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1.
Kidney Int ; 106(3): 326-336, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39174192

RESUMEN

The term atypical hemolytic uremic syndrome has been in use since the mid-1970s. It was initially used to describe the familial or sporadic form of hemolytic uremic syndrome as opposed to the epidemic, typical form of the disease. Over time, the atypical hemolytic uremic syndrome term has evolved into being used to refer to anything that is not Shiga toxin-associated hemolytic uremic syndrome. The term describes a heterogeneous group of diseases of disparate causes, a circumstance that makes defining disease-specific natural history and/or targeted treatment approaches challenging. A working group of specialty-specific experts in the thrombotic microangiopathies was convened to review the validity of this broad term in an era of swiftly advancing science and targeted therapeutics. A Delphi approach was used to define and interrogate some of the key issues related to the atypical hemolytic uremic syndrome nomenclature.


Asunto(s)
Síndrome Hemolítico Urémico Atípico , Técnica Delphi , Terminología como Asunto , Humanos , Síndrome Hemolítico Urémico Atípico/genética , Síndrome Hemolítico Urémico Atípico/diagnóstico , Consenso , Nefrología/normas
2.
N Engl J Med ; 385(21): 1974-1980, 2021 11 18.
Artículo en Inglés | MEDLINE | ID: mdl-34788508

RESUMEN

We describe two cases of acquired parathyroid hormone (PTH) resistance consequent to the development of serum PTH type 1 receptor (PTH1R) autoantibodies, which block PTH binding and signaling. Both cases were associated with other autoimmune manifestations, and one case was associated with atypical membranous glomerulonephritis. In vitro binding and signaling assays identified the presence of PTH1R-blocking IgG autoantibodies, which were not present in serum samples from patients with other renal or autoimmune disorders. (Funded by the Intramural Research Programs of the National Institute of Diabetes and Digestive and Kidney Diseases and others.).


Asunto(s)
Autoanticuerpos/sangre , Hipocalcemia/etiología , Hormona Paratiroidea/metabolismo , Receptor de Hormona Paratiroídea Tipo 1/inmunología , Adulto , Anciano , Análisis Mutacional de ADN , Femenino , Glicopéptidos/sangre , Humanos , Hipocalcemia/genética , Inmunoglobulina G/sangre , Inmunofenotipificación , Glomérulos Renales/patología , Microscopía Electrónica , Mutación , Seudohipoparatiroidismo/genética
3.
J Biol Chem ; 298(3): 101605, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35065076

RESUMEN

Anti-phospholipase A2 receptor autoantibody (PLA2R-Ab) plays a critical role in the pathogenesis of primary membranous nephropathy (PMN), an autoimmune kidney disease characterized by immune deposits in the glomerular subepithelial spaces and proteinuria. However, the mechanism of how PLA2R-Abs interact with the conformational epitope(s) of PLA2R has remained elusive. PLA2R is a single transmembrane helix receptor containing ten extracellular domains that begin with a CysR domain followed by a FnII and eight CTLD domains. Here, we examined the interactions of PLA2R-Ab with the full PLA2R protein, N-terminal domain truncations, and C-terminal domain deletions under either denaturing or physiological conditions. Our data demonstrate that the PLA2R-Abs against the dominant epitope (the N-terminal CysR-CTLD1 triple domain) possess weak cross-reactivities to the C-terminal domains beyond CTLD1. Moreover, both the CysR and CTLD1 domains are required to form a conformational epitope for PLA2R-Ab interaction, with FnII serving as a linker domain. Upon close examination, we also observed that patients with newly diagnosed PMN carry two populations of PLA2R-Abs in sera that react to the denatured CysR-CTLD3 (the PLA2R-Ab1) and denatured CysR-CTLD1 (the PLA2R-Ab2) domain complexes on Western blots, respectively. Furthermore, the PLA2R-Ab1 appeared at an earlier time point than PLA2R-Ab2 in patients, whereas the increased levels of PLA2R-Ab2 coincided with the worsening of proteinuria. In summary, our data support that an integrated folding of the three PLA2R N-terminal domains, CysR, FnII, and CTLD1, is a prerequisite to forming the PLA2R conformational epitope and that the dominant epitope-reactive PLA2R-Ab2 plays a critical role in PMN clinical progression.


