RESUMO
RATIONALE & OBJECTIVE: Kidney transplant patients with glomerulonephritis (GN) as their native disease commonly have received pretransplant immunosuppression (PTI). This may contribute to the immunosuppression burden potentially increasing the risk for infections after transplantation. STUDY DESIGN: Single-center, retrospective cohort study. SETTING & PARTICIPANTS: Recipients of a kidney transplant from January 2005 until May 2020 at a tertiary care university teaching hospital. EXPOSURE: Patients with GN as their native kidney disease who received PTI for treatment of GN (n=184) were compared with nondiabetic recipients of kidney transplants who did not receive PTI (n = 579). OUTCOME: First occurrence after transplantation of an infection outcome, either viral (BK or cytomegalovirus [CMV] infection) or bacterial. ANALYTICAL APPROACH: Cox regression analysis adjusted for age at transplant, sex, race, donor type, year of transplant surgery, dialysis vintage, receipt of T-cell depleting induction, and CMV transplant status. RESULTS: Over a median follow-up period of 5.7 years, patients with GN PTI were not at an increased risk for developing any first viral infection compared with controls (adjusted HR [AHR] 0.69 [95% CI, 0.52-0.91]) nor at increased risk for specific viral infections: BK infection 19.6% vs 26.3% (AHR 0.72 [95% CI, 0.50-1.05]) or CMV infection, 24.5% vs 29.0% (AHR, 0.76 [95% CI, 0.54-1.07]), respectively. There was also no increased risk of developing a first bacterial infection: 54.5% vs 57.5% (AHR, 0.90 [95% CI, 0.71-1.13]). These findings of no increased risk for infection were independent of the type of PTI used (cyclophosphamide, rituximab, mycophenolate mofetil, or calcineurin inhibitor) or the type of T-cell depleting induction therapy (alemtuzumab or antithymocyte globulin) administered. LIMITATIONS: Single-center study, no data on methylprednisone use for PTI, unmeasured confounding. CONCLUSIONS: Use of PTI for the treatment of GN was not associated with an increased risk of viral (BK or CMV) or bacterial infection after transplantation. Additional surveillance for infection after transplantation for patients who received PTI may not be necessary. PLAIN-LANGUAGE SUMMARY: Many kidney transplant patients have glomerular disease as the cause of kidney failure. These patients may be exposed to immunosuppression before transplantation, which could increase the risk for infections after receipt of a transplanted kidney. We identified kidney transplant recipients at a university teaching hospital who received immunosuppression before transplant for the treatment of glomerular kidney disease. We examined their risk for infection after transplantation by comparing it with the risk among transplant patients who were not exposed to immunosuppression before transplant. We observed no increased risk for infection after exposure to prior immunosuppression. Therefore, patients exposed to significant amounts of immunosuppression before transplantation may not require special surveillance or medication adjustment for fear of infection after their receipt of a kidney transplant.
Assuntos
Glomerulonefrite , Imunossupressores , Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Masculino , Feminino , Glomerulonefrite/epidemiologia , Glomerulonefrite/etiologia , Estudos Retrospectivos , Pessoa de Meia-Idade , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Adulto , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/imunologia , Terapia de Imunossupressão/efeitos adversos , Terapia de Imunossupressão/métodos , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/etiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologiaRESUMO
BACKGROUND: Kidney transplant patients with glomerulonephritis (GN) as their native disease may receive significant amounts of pre-transplant immunosuppression (PTI), which could increase the risk for development of malignancy post-transplant. METHODS: We conducted a single-center, retrospective study of kidney transplant recipients from January 2005 until May 2020. Patients with GN as their native kidney disease who received PTI for treatment of GN (n = 184) were compared with a control cohort (n = 579) of non-diabetic, non-PTI-receiving kidney transplant patients. We calculated hazard ratios (HR) with 95% confidence intervals (95% CI) for outcomes of first occurrence of solid or hematologic malignancy, non-melanoma skin cancer (NMSC) and post-transplant lymphoproliferative disorder (PTLD). RESULTS: Over a median follow-up of 5.7 years, PTI for GN was associated with significantly increased risk for malignancy compared with controls [13.0% vs 9.7%, respectively; adjusted HR 1.82 (95% CI 1.10-3.00)], but not for NMSC [10.3% vs 11.4%, respectively; adjusted HR 1.09 (95% CI 0.64-1.83)] or PTLD [3.3% vs 3.1%, respectively; adjusted HR 1.02 (95% CI 0.40-2.61)]. The risk for malignancy was significantly increased in those who received cyclophosphamide [HR 2.59 (95% CI 1.48-4.55)] or rituximab [HR 3.82 (95% CI 1.69-8.65)] pre-transplant, and particularly in those who received both cyclophosphamide and rituximab, but not for calcineurin inhibitors or mycophenolate. CONCLUSION: The use of PTI for treatment of GN, especially cyclophosphamide or even with rituximab, is associated with increased risk for development of solid or hematologic malignancy post-transplant. These data highlight potential risks with treatment of GN and underscore the importance of post-transplant malignancy surveillance in this patient population.
