética , Fosfatidilinositol 3-Quinasa Clase I/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proliferación Celular , Ratones , Mutación , Glomerulonefritis/genética , Glomerulonefritis/patología , Glomerulonefritis Membranoproliferativa/genética , Glomerulonefritis Membranoproliferativa/patología , Glomerulonefritis Membranoproliferativa/inmunologíaRESUMEN
Membranoproliferative glomerulonephritis (MPGN) is no longer a disease but a pattern of injury in various diseases. Characterized by electron-dense deposits, mesangial proliferation, and duplication of the glomerular basement membrane, MPGN was previously classified by findings seen by electron microscopy. However, recognizing complement dysfunction in relation to cases with the MPGN pattern of injury substantially changed our view of its pathogenesis. A new classification, including immune complex-mediated and complement-mediated MPGN, has become preferable and has been adopted by international guidelines. Despite these advancements, accurate diagnosis of MPGN remains a clinical challenge, given the pathological and clinical similarities between immune complex-mediated and complement-mediated MPGN. Additional testing, such as molecular and genetic testing, is often necessary. Here, we will summarize our current understanding of the MPGN pattern of injury from a pathology perspective as an introductory article in the following chapters.
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Glomerulonefritis Membranoproliferativa , Humanos , Glomerulonefritis Membranoproliferativa/patología , Glomerulonefritis Membranoproliferativa/inmunología , Glomerulonefritis Membranoproliferativa/diagnóstico , Microscopía Electrónica , Proteínas del Sistema Complemento/genética , Proteínas del Sistema Complemento/inmunología , Membrana Basal Glomerular/patología , Membrana Basal Glomerular/inmunología , Glomérulos Renales/patología , Glomérulos Renales/inmunologíaRESUMEN
Membranoproliferative glomerulonephritis (MPGN) is a rare glomerular disease characterized by mesangial hypercellularity and thickening of the glomerular basement membrane (GBM). MPGN can be idiopathic or associated with malignancy, systemic immune complex disorders and chronic infections. It has rarely been associated with solid organ tumors, such as lung, gastric, breast or prostate cancer. We report a patient with MPGN and coexisting colorectal carcinoma. A 48-year-old man presented with anemia, loss of weight, hypertension, and nephrotic syndrome. The renal biopsy findings were compatible with type 1 MPGN. The antineutrophilic cytoplasmic antibodies, antinuclear antibodies, anti-GBM, serologic markers of hepatitis B and hepatitis C and tumor markers were negative. After ruling out the secondary causes of MPGN, the patient was treated with pulse doses of methylprednisolone and a single dose of cyclophosphamide. However, due to the worsening anemia and rectal bleeding, a colonoscopy was performed, which established a diagnosis of adenocarcinoma of the descending colon. The patient was treated with left hemicolectomy and oral corticosteroids. Within a year after the cancer treatment, the patient experienced a complete resolution of the proteinuria and improvement of the kidney function. Although rare, MPGN can be associated with hematologic malignancies and solid organ tumors. The most common causes of secondary MPGN should be ruled out before starting specific treatment. In our patient, cancer treatment has led to a subsequent remission of the nephrotic syndrome, which indicated that this association was not coincidental but rather causal. In patients with a tumor and concomitant glomerulopathy which is suspected to be paraneoplastic in etiology, the treatment of the underlying malignancy should be prioritized.
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Glomerulonefritis Membranoproliferativa , Humanos , Masculino , Persona de Mediana Edad , Glomerulonefritis Membranoproliferativa/patología , Glomerulonefritis Membranoproliferativa/diagnóstico , Adenocarcinoma/patología , Adenocarcinoma/complicaciones , Colectomía , Resultado del Tratamiento , Biopsia , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/complicaciones , ColonoscopíaRESUMEN
CONTEXT: IgM-dominant immune complex-mediated glomerulonephritis (IgM-dominant ICMGN) is a rare renal entity, characterized by a membranoproliferative pattern by light microscopy, dominant IgM staining by immunofluorescent staining, and subendothelial deposits by electron microscopy. This study was to investigate if some of IgM-ICMGN were associated with autoimmune disorders induced by hydralazine. DESIGN: Seven IgM-dominant ICMGN cases were identified over 8 years. Their pathologic phenotypes and clinical scenarios were analyzed in detail. RESULTS: Patients' ages ranged from 47 to 87 years old with 5 women and two men. Six of seven patients had drug-induced autoimmune phenomenon (hydralazine-induced positive ANCA and ANA). All of them had renal dysfunction and some proteinuria. Most pathologic features showed a membranoproliferative pattern of glomerulonephritis with dominant IgM deposits at subendothelial spaces. IgM nephropathy (a variant of focal segmental glomerulosclerosis), chronic thrombotic microangiopathy, and cryoglobulinemic glomerulopathy were ruled out in the cases. CONCLUSION: The hydralazine-induced autoimmune phenomenon can be seen in IgM-dominant ICMGN, which should be classified as a subtype of membranoproliferative glomerulonephritis.
