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The type of monoclonal light chain nephropathy is thought to be largely a function of the structural and physiochemical properties of light chains; hence most affected patients have only one light chain kidney disease type. Here, we report the first series of kidney light chain deposition disease (LCDD) concomitant with light chain amyloidosis (LCDD+AL), with or without light chain cast nephropathy (LCCN). Our LCDD+AL cohort consisted of 37 patients (54% females, median age 70 years (range 40-86)). All cases showed Congo red-positive amyloid deposits staining for one light chain isotype on immunofluorescence (62% lambda), and LCDD with diffuse linear staining of glomerular and tubular basement membranes for one light chain isotype (97% same isotype as the amyloidogenic light chain) and ultrastructural non-fibrillar punctate deposits. Twelve of 37 cases (about 1/3 of patients) had concomitant LCCN of same light chain isotype. Proteomic analysis of amyloid and/or LCDD deposits in eight revealed a single light chain variable domain mutable subgroup in all cases (including three with separate microdissections of LCDD and amyloid light chain deposits). Clinical data on 21 patients showed proteinuria (100%), hematuria (75%), kidney insufficiency and nephrotic syndrome (55%). Extra-kidney involvement was present in 43% of the patients. Multiple myeloma occurred in 68% (about 2/3) of these patients; none had lymphoma. On follow up (median 16 months), 63% developed kidney failure and 56% died. The median kidney and patient survivals were 12 and 32 months, respectively. LCDD+AL mainly affected patients 60 years of age or older. Thus, LCDD+AL could be caused by two pathological light chains produced by subclones stemming from one immunoglobulin light chain lambda or kappa rearrangement, with a distinct mutated complementary determining region.
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Amiloidose , Nefropatias , Mieloma Múltiplo , Adulto , Idoso , Idoso de 80 Anos ou mais , Amiloidose/complicações , Amiloidose/diagnóstico , Amiloidose/patologia , Feminino , Humanos , Cadeias Leves de Imunoglobulina , Rim/patologia , Nefropatias/complicações , Nefropatias/etiologia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , ProteômicaRESUMO
Neutralizing monoclonal antibodies such as bamlanivimab emerged as promising agents in treating kidney transplant recipients with COVID-19. However, the impact of bamlanivimab on kidney allograft histology remains unknown. We report a case of a kidney transplant recipient who received bamlanivimab for COVID-19 with subsequent histologic findings of diffuse peritubular capillary C4d staining. A 33-year-old man with end-stage kidney disease secondary to hypertension who received an ABO compatible kidney from a living donor, presented for his 4-month protocol visit. He was diagnosed with COVID-19 44 days prior to his visit and had received bamlanivimab with an uneventful recovery. His 4-month surveillance biopsy showed diffuse C4d staining of the peritubular capillaries without other features of antibody-mediated rejection (ABMR). Donor-specific antibodies were negative on repeat evaluations. ABMR gene expression panel was negative. His creatinine was stable at 1.3 mg/dl, without albuminuria. Given the temporal relationship between bamlanivimab and our observations of diffuse C4d staining of the peritubular capillaries, we hypothesize that bamlanivimab might bind to angiotensin-converting enzyme 2, resulting in classical complement pathway and C4d deposition. We elected to closely monitor kidney function which has been stable at 6 months after the biopsy. In conclusion, diffuse C4d may present following bamlanivimab administration without any evidence of ABMR.