Asunto(s)
Glomerulonefritis Membranosa , Receptores de Fosfolipasa A2 , Autoanticuerpos/inmunología , Autoanticuerpos/metabolismo , Epítopos , Femenino , Glomerulonefritis Membranosa/genética , Glomerulonefritis Membranosa/inmunología , Glomerulonefritis Membranosa/orina , Humanos , Masculino , Proteinuria/genética , Proteinuria/inmunología , Receptores de Fosfolipasa A2/química , Receptores de Fosfolipasa A2/inmunología
4.
Kidney Int ; 99(1): 227-237, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33181156

RESUMEN

The effects of SARS-CoV-2 infection on individuals with immune-mediated glomerulonephritis, who are often undergoing immunosuppressive treatments, are unknown. Therefore, we created the International Registry of COVID infection in glomerulonephritis (IRoc-GN) and identified 40 patients with glomerulonephritis and COVID-19 followed in centers in North America and Europe. Detailed information on glomerulonephritis diagnosis, kidney parameters, and baseline immunosuppression prior to infection were recorded, as well as clinical presentation, laboratory values, treatment, complications, and outcomes of COVID-19. This cohort was compared to 80 COVID-positive control cases from the general population without glomerulonephritis matched for the time of infection. The majority (70%) of the patients with glomerulonephritis and all the controls were hospitalized. Patients with glomerulonephritis had significantly higher mortality (15% vs. 5%, respectively) and acute kidney injury (39% vs. 14%) than controls, while the need for kidney replacement therapy was not statistically different between the two groups. Receiving immunosuppression or renin-angiotensin-aldosterone system inhibitors at presentation did not increase the risk of death or acute kidney injury in the glomerulonephritis cohort. In the cohort with glomerulonephritis, lower serum albumin at presentation and shorter duration of glomerular disease were associated with greater risk of acute kidney injury and need for kidney replacement therapy. No differences in outcomes occurred between patients with primary glomerulonephritis versus glomerulonephritis associated with a systemic autoimmune disease (lupus or vasculitis). Thus, due to the higher mortality and risk of acute kidney injury than in the general population without glomerulonephritis, patients with glomerulonephritis and COVID-19 should be carefully monitored, especially when they present with low serum albumin levels.


Asunto(s)
Lesión Renal Aguda/epidemiología , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , COVID-19/inmunología , Glomerulonefritis/inmunología , Inmunosupresores/efectos adversos , Lesión Renal Aguda/etiología , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/complicaciones , COVID-19/mortalidad , COVID-19/virología , Europa (Continente)/epidemiología , Femenino , Glomerulonefritis/complicaciones , Glomerulonefritis/tratamiento farmacológico , Glomerulonefritis/mortalidad , Humanos , Cooperación Internacional , Masculino , Persona de Mediana Edad , América del Norte/epidemiología , Sistema de Registros/estadística & datos numéricos , Estudios Retrospectivos , SARS-CoV-2/inmunología
5.
J Am Soc Nephrol ; 31(1): 208-217, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31843984

RESUMEN

BACKGROUND: Circulating serum autoantibodies against the M-type phospholipase A2 receptor (PLA2R-AB) are a key biomarker in the diagnosis and monitoring of primary membranous nephropathy (MN). However, little is known about the appearance and trajectory of PLA2R-AB before the clinical diagnosis of MN. METHODS: Using the Department of Defense Serum Repository, we analyzed PLA2R-AB in multiple, 1054 longitudinal serum samples collected before diagnosis of MN from 134 individuals with primary MN, 35 individuals with secondary MN, and 134 healthy volunteers. We evaluated the presence and timing of non-nephrotic range proteinuria (NNRP) and serum albumin measurements in relation to PLA2R-AB status. RESULTS: Analysis of PLA2R-AB in longitudinal serum samples revealed seropositivity in 44% (59 out of 134) of primary MN cases, 3% (one out of 35) of secondary MN cases, and in 0% of healthy controls. Among patients with MN, PLA2R-AB were detectable at a median of 274 days before renal biopsy diagnosis (interquartile range, 71-821 days). Approximately one third of the participants became seropositive within 3 months of MN diagnosis. Of the 21 individuals with documented prediagnostic NNRP, 43% (nine out of 21) were seropositive before NNRP was first documented and 28.5% (six out of 21) were seropositive at the same time as NNRP; 66% (39 out of 59) of those seropositive for PLA2R-AB had hypoalbuminemia present at the time antibody was initially detected. Twelve participants (20%) were seropositive before hypoalbuminemia became apparent, and eight participants (14%) were seropositive after hypoalbuminemia became apparent. CONCLUSIONS: Circulating PLA2R-AB are detectable months to years before documented NNRP and biopsy-proven diagnosis in patients with MN.