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Hidralazina , Inmunoglobulina M , Humanos , Persona de Mediana Edad , Femenino , Hidralazina/efectos adversos , Masculino , Anciano de 80 o más Años , Anciano , Glomerulonefritis Membranoproliferativa/inmunología , Glomerulonefritis Membranoproliferativa/patología , Glomerulonefritis Membranoproliferativa/inducido químicamente , Antihipertensivos/efectos adversos , Glomerulonefritis/inmunología , Glomerulonefritis/inducido químicamente , Glomerulonefritis/patología , Complejo Antígeno-AnticuerpoRESUMEN
BACKGROUND: Membranoproliferative glomerulonephritis (MPGN) can be divided into immune-complex MPGN (IC-MPGN) and C3 glomerulopathy (C3G), which includes dense deposit disease (DDD) and C3 glomerulonephritis (C3GN). These conditions result from abnormalities in different complement pathways and may lead to different prognoses. However, there are limited studies describing the respective clinical courses. METHODS: In this study, Japanese pediatric patients diagnosed with MPGN based on kidney biopsies conducted between February 2002 and December 2022 were reclassified as having IC-MPGN or C3G (DDD or C3GN). We retrospectively analyzed the clinical characteristics and outcomes of these patients. RESULTS: Out of 25 patients with MPGN, three (12.0%) were diagnosed with DDD, 20 (80.0%) with C3GN, and two (8.0%) with IC-MPGN. There were 13 (65.0%) patients and one (33.3%) patient in remission after treatment for C3GN and DDD, respectively, and no patients with IC-MPGN achieved remission. The median follow-up period was 5.3 (2.5-8.9) years, and none of the patients in either group progressed to an estimated glomerular filtration rate < 15 ml/min/1.73 m2. Patients with C3GN presenting mild to moderate proteinuria (n = 8) received a renin-angiotensin system inhibitor (RAS-I) alone, and these patients exhibited a significant decrease in the urinary protein creatinine ratio and a notable increase in serum C3 levels at the last follow-up. CONCLUSIONS: Most patients with MPGN were diagnosed with C3GN. The remission rate for C3GN was high, and no patients developed kidney failure during the approximately 5-year follow-up. Additionally, patients with C3GN with mild to moderate proteinuria had good outcomes with RAS-I alone, but continued vigilance is necessary to determine long-term prognosis.