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COVID-19 , Transplante de Rim , Adulto , Aloenxertos , Anticorpos Monoclonais Humanizados , Anticorpos Neutralizantes , Biópsia , Capilares , Complemento C4b , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/etiologia , Humanos , Rim , Transplante de Rim/efeitos adversos , Masculino , Fragmentos de Peptídeos , SARS-CoV-2 , Coloração e RotulagemRESUMO
RATIONALE & OBJECTIVE: Data on kidney transplantation outcomes among patients with monoclonal gammopathy of renal significance (MGRS) are lacking. STUDY DESIGN: Case series of patients with MGRS, some of whom received clone-directed therapies before kidney transplantation. SETTING & PARTICIPANTS: 28 patients who underwent kidney transplantation from 1987 through 2016 after diagnosis with MGRS-associated lesions including light-chain deposition disease (LCDD), C3 glomerulopathy with monoclonal gammopathy (C3G-MG), and light-chain proximal tubulopathy (LCPT). FINDINGS: Of the 19 patients with LCDD, 10 were treated before kidney transplantation and 9 were treatment-naive. Among the treated patients with LCDD, 3 (30%) experienced histologic recurrence, 2 (20%) grafts failed, and 2 (20%) died during a median follow-up of 70 (range, 3-162) months after transplant. In the treatment-naive LCDD group, 8 (89%) had histologic recurrence, 6 (67%) grafts failed, and 4 (44%) patients died during a median follow-up of 60 (range, 35-117) months. Of the 5 patients who had a complete response before transplant, none died, and only 1 experienced graft failure, 162 months after transplant. Of 5 patients with C3G-MG, 3 were treatment-naive before transplant. Both patients who were treated before transplant had histologic recurrence, and 1 experienced graft failure and died. Among the 3 patients with treatment-naive C3G-MG, histologic recurrence occurred in all, and graft loss and death were observed in 2 and 1, respectively. In the LCPT group (n=4), histologic recurrence was observed in all 3 patients who did not receive clone-directed therapies before transplant, and 2 of these patients died, 1 with a functioning kidney. The 1 patient with LCPT who received therapy before transplant did not have histologic recurrence or graft loss and survived. LIMITATIONS: Small sample size, nonstandardized clinical management, retrospective design. CONCLUSIONS: Recurrence is very common in all MGRS-associated lesions after kidney transplant. Achieving a complete hematologic response may reduce the risks of recurrence, graft loss, and death. More studies are needed to determine the effects of hematologic response on outcomes for each MGRS-associated lesion.
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Nefropatias , Transplante de Rim , Gamopatia Monoclonal de Significância Indeterminada , Paraproteinemias , Humanos , Rim , Transplante de Rim/efeitos adversos , Paraproteinemias/complicações , Estudos RetrospectivosRESUMO
Longer survival using modern therapies has increased the number of patients with immunoglobulin light-chain amyloidosis receiving kidney transplantation. We evaluated 60 patients with immunoglobulin light chain amyloidosis who underwent kidney transplantation based on their hematologic response for outcomes of death, graft failure, and complications. Patient hematologic responses (light-chain in blood or urine) prior to kidney transplantation were three patients had no response, five had a partial response, six had a very good partial response, 37 had a complete response, and nine were treatment-naive patients (never treated for this disorder). After transplantation, seven of nine treatment-naive patients achieved a complete response. The median follow-up for the entire transplant cohort was 61 months. The estimated median overall survival from the time of kidney transplantation was 123 months for the entire group. Median overall survival was not reached for the very good partial response plus complete response groups, it was 47 months for no response plus partial response groups, and 117 months for the treatment-naive group (all significantly different). Median overall survival of very good partial response was 81 months, while the median was not reached in the complete response group (no significant difference). The time to amyloid recurrence was significantly longer in complete response compared to very good partial response (median 181 vs 81 months). Death-censored graft survival at one- and five-years was 98.3%, and 95.8%, respectively for all groups. Of the 60 patients, three had allograft failure, 19 died with a functioning graft, and 13 had an amyloid recurrence. Thus, outcomes after kidney transplant in patients with immunoglobulin light-chain amyloidosis seem acceptable if a very good partial response or complete response is achieved either before or after transplantation.
