RESUMO
A definite causal link between pegylated liposomal doxorubicin (PLD) and kidney-limited thrombotic microangiopathy (TMA) remains unestablished. Here, we report 2 cases of PLD-induced kidney-limited TMA, 1 in a patient with myxofibrosarcoma and the other in a patient with liposarcoma. The 2 patients received a high cumulative dose of PLD, and both presented with a rise in serum creatinine and proteinuria. Kidney biopsy revealed TMA with chronic mesangiolysis and capillary wall double contouring. Neither patient had concomitant exposure to TMA-causing drugs, such as gemcitabine, anti-vascular endothelial growth factor agents, or mammalian target of rapamycin inhibitors. The work-up for secondary causes of TMA was negative in both patients. The cessation of PLD therapy led to improvement or stabilization in serum creatinine and proteinuria in both patients. These 2 cases provide a clear causal link between PLD and kidney-limited TMA. The high cumulative dose of PLD increases the risk of kidney TMA. Early recognition of PLD-induced kidney TMA can lead to timely cessation of PLD therapy and potentially preserve kidney function.
Assuntos
Doxorrubicina/análogos & derivados , Rim , Microangiopatias Trombóticas , Humanos , Adulto , Creatinina , Rim/patologia , Microangiopatias Trombóticas/induzido quimicamente , Microangiopatias Trombóticas/diagnóstico , Microangiopatias Trombóticas/patologia , Proteinúria/patologia , PolietilenoglicóisRESUMO
Membranous nephropathy (MN) is one of the most common de novo glomerular diseases developing in patients after allogeneic hematopoietic stem cell transplantation (HSCT). Most authors have used immunosuppression for its treatment to target the underlying immune-mediated processes, akin to graft-versus-host disease, but the optimal management is currently unclear. Limited reports in the literature described the use of a conservative approach with success, particularly in cases with lower risks of progression, such as non-nephrotic-range proteinuria or early reduction of proteinuria by 6 months. We report two cases of post-HSCT MN with moderate risk features, namely prolonged durations of nephrotic-range proteinuria, that spontaneously resolved with conservative treatment. Patient 1 was of advanced age and in an immunocompromised state, while patient 2 was in need of a greater graft-versus-disease effect from the donor's immune system, which necessitated a balance between the risk of immunosuppression and the risk of progressive kidney function loss. These cases demonstrated that conservative treatment can be a reasonable approach in selected patients with post-HSCT MN, including those with moderate risk.
RESUMO
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by factor-induced dysregulation of phosphate and vitamin D metabolism resulting in alterations in bone formation, leading to bone pain and fractures. While the true incidence is likely underestimated, less than 500 cases of TIO have been reported since initial description in 1947. TIO cases have classically been associated with mesenchymal tumors of bone and soft tissue, but have also rarely been linked to malignant tumors, with scant reports implicating non-mesenchymal tumors. TIO is mediated through inappropriate tumor overproduction of fibroblast growth factor 23 (FGF23). Increased FGF23 secretion leads to hypophosphatemia by (1) reduced phosphate reabsorption via activation of the proximal renal tubular epithelial cells to internalize sodium phosphate cotransporters and (2) reduced activation of vitamin D3 via inhibition of the renal enzyme 1-α hydroxylase. Low circulating levels of active vitamin D lead to reduced intestinal phosphate absorption and impaired mineralization of osteoid matrix. TIO in breast cancer poses a distinct diagnostic challenge due to the common adjunct oncologic management with bone protection therapy such as denosumab or bisphosphonates. These agents can be culprits of hypophosphatemia and hypocalcemia, rendering timely diagnosis of TIO difficult. Delay of diagnosis of TIO can result in worsening functional status, and early morbidity and mortality. To date, there has been one prior case report of TIO in breast cancer, and herein we describe two additional cases of TIO in this setting.