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Complemento C3 , Glomerulonefritis Membranoproliferativa , Humanos , Glomerulonefritis Membranoproliferativa/inmunología , Glomerulonefritis Membranoproliferativa/tratamiento farmacológico , Glomerulonefritis Membranoproliferativa/patología , Glomerulonefritis Membranoproliferativa/diagnóstico , Glomerulonefritis Membranoproliferativa/sangre , Niño , Masculino , Femenino , Estudios Retrospectivos , Japón , Preescolar , Adolescente , Complemento C3/análisis , Biopsia , Riñón/patología , Riñón/inmunología , Tasa de Filtración Glomerular , Proteinuria/etiología , Proteinuria/tratamiento farmacológico , Estudios de Seguimiento , Resultado del Tratamiento , Pueblos del Este de AsiaRESUMEN
C3 glomerulopathy (C3G) is a rare disease resulting from dysregulation of the alternative pathway of complement. C3G includes C3 glomerulonephritis (C3GN) and dense deposit disease (DDD), both of which are characterized by bright glomerular C3 staining on immunofluorescence studies. However, on electron microscopy (EM), DDD is characterized by dense osmiophilic mesangial and intramembranous deposits along the glomerular basement membranes (GBM), while the deposits of C3GN are not dense. Why the deposits appear dense in DDD and not in C3GN is not known. We performed laser microdissection (LCM) of glomeruli followed by mass spectrometry (MS) in 12 cases each of DDD, C3GN, and pretransplant kidney control biopsies. LCM/MS showed marked accumulation of complement proteins C3, C5, C6, C7, C8, C9 and complement regulating proteins CFHR5, CFHR1, and CFH in C3GN and DDD compared to controls. C3, CFH and CFHR proteins were comparable in C3GN and DDD. Yet, there were significant differences. First, there was a six-to-nine-fold increase of C5-9 in DDD compared to C3GN. Secondly, an unexpected finding was a nine-fold increase in apolipoprotein E (ApoE) in DDD compared to C3GN. Most importantly, immunohistochemical and confocal staining for ApoE mirrored the dense deposit staining in the GBM in DDD but not in C3GN or control cases. Validation studies using 31 C3G cases confirmed the diagnosis of C3GN and DDD in 80.6 % based on ApoE staining. Overall, there is a higher burden of terminal complement pathway proteins in DDD compared to C3GN. Thus, our study shows that dense deposits in DDD are enriched with ApoE compared to C3GN and control cases. Hence, ApoE staining may be used as an adjunct to EM for the diagnosis of DDD and might be valuable when EM is not available.
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Glomerulonefritis Membranoproliferativa , Glomerulonefritis , Humanos , Glomerulonefritis Membranoproliferativa/patología , Glomerulonefritis/patología , Glomérulos Renales/patología , Apolipoproteínas E/genética , ApolipoproteínasAsunto(s)
Glomerulonefritis Membranoproliferativa , Parvovirus B19 Humano , Humanos , Parvovirus B19 Humano/aislamiento & purificación , Glomerulonefritis Membranoproliferativa/virología , Glomerulonefritis Membranoproliferativa/etiología , Glomerulonefritis Membranoproliferativa/patología , Infecciones por Parvoviridae/complicaciones , Infecciones por Parvoviridae/diagnóstico , Femenino , MasculinoRESUMEN
Introduction: Pauci-immune crescentic glomerulonephritis (PICN) is an important cause of rapidly progressive renal failure. 10-40% of PICN cases have ANCA (antineutrophil cytoplasmic antibody) negative serology. The present study compared clinico-pathologic features, Brix's renal risk score, Berden's histopathological classes and differences in outcome between ANCAnegative vs ANCA positive PICN patients. Materials and Methods: Sixty-one patients of biopsy-proven PICN were studied. Biochemical findings and ANCA serology were recorded. Renal biopsy slides were reviewed along with direct immunofluorescence. Clinical and histological features were compared between ANCA negative and positive PICN using the Man Whitney U test and Chi-square test. Patients were compared for distribution in Berden's histological classes and Brix's renal risk categories. Patient and renal survival were compared using Kaplan-Meier survival analysis. Results: ANCA negative PICN patients were younger (44.9 ± 16.5 years vs 53.6 ± 15.1 years, P = 0.049). Nasal (0 vs 18%, P = 0.035) and pulmonary involvement (9% vs 38%, P = 0.014) were lower in ANCA negative group. Both ANCA groups had similar renal biochemical profiles, percentage normal glomeruli, 16.3 ± 18.2 vs 21.7 ± 20.4 and percentage glomeruli with crescents, 64.5 ± 28.1 vs 64.3 ± 27.1. Twenty-seven per cent of ANCA negative cases fell in the sclerotic class in Berden's classification vs just 2.5% in ANCA positive group (p = 0.037) without significant difference in Brix's renal risk categories (p = 0.329). Thirteen per cent of ANCA negative patients achieved complete remission on treatment compared to 33% in ANCA positive patients. Patient survival and overall probability of progressing to ESRD were similar in the two groups. Conclusion: ANCA negative PICN cases present at younger ages. Nasal and pulmonary involvement is uncommon in these patients. Patient survival and progression to ESRD are similar in both ANCA groups.