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Amiloidose , Amiloidose de Cadeia Leve de Imunoglobulina , Transplante de Rim , Amiloidose/diagnóstico , Amiloidose/cirurgia , Humanos , Cadeias Leves de Imunoglobulina , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Amiloidose de Cadeia Leve de Imunoglobulina/terapia , Transplante de Rim/efeitos adversos , Recidiva Local de Neoplasia , Resultado do TratamentoRESUMO
Recurrence of primary membranous nephropathy after transplantation occurs in up to 44% of patients and is driven by PLA2R antibody. Here, we asked whether genetic determinants could improve risk prediction. First, we sequenced PLA2R1 and HLA-D loci in 248 patients with primary membranous nephropathy and identified two independent single nucleotide polymorphisms (SNPs) at risk for primary membranous nephropathy at each locus. These were rs9271188 (intergenic between HLA-DRB1 and HLA-DQA1,) and rs9275086 (intergenic between HLA-DQB1 and HLA-DQA2) at the HLA-D locus along with rs6726925 and rs13018963 at the PLA2R1 locus. Then we investigated whether primary membranous nephropathy at-risk variants were associated with recurrence in a retrospective cohort of 105 donor-recipient pairs and a replication cohort of 40 pairs. Seven SNPs located between HLA-DRB1 and HLA-DQA1 in linkage disequilibrium with rs9271188, and three SNPs in the PLA2R1 region predicted recurrence when presented by the donor, but not when presented by the recipient. The two SNPs in the HLA-D region most strongly associated with recurrence (rs9271705 and rs9271550) were confirmed in the replication cohort. A genetic risk score based on the two best predictors at each locus (rs9271705, rs9271550, rs17830558, and rs3828323) identified a group of patients with high risk of recurrence. Thus, our results suggest that the graft contributes to recurrence of primary membranous nephropathy through the disease susceptibility HLA-D and PLA2R1 SNPs in an autoimmune milieu. Further studies are needed before implementation of genetic testing for these in donor selection.
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Glomerulonefrite Membranosa , Transplante de Rim , Alelos , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/genética , Humanos , Transplante de Rim/efeitos adversos , Polimorfismo de Nucleotídeo Único , Receptores da Fosfolipase A2/genética , Estudos RetrospectivosRESUMO
Fibrillary glomerulonephritis (FGN) was previously defined by glomerular deposition of haphazardly oriented fibrils that stain with antisera to immunoglobulins but do not stain with Congo red. We report what is to our knowledge the first series of immunoglobulin-negative FGN, consisting of 9 adults (7 women and 2 men) with a mean age at diagnosis of 66 years. Patients presented with proteinuria (100%; mean protein excretion, 3g/d), hematuria (100%), and elevated serum creatinine level (100%). Comorbid conditions included carcinoma in 3 and hepatitis C virus infection in 2; no patient had hypocomplementemia or monoclonal gammopathy. Histologically, glomeruli were positive for DNAJB9, showed mostly mild mesangial hypercellularity and/or sclerosis, and were negative for immunoglobulins by immunofluorescence on frozen and paraffin tissue. Ultrastructurally, randomly oriented fibrils measuring 13 to 20nm in diameter were seen intermingling with mesangial matrix in all and infiltrating glomerular basement membranes in 5. On follow-up (mean duration, 21 months), 2 had disease remission, 4 had persistently elevated serum creatinine levels and proteinuria, and 3 required kidney replacement therapy. Thus, rare cases of FGN are not associated with glomerular immunoglobulin deposition, and the diagnosis of FGN in these cases can be confirmed by DNAJB9 immunostaining. Pathogenesis remains to be elucidated.
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Glomerulonefrite/metabolismo , Proteínas de Choque Térmico HSP40/metabolismo , Imunoglobulina G/metabolismo , Proteínas de Membrana/metabolismo , Chaperonas Moleculares/metabolismo , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Creatinina/metabolismo , Feminino , Membrana Basal Glomerular/ultraestrutura , Mesângio Glomerular/ultraestrutura , Glomerulonefrite/epidemiologia , Glomerulonefrite/patologia , Glomerulonefrite/terapia , Hematúria/metabolismo , Humanos , Imunossupressores/uso terapêutico , Cirrose Hepática/epidemiologia , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Proteinúria/metabolismo , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Terapia de Substituição Renal , EscleroseRESUMO
BACKGROUND: Nephrosclerosis, nephron size, and nephron number vary among kidneys transplanted from living donors. However, whether these structural features predict kidney transplant recipient outcomes is unclear. METHODS: Our study used computed tomography (CT) and implantation biopsy to investigate donated kidney features as predictors of death-censored graft failure at three transplant centers participating in the Aging Kidney Anatomy study. We used global glomerulosclerosis, interstitial fibrosis/tubular atrophy, artery luminal stenosis, and arteriolar hyalinosis to measure nephrosclerosis; mean glomerular volume, cortex volume per glomerulus, and mean cross-sectional tubular area to measure nephron size; and calculations from CT cortical volume and glomerular density on biopsy to assess nephron number. We also determined the death-censored risk of graft failure with each structural feature after adjusting for the predictive clinical characteristics of donor and recipient. RESULTS: The analysis involved 2293 donor-recipient pairs. Mean recipient follow-up was 6.3 years, during which 287 death-censored graft failures and 424 deaths occurred. Factors that predicted death-censored graft failure independent of both donor and recipient clinical characteristics included interstitial fibrosis/tubular atrophy, larger cortical nephron size (but not nephron number), and smaller medullary volume. In a subset with 12 biopsy section slides, arteriolar hyalinosis also predicted death-censored graft failure. CONCLUSIONS: Subclinical nephrosclerosis, larger cortical nephron size, and smaller medullary volume in healthy donors modestly predict death-censored graft failure in the recipient, independent of donor or recipient clinical characteristics. These findings provide insights into a graft's "intrinsic quality" at the time of donation, and further support the use of intraoperative biopsies to identify kidney grafts that are at higher risk for failure.