Assuntos
Glomerulonefrite , Neoplasias Hematológicas , Transplante de Rim , Transtornos Linfoproliferativos , Neoplasias , Humanos , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , Rituximab/efeitos adversos , Terapia de Imunossupressão/efeitos adversos , Glomerulonefrite/etiologia , Ciclofosfamida , Neoplasias/etiologia , Neoplasias/complicações , Transtornos Linfoproliferativos/epidemiologia , Transtornos Linfoproliferativos/etiologia , Transplantados , Fatores de RiscoRESUMO
Evaluation of hematuria and microscopic examination of urine sediment are commonly used tools by nephrologists in their assessment of glomerular diseases. Certain morphological aspects of urine red blood cells (RBCs) seen by microscopy may help in identifying the source of hematuria as glomerular or not. Recognized signs of glomerular injury are RBC casts or dysmorphic RBCs, in particular acanthocytes (ring-shaped RBCs with protruding blebs). Despite being a highly operator-dependent test, urine sediment examination revealing these signs of glomerular hematuria has demonstrated specificities and positive predictive values ranging between 90%-100% for diagnosing glomerular disease, although sensitivity can be quite variable. Hematuria is a commonly used tool for diagnosing patients with proliferative glomerulonephritis such as IgA nephropathy, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, and lupus nephritis, sometimes even as a surrogate for kidney involvement. Studies examining the role for hematuria in monitoring and predicting adverse outcomes in these diseases have shown inconsistent results, possibly due to inconsistent definitions that often fail to consider specific markers of glomerular hematuria such as dysmorphic RBCs, acanthocytes, or RBC casts. A consensus definition of what constitutes glomerular hematuria would help standardize use in future studies and likely improve the diagnostic and prognostic value of hematuria as a marker of glomerulonephritis.
Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Glomerulonefrite por IGA , Glomerulonefrite , Biomarcadores , Glomerulonefrite/complicações , Glomerulonefrite/diagnóstico , Hematúria/diagnóstico , Hematúria/etiologia , Humanos , Glomérulos Renais , MicroscopiaRESUMO
BACKGROUND: IgA nephropathy (IgAN) is the leading primary GN worldwide. The disease is thought to result from glomerular deposition of circulating immune complexes of IgG bound to galactose-deficient IgA1 (Gd-IgA1). However, routine immunofluorescence microscopy fails to detect IgG in many kidney biopsies from patients with IgAN and the specificity of IgG in immunodeposits has not been tested. METHODS: We used remnant frozen kidney-biopsy specimens from 34 patients with IgAN; 14 were IgG-positive and 20 were IgG-negative by routine immunofluorescence microscopy. Six patients with primary membranous nephropathy (MN) and eight with lupus nephritis (LN) served as controls. IgG in the kidney tissue was extracted and its amount determined by ELISA. IgG molecular integrity was assessed by SDS-PAGE immunoblotting. Antigenic specificity of extracted IgG was determined by ELISA using phospholipase A2 receptor (PLA2R) or Gd-IgA1 as antigen. In addition, ten other IgAN cases, six IgG-positive and four IgG-negative by routine immunofluorescence, were used for colocalization studies by confocal microscopy. RESULTS: IgG extracted from MN but not IgAN immunodeposits reacted with PLA2R. Conversely, IgG extracted from IgAN but not MN or LN immunodeposits reacted with Gd-IgA1. Even IgAN kidney-biopsy specimens without IgG by routine immunofluorescence microscopy had IgG specific for Gd-IgA1. Confocal microscopy confirmed the presence of IgG in the IgAN biopsies with colocalization of glomerular IgA and IgG. CONCLUSIONS: These results reveal for the first time that IgAN kidney biopsies, with or without IgG by routine immunofluorescence, contain Gd-IgA1-specific IgG autoantibodies. These findings support the importance of these autoantibodies in the pathogenesis of IgAN.