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Glomerulonefritis Membranoproliferativa , Glomerulonefritis , Fallo Renal Crónico , Humanos , Glomerulonefritis/patología , Anticuerpos Anticitoplasma de Neutrófilos , Riñón/patología , Glomérulos Renales/patología , Glomerulonefritis Membranoproliferativa/patología , Enfermedad Aguda , Fallo Renal Crónico/patología , Estudios RetrospectivosAsunto(s)
Trasplante de Riñón , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anticuerpos Monoclonales , Glomerulonefritis/etiología , Glomerulonefritis/patología , Glomerulonefritis/diagnóstico , Glomerulonefritis/inmunología , Glomerulonefritis Membranoproliferativa/patología , Glomerulonefritis Membranoproliferativa/etiología , Riñón/patología , Trasplante de Riñón/efectos adversos , Anciano , Anciano de 80 o más AñosRESUMEN
BACKGROUND: C3 glomerulopathy (C3G) is a complement-mediated disease. Although genetic studies are not required for diagnosis, they are valuable for treatment planning and prognosis prediction. The aim of this study is to investigate the clinical phenotypes, kidney survival, and response to mycophenolate mofetil (MMF) treatment in pediatric C3G patients with and without mutations in complement-related genes. METHODS: Sixty pediatric C3G patients were included, divided into two groups based on complement-related gene mutations. Demographic and clinical-pathological findings, treatment modalities, and outcome data were compared, and Kaplan-Meier analysis was performed for kidney survival. RESULTS: Out of the 60 patients, 17 had mutations. The most common mutation was in the CFH gene (47%). The mean age at diagnosis was higher in the group with mutation (12.9 ± 3.6 vs. 11.2 ± 4.1 years, p = 0.039). While the patients without mutation most frequently presented with nephritic syndrome (44.2%), the mutation group was most likely to have asymptomatic urinary abnormalities (47.1%, p = 0.043). Serum parameters and histopathological characteristics were similar, but hypoalbuminemia was more common in patients without mutation. During 45-month follow-up,10 patients progressed to chronic kidney disease stage 5 (CKD5), with 4 having genetic mutation. The time to develop CKD5 was longer in the mutation group but not significant. MMF treatment had no effect on progression in either group. CONCLUSIONS: This study is the largest pediatric C3G study examining the relationship between genotype and phenotype. We showed that the mutation group often presented with asymptomatic urinary abnormalities, was diagnosed relatively late but was not different from the without mutation group in terms of MMF treatment response and kidney survival.
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Glomerulonefritis Membranoproliferativa , Glomerulonefritis , Enfermedades Renales , Fallo Renal Crónico , Humanos , Niño , Complemento C3/genética , Ácido Micofenólico/uso terapéutico , Glomerulonefritis Membranoproliferativa/patología , Mutación , Glomerulonefritis/tratamiento farmacológico , Enfermedades Renales/tratamiento farmacológicoRESUMEN
BACKGROUND: Fibronectin glomerulopathy is a rare genetic nephropathy with only a few cases of post-transplant recurrence being reported previously. We highlight a case that was initially misdiagnosed and emphasize the importance of full immunofluorescence and electron microscopy evaluation in allograft biopsies. CASE PRESENTATION: A 36-year-old male with a history of end-stage kidney disease secondary to biopsy-proven type 1 membranoproliferative glomerulonephritis (MPGN) status-post living unrelated donor kidney transplant 12 years prior, presented with increasing creatinine and proteinuria. Biopsy was performed and was consistent with fibronectin glomerulopathy. Subsequent genetic testing revealed an FN1 mutation, the primary gene associated with this condition. CONCLUSIONS: Full histologic evaluation of the allograft biopsy corrected the diagnosis and additionally suggested that the patient's mother, who had expired in her 30s and had received a diagnosis of type 1 MPGN on autopsy, likely also had fibronectin glomerulopathy, enabling appropriate genetic counseling for the family.
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Glomerulonefritis Membranoproliferativa , Humanos , Masculino , Femenino , Adulto , Glomerulonefritis Membranoproliferativa/patología , Recurrencia Local de Neoplasia/complicaciones , Biopsia , Riñón/patología , Aloinjertos/patologíaRESUMEN
Fibronectin glomerulopathy (FNG) is an autosomal dominant disease, and nearly half of patients are involved in a mutation of the fibronectin gene (FN1). By using electrotransformation, we generated an induced pluripotent stem cell (iPSC) line from peripheral blood mononuclear cells (PBMCs) of a 32-years-old female patient who carried a heterozygous NM_212482.2(C.5888-1G > C) mutation in the FN1 gene. This cellular model is a useful tool to investigate pathogenic mechanisms in FNG and to develop potential treatments for FNG.