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Rejeição de Enxerto , Transplante de Rim/efeitos adversos , Rim/patologia , Doadores Vivos , Adulto , Idoso , Biópsia , Feminino , Humanos , Rim/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Néfrons/patologia , Tomografia Computadorizada por Raios XRESUMO
The association of fibrillary glomerulonephritis (FGN) with monoclonal gammopathy has been controversial, although monotypic FGN is currently classified as a monoclonal gammopathy of renal significance (MGRS) lesion. To define this lesion, we correlated findings by immunofluorescence on frozen and paraffin tissue, IgG subtype staining and serum protein electrophoresis with immunofixation in patients with monotypic FGN. Immunofluorescence was performed on paraffin sections from 35 cases of DNAJB9-associated FGN that showed apparent light chain restriction of glomerular IgG deposits by standard immunofluorescence on frozen tissue. On paraffin immunofluorescence, 15 cases (14 lambda and one kappa restricted cases on frozen tissue immunofluorescence) showed no light chain restriction, 19 showed similar light chain restriction, and one was negative for both light chains. Seven of the 15 cases with masked polyclonal deposits also had IgG subclass restriction and these cases would have been diagnosed as a form of monoclonal protein-associated glomerulonephritis if paraffin immunofluorescence was not performed. Monotypic FGN (confirmed by paraffin immunofluorescence and IgG subclass restriction) accounted for only one of 151 (0.7%) patients with FGN encountered during the last two years. Only one of 11 of cases had a detectable circulating monoclonal protein on serum protein electrophoresis with immunofixation. We propose that paraffin immunofluorescence is required to make the diagnosis of lambda-restricted monotypic FGN as it unmasked polytypic deposits in over half of patients. When confirmed by paraffin immunofluorescence and IgG subclass staining, DNAJB9-positive monotypic FGN is very rare and is not associated with monoclonal gammopathy in the vast majority of patients. Thus, there is a question whether this lesion should be included in MGRS-related diseases.
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Glomerulonefrite , Gamopatia Monoclonal de Significância Indeterminada , Paraproteinemias , Glomerulonefrite/diagnóstico , Proteínas de Choque Térmico HSP40 , Humanos , Imunoglobulina G , Glomérulos Renais , Proteínas de Membrana , Chaperonas Moleculares , Paraproteinemias/complicações , Paraproteinemias/diagnósticoRESUMO
We report a case of a patient who developed dialysis-requiring acute kidney injury (AKI) after the use of canagliflozin. A 66-year-old man with type 2 diabetes who was recovering from left knee septic arthritis at a rehabilitation facility was admitted with oliguric AKI 5 days after starting treatment with canagliflozin, an inhibitor of sodium/glucose cotransporter 2 (SGLT2). The patient presented with hematuria, non-nephrotic-range proteinuria, and serum creatinine level of 6.8 (baseline, 1.1-1.3) mg/dL. There was no recent use of radiocontrast agents or exposure to other nephrotoxins. The patient subsequently required hemodialysis. Due to recent antibiotic use (ampicillin-sulbactam), acute interstitial nephritis was considered in the differential diagnosis. Kidney biopsy was performed, which showed the presence of osmotic nephropathy. The patient's kidney function returned to baseline after 2 weeks of hemodialysis. This case provides evidence of an association of osmotic nephropathy with the use of canagliflozin and discusses potential mechanisms. We recommend kidney biopsy for cases of severe AKI associated with SGLT2 inhibitors to better understand the relationship of this complication with the use of this class of medications.