Assuntos
Neoplasias da Mama , Fatores de Crescimento de Fibroblastos/metabolismo , Hipofosfatemia , Osteomalacia , Síndromes Paraneoplásicas , Feminino , Fator de Crescimento de Fibroblastos 23 , HumanosRESUMO
BACKGROUND: Despite increasing recognition of the importance of immune checkpoint inhibitor-associated AKI, data on this complication of immunotherapy are sparse. METHODS: We conducted a multicenter study of 138 patients with immune checkpoint inhibitor-associated AKI, defined as a ≥2-fold increase in serum creatinine or new dialysis requirement directly attributed to an immune checkpoint inhibitor. We also collected data on 276 control patients who received these drugs but did not develop AKI. RESULTS: Lower baseline eGFR, proton pump inhibitor use, and combination immune checkpoint inhibitor therapy were each independently associated with an increased risk of immune checkpoint inhibitor-associated AKI. Median (interquartile range) time from immune checkpoint inhibitor initiation to AKI was 14 (6-37) weeks. Most patients had subnephrotic proteinuria, and approximately half had pyuria. Extrarenal immune-related adverse events occurred in 43% of patients; 69% were concurrently receiving a potential tubulointerstitial nephritis-causing medication. Tubulointerstitial nephritis was the dominant lesion in 93% of the 60 patients biopsied. Most patients (86%) were treated with steroids. Complete, partial, or no kidney recovery occurred in 40%, 45%, and 15% of patients, respectively. Concomitant extrarenal immune-related adverse events were associated with worse renal prognosis, whereas concomitant tubulointerstitial nephritis-causing medications and treatment with steroids were each associated with improved renal prognosis. Failure to achieve kidney recovery after immune checkpoint inhibitor-associated AKI was independently associated with higher mortality. Immune checkpoint inhibitor rechallenge occurred in 22% of patients, of whom 23% developed recurrent associated AKI. CONCLUSIONS: This multicenter study identifies insights into the risk factors, clinical features, histopathologic findings, and renal and overall outcomes in patients with immune checkpoint inhibitor-associated AKI.
Assuntos
Injúria Renal Aguda/induzido quimicamente , Antígeno B7-H1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/terapia , Idoso , Feminino , Humanos , Rim/patologia , Masculino , Pessoa de Meia-Idade , Nefrite Intersticial/induzido quimicamente , Estudos Retrospectivos , Fatores de RiscoRESUMO
Although cord blood transplantation (CBT) extends allograft access, patient comorbidities, chemoradiation, and nephrotoxic medications all contribute to acute kidney injury (AKI) risk. We analyzed AKI in adult myeloablative CBT recipients who underwent transplantation from 2006 to 2017 for hematologic malignancies using cyclosporine A (CSA)/mycophenolate mofetil immunosuppression. Maximum grades of AKI were calculated using Kidney Disease: Improving Global Outcomes (grade 1, 1.5 to <2-fold; grade 2, 2 to <3-fold; or grade 3, ≥3-fold over baseline) definitions. In total, 153 patients (median 51 years [range, 23-65], 114/153 [75%] acute leukemia, 27/153 [18%] African, 88/153 [58%] cytomegalovirus seropositive, median age-adjusted hematopoietic cell comorbidity index 3 [range, 0-9], median pretransplant albumin 4.0 g/dL [range, 2.6-5.2]) underwent transplantation. The day 100 cumulative incidence of grade 1-3 AKI was 83% (95% confidence interval [CI], 77%-89%) (predominantly grade 2, median onset 40 days, range 0 to 96), and grade 2-3 AKI incidence was 54% (95% CI, 46%-62%) (median onset 43 days, range 0 to 96). Mean CSA level preceding AKI onset was high (360 ng/mL, target range 300-350). In multivariate analysis, African ancestry, addition of haploidentical CD34+ cells, low day -7 albumin, critical illness/intensive care admission, and nephrotoxic drug exposure (predominantly CSA and/or foscarnet) were associated with AKI. In a day 100 landmark analysis, 6% of patients with no prior AKI had chronic kidney disease (CKD) at 2 years versus 43% with prior grade 1 and 38% with prior grade 2-3 AKI (overall P= .02). Adult CBT recipients are at significant AKI risk, and AKI is associated with increased risk of CKD. Prevention strategies, early recognition, and prompt intervention are critical to mitigate kidney injury.
