Association of renal function with mortality among hospitalized patients treated with remdesivir for COVID-19.

BACKGROUND AND AIM: Renal dysfunction is associated with poor outcomes in patients with coronavirus disease 2019 (COVID-19). In an effort to improve outcomes, intravenous remdesivir has been broadly used for the treatment of COVID-19 even in patients with low estimated glomerular filtration rate (eGFR). Our study assessed the residual risk of outcomes of patients with low eGFR despite treatment with remdesivir for COVID-19, during a timeframe prior to the expanded label across all levels of renal function. METHODS: We conducted an observational, retrospective, multi-site cohort study of adults hospitalized with COVID-19 treated with at least one dose of remdesivir between November 6, 2020, and November 5, 2021. Electronic medical records were reviewed to obtain patient characteristics, related laboratory data, and outcomes. The primary endpoint was all-cause mortality by day 28. Multivariable logistic regression was used to evaluate association between groups. RESULTS: The study population consisted of 3024 patients hospitalized with COVID-19 and treated with remdesivir. The median age was 67 [IQR 55, 77] years; 42.7% were women, and 88.6% were white. The median eGFR was 76.6 mL/min/1.73 m2 [IQR 52.5, 95.2]; the majority (67.2%) of patients had an eGFR ≥ 60, while 9% had an eGFR <30. All-cause mortality by day 28 was 8.7%. All-cause mortality rates were significantly higher among patients with impaired renal function (Odds Ratio [OR] 1.63 for patients with eGFR 30-59; OR 1.46 for eGFR 15-29; OR 2.42 for eGFR <15 and OR 5.44 for patients on dialysis) compared to patients with eGFR ≥60 mL/min/1.73m2. CONCLUSIONS: Lower eGFR remains an independent risk factor for mortality in COVID-19 even in patients treated with remdesivir.

AI-driven translations for kidney transplant equity in Hispanic populations.

Health equity and accessing Spanish kidney transplant information continues being a substantial challenge facing the Hispanic community. This study evaluated ChatGPT's capabilities in translating 54 English kidney transplant frequently asked questions (FAQs) into Spanish using two versions of the AI model, GPT-3.5 and GPT-4.0. The FAQs included 19 from Organ Procurement and Transplantation Network (OPTN), 15 from National Health Service (NHS), and 20 from National Kidney Foundation (NKF). Two native Spanish-speaking nephrologists, both of whom are of Mexican heritage, scored the translations for linguistic accuracy and cultural sensitivity tailored to Hispanics using a 1-5 rubric. The inter-rater reliability of the evaluators, measured by Cohen's Kappa, was 0.85. Overall linguistic accuracy was 4.89 ± 0.31 for GPT-3.5 versus 4.94 ± 0.23 for GPT-4.0 (non-significant p = 0.23). Both versions scored 4.96 ± 0.19 in cultural sensitivity (p = 1.00). By source, GPT-3.5 linguistic accuracy was 4.84 ± 0.37 (OPTN), 4.93 ± 0.26 (NHS), 4.90 ± 0.31 (NKF). GPT-4.0 scored 4.95 ± 0.23 (OPTN), 4.93 ± 0.26 (NHS), 4.95 ± 0.22 (NKF). For cultural sensitivity, GPT-3.5 scored 4.95 ± 0.23 (OPTN), 4.93 ± 0.26 (NHS), 5.00 ± 0.00 (NKF), while GPT-4.0 scored 5.00 ± 0.00 (OPTN), 5.00 ± 0.00 (NHS), 4.90 ± 0.31 (NKF). These high linguistic and cultural sensitivity scores demonstrate Chat GPT effectively translated the English FAQs into Spanish across systems. The findings suggest Chat GPT's potential to promote health equity by improving Spanish access to essential kidney transplant information. Additional research should evaluate its medical translation capabilities across diverse contexts/languages. These English-to-Spanish translations may increase access to vital transplant information for underserved Spanish-speaking Hispanic patients.

Comparable outcomes of outpatient remdesivir and sotrovimab among high-risk patients with mild to moderate COVID-19 during the omicron BA.1 surge.

Studies conducted prior to SARS-CoV-2 Omicron demonstrated that sotrovimab and remdesivir reduced hospitalization among high-risk outpatients with mild to moderate COVID-19. However, their effectiveness has not been directly compared. This study examined all high-risk outpatients with mild to moderate COVID-19 who received either remdesivir or sotrovimab at Mayo Clinic during the Omicron BA.1 surge from January to March 2022. COVID-19-related hospitalization or death within 28 days were compared between the two treatment groups. Among 3257 patients, 2158 received sotrovimab and 1099 received remdesivir. Patients treated with sotrovimab were younger and had lower comorbidity but were more likely to be immunocompromised than remdesivir-treated patients. The majority (89%) had received at least one dose of COVID-19 vaccine. COVID-19-related hospitalization (1.5% and 1.0% in remdesivir and sotrovimab, respectively, p = .15) and mortality within 28 days (0.4% in both groups, p = .82) were similarly low. A propensity score weighted analysis demonstrated no significant difference in the outcomes between the two groups. We demonstrated favorable outcomes that were not significantly different between patients treated with remdesivir or sotrovimab.