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Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/diagnóstico por imagem , Canagliflozina/efeitos adversos , Nefrose/induzido quimicamente , Nefrose/diagnóstico por imagem , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Injúria Renal Aguda/metabolismo , Idoso , Diuréticos Osmóticos/efeitos adversos , Humanos , Masculino , Nefrose/metabolismoRESUMO
Dysproteinemic kidney diseases occur when B- or plasma cell clones produce pathogenic monoclonal immunoglobulins or light chains that cause kidney damage. The clinical presentation of these disorders ranges from sub-nephrotic-range proteinuria or microscopic hematuria with preserved kidney function to severe nephrotic syndrome to severe acute kidney injury or rapidly progressive glomerulonephritis. These monoclonal immunoglobulins can cause a variety of histologic patterns of injury, including cast nephropathy, glomerular and tubular deposition diseases, amyloidosis, and inflammatory glomerulonephritis. The underlying clonal disorder may meet criteria for overt multiple myeloma or systemic lymphoma. In recent years, there has been increased recognition and study of dysproteinemic kidney diseases that occur in the setting of smaller clonal plasma and B-cell populations, which are classified as monoclonal gammopathies of renal significance. Regardless of clonal cell burden, the goal of treatment is to achieve a hematologic response (ie, improvement or resolution of the monoclonal protein) by eradicating the underlying clone. Organ-specific responses are dependent on achieving hematologic response. Without appropriate treatment, many of these disorders are associated with high rates of progressive kidney disease and end-stage kidney disease. In this installment of AJKD's Core Curriculum in Nephrology, we review the pathogenesis, diagnosis, and treatment of dysproteinemic kidney diseases.
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Competência Clínica , Currículo , Educação de Pós-Graduação em Medicina/métodos , Nefrologia/educação , Paraproteinemias/diagnóstico , Paraproteinemias/terapia , Amiloidose/diagnóstico , Amiloidose/terapia , Antineoplásicos/uso terapêutico , Biópsia por Agulha , Feminino , Humanos , Imuno-Histoquímica , Imunossupressores/uso terapêutico , Masculino , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/terapia , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/terapia , Medição de Risco , Resultado do TratamentoRESUMO
Classic anti-glomerular basement membrane (GBM) disease presents with rapidly progressive glomerulonephritis (GN) with or without pulmonary hemorrhage. On biopsy typical disease displays bright polytypic linear GBM staining for IgG by immunofluorescence and diffuse crescentic/necrotizing GN on light microscopy. Here, we studied 20 patients with atypical anti-GBM nephritis typified by bright linear GBM staining for immunoglobulins but without a diffuse crescentic phenotype. Patients had hematuria, proteinuria, and mild renal insufficiency, without pulmonary hemorrhage. Light microscopy showed endocapillary proliferative GN in 9 patients, mesangial proliferative GN in 6, membranoproliferative GN in 3, and focal segmental glomerulosclerosis with mesangial hypercellularity in 2. Eight of the 20 showed features of microangiopathy. Crescents/necrosis were absent in 12 and were focal in 8 patients. Bright linear GBM staining for IgG was seen in 17 patients, IgM in 2, and IgA in 1 patient, which was polytypic in 10 patients and monotypic in 10 patients. No circulating α3NC1 antibodies were detected by commercial ELISA. The 1-year patient and renal survival rates were 93% and 85%, respectively. Thus, atypical anti-GBM nephritis is a rare variant of anti-GBM disease characterized clinically by an indolent course, no pulmonary involvement, and undetectable circulating α3NC1 antibodies. Further studies are needed to characterize the molecular architecture of GBM autoantigens in these patients and establish optimal therapy.