Assuntos
Injúria Renal Aguda , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Transplante de Células-Tronco Hematopoéticas , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Adulto , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Humanos , Incidência , Rim , Estudos Retrospectivos , Fatores de RiscoRESUMO
Immune-related adverse events (IrAEs) affecting the gastrointestinal (GI) tract and liver are among the most frequent and most severe inflammatory toxicities from contemporary immunotherapy. Inflammation of the colon and or small intestines (entero)colitis is the single most common GI IrAE and is an important cause of delay of discontinuation of immunotherapy. The severity of these GI IrAEs can range from manageable with symptomatic treatment alone to life-threatening complications, including perforation and liver failure. The frequency and severity of GI IrAEs is dependent on the specific immunotherapy given, with cytotoxic T lymphocyte antigen (CTLA)-4 blockade more likely to induce severe GI IrAEs than blockade of either programmed cell death protein 1 (PD-1) or PD-1 ligand (PD-L1), and combination therapy showing the highest rate of GI IrAEs, particularly in the liver. To date, we have minimal prospective data on the appropriate diagnosis and management of GI IrAEs, and recommendations are based largely on retrospective data and expert opinion. Although clinical diagnoses of GI IrAEs are common, biopsy is the gold standard for diagnosis of both immunotherapy-induced enterocolitis and hepatitis and can play an important role in excluding competing, though less common, diagnoses and ensuring optimal management. GI IrAEs typically respond to high-dose corticosteroids, though a significant fraction of patients requires secondary immune suppression. For colitis, both TNF-α blockade with infliximab and integrin inhibition with vedolizumab have proved highly effective in corticosteroid-refractory cases. Detailed guidelines have been published for the management of low-grade GI IrAEs. In the setting of more severe toxicities, involvement of a GI specialist is generally recommended. The purpose of this review is to survey the available literature and provide management recommendations focused on the GI specialist.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/terapia , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/terapia , Inibidores de Checkpoint Imunológico/efeitos adversos , Imunoterapia/efeitos adversos , Neoplasias/terapia , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/imunologia , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Gastroenteropatias/epidemiologia , Gastroenteropatias/patologia , História do Século XXI , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/uso terapêutico , Agências Internacionais/organização & administração , Agências Internacionais/normas , Cuidados Paliativos/organização & administração , Cuidados Paliativos/normas , Medicina Paliativa/organização & administração , Medicina Paliativa/normas , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Índice de Gravidade de Doença , Sociedades Médicas/organização & administração , Sociedades Médicas/normasRESUMO
Despite the success and ongoing promise of monoclonal antibody-targeted immune checkpoint inhibitor immunotherapy of advanced malignancies, in particular, antibodies directed against CTLA-4 and PD-1/PD-L1, the development of immune-related adverse events (irAEs) remains a constraint of this type of therapy. Although rarely fatal, the occurrence of irAEs may necessitate discontinuation of immunotherapy, as well as administration of corticosteroids or other immunosuppressive therapies that may not only compromise efficacy but also predispose for development of opportunistic infection. Clearly, retention of efficacy of immune checkpoint-targeted therapies with concurrent attenuation of immune-mediated toxicity represents a formidable challenge. In this context, the current brief review examines mechanistic relationships between these events, as well as recent insights into immunopathogenesis, and strategies which may contribute to resolving this issue. These sections are preceded by brief overviews of the discovery and functions of CTLA-4 and PD-1, as well as the chronology of the development of immunotherapeutic monoclonal antibodies which target these immune checkpoint inhibitors.
Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Imunoterapia/efeitos adversos , Neoplasias/terapia , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/imunologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/uso terapêutico , Oncologia/métodos , Oncologia/tendências , Neoplasias/epidemiologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologiaRESUMO
The immune checkpoints associated with the CTLA-4 and PD-1 pathways are critical modulators of immune activation. These pathways dampen the immune response by providing brakes on activated T cells, thereby ensuring more uniform and controlled immune reactions and avoiding immune hyper-responsiveness and autoimmunity. Cancer cells often exploit these regulatory controls through a variety of immune subversion mechanisms, which facilitate immune escape and tumor survival. Immune checkpoint inhibitors (ICI) effectively block negative regulatory signals, thereby augmenting immune attack and tumor killing. This process is a double-edged sword in which release of regulatory controls is felt to be responsible for both the therapeutic efficacy of ICI therapy and the driver of immune-related adverse events (IrAEs). These adverse immune reactions are common, typically low-grade and may affect virtually every organ system. In the early clinical trials, lung IrAEs were rarely described. However, with ever-expanding clinical applications and more complex ICI-containing regimens, lung events, in particular, pneumonitis, have become increasingly recognized. ICI-related lung injury is clinically distinct from other types of lung toxicity and may lead to death in advanced stage disease. Thus, knowledge regarding the key characteristics and optimal treatment of lung-IrAEs is critical to good outcomes. This review provides an overview of lung-IrAEs, including risk factors and epidemiology, as well as clinical, radiologic, and histopathologic features of ICI-related lung injury. Management principles for ICI-related lung injury, including current consensus on steroid refractory pneumonitis and the use of other immune modulating agents in this setting are also highlighted.