Asunto(s)
Autoanticuerpos/sangre , Glomerulonefritis Membranosa/sangre , Receptores de Fosfolipasa A2/inmunología , Adulto , Estudios de Casos y Controles , Femenino , Glomerulonefritis Membranosa/diagnóstico , Glomerulonefritis Membranosa/inmunología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
7.
Clin Immunol ; 198: 102-105, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30472267

RESUMEN

Owing to an increasing shortage of donor organs, the majority of patients with end-stage kidney disease remains reliant on extracorporeal hemodialysis (HD) in order to counter the lifelong complications of a failing kidney. While HD remains a life-saving option for these patients, mounting evidence suggests that it also fuels a vicious cycle of thromboinflammation that can increase the risk of cardiovascular disease. During HD, blood-borne innate immune systems become inappropriately activated on the biomaterial surface, instigating proinflammatory reactions that can alter endothelial and vascular homeostasis. Complement activation, early during the HD process, has been shown to fuel a multitude of detrimental thromboinflammatory reactions that collectively contribute to patient morbidity. Here we discuss emerging aspects of complement's involvement in HD-induced inflammation and put forth the concept that targeted intervention at the level of C3 might constitute a promising therapeutic approach in HD patients.


Asunto(s)
Complemento C3/antagonistas & inhibidores , Inactivadores del Complemento/uso terapéutico , Inflamación/tratamiento farmacológico , Diálisis Renal/efectos adversos , Humanos
8.
J Clin Apher ; 34(4): 495-498, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30537217

RESUMEN

Idiopathic membranous nephropathy is the most common cause of nephrotic syndrome in nondiabetic adults. The antibody most often implicated is the M-type phospholipase A2 receptor (PLA2R) antibody, found in >70% of primary membranous nephropathy cases. First-line therapy is immunosuppressive in nature, but for patients who are treatment-resistant there is a significant risk of end-stage renal disease and mortality. Hypercholesterolemia is not only a side effect of nephrotic syndrome, but also its presence may worsen renal function. A recent single-arm observational study in Japan found that low-density lipoprotein apheresis (LDL-A) was able to ameliorate nephrotic syndrome in half of patients who were resistant to medication. We present a case of treatment resistant PLA2R negative membranous nephropathy who had significant improvement following two courses of LDL-A. To our knowledge, this is the first such reported case in the United States.


Asunto(s)
Eliminación de Componentes Sanguíneos , Glomerulonefritis Membranosa/terapia , Lipoproteínas LDL/aislamiento & purificación , Humanos , Síndrome Nefrótico/prevención & control , Receptores de Fosfolipasa A2/deficiencia , Receptores de Fosfolipasa A2/inmunología , Terapia Recuperativa/métodos , Resultado del Tratamiento , Estados Unidos
9.
Mol Genet Metab ; 125(1-2): 181-191, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30064963

RESUMEN

Alström Syndrome is a ciliopathy associated with obesity, insulin resistance/type 2 diabetes mellitus, cardiomyopathy, retinal degeneration, hearing loss, progressive liver and kidney disease, and normal cognitive function. ALMS1, the protein defective in this disorder, localizes to the cytoskeleton, microtubule organizing center, as well as the centrosomes and ciliary basal bodies and plays roles in formation and maintenance of cilia, cell cycle regulation, and endosomal trafficking. Kidney disease in this disorder has not been well characterized. We performed comprehensive multisystem evaluations on 38 patients. Kidney function decreased progressively; eGFR varied inversely with age (p = 0.002). Eighteen percent met the definition for chronic kidney disease (eGFR < 60 mL/min/1.73 m2 and proteinuria); all were adults with median age of 32.8 (20.6-37.9) years. After adjusting for age, there were no significant associations of kidney dysfunction with type 2 diabetes mellitus, dyslipidemia, hypertension, cardiomyopathy or portal hypertension suggesting that kidney disease in AS is a primary manifestation of the syndrome due to lack of ALMS1 protein. Approximately one-third of patients had hyperechogenicity of the renal parenchyma on imaging. While strict control of type 2 diabetes mellitus may decrease kidney-related morbidity and mortality in Alström syndrome, identification of novel targeted therapies is needed.