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Doença Antimembrana Basal Glomerular/patologia , Rim/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Feminino , Imunofluorescência , Humanos , Rim/ultraestrutura , Masculino , Pessoa de Meia-Idade , Adulto JovemAssuntos
Injúria Renal Aguda , Biópsia/métodos , COVID-19 , Rim/patologia , Proteinúria , Insuficiência Renal Crônica , SARS-CoV-2/isolamento & purificação , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/patologia , Injúria Renal Aguda/virologia , População Negra/estatística & dados numéricos , COVID-19/etnologia , COVID-19/patologia , COVID-19/fisiopatologia , Feminino , Humanos , Rim/fisiopatologia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteinúria/diagnóstico , Proteinúria/etiologia , Proteinúria/virologia , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/patologia , Fatores de Risco , Índice de Gravidade de Doença , Estados UnidosRESUMO
COVID-19 is a systemic disease, and the kidney is one of the target organs of infection. Kidney injury is common and can occur in up to 40% of patients. Several glomerular diseases have been reported in association with COVID-19. Some are likely related to COVID-19 whereas many are likely coincidental. Glomerular diseases that are frequently reported in COVID-19 and have a plausible mechanistic explanation are likely to be related to COVID-19. In contrast, glomerular diseases that are seldom reported and have no known plausible mechanism, are likely to be unrelated. Collapsing glomerulopathy (CG) is by far the most prevalent. Its association with COVID-19, resembling HIV and CG, led to the newly proposed term "COVID-19 associated nephropathy" or "COVAN." High-risk APOL1 genotypes are the major risk factor in COVAN patients. Podocytopathy, membranous nephropathy (MN), pauci-immune crescentic glomerulonephritis (GN), and thrombotic microangiopathy (TMA) are also reported. In kidney allografts, CG remains the most common glomerular pathology. Patients typically present with acute kidney injury (AKI) or abnormal urinary findings at the time of or shortly after COVID-19 diagnosis. Treatment of glomerular disease in patients with COVID-19 is challenging. Providers should cautiously consider balancing risks and benefit of immunosuppression, particularly in patients with active diseases. Short-term outcomes vary but generally remain poor with high morbidity and mortality. Future study of long-term outcomes is needed to improve our understanding of glomerular disease associated with COVID-19.
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Introduction: Data on kidney transplantation (KTx) outcomes of patients with multiple myeloma (MM) are very limited. Methods: We investigated the outcomes of patients with MM who underwent KTx between 1994 and 2019. Results: A total of 12 transplants from 11 patients were included. At the time of KTx, 6 were classified as having stringent complete response (CR), 2 as CR, 2 as very good partial response (VGPR), and 2 as partial response (PR). With a median follow-up of 40 (minimum-maximum, 5-92) months after KTx, hematologic progression occurred in 9 transplants (75%). There were 3 grafts (25%) that failed, and 5 patients (45.5%) experienced death with functioning allografts. Graft survival at 1 and 5 years was 82.5% and 66%, respectively. Progression-free survival (PFS) rates of the cohort at 1, 3, and 5 years were 83.3%, 55.6%, and 44.4%, respectively. The estimated median PFS of patients who received bortezomib at any time (pre-KTx and/or post-KTx) was not reached, whereas it was 24 months for those who never received bortezomib (P = 0.281). Overall survival (OS) rates of the cohort at 1, 3, and 5 years were 81.8%, 61.4%, and 61.4%, respectively. OS of patients who received bortezomib at any time was 87.5%, 72.9%, and 72.9%, and that for those who never received bortezomib was 66.7%, 33.3%, and 33.3% (P = 0.136). All deaths occurred owing to hematologic progression or treatment-related complications. Conclusion: Kidney transplant outcomes of patients with myeloma who received bortezomib before or after KTx seem to be more favorable. Nevertheless, relapse after KTx in MM is still common. More studies are needed to better determine who benefits from a KTx.