Assuntos
Fatores Imunológicos/efeitos adversos , Imunoterapia/efeitos adversos , Pneumopatias/induzido quimicamente , Pneumopatias/terapia , Neoplasias/terapia , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/imunologia , História do Século XXI , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Fatores Imunológicos/uso terapêutico , Agências Internacionais/organização & administração , Agências Internacionais/normas , Pneumopatias/epidemiologia , Cuidados Paliativos/organização & administração , Cuidados Paliativos/normas , Medicina Paliativa/organização & administração , Medicina Paliativa/normas , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Índice de Gravidade de Doença , Sociedades Médicas/organização & administração , Sociedades Médicas/normasRESUMO
Immune checkpoint inhibitors (ICIs) frequently result in cutaneous immune-related adverse events (IrAEs). Although the majority of these events are mild-to-moderate in severity, up to 5% are severe, which may lead to morbidity and dose interruption or discontinuation of ICI therapy. In addition, up to 25% of dermatologic IrAEs are corticosteroid-refractory or corticosteroid-dependent. These 2020 MASCC recommendations cover the diagnosis and management of cutaneous IrAEs with a focus on moderate-to-severe and corticosteroid-resistant events. Although the usage of immune-suppressive therapy has been advocated in this setting, there is a lack of randomized clinical trial data to provide a compelling level of evidence of its therapeutic benefit.
Assuntos
Toxidermias/terapia , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias/terapia , Cuidados Paliativos , Toxidermias/etiologia , Toxidermias/patologia , História do Século XXI , Humanos , Imunoterapia/efeitos adversos , Agências Internacionais/organização & administração , Agências Internacionais/normas , Neoplasias/imunologia , Cuidados Paliativos/métodos , Cuidados Paliativos/normas , Medicina Paliativa/organização & administração , Medicina Paliativa/normas , Índice de Gravidade de Doença , Sociedades Médicas/organização & administração , Sociedades Médicas/normasRESUMO
Immune checkpoint inhibitors (ICIs) have emerged as the newest pillar of cancer treatment. Immune-mediated toxicities, stemming from increased activity within the T cell lineage, range from asymptomatic or mild complications to those that are fulminant and potentially fatal. Although they are of variable occurrence, cardiovascular, rheumatic, and renal immune-mediated toxicities are among the most serious of these adverse events. We present MASCC recommendations with respect to the workup and management of cardiovascular, rheumatic, and renal immune-mediated toxicities with a focus on presentations that require treatment with immunomodulating agents.
Assuntos
Doenças Cardiovasculares/terapia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/terapia , Inibidores de Checkpoint Imunológico/efeitos adversos , Imunoterapia/efeitos adversos , Nefropatias/terapia , Doenças Reumáticas/terapia , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/imunologia , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , História do Século XXI , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/uso terapêutico , Agências Internacionais/organização & administração , Agências Internacionais/normas , Nefropatias/induzido quimicamente , Nefropatias/epidemiologia , Neoplasias/epidemiologia , Neoplasias/imunologia , Neoplasias/terapia , Cuidados Paliativos/organização & administração , Cuidados Paliativos/normas , Medicina Paliativa/organização & administração , Medicina Paliativa/normas , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Doenças Reumáticas/induzido quimicamente , Doenças Reumáticas/epidemiologia , Índice de Gravidade de Doença , Sociedades Médicas/organização & administração , Sociedades Médicas/normasRESUMO
Immune checkpoint inhibitors (ICIs) have emerged as the newest pillar of cancer treatment, transforming outcomes in melanoma and showing benefit in a range of malignancies. Immune-mediated toxicities, stemming from increased activity within the T cell lineage, range from asymptomatic or mild complications to those that are fulminant and potentially fatal. Immune-mediated endocrinopathies include hypophysitis, thyroiditis, and insulin-dependent diabetes mellitus. These presentations, which may be vague and non-specific, can be life-threatening if not diagnosed and treated appropriately. This review considers the work-up and management of immune-mediated endocrinopathies and also considers the role of advanced practice practitioners in the management of immune-mediated toxicities. These state-of-the-art MASCC recommendations represent a comprehensive overview of the management and clinical work-up in those in whom the diagnosis should be considered.