Clinical outcomes of COVID-19 treated with remdesivir across the continuum of care.

Introduction: During the early phase of the coronavirus disease 2019 (COVID-19), remdesivir was only approved for hospitalized patients. Our institution developed hospital-based, outpatient infusion centers for selected hospitalized patients with COVID-19 who had clinical improvement to allow for early dismissal. The outcomes of patients who transitioned to complete remdesivir in the outpatient setting were examined. Methods: Retrospective study of all hospitalized adult patients with COVID-19 who received at least one dose of remdesivir from November 6, 2020, to November 5, 2021, at one of the Mayo Clinic hospitals. Results: Among 3029 hospitalized patients who received treatment with remdesivir for COVID-19, the majority (89.5%) completed the recommended 5-day course. Among them, 2169 (80%) patients completed treatment during hospitalization, whereas 542 (20.0%) patients were dismissed to complete remdesivir in outpatient infusion centers. Patients who completed the treatment in the outpatient setting had lower odds of death within 28 days (aOR 0.14, 95% CI 0.06-0.32, p < 0.001). However, their rate of subsequent hospital encounters within 30 days was higher (aHR 1.88, 95% CI 1.27-2.79, p = 0.002). Among patients treated with remdesivir only in the inpatient setting, the adjusted odds of death within 28 days were significantly higher among those who did not complete the 5-day course of remdesivir (aOR 2.07, 95% CI 1.45-2.95, p < 0.001). Conclusions: This study describes the clinical outcomes of a strategy of transitioning remdesivir therapy from inpatient to outpatient among selected patients. Mortality was lower among patients who completed the 5-day course of remdesivir.

Evaluation of a Telemedicine pharmaceutical care program for coordination patient's transfer between hospital and primary care, using Telepharmacy.

OBJECTIVE: To report our experience with Telemedicine projects: a Telepharmacy Hospital Pharmacy/Primary Care Pharmacy Coordination Program and a Hospital Pharmacy/Primary Care Pharmacy  Electronic Cross-consultation Program. Results are reported in terms of  medication adherence, perceived quality and satisfaction, and economic  impact. METHOD: A) Telepharmacy Hospital Pharmacy/Primary Care Pharmacy Coordination Program: Phases of development: 1) Creation of a  work group; 2) definition of patient inclusion criteria; 3) selection of medicines; 4) integration of hospital and primary care pharmaceutical care; 5)  setting up of facilities in primary care; 6) logistics design; 7) creation of the Telemedicine system; 8) provision of training to primary care pharmacists; 9) establishment of a pharmaceutical care protocol; 10) obtaining patient informed consent. Medication adherence was evaluated using  dispensing records. Results were assessed based on a quality questionnaire.  Pharmacist evaluation was performed using a satisfaction questionnaire. The economic impact of the programs was assessed from patient's perspective from the estimated 1-year avoided direct costs of traveling from home to the  hospital. B) Webbased cross-consultation system: mining was performed of  web data from August 2018-June 2019. Analyzed items: hospital pharmacoterapeutic area, reasons, and results of consultation in primary and  hospital care. RESULTS: A) Telepharmacy Hospital Pharmacy / Primary Care Pharmacy Coordination Program: sample: 51 patients, 58% male. Mean  age  62.8 ± 18.0 years. 83.0% were pensioners; 69% were involved in an enteral  nutrition program. Baseline and post-intervention medication adherence, 95.82  ± 8.03 vs 85.23 ± 23.02 (p = 0.007). Patients  took 3.3 ± 1.4 hours to travel to the hospital; all patients assumed traveling costs. Average avoided cost per patient per year, €76.08 ± 38.77.  Average score on the satisfaction questionnaire, 9.4 ± 1.3 over 10. The most valued items were work/family reconciliation and cost savings. No items were identified as negative in the program. Pharmacist satisfaction was 9.0 ± 1.2 over 10. B) Electronic cross-consultation program: 458  consultations, 190 from secondary to primary care, and 268 from primary to secondary care. CONCLUSIONS: The Telemedicine programs enabled coordination of drug therapy monitoring between the hospital and the primary care pharmacy. Patients and professionals reported a high level of satisfaction with  the Telepharmacy Hospital Pharmacy/Primary Care Pharmacy Coordination Program, which had a very positive economic impact. Finally, the  two Telepharmacy programs integrate humanization strategies.

