Publications by authors named "Javier A Neyra"

80 Publications

A Team-Based Approach for Testing Biomarkers of Kidney Disease Progression.

Authors:
Javier A Neyra

Kidney Int 2021 Jul 16. Epub 2021 Jul 16.

Division of Nephrology, Bone and Mineral Metabolism, Department of Internal Medicine, University of Kentucky Medical Center, Lexington, KY. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.kint.2021.06.035DOI Listing
July 2021

International Medical Graduates in Nephrology: Impressions of the Implications of Visa Status in a Cohort of Program Directors and Division Chiefs.

Kidney Med 2021 May-Jun;3(3):451-453. Epub 2021 Feb 18.

Division of Nephrology, Bone and Mineral Metabolism, Department of Internal Medicine, University of Kentucky, Lexington, KY.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.xkme.2020.12.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178450PMC
February 2021

Incidence and Outcomes of Acute Kidney Injury in COVID-19: A Systematic Review.

Blood Purif 2021 Jun 15:1-14. Epub 2021 Jun 15.

Division of Nephrology, Bone and Mineral Metabolism, University of Kentucky Medical Center, Lexington, Kentucky, USA.

Background And Objectives: The recent worldwide pandemic of COVID-19 has been a serious, multidimensional problem that has left a detrimental worldwide impact on individuals of all ages and several organ systems. The typical manifestation of kidney involvement is acute kidney injury (AKI); however, there is a lack of consensus data regarding AKI epidemiology in COVID-19. This systematic literature review aims to bridge this knowledge gap.

Design, Setting, Participants, And Measurements: MEDLINE and Cochrane library were systematically searched for the literature related to AKI in COVID-19 patients of all ages. MedRxIV was searched for relevant unpublished manuscripts. Two reviewers independently assessed the literature on the incidence of AKI and mortality, extracting the need for kidney replacement therapy (KRT).

Results: Sixty studies (n = 43,871 patients) were included in this review. The pooled incidence of AKI among COVID-19 patients was 19.45% (95% confidence intervals [95% CI]: 14.63-24.77%), while the pooled incidence of AKI COVID-19 patients requiring KRT was 39.04% (16.38-64.57%). The pooled proportion of COVID+ patients was significantly lower at 8.83% (5.64% to 12/66%). The overall mortality of COVID-19 patients was calculated to be 17.71% (95% CI: 11.49-24.93%), while the mortality among patients with AKI was higher at 54.24% (95% CI: 44.70-63.63%).

Conclusion: This comprehensive systematic review summarizes the available literature pertaining to AKI epidemiology in COVID-19 patients and highlights the incidence, associated mortality, and the need for KRT in this susceptible population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000514940DOI Listing
June 2021

We Won't Get Fooled Again: Finding the Who to Follow After Acute Kidney Injury.

Am J Kidney Dis 2021 07 27;78(1):16-18. Epub 2021 Apr 27.

Division of Nephrology, Kingston Health Sciences Center, Queen's University, Kingston, Ontario, Canada.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.ajkd.2021.02.325DOI Listing
July 2021

Association of Phosphate Containing Solutions with Incident Hypophosphatemia in Critically Ill Patients Requiring Continuous Renal Replacement Therapy.

Blood Purif 2021 Apr 29:1-8. Epub 2021 Apr 29.

Division of Nephrology, Bone and Mineral Metabolism, Department of Internal Medicine, University of Kentucky Medical Center, Lexington, Kentucky, USA.

Background: Hypophosphatemia in critically ill patients is a common electrolyte disturbance associated with a myriad of adverse effects. Critically ill patients requiring continuous renal replacement therapy (CRRT) are at high risk of hypophosphatemia and often require phosphate supplementation during therapy. The aim of this study was to evaluate the association of phosphate versus non-phosphate containing CRRT solutions with incident hypophosphatemia in critically ill patients requiring CRRT.

Materials And Methods: This is a single-center, retrospective, cohort study at a tertiary academic medical center of 1,396 adult patients requiring CRRT during their intensive care unit stay comprising 7,529 (phosphate containing) and 4,821 (non-phosphate containing) cumulative days of CRRT. Multivariable logistic regression was used to model the primary outcome of hypophosphatemia during CRRT according to exposure to phosphate versus non-phosphate containing CRRT solutions.

Results: Incident hypophosphatemia during CRRT, serum phosphate <2.5 mg/dL or 0.81 mmol/L, was significantly higher in the non-phosphate versus phosphate containing solution group: 304/489 (62%) versus 175/853 (21%) (p < 0.001). Cumulative phosphate supplementation was also significantly higher in the non-phosphate versus phosphate containing solution group: 79 (IQR: 0-320) versus 0 (0-16) mmol (p < 0.001). Non-phosphate solutions were associated with an 8-fold increase in the incidence of hypophosphatemia (adjusted OR 8.05; 95% CI 5.77, 11.26; p < 0.001).