Assuntos
Autoanticorpos/imunologia , Glomerulonefrite por IGA/imunologia , Imunoglobulina A/imunologia , Glomérulos Renais/imunologia , Adulto , Idoso , Especificidade de Anticorpos , Feminino , Galactose/deficiência , Humanos , Imunoglobulina A/metabolismo , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
IgA nephropathy is the most common primary glomerulonephritis worldwide. Its frequent coexistence with inflammatory, infectious, or malignant processes raises the possibility of a pathologic rather than coincidental association. Major strides have been made to elucidate the underlying pathophysiologic events that culminate in the development of primary IgA nephropathy. Whether secondary forms of the disease share common pathways triggered by underlying disorders or different mechanisms leading to similar pathologic findings remains to be determined. In this article we describe the most frequent etiologies for secondary IgA nephropathy and review the available literature for the pathophysiology.
Assuntos
Glomerulonefrite por IGA/etiologia , Infecções/complicações , Doenças Inflamatórias Intestinais/complicações , Hepatopatias/complicações , Doenças Autoimunes/complicações , HumanosRESUMO
Improved understanding of glomerular disease mechanisms over the past decade has led to the emergence of new and targeted therapeutic strategies for chronic kidney disease (CKD). Most promising among these are the administration of recombinant mutated human angiopoietin-like 4, sialic acid-related sugars that induce sialylation in vivo, compounds related to Bis-T-23, and immune depletion of the soluble urokinase receptor from the circulation. Taking these therapeutic strategies into clinical trials will be the first step away from repurposed and relatively toxic drugs currently used for treating kidney disease.
Assuntos
Glomérulos Renais/patologia , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/patologia , Proteína 4 Semelhante a Angiopoietina , Angiopoietinas/uso terapêutico , Animais , Humanos , Proteinúria/tratamento farmacológicoRESUMO
Rationale & Objective: About 25%-40% of patients with inflammatory bowel disease (IBD) may have extraintestinal manifestations, mainly involving the liver, skin, and joints. Kidney involvement in patients with IBD has been reported, but there are no estimates of its prevalence in population-based studies in the United States. We compared the frequency of acute kidney injury (AKI) among hospitalizations with IBD with that among hospitalizations with collagen vascular diseases and hospitalizations with neither condition. Study Design: Retrospective, population-based cohort study. Setting & Participants: Healthcare Cost and Utilization Project-Nationwide Inpatient Sample database. Outcomes: AKI and AKI requiring dialysis. Analytical Approach: Regression models were used to compare the occurrence of AKI among groups. Inverse probability of treatment weighting was applied to balance groups on covariates. Results: The final sample comprised 5,735,804 hospitalizations, including 57,121 with IBD, 159,930 with collagen vascular diseases, and 5,518,753 with neither IBD nor collagen vascular diseases. AKI was observed in 13%, 15%, and 12.2% of hospitalizations with IBD, collagen vascular diseases, and the general population, respectively. When adjusting for demographic, hospital, and clinical characteristics using inverse probability of treatment weighting, hospitalizations with IBD had higher odds of being diagnosed with AKI than both those with collagen vascular diseases (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.27-1.38) and the general population (OR, 1.27; 95% CI, 1.23-1.31) and also had higher odds of being diagnosed with AKI requiring dialysis than those with collagen vascular diseases (OR, 1.59; 95% CI, 1.31-1.94) or than the general population (OR, 1.45; 95% CI, 1.25-1.68). Limitations: Cross-sectional analysis, underreporting of International Classification of Diseases codes, and analyses relevant to in-hospital stays only. Conclusions: The prevalence and risk of AKI among hospitalizations with IBD is greater than that of hospitalizations with collagen vascular diseases and the general population. Coexisting kidney disease should be considered among patients with a known diagnosis of IBD.