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Fibronectinas , Glomerulonefritis Membranoproliferativa , Células Madre Pluripotentes Inducidas , Adulto , Femenino , Humanos , Glomerulonefritis Membranoproliferativa/metabolismo , Glomerulonefritis Membranoproliferativa/patología , Células Madre Pluripotentes Inducidas/metabolismo , Leucocitos Mononucleares , Mutación , Fibronectinas/genéticaRESUMEN
Complement 3 glomerulopathy (C3G) is an ultra-rare, progressive kidney disease resulting from dysregulation of the alternative complement pathway. Clinical presentation of C3G is heterogeneous and definitive diagnosis relies on kidney biopsy and immunofluorescence staining. The term C3G encompasses two subgroups, dense deposit disease and C3 glomerulonephritis, distinguished via electron microscopy. In this podcast article, the authors discuss the challenges associated with C3G diagnosis and the central role of kidney biopsy. Using an illustrative case study, key histological observations are described, and best practices are discussed from the perspectives of a nephrologist and a nephropathologist. Podcast Audio (MP4 141866 KB).
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Complemento C3 , Glomerulonefritis Membranoproliferativa , Humanos , Complemento C3/metabolismo , Glomerulonefritis Membranoproliferativa/diagnóstico , Glomerulonefritis Membranoproliferativa/patología , Vía Alternativa del Complemento , Riñón , BiopsiaRESUMEN
A 67-year-old man complained of lower limb edema with a purpuric skin rash. Laboratory tests revealed proteinuria, elevated serum creatinine levels, and low serum albumin levels. The patient was also positive for cryoglobulin in serum, immunoglobulin (Ig) M gammopathy, hypocomplementemia, and rheumatoid factor. He was negative for anti-hepatitis C virus antibodies. A pathological analysis of the renal tissue revealed membranoproliferative glomerulonephritis, common histological features of cryoglobulinemic vasculitis (CV), and mucosa-associated lymphoid tissue lymphoma invasion. Although hematologic malignancy is a rare cause of type II CV, these clinical findings suggest that mucosa-associated lymphoid tissue lymphoma (MALT) lymphoma may have been the cause in the present case.
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Crioglobulinemia , Glomerulonefritis Membranoproliferativa , Glomerulonefritis , Linfoma de Células B de la Zona Marginal , Masculino , Humanos , Anciano , Glomerulonefritis Membranoproliferativa/complicaciones , Glomerulonefritis Membranoproliferativa/patología , Linfoma de Células B de la Zona Marginal/complicaciones , Linfoma de Células B de la Zona Marginal/diagnóstico , Crioglobulinemia/complicaciones , Crioglobulinemia/diagnóstico , Glomerulonefritis/complicacionesRESUMEN
BACKGROUND: C3 glomerulonephritis (C3GN) is a subtype of C3 glomerulopathy (C3G), characterized by dysregulation of the alternative pathway of complement and by dominant C3 by immunofluorescence on the kidney biopsy. There is no approved treatment for patients with C3G. Immunosuppressive drugs as well as biologics have been used with limited success. In recent decades, substantial advances in the understanding of the complement system have led to the development of new complement inhibitors. Avacopan (CCX168) is an orally administered small-molecule C5aR antagonist that blocks the effects of C5a, one of the most potent pro-inflammatory mediators of the complement system. CASE REPORT: We describe a child with biopsy-proven C3GN treated with avacopan. She was enrolled in the ACCOLADE double-blind placebo-controlled Phase 2 study (NCT03301467), where during the first 26 weeks she was randomized to receive an avacopan-matching placebo orally twice daily, while in the following 26 weeks, the study was open-label and she received avacopan. After a wash-out period, she was restarted on avacopan through an expanded access program. CONCLUSIONS: In this case, use of avacopan in a pediatric patient with C3GN was safe and well tolerated. On avacopan, the patient was able to discontinue mycophenolate mofetil (MMF) while maintaining remission.