Discussion/conclusions: The use of phosphate containing CRRT solutions was independently associated with reduced risk of incident hypophosphatemia and decreased phosphate supplementation during CRRT. Interventional studies to confirm these findings are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000514418DOI Listing
April 2021

Survey of Current Practices of Outpatient Hemodialysis for AKI Patients.

Kidney Int Rep 2021 Apr 28;6(4):1156-1160. Epub 2021 Jan 28.

Department of Internal Medicine, Division of Nephrology, Bone and Mineral Metabolism, University of Kentucky Medical Center, Lexington, Kentucky, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ekir.2021.01.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071612PMC
April 2021

CRRT prescription and delivery of dose.

Semin Dial 2021 Apr 28. Epub 2021 Apr 28.

Department of Internal Medicine, Division of Nephrology, University of Alabama, Birmingham, AL, USA.

Continuous renal replacement therapy (CRRT) is the preferred modality of extracorporeal renal support for critically ill patients with acute kidney injury (AKI). The dose of CRRT is reported as effluent flow in ml/kg body weight per hour (ml/kg/h). Solid evidence supports that the delivered CRRT effluent dose for critically ill patients with AKI should be 20-25 ml/kg/h on average. To account for treatment interruptions and the natural decline in filter efficiency over time, it is recommended to prescribe 25-30 ml/kg/h of effluent dose. However, transient higher doses of CRRT in specific clinical scenarios may be needed to accommodate specific solute control needs of a particular patient at a given time. Consequently, there should be consideration of the potential adverse consequences of non-selective clearance such as undesired antimicrobials and nutrients removal. In this manuscript, we provide a summary of evidence related to CRRT dose, practical aspects for its calculation at the time of prescribing CRRT, and considerations for addressing the expected gap between prescribed and delivered CRRT dose. We also provide a framework for monitoring and implementation of CRRT dose as a quality indicator of CRRT delivery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/sdi.12974DOI Listing
April 2021

Improving the quality of care for patients requiring continuous renal replacement therapy.

Semin Dial 2021 Apr 3. Epub 2021 Apr 3.

Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN, USA.

Continuous renal replacement therapy (CRRT) is the preferred extracorporeal kidney support therapy employed to support critically ill patients with acute or chronic kidney dysfunction in intensive care units. Significant heterogeneity in CRRT practice exists in part due to variable logistics, resources, and scarcity of evidence-based CRRT practices. Importantly, homogenization of practice patterns by developing substantial evidence and effective dissemination among providers is essential for optimizing CRRT practices. The emphasis on quality of CRRT delivery has prompted identification of potential quality indicators, development of multifaceted quality improvement initiatives, effective computer science utilization, and a surge of multidisciplinary quality assurance teams that advocate for "best" CRRT practices. This manuscript provides an overview of quality improvement methodologies and reviews candidate quality indicators of CRRT and the impact of quality improvement on enhancing CRRT delivery practices.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/sdi.12968DOI Listing
April 2021

Acute Kidney Disease to Chronic Kidney Disease.

Crit Care Clin 2021 Apr 13;37(2):453-474. Epub 2021 Feb 13.

Department of Medicine, Veterans Affairs Medical Center, 3350 La Jolla Village Drive, San Diego, CA 92161, USA.

Acute kidney injury (AKI) and chronic kidney disease are common interconnected syndromes that represent a public health problem. Acute kidney disease (AKD) is defined as the post-AKI status of acute or subacute kidney damage/dysfunction manifested by persistence of AKI beyond 7 to 90 days after the initial AKI diagnosis. Limited clinical data exist regarding AKD epidemiology but its incidence is observed in ∼25% of AKI survivors. Useful risk-stratification tools to predict risk of AKD and its prognosis are needed. Interventions on fluid management, nephrotoxic exposure, and follow-up care hold promise to ameliorate the burden of AKD and its complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ccc.2020.11.013DOI Listing
April 2021

Comparison of Approaches for Prediction of Renal Replacement Therapy-Free Survival in Patients with Acute Kidney Injury.

Blood Purif 2021 25;50(4-5):621-627. Epub 2021 Feb 25.

Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Background/aims: Acute kidney injury (AKI) in critically ill patients is common, and continuous renal replacement therapy (CRRT) is a preferred mode of renal replacement therapy (RRT) in hemodynamically unstable patients. Prediction of clinical outcomes in patients on CRRT is challenging. We utilized several approaches to predict RRT-free survival (RRTFS) in critically ill patients with AKI requiring CRRT.