As a nephrologist, we have evaluated many patients with inflammatory bowel disease with various forms of kidney disease, both inflammatory and noninflammatory. Based on a multitude of factors, we have always wondered if there are shared immune mechanisms between the gut and kidney that could explain the underlying inflammation in both organs. In addition, based on recent studies of other autoimmune/inflammatory diseases, there is growing interest in the role of the gut microbiome (microorganisms that reside in our gut) and its influence on the immune system as well as how both the altered microbiome and immune system affect the kidneys. As a first step, we wanted to understand if some forms of kidney disease are more prevalent in patients with inflammatory bowel disease than in the general population, which possibly suggests a shared pathogenesis.
RESUMO
Infections are increasingly recognized as a common complication of chimeric antigen receptor (CAR) T-cell therapy. The incidence of clinically-defined infection after CD19.CAR T-cell therapy for relapsed/refractory lymphoma ranges from 60-90% in the first year after CAR T-cell therapy and is the most common cause for non-relapse mortality. However, infectious risk after CAR T-cell therapy targeting other malignancies is not well understood. Herein, we report for the first time, infectious complications after CD30.CAR T-cell treatment for patients with Hodgkin's lymphoma and peripheral T-cell lymphoma. Since CD30 is only expressed on a subset of activated T and B-cells, we hypothesized that CD30.CAR T-cell patients would have reduced incidence and severity of infections after infusion compared to CD19.CAR T-cell patients. We retrospectively evaluated all 64 patients who received CD30.CAR T-cells at a single institution between 2016-2021, and assessed infections within one year after cell infusion, comparing these data to a contemporary cohort of 50 patients who received CD19.CAR T-cells at the same institution between 2018-2021. 23 CD30.CAR T-cell patients (36%) and 18 CD19.CAR T-cell patients (36%) developed a microbiologically confirmed infection. Infection severity and bacterial infections were higher in the CD19.CAR T-cell group compared to CD30.CAR T-cell recipients who more commonly had grade 1 respiratory viral infections. Our data reflect expected outcomes for severity and infection type in CD19.CAR T-cell patients and provide a benchmark for comparison with the novel CD30.CAR T-cell product. Although our findings require replication in a larger cohort, they have implications for antimicrobial prophylaxis guidelines after CD30.CAR T-cell therapy. KEY POINTS: 1) The incidence of infections within the first year after CD30.CAR T-cell therapy was equivalent to that following CD19.CAR T-cell therapy2) Viral infections were more common after CD30.CAR T-cell therapy but bacterial infections predominated after CD19.CAR T-cell therapy.
RESUMO
Rapidly progressive dementia is a neurological condition that results in subacute deterioration in cognitive, behavioral and motor function. The most serious diagnosis for a patient with rapidly progressive dementia is Creutzfeldt-Jakob Disease (CJD), a prion-related illness that typically results in death within one year. However, there are numerous autoimmune, infectious and toxic-metabolic causes of rapidly progressive dementia that are potentially reversible with treatment. Thus, the differential diagnosis for a rapidly progressive dementia is critically important. In this article, the authors discuss a case of CJD diagnosed at a St. Paul hospital to illustrate the differential diagnosis of rapidly progressive dementia and highlight the role of neuroimaging.