Asunto(s)
Síndrome de Alstrom/genética , Dislipidemias/genética , Obesidad/genética , Proteínas/genética , Adulto , Síndrome de Alstrom/complicaciones , Síndrome de Alstrom/metabolismo , Síndrome de Alstrom/patología , Cardiomiopatías/complicaciones , Cardiomiopatías/genética , Cardiomiopatías/metabolismo , Cardiomiopatías/patología , Proteínas de Ciclo Celular , Dislipidemias/complicaciones , Dislipidemias/metabolismo , Dislipidemias/patología , Femenino , Humanos , Resistencia a la Insulina/genética , Riñón/metabolismo , Riñón/patología , Enfermedades Renales/complicaciones , Enfermedades Renales/genética , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Masculino , Mutación , Obesidad/complicaciones , Obesidad/metabolismo , Obesidad/patología , Degeneración Retiniana
13.
J Am Soc Nephrol ; 26(2): 291-301, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25205735

RESUMEN

Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults. Recent clinical studies established that >70% of patients with idiopathic (also called primary) MN (IMN) possess circulating autoantibodies targeting the M-type phospholipase A2 receptor-1 (PLA2R) on the surface of glomerular visceral epithelial cells (podocytes). In situ, these autoantibodies trigger the formation of immune complexes, which are hypothesized to cause enhanced glomerular permeability to plasma proteins. Indeed, the level of autoantibody in circulation correlates with the severity of proteinuria in patients. The autoantibody only recognizes the nonreduced form of PLA2R, suggesting that disulfide bonds determine the antigenic epitope conformation. Here, we identified the immunodominant epitope region in PLA2R by probing isolated truncated PLA2R extracellular domains with sera from patients with IMN that contain anti-PLA2R autoantibodies. Patient sera specifically recognized a protein complex consisting of the cysteine-rich (CysR), fibronectin-like type II (FnII), and C-type lectin-like domain 1 (CTLD1) domains of PLA2R only under nonreducing conditions. Moreover, absence of either the CysR or CTLD1 domain prevented autoantibody recognition of the remaining domains. Additional analysis suggested that this three-domain complex contains at least one disulfide bond required for conformational configuration and autoantibody binding. Notably, the three-domain complex completely blocked the reactivity of autoantibodies from patient sera with the full-length PLA2R, and the reactivity of patient sera with the three-domain complex on immunoblots equaled the reactivity with full-length PLA2R. These results indicate that the immunodominant epitope in PLA2R is exclusively located in the CysR-FnII-CTLD1 region.


Asunto(s)
Autoanticuerpos/inmunología , Glomerulonefritis Membranosa/inmunología , Epítopos Inmunodominantes/inmunología , Receptores de Fosfolipasa A2/inmunología , Autoanticuerpos/sangre , Cisteína/inmunología , Fibronectinas/inmunología , Glomerulonefritis Membranosa/sangre , Glomerulonefritis Membranosa/patología , Células HEK293 , Humanos , Epítopos Inmunodominantes/química , Lectinas Tipo C/inmunología , Podocitos/inmunología , Podocitos/patología
15.
Cancer ; 120(9): 1426-32, 2014 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-24474396

RESUMEN

BACKGROUND: Thrombotic microangiopathy (TMA) is a complication that developed in some patients receiving 12 Gy total body irradiation (TBI) in addition to lymphodepleting preparative chemotherapy prior to infusion of autologous tumor-infiltrating lymphocytes (TIL) with high-dose aldesleukin (IL-2). This article describes the incidence, presentation, and course of radiation-associated TMA. METHODS: The data for patients with metastatic melanoma who received ACT with TIL plus aldesleukin following myeloablative chemotherapy and 12-Gy TBI was examined, in order to look at patient characteristics and the natural history of TMA. RESULTS: The median time to presentation was approximately 8 months after completing TBI. The estimated cumulative incidence of TMA was 31.2% (median follow-up of 24 months). Noninvasive criteria for diagnosis included newly elevated creatinine levels, new-onset hypertension, new-onset anemia, microscopic hematuria, thrombocytopenia, low haptoglobin, and elevated lactate dehydrogenase values. Once diagnosed, patients were managed with control of their hypertension with multiple agents and supportive red blood cell transfusions. TMA typically stabilized or improved and no patient progressed to dialysis. TMA was associated with a higher probability of an antitumor response. CONCLUSIONS: TMA occurs in approximately a third of patients treated with a lymphodepleting preparative chemotherapy regimen with TBI prior to autologous T cell therapy. The disease has a variable natural history, however, no patient developed end-stage renal failure. Successful management with supportive care and aggressive hypertension control is vital to the safe application of a systemic therapy that has shown curative potential for patients with disseminated melanoma.