OBJETIVO: Analizar estrategias de Telemedicina y colaboración entre atención  primaria y atención hospitalaria: programa de Telefarmacia de Coordinación  entre los Equipos Asistenciales de Farmacia Hospitalaria y Atención Primaria y  la plataforma e-interconsulta. Describir la implantación del programa  Telefarmacia de Coordinación entre los Equipos Asistenciales de Farmacia  Hospitalaria y Atención Primaria y evaluar los resultados sobre adherencia  terapéutica, calidad percibida y satisfacción y económicos, así como las e- interconsultas realizadas entre atención hospitalaria y atención primaria.Método: A) Telefarmacia de Coordinación entre los Equipos Asistenciales de  Farmacia Hospitalaria y Atención Primaria: fases de implantación: 1) creación  del grupo de trabajo; 2) establecimiento de criterios de inclusión de pacientes;  3) selección de medicamentos; 4) integración de la documentación de la  atención farmacéutica; 5) acondicionamiento hospide la consulta de atención  primaria; 6) diseño logístico; 7) creación del sistema de Telemedicina; 8)  formación a farmacéuticos de atención primaria; 9) protocolización de la  atención farmacéutica; 10) información al paciente y consentimiento  informado. La adherencia se evaluó por registro de dispensaciones. Evaluación  de los resultados mediante cuestionario de calidad percibida. Evaluación por  farmacéuticos mediante encuesta de satisfacción. Análisis del impacto  económico según costes directos estimados de los desplazamientos evitados  desde el domicilio hasta el hospital durante un año. B) Plataforma e- interconsulta: explotación de los datos de la plataforma web de agosto de  2018 a junio de 2019. Se analizó: área farmacoterapéutica en atención  hospitalaria, motivos y resultados de las mismas en atención primaria y  atención hospitalaria. RESULTADOS: A) Telefarmacia de Coordinación entre los Equipos Asistenciales de Farmacia Hospitalaria y Atención Primaria: 51 pacientes incluidos, 58% varones. 62,8 ± 18,0 años de media de edad. 83,0% pensionistas; 69% adscritos al programa de nutrición enteral  domiciliaria. Adherencia previa y tras la implantación del programa: 95,82 ±  8,03 versus 85,23 ± 23,02 (p = 0,007). Los pacientes emplearon una media de 3,3 ± 1,4 horas en el desplazamiento al servicio de farmacia del hospital; el 100% asumió el gasto de los desplazamientos. Coste medio evitado por paciente/año: 76,08 ± 38,77 €. Media de valoración de la encuesta de satisfacción: 9,4 ± 1,3 sobre 10. Resultado de la encuesta de  satisfacción a farmacéuticos: 9,0 ± 1,2. B) Plataforma e-interconsulta: 458  consultas realizadas: 190 desde atención hospitalaria a atención primaria, y  268 desde atención primaria a atención hospitalaria. CONCLUSIONES: Estos programas de Telemedicina permiten un seguimiento farmacoterapéutico coordinado del paciente externo entre  farmacia hospitalaria y atención primaria. El programa Telefarmacia de Coordinación entre los Equipos Asistenciales de Farmacia Hospitalaria y  Atención Primaria cuenta con una alta valoración de calidad percibida por  pacientes y farmacéuticos y un elevado impacto económico para el paciente.  Ambos proyectos integran estrategias de humanización que facilitan  proporcionar una atención farmacéutica más cercana al paciente, evitándole  desplazamientos innecesarios al hospital.

Evaluación de un programa de atención farmacéutica en Telemedicina para la coordinación de la transición del paciente, entre atención hospitalaria – primaria, mediante Telefarmacia / Evaluation of a Telemedicine pharmaceutical care program for coordination patient’s transfer between hospital and primary care, using Telepharmacy

Objetivo: Analizar estrategias de Telemedicina y colaboración entreatención primaria y atención hospitalaria: programa de Telefarmacia deCoordinación entre los Equipos Asistenciales de Farmacia Hospitalariay Atención Primaria y la plataforma e-interconsulta. Describir la implantación del programa Telefarmacia de Coordinación entre los EquiposAsistenciales de Farmacia Hospitalaria y Atención Primaria y evaluar losresultados sobre adherencia terapéutica, calidad percibida y satisfaccióny económicos, así como las e-interconsultas realizadas entre atenciónhospitalaria y atención primaria.Método: A) Telefarmacia de Coordinación entre los Equipos Asistenciales de Farmacia Hospitalaria y Atención Primaria: fases de implantación: 1) creación del grupo de trabajo; 2) establecimiento de criteriosde inclusión de pacientes; 3) selección de medicamentos; 4) integración dela documentación de la atención farmacéutica; 5) acondicionamiento. de la consulta de atención primaria; 6) diseño logístico; 7) creación delsistema de Telemedicina; 8) formación a farmacéuticos de atención primaria; 9) protocolización de la atención farmacéutica; 10) información alpaciente y consentimiento informado. La adherencia se evaluó por registro de dispensaciones. Evaluación de los resultados mediante cuestionariode calidad percibida. Evaluación por farmacéuticos mediante encuestade satisfacción. Análisis del impacto económico según costes directosestimados de los desplazamientos evitados desde el domicilio hasta elhospital durante un año. B) Plataforma e-interconsulta: explotación delos datos de la plataforma web de agosto de 2018 a junio de 2019. (AU)