Assuntos
Doenças do Sistema Endócrino/terapia , Inibidores de Checkpoint Imunológico/efeitos adversos , Imunoterapia/efeitos adversos , Neoplasias/terapia , Papel do Médico , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/imunologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/terapia , Doenças do Sistema Endócrino/induzido quimicamente , Doenças do Sistema Endócrino/epidemiologia , História do Século XXI , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/uso terapêutico , Agências Internacionais/organização & administração , Agências Internacionais/normas , Oncologia/organização & administração , Oncologia/normas , Neoplasias/epidemiologia , Neoplasias/imunologia , Cuidados Paliativos/organização & administração , Cuidados Paliativos/normas , Medicina Paliativa/organização & administração , Medicina Paliativa/normas , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Índice de Gravidade de Doença , Sociedades Médicas/organização & administração , Sociedades Médicas/normasRESUMO
Immunologic control of malignancy has long been recognized as an important determinant of disease progression. Recent advances in immunology have led to the focus on several mechanisms that can be targeted to achieve tumor suppression. In particular, checkpoint inhibition has evolved in less than a decade to become one of the most important strategies in cancer therapy, with a meaningful improvement in patient survival. Six agents have been approved for clinical use to date and many more are in the industry pipeline. The spectrum of malignancies responsive to immunotherapy ranges from advanced melanoma, for which the first immune checkpoint inhibitor ipilimumab was approved, to Hodgkin lymphoma, non-small cell lung cancer, renal cell carcinoma, and others. Notwithstanding its clinical benefits, checkpoint inhibition carries a risk for significant off-target toxicity stemming from the immune system activation. In this review, we discuss general principles of checkpoint inhibition, mechanisms of toxicity, and kidney complications of the treatment and propose diagnostic and treatment strategies when kidney injury occurs.
Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/imunologia , Imunoterapia/efeitos adversos , Nefropatias/induzido quimicamente , Nefropatias/imunologia , Idoso , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Humanos , Imunoterapia/tendências , Nefropatias/diagnóstico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , MasculinoRESUMO
Immune checkpoint inhibitors (CPIs), monoclonal antibodies that target inhibitory receptors expressed on T cells, represent an emerging class of immunotherapy used in treating solid organ and hematologic malignancies. We describe the clinical and histologic features of 13 patients with CPI-induced acute kidney injury (AKI) who underwent kidney biopsy. Median time from initiation of a CPI to AKI was 91 (range, 21 to 245) days. Pyuria was present in 8 patients, and the median urine protein to creatinine ratio was 0.48 (range, 0.12 to 0.98) g/g. An extrarenal immune-related adverse event occurred prior to the onset of AKI in 7 patients. Median peak serum creatinine was 4.5 (interquartile range, 3.6-7.3) mg/dl with 4 patients requiring hemodialysis. The prevalent pathologic lesion was acute tubulointerstitial nephritis in 12 patients, with 3 having granulomatous features, and 1 thrombotic microangiopathy. Among the 12 patients with acute tubulointerstitial nephritis, 10 received treatment with glucocorticoids, resulting in complete or partial improvement in renal function in 2 and 7 patients, respectively. However, the 2 patients with acute tubulointerstitial nephritis not given glucocorticoids had no improvement in renal function. Thus, CPI-induced AKI is a new entity that presents with clinical and histologic features similar to other causes of drug-induced acute tubulointerstitial nephritis, though with a longer latency period. Glucocorticoids appear to be a potentially effective treatment strategy. Hence, AKI due to CPIs may be caused by a unique mechanism of action linked to reprogramming of the immune system, leading to loss of tolerance.