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Glomerulonefritis Membranoproliferativa , Glomerulonefritis , Niño , Femenino , Humanos , Complemento C3 , Glomerulonefritis/tratamiento farmacológico , Glomerulonefritis Membranoproliferativa/patología , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: As messenger RNA (mRNA)-based vaccines for coronavirus disease 2019 (COVID-19) have been administered to millions of individuals worldwide, cases of de novo and relapsing glomerulonephritis after mRNA COVID-19 vaccination are increasing in the literature. While most previous publications reported glomerulonephritis after the first or second dose of an mRNA vaccine, few reports of glomerulonephritis occurring after the third dose of an mRNA vaccine currently exist. CASE PRESENTATION: We report a case of rapidly progressive glomerulonephritis in a patient following the third dose of an mRNA COVID-19 vaccine. A 77-year-old Japanese man with a history of hypertension and atrial fibrillation was referred to our hospital for evaluation of anorexia, pruritus, and lower extremity edema. One year before referral, he received two mRNA vaccines (BNT162b2) for COVID-19. Three months before the visit, he received a third mRNA vaccine (mRNA-1273) for COVID-19. On admission, the patient presented severe renal failure with a serum creatinine level of 16.29 mg/dL, which had increased from 1.67 mg/dL one month earlier, prompting us to initiate hemodialysis. Urinalysis showed nephrotic-range proteinuria and hematuria. Renal biopsy revealed mild mesangial proliferation and expansion, a lobular appearance, and double contours of the glomerular basement membrane. Renal tubules had severe atrophy. Immunofluorescence microscopy showed strong mesangial staining for IgA, IgM, and C3c. Electron microscopy exhibited mesangial and subendothelial electron-dense deposits, leading to a diagnosis of IgA nephropathy with membranoproliferative glomerulonephritis-like changes. The kidney function remained unchanged after steroid therapy. CONCLUSIONS: Although the link between renal lesions and mRNA vaccines remains unclear, a robust immune response induced by mRNA vaccines may play a role in the pathogenesis of glomerulonephritis. Further studies of the immunological effects of mRNA vaccines on the kidney are warranted.
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COVID-19 , Glomerulonefritis por IGA , Glomerulonefritis Membranoproliferativa , Glomerulonefritis , Masculino , Humanos , Anciano , Glomerulonefritis por IGA/diagnóstico , Glomerulonefritis Membranoproliferativa/patología , Vacunas contra la COVID-19 , Vacuna BNT162 , COVID-19/complicaciones , Glomerulonefritis/patologíaRESUMEN
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for hematologic malignancies and non-malignant disorders, such as aplastic anemia, fanconi anemia, and certain immune deficiencies. Post-transplantation kidney injury is a common complication and involves a wide spectrum of structural abnormalities, including glomerular (MSPGN, mesangial proliferative glomerulonephritis; FSGS, focal segmental glomerulosclerosis; MPGN, membranoproliferative glomerulonephritis; MCD, minimal change disease), vascular (TMA, thrombotic microangiopathy), and/or tubulointerstitial (TIN, tubulointerstitial nephritis; ATI, acute tubular injury). Renal biopsy is the gold-standard examination for defining multiple etiologies of kidney impairment. Although kidney injury following HSCT has been studied, little is known about the effects of allo-HSCT on renal pathology in pediatric patients. METHODS: We retrospectively analyzed renal biopsy specimens from children with kidney injury after allo-HSCT and correlated results with clinical data in the last 10 years. RESULTS: Among 25 children (18 males and 7 females), three patients had proteinuria indicating nephrotic syndrome (24-hour urinary total protein/weight > 50 mg/kg/d), nine patients had severely reduced estimated glomerular filtration rate (eGFR < 30 ml/min/1.73 m2) and four patients received kidney replacement therapy (KRT). The main pathologies identified from kidney biopsies were MSPGN (n = 12), FSGS (n = 12), MPGN (n = 5), TMA (n = 4), MCD (n = 3), diffuse glomerular fibrosis (DGF, n = 2), ATI and TIN, in isolation or combined with other pathologies. The median follow-up time was 16.5 (0.5 ~ 68.0) months. Three patients died of recurrent malignancy and/or severe infection, one child developed to end-stage renal disease (ESRD), six patients (24%) had elevated serum creatinine (SCr > 100µmol/l) and nine patients (36%) still had proteinuria. CONCLUSIONS: This study evaluates histomorphologic findings from kidney biopsies of pediatric recipients following allo-HSCT. Detailed evaluation of renal biopsy samples is helpful to elucidate the nature of renal insult, and may potentially identify treatable disease processes.