Objective: To report our experience with Telemedicine projects: aTelepharmacy Hospital Pharmacy/Primary Care Pharmacy CoordinationProgram and a Hospital Pharmacy/Primary Care Pharmacy ElectronicCross-consultation Program. Results are reported in terms of medicationadherence, perceived quality and satisfaction, and economic impact.Method: A) Telepharmacy Hospital Pharmacy/Primary Care PharmacyCoordination Program: Phases of development: 1) Creation of a workgroup; 2) definition of patient inclusion criteria; 3) selection of medicines;4) integration of hospital and primary care pharmaceutical care; 5) setting up of facilities in primary care; 6) logistics design; 7) creation of theTelemedicine system; 8) provision of training to primary care pharmacists;9) establishment of a pharmaceutical care protocol; 10) obtaining patientinformed consent. Medication adherence was evaluated using dispensingrecords. Results were assessed based on a quality questionnaire. Pharmacist evaluation was performed using a satisfaction questionnaire. Theeconomic impact of the programs was assessed from patient’s perspectivefrom the estimated 1-year avoided direct costs of traveling from home tothe hospital. B) Webbased cross-consultation system: mining was performed of web data from August 2018-June 2019. Analyzed items: hospitalpharmacoterapeutic area, reasons, and results of consultation in primaryand hospital care.Results: A) Telepharmacy Hospital Pharmacy / Primary Care Pharmacy Coordination Program: sample: 51 patients, 58% male. Meanage 62.8 ± 18.0 years. 83.0% were pensioners; 69% were involved inan enteral nutrition program. Baseline and post-intervention medicationadherence, 95.82 ± 8.03 vs 85.23 ± 23.02 (p = 0.007). Patients took3.3 ± 1.4 hours to travel to the hospital; all patients assumed travelingcosts. Average avoided cost per patient per year, €76.08 ± 38.77. Average score on the satisfaction questionnaire, 9.4 ± 1.3 over 10. (AU)

Characterization of a novel thermophilic metagenomic GH5 endoglucanase heterologously expressed in Escherichia coli and Saccharomyces cerevisiae.

BACKGROUND: Endoglucanases from thermophilic microorganisms are a valuable resource as they can be used in a wide variety of biotechnological applications including the valorisation of biomass and the production of biofuels. In the present work we analysed the metagenome from the hot spring Muiño da Veiga, located in the northwest of Spain (in the Galicia region), in search for novel thermostable endoglucanases. RESULTS: Sequence analysis of the metagenome revealed a promising enzyme (Cel776). Predictions on protein structure and conserved amino acid sequences were conducted, as well as expression in heterologous systems with Escherichia coli and Saccharomyces cerevisiae as the host. Cel776Ec was correctly expressed and purified by taking advantage of the His-Tag system, with a yield of 0.346 U/mL in the eluted fraction. Cel776Sc was expressed extracellulary and was easily recovered from the supernatant without the need of further purification, requiring only a concentration step by ultrafiltration, with a significantly higher yield of 531.95 U/mL, revealing a much more suitable system for production of large amounts of the enzyme. Their biochemical characterization revealed biotechnologically interesting enzymes. Both Cel776Ec and Cel776Sc had an optimal temperature of 80 °C and optimal pH of 5. Cel776Ec exhibited high thermostability maintaining its activity for 24 h at 60 °C and maintained its activity longer than Cel776Sc at increasing incubation temperatures. Moreover, its substrate specificity allowed the degradation of both cellulose and xylan. Whereas Cel776Ec was more active in the presence of calcium and magnesium, manganese was found to increase Cel776Sc activity. A stronger inhibitory effect was found for Cel776Ec than Cel776Sc adding detergent SDS to the reaction mix, whereas EDTA only significantly affected Cel776Sc activity. CONCLUSIONS: Our study reports the discovery of a new promising biocatalyst for its application in processes, such as the production of biofuel and the saccharification of plant biomass, due to its bifunctional enzymatic activity as an endoglucanase and as a xylanase, as well as highlights the advantages of a yeast expression system over bacteria.

Comparison of hospitalization outcomes for delivery and resource utilization between pregnant women with kidney transplants and chronic kidney disease in the United States.

BACKGROUND: This study aimed to assess outcomes of delivery hospitalizations, including acute kidney injury (AKI), obstetric and foetal events and resource utilization among pregnant women with kidney transplants compared with pregnant women with no known kidney disease and those with chronic kidney disease (CKD) Stages 3-5. METHOD: Hospitalizations for delivery in the US were identified using the enhanced delivery identification method in the National Inpatient Sample dataset from the years 2009 to 2014. Diagnoses of CKD Stages 3-5, kidney transplantation, along with obstetric events, delivery methods and foetal events were identified using ICD-9-CM diagnosis and procedure codes. Patients with no known kidney disease group were identified by excluding any diagnoses of CKD, end stage kidney disease, and kidney transplant. Multivariable logistic regression accounting for the survey weights and matched regression was conducted to investigate the risk of maternal and foetal complications in women with kidney transplants, compared with women with no kidney transplants and no known kidney disease, and to women with CKD Stages 3-5. RESULT: A total of 5, 408, 215 hospitalizations resulting in deliveries were identified from 2009 to 2014, including 405 women with CKD Stages 3-5, 295 women with functioning kidney transplants, and 5, 405, 499 women with no known kidney disease. Compared with pregnant women with no known kidney disease, pregnant kidney transplant recipients were at higher odds of hypertensive disorders of pregnancy (OR = 3.11, 95% CI [2.26, 4.28]), preeclampsia/eclampsia/HELLP syndrome (OR = 3.42, 95% CI [2.54, 4.60]), preterm delivery (OR = 2.46, 95% CI [1.75, 3.45]), foetal growth restriction (OR = 1.74, 95% CI [1.01, 3.00]) and AKI (OR = 10.46, 95% CI [5.33, 20.56]). There were no significant differences in rates of gestational diabetes or caesarean section. Pregnant women with kidney transplants had 1.30-times longer lengths of stay and 1.28-times higher costs of hospitalization. However, pregnant women with CKD Stages 3-5 were at higher odds of AKI (OR = 5.29, 95% CI [2.41, 11.59]), preeclampsia/eclampsia/HELLP syndrome (OR = 1.72, 95% CI [1.07, 2.76]) and foetal deaths (OR = 3.20, 95% CI [1.06, 10.24]), and had 1.28-times longer hospital stays and 1.37-times higher costs of hospitalization compared with pregnant women with kidney transplant. CONCLUSION: Pregnant women with kidney transplant were more likely to experience adverse events during delivery and had longer lengths of stay and higher total charges when compared with women with no known kidney disease. However, pregnant women with moderate to severe CKD were more likely to experience serious complications than kidney transplant recipients.