Assuntos
Síndrome de Creutzfeldt-Jakob/diagnóstico , Hospitalização , Biomarcadores/líquido cefalorraquidiano , Demência/etiologia , Diagnóstico Diferencial , Imagem de Difusão por Ressonância Magnética , Progressão da Doença , Eletrocardiografia , Feminino , Humanos , Aumento da Imagem , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Exame Neurológico , Príons/líquido cefalorraquidiano , Processamento de Sinais Assistido por ComputadorRESUMO
BACKGROUND: Hematuria is frequently present in podocytopathies, but its significance and prognostic value is not well described in these proteinuric kidney diseases. This study describes the prevalence and association between hematuria and kidney-related outcomes in these disorders. METHODS: Hematuria was assessed at the initial urinalysis in participants with the following podocytopathies, membranous nephropathy, minimal change disease, and focal segmental glomerulosclerosis, in the Nephrotic Syndrome Study Network (NEPTUNE) and Cure Glomerulonephropathy (CureGN) cohorts with >24 months of follow-up. Multivariable Cox proportional hazards models were fit for time to composite outcome (end-stage kidney disease or 40% decline in estimated glomerular filtration rate (eGFR) and eGFR <60 ml/min/1.73 m2) and proteinuria remission (UPCR <0.3 mg/mg). RESULTS: Among the 1,516 adults and children in the study, 528 (35%) participants had focal segmental glomerulosclerosis, 499 (33%) had minimal change disease, and 489 (32%) had membranous nephropathy. Median (IQR) time from biopsy until the initial study urinalysis was 260 days (49, 750), and 498 (33%) participants were positive for hematuria. Participants with hematuria compared to those without, were older (37 [16, 55] vs 33 years [12, 55]), more likely to have an underlying diagnosis of membranous nephropathy (44% vs 27%), had shorter time since biopsy (139 [27, 477] vs 325 [89, 878] days) and higher UPCR (3.8 [1.4, 8.0] vs 0.9 [0.1, 3.1]g/g). After adjusting for diagnosis, age, sex, UPCR, eGFR, time since biopsy, and study cohort, hematuria was associated with a higher riskof reaching the composite outcome (HR 1.31 [1.04, 1.65], p-value 0.02) and lower rate of reaching proteinuria remission (HR 0.80 [0.65-0.98], p-value 0.03). CONCLUSIONS: Hematuria is prevalent among participants with the three podocytopathies and is significantly and independently associated with worse kidney-related outcomes, including both progressive loss of kidney function remission of proteinuria.
RESUMO
A 53 year old female with ESRD on hemodialysis presented with headache, vomiting, and lethargy that had started 2 h prior to presentation. Magnetic resonance imaging revealed parenchymal hemorrhage in the temporal, occipital, and cerebellar white matter. Magnetic resonance venography disclosed hypoplastic transverse sinus. On cerebral angiogram there was no evidence of cerebral aneurysm, vasculitis or vascular malformation. Angiogram demonstrated a high-grade stenosis was present in the left internal jugular vein (IJV) just below the anastomosis of the graft. There was retrograde high flow in the left IJV above the anastomosis of the graft, which fills a small left transverse venous sinus. There was also filling of the multiple abnormally enlarged leptomeningeal veins over the surface of the left cerebral and left cerebellar hemispheres. Retrograde blood flow was due to IJV stenosis which led to cerebral venous hypertension and intraparenchymal brain hemorrhage. She then underwent occlusion of her left brachiojugular dialysis graft. Thereafter, her mental status markedly improved and her headache resolved. Since IJV stenosis and hypoplastic transverse sinuses are not rare, patients with jugular grafts should probably be closely watched for symptoms of increased intracranial pressure. As awareness of vein preservation in CKD patients grows, the prevalence of CVS would probably decline in future.