Assuntos
Injúria Renal Aguda/patologia , Anticorpos Monoclonais/efeitos adversos , Antineoplásicos/efeitos adversos , Fatores Imunológicos/antagonistas & inibidores , Imunoterapia/efeitos adversos , Neoplasias/tratamento farmacológico , Nefrite Intersticial/patologia , Microangiopatias Trombóticas/patologia , Injúria Renal Aguda/sangue , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/terapia , Adulto , Idoso , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Biópsia , Creatinina/sangue , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunoterapia/métodos , Rim/irrigação sanguínea , Rim/patologia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Neoplasias/imunologia , Nefrite Intersticial/sangue , Nefrite Intersticial/induzido quimicamente , Nefrite Intersticial/terapia , Diálise Renal , Microangiopatias Trombóticas/sangue , Microangiopatias Trombóticas/induzido quimicamente , Microangiopatias Trombóticas/terapiaRESUMO
BACKGROUND: Hyponatremia is prognostic of higher mortality in some cancers but has not been well studied in others. We used a longitudinal design to determine the incidence and prognostic importance of euvolemic and hypervolemic hyponatremia in patients following diagnosis with lymphoma, breast (BC), colorectal (CRC), small cell lung (SCLC), or non-small cell lung cancer (NSCLC). METHODS: Medical record and tumor registry data from two large integrated delivery networks were combined for patients diagnosed with lymphoma, BC, CRC, or lung cancers (2002-2010) who had ≥1 administration of radiation/chemotherapy within 6 months of diagnosis and no evidence of hypovolemic hyponatremia. Hyponatremia incidence was measured per 1000 person-years (PY). Cox proportional hazard models assessed the prognostic value of hyponatremia as a time-varying covariate on overall survival (OS) and progression-free survival (PFS). RESULTS: Hyponatremia incidence (%, rate) was 76 % each, 1193 and 2311 per 1000 PY, among NSCLC and SCLC patients, respectively; 37 %, 169 in BC; 64 %, 637 in CRC, and 60 %, 395 in lymphoma. Hyponatremia was negatively associated with OS in BC (HR 3.7; P = <.01), CRC (HR 2.4; P < .01), lung cancer (HR 2.4; P < .01), and lymphoma (HR 4.5; P < .01). Hyponatremia was marginally associated with shorter PFS (HR 1.3, P = .07) across cancer types. CONCLUSIONS: The incidence of hyponatremia is higher than previously reported in lung cancer, is high in lymphoma, BC, and CRC and is a negative prognostic indicator for survival. Hyponatremia incidence in malignancy may be underestimated. The effects of hyponatremia correction on survival in cancer patients require further study.
Assuntos
Hiponatremia/epidemiologia , Neoplasias/terapia , Adulto , Idoso , Neoplasias da Mama/complicações , Neoplasias da Mama/terapia , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia/métodos , Quimiorradioterapia/estatística & dados numéricos , Neoplasias Colorretais/complicações , Neoplasias Colorretais/terapia , Feminino , Humanos , Hiponatremia/complicações , Incidência , Estudos Longitudinais , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/terapia , Linfoma/complicações , Linfoma/terapia , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/complicações , Carcinoma de Pequenas Células do Pulmão/terapia , Estados Unidos/epidemiologiaRESUMO
Polyomavirus-associated nephropathy (PVAN) is common in patients who have undergone kidney transplantation and has been reported in hematopoietic stem cell (HSC) transplant recipients. Aside from reduction of immunosuppression, few therapeutic options exist for treatment of PVAN. We report a case of PVAN in a severely immunocompromised allogeneic HSC transplant recipient that was treated with brincidofovir without reduction of immunosuppression. We review our institutional experience of PVAN in HSC transplantation and discuss the potential use of brincidofovir for treatment.