Quantitative Alterations in Complement Alternative Pathway and Related Genetic Analysis in Severe Phenotype Preeclampsia.

Background: Preeclampsia and hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome share many clinical and biologic features with thrombotic microangiopathy syndromes caused by complement abnormalities. Our hypothesis was that similar functional and genetic alterations in the complement alternative pathway (CAP) are present in these disorders of pregnancy. Methods: We conducted quantitative analysis of proteins involved in CAP using ELISA and nephelometry on prospectively collected blood samples from patients with severe phenotype preeclampsia (defined as delivery ≤34 weeks due to preeclampsia), HELLP syndrome, or eclampsia, and matched normotensive controls (n=25 in each arm) between 2011 and 2016. Sequencing was performed to interrogate 14 genes encoding CAP components. Results: Both groups were similar in age, gravidity, parity, marital status, and race. The study group had a higher BMI (mean±SD, 32±8 versus 25±4 kg/m2; P=0.002) and earlier gestational age at delivery (32.5±3.6 versus 40.3±1 weeks; P<0.001). Serologic studies demonstrated elevated Bb subunit (median [range], 1.2 [0.5-4.3] versus 0.6 [0.5-1] µg/ml; P<0.001), complement C5 concentration (28 [18-33] versus 24 [15-34] mg/dl; P=0.03), and sMAC (371 [167-761] versus 184 [112-249] ng/ml; P<0.001) concentrations in patients with preeclampsia. Two thirds of patients with preeclampsia had at least one nonsynonymous sequence variant in CAP genes. Conclusion: Patients with severe phenotype preeclampsia manifest functional alterations in CAP activation. Genetic variants in the CAP genes were detected in several patients, but a larger population study is necessary to fully evaluate genetic risk. Genetic screening and complement-targeted treatment may be useful in risk stratification and novel therapeutic approaches.

Pregnancy in Kidney Transplant Recipients.

Women with end-stage kidney disease commonly have difficulty conceiving through spontaneous pregnancy, and many suffer from infertility. Kidney transplantation restores the impairment in fertility and increases the possibility of pregnancy. In addition, the number of female kidney transplant recipients of reproductive age has been increasing. Thus, preconception counseling, contraceptive management, and family planning are of great importance in the routine care of this population. Pregnancy in kidney transplant recipients is complicated by underlying maternal comorbidities, kidney allograft function, the effect of pregnancy on the transplanted kidney, and the effect of the maternal health on the fetus, in addition to immunosuppressive medications and their potential teratogenesis. Given the potential maternal and fetal risks, and possible complications during pregnancy, pretransplant and prepregnancy counseling for women of reproductive age are crucial, including delivery of information regarding contraception and timing for pregnancy, fertility and pregnancy rates, the risk of immunosuppression on the fetus, the risk of kidney allograft, and other maternal complications. In this article, we discuss aspects related to pregnancy among kidney transplant recipients and their management.

Treatment of C3 Glomerulopathy in Adult Kidney Transplant Recipients: A Systematic Review.