Asunto(s)
Melanoma/terapia , Traumatismos por Radiación/etiología , Microangiopatías Trombóticas/etiología , Irradiación Corporal Total/efectos adversos , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/administración & dosificación , Femenino , Humanos , Inmunoterapia Adoptiva/efectos adversos , Inmunoterapia Adoptiva/métodos , Interleucina-2/administración & dosificación , Interleucina-2/efectos adversos , Interleucina-2/análogos & derivados , Linfocitos Infiltrantes de Tumor/trasplante , Masculino , Melanoma/sangre , Persona de Mediana Edad , Proyectos Piloto , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Resultado del Tratamiento , Vidarabina/administración & dosificación , Vidarabina/análogos & derivados , Adulto Joven
16.
Am J Kidney Dis ; 62(3): 403-41, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23871408

RESUMEN

Glomerulonephritis (GN) is an important cause of morbidity and mortality in patients of all ages throughout the world. Because these disorders are relatively rare, it is difficult to perform randomized clinical trials to define optimal treatment for many of the specific glomerulopathies. In the absence of high-grade evidence to guide the care of glomerular diseases, in June 2012, KDIGO (Kidney Disease: Improving Global Outcomes) published an international clinical guideline for GN. The Work Group report represents an important review of the literature in this area and offers valid and useful guidelines for the most common situations that arise in the management of patients with glomerular disease. This commentary, developed by a panel of clinical experts convened by the National Kidney Foundation, attempts to put the GN guideline into the context of the US health care system. Overall, we support the vast majority of the recommendations and highlight select areas in which epidemiological factors and medical practice patterns in this country justify modifications and adjustments in order to achieve favorable outcomes. There remain large gaps in our knowledge of the best approaches to treat glomerular disease and we strongly endorse an expanded clinical research effort to improve the health and long-term outcomes of children and adults with GN.


Asunto(s)
Glomerulonefritis/diagnóstico , Glomerulonefritis/terapia , Guías de Práctica Clínica como Asunto/normas , Informe de Investigación/normas , Glomerulonefritis/epidemiología , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto/normas , Estados Unidos
17.
J Am Soc Nephrol ; 23(10): 1617-30, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22859855

RESUMEN

Exciting progress recently has been made in our understanding of idiopathic membranous nephropathy, as well as treatment of this disease. Here, we review important advances regarding the pathogenesis of membranous nephropathy. We will also review the current approach to treatment and its limitations and will highlight new therapies that are currently being explored for this disease including Rituximab, mycophenolate mofetil, and adrenocorticotropic hormone, with an emphasis on results of the most recent clinical trials.


Asunto(s)
Glomerulonefritis Membranosa/terapia , Hormona Adrenocorticotrópica/uso terapéutico , Alquilantes/uso terapéutico , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Inhibidores de la Calcineurina , Ensayos Clínicos como Asunto , Glomerulonefritis Membranosa/etiología , Glomerulonefritis Membranosa/inmunología , Humanos , Inmunosupresores/uso terapéutico , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapéutico , Receptores de Fosfolipasa A2/inmunología , Rituximab
18.
medRxiv ; 2023 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-37790554

RESUMEN

Background: Phospholipase A2 receptor-associated membranous nephropathy (PLA2R-MN) is an anti-PLA2R antibody (PLA2R-Ab) mediated autoimmune kidney disease. Although antibody titer correlates closely with disease activity, whether it can provide longer-term predictions on disease course and progression is unclear. Rituximab, a B-cell depletion therapy, has become the first-line treatment option for PLA2R-MN; however, the response to Rituximab varies among patients. Methods: We developed a flow cytometry-based test that detects and quantifies PLA2R antigen-specific memory B cells (PLA2R-MBCs) in peripheral blood, the primary source for PLA2R-Ab production upon disease relapse. We applied the test to 159 blood samples collected from 28 patients with PLA2R-MN (at diagnosis, during and after immunosuppressive treatment, immunological remission, and relapse) to evaluate the relationship between circulating PLA2R-MBC levels and disease activity. Results: The level of PLA2R-MBCs in healthy controls (n=56) is less than or equal to 1.5% of the total MBC compartment. High circulating PLA2R-MBC levels were detected in two patients post-Rituximab despite achieving immunologic and proteinuric remission, as well as in two patients with negative serum autoantibody but increasing proteinuria. Elimination of these cells with Rituximab improved clinical outcomes. Moreover, five patients exhibited elevated PLA2R-MBC levels before disease relapse, followed by a rapid decline to baseline when relapse became clinically evident. COVID-19 vaccination or SARS-CoV-2 infection significantly affected the dynamics of circulating PLA2R-MBCs. Conclusions: This study suggests that monitoring PLA2R-MBC levels in patients with PLA2R-MN may help refine and individualize immunosuppressive therapy and predict disease course and progression. The technology and findings may also have broader applications in the clinical management of other autoimmune diseases.