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Glomerulonefritis Membranoproliferativa , Glomerulonefritis Membranosa , Glomeruloesclerosis Focal y Segmentaria , Trasplante de Células Madre Hematopoyéticas , Enfermedades Renales , Niño , Femenino , Humanos , Masculino , Biopsia/efectos adversos , Glomerulonefritis Membranoproliferativa/complicaciones , Glomerulonefritis Membranoproliferativa/patología , Glomerulonefritis Membranosa/complicaciones , Glomerulonefritis Membranosa/patología , Glomeruloesclerosis Focal y Segmentaria/complicaciones , Glomeruloesclerosis Focal y Segmentaria/patología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Riñón/patología , Proteinuria/complicaciones , Estudios RetrospectivosRESUMEN
Membranoproliferative glomerulonephritis (MPGN) is subdivided into immune-complex-mediated glomerulonephritis (IC-MPGN) and C3 glomerulopathy (C3G). Classically, MPGN has a membranoproliferative-type pattern, but other morphologies have also been described depending on the time course and phase of the disease. Our aim was to explore whether the two diseases are truly different, or merely represent the same disease process. All 60 eligible adult MPGN patients diagnosed between 2006 and 2017 in the Helsinki University Hospital district, Finland, were reviewed retrospectively and asked for a follow-up outpatient visit for extensive laboratory analyses. Thirty-seven (62%) had IC-MPGN and 23 (38%) C3G (including one patient with dense deposit disease, DDD). EGFR was below normal (≤60 mL/min/1.73 m2) in 67% of the entire study population, 58% had nephrotic range proteinuria, and a significant proportion had paraproteins in their serum or urine. A classical MPGN-type pattern was seen in only 34% of the whole study population and histological features were similarly distributed. Treatments at baseline or during follow-up did not differ between the groups, nor were there significant differences observed in complement activity or component levels at the follow-up visit. The risk of end-stage kidney disease and survival probability were similar in the groups. IC-MPGN and C3G have surprisingly similar characteristics, kidney and overall survival, which suggests that the current subdivision of MPGN does not add substantial clinical value to the assessment of renal prognosis. The high proportion of paraproteins in patient sera or in urine suggests their involvement in disease development.
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Glomerulonefritis Membranoproliferativa , Glomerulonefritis , Enfermedades Renales , Adulto , Humanos , Glomerulonefritis Membranoproliferativa/patología , Pronóstico , Estudios Retrospectivos , Glomerulonefritis/patología , ParaproteínasRESUMEN
Despite the reports on glomerulonephritis associated with COVID-19 mRNA vaccines, no study has reported about the dense deposit disease (DDD). Here, we present a case of hilar lymphadenopathy after the COVID-19 mRNA vaccination, following which the patient developed tubulointerstitial nephritis (TIN) and DDD. A 74-year-old man received his second dose of mRNA vaccine, and on the next day, he developed fever, urticaria, and dyspnea. On further examination, he had pleural effusion and right hilar lymphadenopathies, which were improved with conservative therapy. After 48 days of the second vaccination, he developed renal dysfunction and new-onset hematuria. Light microscopy findings by renal biopsy revealed apparent mesangial cell proliferation, increased mesangial matrix in the glomeruli, and diffuse inflammatory cell infiltration in the interstitium. Immunofluorescence analysis revealed 1 + positive results for IgG and IgM, negative results for IgA, and 2 + positive results for C3 with a garland pattern on the capillary walls. Electron microscopy revealed that severe cell proliferation in the capillary rumen, and continuous, thickened, and highly dark-stained spotty dense deposits in the glomerular basement membrane; and noncontinuous spotty dense deposits in the tubular basement membrane. Based on the decrease in C3 and pathological findings, TIN accompanied with DDD was diagnosed. The mRNA vaccine might have contributed to the development of lymphadenopathies, TIN, and DDD in this case. Moreover, TIN and DDD might be associated with the activated alternative pathway induced by the mRNA vaccine.