BACKGROUND: C3 glomerulopathy (C3G), a rare glomerular disease mediated by alternative complement pathway dysregulation, is associated with a high rate of recurrence and graft loss after kidney transplantation (KTx). We aimed to assess the efficacy of different treatments for C3G recurrence after KTx. METHODS: Databases (MEDLINE, EMBASE, and Cochrane Database) were searched from inception through 3 May, 2019. Studies were included that reported outcomes of adult KTx recipients with C3G. Effect estimates from individual studies were combined using the random-effects, generic inverse variance method of DerSimonian and Laird., The protocol for this meta-analysis is registered with PROSPERO (no. CRD42019125718). RESULTS: Twelve studies (7 cohort studies and 5 case series) consisting of 122 KTx patients with C3G (73 C3 glomerulonephritis (C3GN) and 49 dense deposit disease (DDD)) were included. The pooled estimated rates of allograft loss among KTx patients with C3G were 33% (95% CI: 12-57%) after eculizumab, 42% (95% CI: 2-89%) after therapeutic plasma exchange (TPE), and 81% (95% CI: 50-100%) after rituximab. Subgroup analysis based on type of C3G was performed. Pooled estimated rates of allograft loss in C3GN KTx patients were 22% (95% CI: 5-46%) after eculizumab, 56% (95% CI: 6-100%) after TPE, and 70% (95% CI: 24-100%) after rituximab. Pooled estimated rates of allograft loss in DDD KTx patients were 53% (95% CI: 0-100%) after eculizumab. Data on allograft loss in DDD after TPE (1 case series, 0/2 (0%) allograft loss at 6 months) and rituximab (1 cohort, 3/3 (100%) allograft loss) were limited. Among 66 patients (38 C3GN, 28 DDD) who received no treatment (due to stable allograft function at presentation and/or clinical judgment of physicians), pooled estimated rates of allograft loss were 32% (95% CI: 7-64%) and 53% (95% CI: 28-77%) for C3GN and DDD, respectively. Among treated C3G patients, data on soluble membrane attack complex of complement (sMAC) were limited to patients treated with eculizumab (N = 7). 80% of patients with elevated sMAC before eculizumab responded to treatment. In addition, all patients who responded to eculizumab had normal sMAC levels after post-eculizumab. CONCLUSIONS: Our study suggests that the lowest incidence of allograft loss (33%) among KTX patients with C3G are those treated with eculizumab. Among those who received no treatment for C3G due to stable allograft function, there is a high incidence of allograft loss of 32% in C3GN and 53% in DDD. sMAC level may help to select good responders to eculizumab.

Diagnostics, Risk Factors, Treatment and Outcomes of Acute Kidney Injury in a New Paradigm.

Acute kidney injury (AKI) is a common clinical condition among patients admitted in the hospitals. The condition is associated with both increased short-term and long-term mortality. With the development of a standardized definition for AKI and the acknowledgment of the impact of AKI on patient outcomes, there has been increased recognition of AKI. Two advances from past decades, the usage of computer decision support and the discovery of AKI biomarkers, have the ability to advance the diagnostic method to and further management of AKI. The increasingly widespread use of electronic health records across hospitals has substantially increased the amount of data available to investigators and has shown promise in advancing AKI research. In addition, progress in the finding and validation of different forms of biomarkers of AKI within diversified clinical environments and has provided information and insight on testing, etiology and further prognosis of AKI, leading to future of precision and personalized approach to AKI management. In this this article, we discussed the changing paradigms in AKI: from mechanisms to diagnostics, risk factors, and management of AKI.

Promises of Big Data and Artificial Intelligence in Nephrology and Transplantation.

Kidney diseases form part of the major health burdens experienced all over the world. Kidney diseases are linked to high economic burden, deaths, and morbidity rates. The great importance of collecting a large quantity of health-related data among human cohorts, what scholars refer to as "big data", has increasingly been identified, with the establishment of a large group of cohorts and the usage of electronic health records (EHRs) in nephrology and transplantation. These data are valuable, and can potentially be utilized by researchers to advance knowledge in the field. Furthermore, progress in big data is stimulating the flourishing of artificial intelligence (AI), which is an excellent tool for handling, and subsequently processing, a great amount of data and may be applied to highlight more information on the effectiveness of medicine in kidney-related complications for the purpose of more precise phenotype and outcome prediction. In this article, we discuss the advances and challenges in big data, the use of EHRs and AI, with great emphasis on the usage of nephrology and transplantation.

The sensitivity and specificity of the routine kidney biopsy immunofluorescence panel are inferior to diagnosing renal immunoglobulin-derived amyloidosis by mass spectrometry.

Immunoglobulin light chain amyloidosis is the most frequent type of renal amyloidosis in the United States, accounting for 81% of cases. Accurate typing is crucial for early diagnosis and treatment of immunoglobulin-derived amyloidosis and to avoid treating other amyloidoses with potentially toxic chemotherapy. Immunofluorescence is the first step to type renal immunoglobulin-derived amyloidosis but the performance characteristics of this method are largely unknown. Here, we establish the sensitivity and specificity of immunofluorescence for diagnosing immunoglobulin-derived amyloidosis in patients whose amyloid typing was performed by the current gold standard of laser microdissection/mass spectrometry. Renal biopsy pathology reports originating from several institutions with a diagnosis of amyloidosis and which had amyloid typing by laser microdissection/mass spectrometry performed at our center were reviewed. Reported immunofluorescence staining for kappa or lambda of 2+ or more, with weak or no staining for the other light chain was considered positive for light chain amyloidosis by immunofluorescence. Based on microdissection/mass spectrometry results, of the 170 cases reviewed, 104 cases were typed as immunoglobulin-derived amyloidosis and 66 were typed as non-immunoglobulin-derived amyloidosis. Immunofluorescence sensitivity for diagnosing immunoglobulin-derived amyloidosis was 84.6%. The remaining 16 cases could not be diagnosed by immunofluorescence due to reported weak staining for all antigens or reported lack of preferential staining for one antigen. Immunofluorescence specificity was 92.4%. Five cases, all amyloid A amyloidosis, were misdiagnosed as immunoglobulin-derived amyloidosis by immunofluorescence. Immunofluorescence failed to accurately differentiate immunoglobulin-derived from non-immunoglobulin-derived amyloidosis in 12.3% of cases of renal amyloidosis. Relying on immunofluorescence alone for determining immunoglobulin-derived vs. non-immunoglobulin-derived amyloidosis may lead to misdiagnosis. Thus, immunofluorescence has inferior sensitivity and specificity compared with laser microdissection/mass spectrometry in the typing of immunoglobulin-derived amyloidosis.