19.
Bone Marrow Transplant ; 58(10): 1112-1120, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37474729

RESUMEN

Kidney complications have been studied in allogeneic hematopoietic stem cell transplant patients but not specifically among chronic graft-versus-host disease (cGVHD) patients. Participants (n = 365) enrolled in the cross-sectional cGVHD natural history study (NCT00092235) were assessed for kidney dysfunction and overall survival. Kidney dysfunction was analyzed for associations in univariate and multivariable analyses. Kidney dysfunction (eGFR < 60) was found in 64 patients, and 29 patients had moderate-severe kidney dysfunction (eGFR < 45). Patients with kidney dysfunction were more likely treated with cyclosporine at evaluation or to have received it for GVHD prophylaxis, or prior treatment of GVHD. Patients with kidney dysfunction were less severely affected by cGVHD of skin, mouth, and joints/fascia. In multivariable modeling, history of cyclosporine use (OR = 2.19, 95% CI 1.13-4.25), angiotensin receptor blocker use (OR = 5.57, 95% CI 1.49-20.84), proteinuria (OR = 2.39, 95% CI 1.19-4.79), lower CRP (OR = 0.95, 95% CI 0.91-0.99), lower C3 (OR = 0.98, 95% CI 0.97-0.99), and lower hemoglobin (OR = 0.70, 95% CI 0.58-0.84) were jointly associated with kidney dysfunction. Overall survival was lower in those with moderate-severe kidney dysfunction (p = 0.015), demonstrating the importance of addressing kidney dysfunction in this population. The association of kidney dysfunction with less severe cGVHD suggests an etiology unrelated to cGVHD but potentially a consequence of drug-related toxicities.


Asunto(s)
Síndrome de Bronquiolitis Obliterante , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Estudios Transversales , Ciclosporina/efectos adversos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Riñón , Enfermedad Crónica
20.
Kidney Int Rep ; 8(4): 805-817, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37069979

RESUMEN

Introduction: Preeclampsia increases the risk for future chronic kidney disease (CKD). Among those diagnosed with CKD, it is unclear whether a prior history of preeclampsia, or other complications in pregnancy, negatively impact kidney disease progression. In this longitudinal analysis, we assessed kidney disease progression among women with glomerular disease with and without a history of a complicated pregnancy. Methods: Adult women enrolled in the Cure Glomerulonephropathy study (CureGN) were classified based on a history of a complicated pregnancy (defined by presence of worsening kidney function, proteinuria, or blood pressure; or a diagnosis of preeclampsia, eclampsia, or hemolysis, elevated liver enzymes, and low platelets [HELLP] syndrome), pregnancy without these complications, or no pregnancy history at CureGN enrollment. Linear mixed models were used to assess estimated glomerular filtration rate (eGFR) trajectories and urine protein-to-creatinine ratios (UPCRs) from enrollment. Results: Over a median follow-up period of 36 months, the adjusted decline in eGFR was greater in women with a history of a complicated pregnancy compared to those with uncomplicated or no pregnancies (-1.96 [-2.67, -1.26] vs. -0.80 [-1.19, -0.42] and -0.64 [-1.17, -0.11] ml/min per 1.73 m2 per year, P = 0.007). Proteinuria did not differ significantly over time. Among those with a complicated pregnancy history, eGFR slope did not differ by timing of first complicated pregnancy relative to glomerular disease diagnosis. Conclusions: A history of complicated pregnancy was associated with greater eGFR decline in the years following glomerulonephropathy (GN) diagnosis. A detailed obstetric history may inform counseling regarding disease progression in women with glomerular disease. Continued research is necessary to better understand pathophysiologic mechanisms by which complicated pregnancies contribute to glomerular disease progression.

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