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Adv Chronic Kidney Dis ; 27(1): 56-66, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32147003


Calcineurin inhibitors (CNIs) are both the savior and Achilles' heel of kidney transplantation. Although CNIs have significantly reduced rates of acute rejection, their numerous toxicities can plague kidney transplant recipients. By 10 years, virtually all allografts will have evidence of CNI nephrotoxicity. CNIs have been strongly associated with hypertension, dyslipidemia, and new onset of diabetes after transplantation-significantly contributing to cardiovascular risk in the kidney transplant recipient. Multiple electrolyte derangements including hyperkalemia, hypomagnesemia, hypercalciuria, metabolic acidosis, and hyperuricemia may be challenging to manage for the clinician. Finally, CNI-associated tremor, gingival hyperplasia, and defects in hair growth can have a significant impact on the transplant recipient's quality of life. In this review, the authors briefly discuss the pharmacokinetics of CNI and discuss the numerous clinically relevant toxicities of commonly used CNIs, cyclosporine and tacrolimus.

Clin J Am Soc Nephrol ; 15(2): 247-256, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-31974287


BACKGROUND AND OBJECTIVES: FSGS recurrence after kidney transplantation is a major risk factor for graft loss. However, the natural history, clinical predictors, and response to treatment remain unclear because of small sample sizes and poor generalizability of single-center studies, and disease misclassification in registry-based studies. We therefore aimed to determine the incidence, predictors, and treatment response of recurrent FSGS in a large cohort of kidney transplant recipients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Post-Transplant Glomerular Disease (TANGO) project is an observational, multicenter, international cohort study that aims to investigate glomerular disease recurrence post-transplantation. Transplant recipients were screened for the diagnosis of idiopathic FSGS between 2005 and 2015 and details were recorded about the transplant, clinical outcomes, treatments, and other risk factors. RESULTS: Among 11,742 kidney transplant recipients screened for FSGS, 176 had a diagnosis of idiopathic FSGS and were included. FSGS recurred in 57 patients (32%; 95% confidence interval [95% CI], 25% to 39%) and 39% of them lost their graft over a median of 5 (interquartile range, 3.0-8.1) years. Multivariable Cox regression revealed a higher risk for recurrence with older age at native kidney disease onset (hazard ratio [HR], 1.37 per decade; 95% CI, 1.09 to 1.56). Other predictors were white race (HR, 2.14; 95% CI, 1.08 to 4.22), body mass index at transplant (HR, 0.89 per kg/m2; 95% CI, 0.83 to 0.95), and native kidney nephrectomies (HR, 2.76; 95% CI, 1.16 to 6.57). Plasmapheresis and rituximab were the most frequent treatments (81%). Partial or complete remission occurred in 57% of patients and was associated with better graft survival. CONCLUSIONS: Idiopathic FSGS recurs post-transplant in one third of cases and is associated with a five-fold higher risk of graft loss. Response to treatment is associated with significantly better outcomes but is achieved in only half of the cases.

J Grad Med Educ ; 11(6): 708-712, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31871574


Background: Digital innovations have the potential to enhance current graduate medical education strategies. Objective: We assessed the scope, reach, and effectiveness of Nephrology Simulator (NephSIM), a free, mobile-optimized, nephrology educational tool designed to teach pathophysiology with a diagnostic approach using interactive cases. Methods: NephSIM, launched in June 2018, was designed as a mobile-optimized website with peer-reviewed content in WordPress. Content, including interactive cases with iterative feedback, infographics, and tutorials, was developed by nephrology fellows and attending nephrologists. The teaching tool was shared via an e-mail subscriber list and Twitter. Website usage data and Twitter analytics were reviewed. Case content was categorized, and the case completion rate was calculated. A self-report survey was sent to subscribers to assess their demographics and experience. Results: Thirty-four cases have been published to date and represent a variety of nephrology topics. There have been 100 745 page views between June 2018 and June 2019, representing 17 922 unique visitors from more than 100 countries. There are 1929 accounts that follow NephSIM on Twitter. Tweets received 124 200 impressions and a 3% engagement rate. Median case completion rate was 69% (interquartile range 64%-78%). Our survey response rate was 17% (76 of 445). Nearly all NephSIM users rated the platform highly in terms of satisfaction and usability, and planned to continue using in the future. Conclusions: The development of a mobile-optimized, case-based teaching approach by nephrology fellows and faculty is feasible and has demonstrated global participation and high levels of learner satisfaction.

BMC Infect Dis ; 19(1): 739, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31438872


BACKGROUND: Incidence of the opportunistic infection Pneumocystis jirovecii pneumonia (PJP) in solid organ transplant patients ranges from 5 to 15% with a mortality of up to 38%. CASE PRESENTATION: We present a liver transplant recipient who developed hypoxemic respiratory failure related to PJP soon after treatment for allograft rejection. His presentation was preceded by severe hypercalcemia of 14.6 mg/dL and an ionized calcium of 1.7 mmol/L which remained elevated despite usual medical management and eventually required renal replacement therapy. As approximately 5% of PJP cases have granulomas, here we review the role of pulmonary macrophages and inflammatory cytokines in the pathophysiology of granuloma-mediated hypercalcemia. We also discuss the interpretation of our patient's laboratory studies, response to medical therapy, and clinical risk factors which predisposed him to PJP. CONCLUSIONS: It is important for clinicians to consider PJP as an etiology of granulomatous pneumonia and non-parathyroid hormone mediated hypercalcemia in chronically immunosuppressed organ transplant recipients for timely diagnosis and management.

Hipercalcemia/diagnóstico , Transplante de Fígado , Pneumocystis carinii , Pneumonia por Pneumocystis/diagnóstico , Sintomas Prodrômicos , Transplantados , Idoso , Diagnóstico Diferencial , Humanos , Hipercalcemia/etiologia , Hospedeiro Imunocomprometido , Transplante de Fígado/efeitos adversos , Masculino , Infecções Oportunistas/complicações , Infecções Oportunistas/diagnóstico , Pneumonia por Pneumocystis/complicações , Índice de Gravidade de Doença
Trends Cardiovasc Med ; 20(6): 204-9, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22137643


Genome-wide association studies (GWAS) of more than 100,000 people have revealed novel loci associated with coronary artery disease and myocardial infarction that present exciting opportunities to discover novel disease pathways. One such recently identified locus is on chromosome 10q11, near the gene for the chemokine CXCL12, which has been implicated in cardiovascular disease in both mouse and human studies. These GWAS demonstrate that CXCL12 may emerge as a potential therapeutic target for atherosclerosis and thrombosis.

Quimiocina CXCL12/genética , Doença da Artéria Coronariana/genética , Infarto do Miocárdio/genética , Animais , Arteriosclerose/enzimologia , Arteriosclerose/genética , Arteriosclerose/patologia , Quimiocina CXCL12/metabolismo , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/patologia , Modelos Animais de Doenças , Estudo de Associação Genômica Ampla , Humanos , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/patologia