Outcomes of Kidney Transplant Patients with Atypical Hemolytic Uremic Syndrome Treated with Eculizumab: A Systematic Review and Meta-Analysis.

BACKGROUND: Kidney transplantation in patients with atypical hemolytic uremic syndrome (aHUS) is frequently complicated by recurrence, resulting in thrombotic microangiopathy in the renal allograft and graft loss. We aimed to assess the use of eculizumab in the prevention and treatment of aHUS recurrence after kidney transplantation. METHODS: Databases (MEDLINE, EMBASE and Cochrane Database) were searched through February 2019. Studies that reported outcomes of adult kidney transplant recipients with aHUS treated with eculizumab were included. Estimated incidence rates from the individual studies were extracted and combined using random-effects, generic inverse variance method of DerSimonian and Laird. Protocol for this systematic review has been registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42018089438). RESULTS: Eighteen studies (13 cohort studies and five case series) consisting of 380 adult kidney transplant patients with aHUS who received eculizumab for prevention and treatment of post-transplant aHUS recurrence were included in the analysis. Among patients who received prophylactic eculizumab, the pooled estimated incidence rates of recurrent thrombotic microangiopathy (TMA) after transplantation and allograft loss due to TMA were 6.3% (95%CI: 2.8-13.4%, I2 = 0%) and 5.5% (95%CI: 2.9-10.0%, I2 = 0%), respectively. Among those who received eculizumab for treatment of post-transplant aHUS recurrence, the pooled estimated rates of allograft loss due to TMA was 22.5% (95%CI: 13.6-34.8%, I2 = 6%). When the meta-analysis was restricted to only cohort studies with data on genetic mutations associated with aHUS, the pooled estimated incidence of allograft loss due to TMA was 22.6% (95%CI: 13.2-36.0%, I2 = 10%). We found no significant publication bias assessed by the funnel plots and Egger's regression asymmetry test (p > 0.05 for all analyses). CONCLUSIONS: This study summarizes the outcomes observed with use of eculizumab for prevention and treatment of aHUS recurrence in kidney transplantation. Our results suggest a possible role for anti-C5 antibody therapy in the prevention and management of recurrent aHUS.

Association between urologic malignancies and end-stage renal disease: A meta-analysis.

AIM: Previous studies have suggested a higher incidence of urologic malignancies in end-stage renal disease (ESRD) patients. However, incidence trends of urologic malignancies in ESRD patients remain unclear. The aims of the present study were: (i) to investigate the pooled incidence/incidence trends; and (ii) to assess the risk of urologic malignancies in ESRD patients. METHODS: A literature search was conducted using MEDLINE, EMBASE and Cochrane Database from inception through April 2017. Studies that reported incidence or odds ratios of urologic malignancies among ESRD patients were included. Pooled odds ratios (OR) and 95%CI were calculated using a random-effect model. The protocol for this meta-analysis is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42017067687). RESULTS: Nineteen observational studies with 1 931 073 ESRD patients were enrolled. The pooled estimated incidence of kidney cancer and urothelial cancers (carcinomas of the bladder, ureters, and renal pelvis) in ESRD patients were 0.3% (95%CI: 0.2-0.5%) and 0.5% (95%CI: 0.3-0.8%), respectively. Meta-regression showed significant positive correlation between incidence of urologic malignancies in ESRD patients and year of study (slopes = +0.05 and +0.07, P < 0.001 for kidney cancer and urothelial cancers, respectively). Compared to non-ESRD status, ESRD was significantly associated with both kidney cancer (pooled OR 6.04; 95% CI 4.70-7.77) and urothelial cancers (pooled OR 4.37; 95% CI 2.40-7.96). CONCLUSION: Our study demonstrates a significant association between ESRD and urologic malignancies. The overall estimated incidence rates of kidney cancer and urothelial cancers are 0.4% and 0.5%, respectively. There is a significant positive correlation between the incidence of urologic malignancies and year of study.

Renal Disorders in Pregnancy: Core Curriculum 2019.

As the incidence of chronic kidney disease increases and women pursue pregnancy at more advanced ages, the management of kidney disease in pregnancy has become increasingly relevant to the practicing nephrologist. Women with kidney disorders face several challenges in pregnancy due to increased physiologic demands on the kidney and risk for disease progression, the potential teratogenicity of medications, and the increased risk for complications such as preeclampsia and preterm delivery. Challenges posed by an underlying disease process in pregnancy, such as autoimmune disease or diabetes mellitus, necessitate an interdisciplinary team to ensure good maternal and fetal outcomes. Rates of acute kidney injury in pregnancy are generally declining worldwide, but remain a significant public health concern in developing countries. Pregnancy may also be the first time that a woman has kidney disease or hypertension diagnosed. An understanding of what constitutes normal physiologic changes in pregnancy is critical in a diagnostic evaluation. In this review, we review physiologic changes in pregnancy, causes and management of acute kidney injury in pregnancy, hypertensive disorders of pregnancy, and how to care for women with chronic kidney disease of various causes, including the use of antihypertensives and immunosuppressants.