Assuntos
Vírus BK , Infecções por Citomegalovirus/tratamento farmacológico , Citosina/análogos & derivados , Transplante de Células-Tronco Hematopoéticas , Nefropatias/tratamento farmacológico , Nefropatias/virologia , Organofosfonatos/uso terapêutico , Infecções por Polyomavirus/tratamento farmacológico , Infecções Tumorais por Vírus/tratamento farmacológico , Citosina/uso terapêutico , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Polyomavirus , Viremia/tratamento farmacológicoRESUMO
Hematopoietic stem cell transplant (HSCT) recipients are at significant risk for BK virus (BKV) reactivation, hemorrhagic cystitis (HC), and renal dysfunction. We prospectively monitored 98 patients who had received HSCT by serial BKV PCR in the urine through day (D) +100 to analyze the relationship between BK viruria and HC, serum creatinine (Cr), and creatinine clearance (CrCl) through D +180 or death. Patients, median age 52 years (range, 20 to 73), received T cell-depleted (50%) or cord blood allografts (21%). Median pre-HSCT BKV IgG titers were 1:10,240. Incremental increase in BKV IgG titers correlated with developing BK viruria ≥ 10(7) copies/mL. By D +100, 53 (54%) patients had BK viruria. BKV load in the urine increased at engraftment and persisted throughout D +100. HC developed in 10 patients (10%); 7 of 10 with BK viruria. In competing risk analyses, BK viruria ≥ 10(7) copies/mL, older age, cytomegalovirus reactivation, and foscarnet use were risk factors for HC. Cr and CrCl at 2, 3, and 6 months after HSCT were similar between patients with and without BK viruria.
Assuntos
Vírus BK/patogenicidade , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Cistite/etiologia , Adulto , Idoso , Vírus BK/crescimento & desenvolvimento , Estudos de Coortes , Cistite/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Linfócitos T/virologia , Adulto JovemAssuntos
Paraproteinemias/complicações , Microangiopatias Trombóticas/etiologia , Injúria Renal Aguda/etiologia , Idoso , Terapia Combinada , Feminino , Humanos , Imunossupressores/uso terapêutico , Glomérulos Renais/patologia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Insuficiência de Múltiplos Órgãos/etiologia , Troca Plasmática , Recidiva , Microangiopatias Trombóticas/patologia , Microangiopatias Trombóticas/terapia , Macroglobulinemia de Waldenstrom/complicaçõesRESUMO
BACKGROUND AND OBJECTIVE: The timing of perioperative nephrotoxic chemotherapy for upper tract urothelial carcinoma (UTUC) remains controversial and strongly depends on predicted platinum eligibility after radical nephroureterectomy (RNU). The study objective was to develop and validate a multivariable nomogram to predict estimated glomerular filtration rate (eGFR) following RNU. METHODS: This was a multi-institutional retrospective study of patients with UTUC treated with RNU from 2000 to 2020 at seven high-volume referral centers. Use of adjuvant chemotherapy was risk-stratified. Patients were retrospectively randomly allocated 2:1 to discovery and validation cohorts. Discovery data were used to identify independent factors associated with GFR at 1-3 mo after RNU on linear regression, and backward selection was applied for model construction. Accuracy was defined as the percentage of predicted eGFR results within 30% of the corresponding observed eGFR. KEY FINDINGS AND LIMITATIONS: We included 1100 patients, of whom 733 were in the discovery and 367 were in the validation cohort. Multivariable predictors of postoperative eGFR decline included advanced age (odds ratio [OR] -0.18, 95% confidence interval [CI] -0.28 to -0.08), diabetes (OR -2.38, 95% CI -4.64 to -0.11), and hypertension (OR -2.24, 95% CI -4.16 to -0.32). Factors associated with favorable postoperative eGFR included larger tumor size (OR 10.57, 95% CI 7.4-13.74 for tumors >5 cm vs ≤2 cm) and preoperative eGFR (OR 0.44, 95% CI 0.39-0.49). A composite nomogram predicted postoperative eGFR with good accuracy in both the discovery (80.5%) and validation (78.6%) cohorts. Limitations include exclusion of patients who received neoadjuvant chemotherapy. CONCLUSIONS: A nomogram that incorporates ubiquitous preoperative clinical variables can predict post-RNU eGFR and was validated with an independent cohort. PATIENT SUMMARY: We developed a tool that uses patient data to predict eligibility for chemotherapy after surgery to remove the kidney and ureter in patients with cancer in the upper urinary tract.