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BACKGROUND: Coexistence of fibrillary glomerulonephritis (FGN) and immunoglobulin A (IgA) nephropathy (IgAN) in the same kidney biopsy (FGN-IgAN) is rare, and the clinicopathologic characteristics and outcome of this dual glomerulopathy are unknown. METHODS: In this study, 20 patients with FGN-IgAN were studied and their characteristics were compared with 40 FGN and 40 IgAN control patients. RESULTS: Concurrent IgAN was present in 1.8% of 847 consecutive FGN cases and was the second most common concurrent glomerulopathy after diabetic nephropathy. FGN-IgAN patients were overwhelmingly White (94%) and contrary to FGN patients were predominantly (60%) males. Compared with IgAN patients, FGN-IgAN patients were older, had higher proteinuria, a higher incidence of renal insufficiency, and a lower incidence of microhematuria and gross hematuria at diagnosis. Six (30%) patients had malignancy, autoimmune disease or hepatitis C infection, but none had a secondary cause of IgAN or clinical features of Henoch-Schonlein purpura. Histologically, all cases exhibited smudgy glomerular staining for immunoglobulin G and DnaJ homolog subfamily B member 9 (DNAJB9) with corresponding fibrillary deposits and granular mesangial staining for IgA with corresponding mesangial granular electron-dense deposits. On follow-up (median 27 months), 10 of 18 (56%) FGN-IgAN patients progressed to end-stage kidney disease (ESKD), including 5 who subsequently died. Serum creatinine at diagnosis was a poor predictor of renal survival. The proportion of patients reaching ESKD or died was higher in FGN-IgAN than in IgAN. The median Kaplan-Meier ESKD-free survival time was 44 months for FGN-IgAN, which was shorter than IgAN (unable to compute, P = 0.013) and FGN (107 months, P = 0.048). CONCLUSIONS: FGN-IgAN is very rare, with clinical presentation and demographics closer to FGN than IgAN. Prognosis is guarded with a median renal survival of 3.6 years. The diagnosis of this dual glomerulopathy requires careful evaluation of immunofluorescence findings, and electron microscopy or DNAJB9 immunohistochemistry.
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INTRODUCTION: mRNA COVID-19 vaccine is more effective than traditional vaccines owing to superior immune activation. Nevertheless, the impact of mRNA COVID-19 vaccine on triggering de novo/relapsing glomerulonephritis (GN) is limited. We report a case series of patients who developed new or relapsing GN postvaccination. METHODS: We evaluated baseline characteristics, vaccine type, and clinical outcomes of 13 patients from our institution who had a new diagnosis or relapse of their GN post-mRNA COVID-19 vaccination. RESULTS: Of 13 patients, 8 patients were newly diagnosed with having GN and 5 patients had relapse. Median age was 62 years (range 19-83 years). Autoimmune disease (38%) was the most prevalent underlying disease followed by cancer (23%). Most patients were White males. IgA nephropathy (IgAN) was the most common GN in our series (5 patients, 38%) followed by membranous nephropathy (MN) (3 patients, 23%). There was 1 patient with IgAN who had evidence of IgA deposits before vaccination suggesting the immune activation after vaccination triggered a flare of the disease. Our case series also included the first case report of tip-variant focal segmental glomerulosclerosis (FSGS), NELL-1-associated MN, and atypical anti-glomerular basement membrane (GBM) nephritis. A total of 77% developed acute kidney injury (AKI) with most being Kidney Disease: Improving Global Outcomes stage 1 (67%). Outcomes are favorable with 80% responding to therapy. CONCLUSION: New cases and relapse of GN can present shortly after mRNA COVID-19 vaccination. New cases of IgAN may result from unmasking of undiagnosed IgAN owing to robust immune activation rather than development of new deposits.
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Fibrillary GN (FGN) is a rare glomerular disease that is diagnosed based on the presence of fibrils in glomeruli. The fibrils are typically noncongophilic, randomly oriented, and measure 12-24 nm. Traditionally, electron microscopy (EM) has been an important tool to aid in the diagnosis of FGN by identifying the fibrils and to distinguish it from other entities that could mimic FGN. However, recently DnaJ homolog subfamily B member 9 (DNAJB9) has emerged as both a specific and sensitive biomarker in patients with FGN. It allows prompt diagnosis and alleviates reliance on EM. DNAJB9 is a cochaperone of heat shock protein 70 and is involved in endoplasmic reticulum protein-folding pathways. But its role in the pathogenesis of FGN remains elusive. DNAJB9 may act as a putative antigen or alternatively it may secondarily bind to misfolded IgG in the glomeruli. These hypotheses need future studies to elucidate the role of DNAJB9 in the pathogenesis of FGN. The treatment regimen for FGN has been limited due to paucity of studies. Most patients receive combination immunosuppressive regimens. Rituximab has been studied the most in FGN and it may delay disease progression. Prognosis of FGN remains poor and 50% require dialysis within 2 years of diagnosis. Despite its poor prognosis in native kidneys, the rate of recurrence post-transplantation is low (20%) and patient as well as allograft outcomes are similar to patients without FGN.