Assuntos
Hemorragia Cerebral/etiologia , Constrição Patológica/complicações , Veias Jugulares/patologia , Diálise Renal/efeitos adversos , Artéria Braquial/diagnóstico por imagem , Hemorragia Cerebral/diagnóstico por imagem , Feminino , Humanos , Veias Jugulares/diagnóstico por imagem , Falência Renal Crônica/terapia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Lobo Parietal/diagnóstico por imagem , Lobo Parietal/patologia , RadiografiaRESUMO
INTRODUCTION: The Cure Glomerulonephropathy Network (CureGN) is a 66-center longitudinal observational study of patients with biopsy-confirmed minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy (IgAN), including IgA vasculitis (IgAV). This study describes the clinical characteristics and treatment patterns in the IgA cohort, including comparisons between IgAN versus IgAV and adult versus pediatric patients. METHODS: Patients with a diagnostic kidney biopsy within 5 years of screening were eligible to join CureGN. This is a descriptive analysis of clinical and treatment data collected at the time of enrollment. RESULTS: A total of 667 patients (506 IgAN, 161 IgAV) constitute the IgAN/IgAV cohort (382 adults, 285 children). At biopsy, those with IgAV were younger (13.0 years vs. 29.6 years, P < 0.001), more frequently white (89.7% vs. 78.9%, P = 0.003), had a higher estimated glomerular filtration rate (103.5 vs. 70.6 ml/min per 1.73 m2, P < 0.001), and lower serum albumin (3.4 vs. 3.8 g/dl, P < 0.001) than those with IgAN. Adult and pediatric individuals with IgAV were more likely than those with IgAN to have been treated with immunosuppressive therapy at or prior to enrollment (79.5% vs. 54.0%, P < 0.001). CONCLUSION: This report highlights clinical differences between IgAV and IgAN and between children and adults with these diagnoses. We identified differences in treatment with immunosuppressive therapies by disease type. This description of baseline characteristics will serve as a foundation for future CureGN studies.
RESUMO
A 17-year-old male with attention deficit hyperactivity disorder was admitted to the hospital with generalized weakness. Vital signs and physical examination were normal. Laboratory data were notable for a creatinine of 4.5 mg/dL (baseline 0.6 mg/dL), estimated glomerular filtration rate of 18 ml/min/1.73 m² and hemoglobin 10 g/dL. Urinalysis revealed only 30 mg/dL protein. Serology for autoimmune workup was negative. Renal ultrasound was normal. Kidney biopsy showed noncaseating granulomas and acute on chronic tubulointerstitial nephritis (TIN) with lymphocytes, macrophages, plasma cells and no eosinophils. Acid fast bacilli and Grocott's methenamine silver stains were negative. Granulomatous interstitial nephritis (GIN) was diagnosed. Prednisone at 60 mg/day was started and tapered. He was then noted to have diarrhea. Colonoscopy showed active enteritis with granulomatous inflammation consistent with Crohn's disease (CD). Azathioprine was started but due to worsening renal function and diarrhea, it was discontinued. He did not tolerate continued higher doses of prednisone because of mood swings and cushingoid features. Infliximab was initiated with improvement in renal function. There was rapid worsening of renal function when infliximab therapy was interrupted but improved when both prednisone and inflixamb were reinitiated.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Doença de Crohn/complicações , Granuloma/tratamento farmacológico , Nefrite Intersticial/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adolescente , Granuloma/etiologia , Humanos , Infliximab , Masculino , Nefrite Intersticial/etiologia , Prednisona/uso terapêuticoRESUMO
A 32-year-old man was admitted with cerebrospinal fluid leakage from a right scalp surgical wound after a resection of recurrent meningioma and reconstruction of skull with muscle flap 3 weeks earlier. On day 4 of admission, he was found to be tachycardic and decreased breath sounds on the right side. Chest x-ray revealed a large right pleural effusion which was found to be exudative after thoracocentesis. Infectious work-up and cytology was negative. CT showed both parietal and visceral pleural masses, which was consistent with meningioma on ultrasound-guided biopsy. He underwent right-side decortication and pleurodesis for recurrent pleural effusion. He declined further treatment and opted for hospice care and expired a month later.