RESUMO
OBJECTIVE: To develop and externally validate a prediction model for severe cisplatin associated acute kidney injury (CP-AKI). DESIGN: Multicenter cohort study. SETTING: Six geographically diverse major academic cancer centers across the US. PARTICIPANTS: Adults (≥18 years) receiving their first dose of intravenous cisplatin, 2006-22. MAIN OUTCOME MEASURES: The primary outcome was CP-AKI, defined as a twofold or greater increase in serum creatinine or kidney replacement therapy within 14 days of a first dose of intravenous cisplatin. Independent predictors of CP-AKI were identified using a multivariable logistic regression model, which was developed in a derivation cohort and tested in an external validation cohort. For the primary model, continuous variables were examined using restricted cubic splines. A simple risk model was also generated by converting the odds ratios from the primary model into risk points. Finally, a multivariable Cox model was used to examine the association between severity of CP-AKI and 90 day survival. RESULTS: A total of 24 717 adults were included, with 11 766 in the derivation cohort (median age 59 (interquartile range (IQR) 50-67)) and 12 951 in the validation cohort (median age 60 (IQR 50-67)). The incidence of CP-AKI was 5.2% (608/11 766) in the derivation cohort and 3.3% (421/12 951) in the validation cohort. Each of the following factors were independently associated with CP-AKI in the derivation cohort: age, hypertension, diabetes mellitus, serum creatinine level, hemoglobin level, white blood cell count, platelet count, serum albumin level, serum magnesium level, and cisplatin dose. A simple risk score consisting of nine covariates was shown to predict a higher risk of CP-AKI in a monotonic fashion in both the derivation cohort and the validation cohort. Compared with patients in the lowest risk category, those in the highest risk category showed a 24.00-fold (95% confidence interval (CI) 13.49-fold to 42.78-fold) higher odds of CP-AKI in the derivation cohort and a 17.87-fold (10.56-fold to 29.60-fold) higher odds in the validation cohort. The primary model had a C statistic of 0.75 and showed better discrimination for CP-AKI than previously published models, the C statistics for which ranged from 0.60 to 0.68 (DeLong P<0.001 for each comparison). Greater severity of CP-AKI was monotonically associated with shorter 90 day survival (adjusted hazard ratio 4.63 (95% CI 3.56 to 6.02) for stage 3 CP-AKI versus no CP-AKI). CONCLUSION: This study found that a simple risk score based on readily available variables from patients receiving intravenous cisplatin could predict the risk of severe CP-AKI, the occurrence of which is strongly associated with death.
Assuntos
Injúria Renal Aguda , Cisplatino , Adulto , Humanos , Pessoa de Meia-Idade , Cisplatino/efeitos adversos , Estudos de Coortes , Creatinina , Fatores de Risco , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Medição de Risco , Estudos RetrospectivosRESUMO
BACKGROUND: Corticosteroids are the mainstay of treatment for immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI), but the optimal duration of therapy has not been established. Prolonged use of corticosteroids can cause numerous adverse effects and may decrease progression-free survival among patients treated with ICPis. We sought to determine whether a shorter duration of corticosteroids was equally efficacious and safe as compared with a longer duration. METHODS: We used data from an international multicenter cohort study of patients diagnosed with ICPi-AKI from 29 centers across nine countries. We examined whether a shorter duration of corticosteroids (28 days or less) was associated with a higher rate of recurrent ICPi-AKI or death within 30 days following completion of corticosteroid treatment as compared with a longer duration (29-84 days). RESULTS: Of 165 patients treated with corticosteroids, 56 (34%) received a shorter duration of treatment and 109 (66%) received a longer duration. Patients in the shorter versus longer duration groups were similar with respect to baseline and ICPi-AKI characteristics. Five of 56 patients (8.9%) in the shorter duration group and 12 of 109 (11%) in the longer duration group developed recurrent ICPi-AKI or died (p=0.90). Nadir serum creatinine in the first 14, 28, and 90 days following completion of corticosteroid treatment was similar between groups (p=0.40, p=0.56, and p=0.89, respectively). CONCLUSION: A shorter duration of corticosteroids (28 days or less) may be safe for patients with ICPi-AKI. However, the findings may be susceptible to unmeasured confounding and further research from randomized clinical trials is needed.