The effect of aspirin on kidney allograft outcomes; a short review to current studies.

CONTEXT: The use of aspirin in chronic kidney disease (CKD) patients has been shown to reduce myocardial infarction but may increase major bleeding. However, its effects in kidney transplant recipients are unclear. EVIDENCE ACQUISITIONS: A literature search was performed using MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from inception through September 2016. We included studies that reported odd ratios, relative risks or hazard ratios comparing outcomes of aspirin use in kidney transplant recipients. Pooled risk ratios (RR) and 95% confidence interval (CI) were assessed using a random-effect, generic inverse variance method. RESULTS: We included 9 studies; enrolling 19759 kidney transplant recipients that compared aspirin with no treatment. Compared to no treatment, aspirin reduced the risk of allograft failure (4 studies; RR: 0.57, 95% CI: 0.33 to 0.99), allograft thrombosis (2 studies; RR: 0.11, 95% CI: 0.02 to 0.53), and major adverse cardiac events (MACEs) or mortality (2 studies; RR: 0.72, 95% CI: 0.59 to 0.88), but not allograft rejection (3 studies; RR: 0.86, 95% CI: 0.45 to 1.65) or delayed graft function (DGF) (2 studies; RR: 1.00, 95% CI: 0.58 to 1.72) in kidney transplant recipients. The data on risk of major or minor bleeding were limited. CONCLUSIONS: Our meta-analysis demonstrates that administration of aspirin in kidney transplant recipients is associated with reduced risks of allograft failure, allograft thrombosis, and MACEs or mortality, but not allograft rejection or DGF. Future studies are needed to assess the risk of bleeding, and ultimately weigh the overall risks and benefits of aspirin use in specific kidney transplant patient populations.

Longitudinal characterization of renal proximal tubular markers in normotensive and preeclamptic pregnancies.

Glomerular damage is common in preeclampsia (PE), but the extent and etiology of tubular injury are not well understood. The aim of this study was to evaluate tubular injury in patients with PE and to assess whether it predates clinical disease. We performed a prospective cohort study of 315 pregnant women who provided urine samples at the end of the second trimester and at delivery. This analysis included women who developed PE (n = 15), gestational hypertension (GH; n = 14), and normotensive controls (NC; n = 44). Urinary markers of tubular injury, α1-microglobulin (A1M), retinol-binding protein (RBP), kidney-injury molecule-1 (KIM1), complement C5b-9, tissue inhibitor metalloproteinase-2 (TIMP-2), and insulin-like growth factor binding protein-7 (IGFBP-7) were measured by enzyme-linked immunosorbent assay (ELISA) and reported in relation to urine creatinine concentration. Second-trimester concentrations of all markers were similar among groups. At delivery, A1M concentrations were higher in the PE group than in the GH and NC groups as an A1M/creatinine ratio >13 (66.7, 8.3, and 35%, respectively, P = 0.01). Concentrations of C5b-9 were higher in the PE group than in the GH and NC groups (medians 9.85, 0.05, and 0.28 ng/mg, respectively, P = 0.003). KIM1, RBP, TIMP-2, and IGFBP-7 concentrations did not differ among groups at delivery. In conclusion, proximal tubular dysfunction, as assessed by A1M and C5b-9, developed during the interval between the end of the second trimester and delivery in patients with PE. However, this was not matched by abnormalities in markers previously associated with tubular cell injury (KIM-1, IGFBP-7, and TIMP-2).

The effects of short sleep duration on proteinuria and chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND: The risks of proteinuria and chronic kidney disease (CKD) in adults who regularly have short sleep duration (short sleepers) are controversial. The aim of this meta-analysis was to assess the effects of short sleep duration on proteinuria and CKD. METHODS: A literature search was conducted using MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews from the inception of the databases through November 2015. Studies that reported relative risks, odd ratios or hazard ratios comparing the risks of proteinuria and CKD in short sleepers were included. Pooled risk ratios (RR) and 95% confidence intervals (CI) were computed utilizing a random-effect, generic inverse variance method. RESULTS: Six observational studies with 252 075 individuals and three observational studies with 37 197 individuals were included in the analyses to assess the risks of CKD and proteinuria in short sleepers, respectively. The pooled RR of CKD in short sleepers was 1.51 (95% CI, 0.99-2.55). When meta-analysis was restricted only to studies with adjusted analysis for confounders assessing the risk of CKD in short sleepers, the pooled RR of CKD was 1.54 (95% CI, 0.80-2.95). The pooled RR of proteinuria in short sleepers was 1.47 (95% CI, 1.26-1.72). CONCLUSIONS: Despite the lack of significant association between short sleep duration and CKD, our meta-analysis suggests a potential association between short sleep duration and proteinuria, a surrogate marker for kidney disease progression. Future study is required to investigate if reversal of short sleep helps reduce proteinuria.