Methods: We used the Medical Information Mart for Intensive Care (MIMIC-III) database to identify patients ≥18 years old with AKI on CRRT, after excluding patients who had ESRD on chronic dialysis, and kidney transplantation. We defined RRTFS as patients who were discharged alive and did not require RRT ≥7 days prior to hospital discharge. We utilized all available biomedical data up to CRRT initiation. We evaluated 7 approaches, including logistic regression (LR), random forest (RF), support vector machine (SVM), adaptive boosting (AdaBoost), extreme gradient boosting (XGBoost), multilayer perceptron (MLP), and MLP with long short-term memory (MLP + LSTM). We evaluated model performance by using area under the receiver operating characteristic (AUROC) curves.

Results: Out of 684 patients with AKI on CRRT, 205 (30%) patients had RRTFS. The median age of patients was 63 years and their median Simplified Acute Physiology Score (SAPS) II was 67 (interquartile range 52-84). The MLP + LSTM showed the highest AUROC (95% CI) of 0.70 (0.67-0.73), followed by MLP 0.59 (0.54-0.64), LR 0.57 (0.52-0.62), SVM 0.51 (0.46-0.56), AdaBoost 0.51 (0.46-0.55), RF 0.44 (0.39-0.48), and XGBoost 0.43 (CI 0.38-0.47).

Conclusions: A MLP + LSTM model outperformed other approaches for predicting RRTFS. Performance could be further improved by incorporating other data types.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000513700DOI Listing
February 2021

Assessment of a modified renal angina index for AKI prediction in critically ill adults.

Nephrol Dial Transplant 2021 Feb 19. Epub 2021 Feb 19.

Department of Internal Medicine, Division of Nephrology, Bone and Mineral Metabolism, University of Kentucky Medical Center, Lexington, KY, USA.

Background: The renal angina index (RAI) is a useful tool for risk-stratification of acute kidney injury (AKI) in critically ill children. We evaluated the performance of a modified adult RAI (mRAI) for the risk-stratification of AKI in critically ill adults.

Methods: We used two independent ICU cohorts: 13,965 adult patients from the University of Kentucky (UKY) and 4,789 from UT Southwestern (UTSW). The mRAI included: diabetes, presence of sepsis, mechanical ventilation, pressor/inotrope use, percentage change in SCr in reference to admission SCr (ΔSCr), and fluid overload percentage within the first day of ICU admission. The primary outcome was AKI stage ≥2 at Day 2-7. Performance and reclassification metrics were determined for the mRAI score compared to ΔSCr alone.

Results: The mRAI score outperformed ΔSCr and readjusted probabilities to predict AKI stage ≥2 at Day 2-7: C-statistic: UKY 0.781 vs. 0.708 (IDI 2.2%) and UTSW 0.766 vs. 0.696 (IDI 1.8%), p<0.001 for both. In the UKY cohort, only 3.3% of patients with mRAI score <10 had the AKI event, while 16.4% of patients with mRAI score of ≥ 10 had the AKI event (NPV 96.8%). Similar findings were observed in the UTSW cohort as part of external validation.

Conclusions: In critically ill adults, the adult mRAI score determined within the first day of ICU admission outperformed changes in SCr for the prediction of AKI stage ≥2 at Day 2-7 of ICU stay. The modified adult RAI is a feasible tool for AKI risk-stratification in adult patients in the ICU.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ndt/gfab049DOI Listing
February 2021

Dose of Continuous Renal Replacement Therapy in Critically Ill Patients: A Bona Fide Quality Indicator.

Nephron 2021 4;145(2):91-98. Epub 2021 Feb 4.

Division of Nephrology, Department of Internal Medicine, Bone and Mineral Metabolism, University of Kentucky, Lexington, Kentucky, USA,

Acute kidney injury (AKI) is common in critically ill patients, and renal replacement therapy (RRT) constitutes an important aspect of acute management during critical illness. Continuous RRT (CRRT) is frequently utilized in intensive care unit settings, particularly in patients with severe AKI, fluid overload, and hemodynamic instability. The main goal of CRRT is to timely optimize solute control, acid-base, and volume status. Total effluent dose of CRRT is a deliverable that depends on multiple factors and therefore should be systematically monitored (prescribed vs. delivered) and iteratively adjusted in a sustainable mode. In this manuscript, we review current evidence of CRRT dosing and provide recommendations for its implementation as a quality indicator of CRRT delivery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000512846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7965247PMC
February 2021

Development, implementation and outcomes of a quality assurance system for the provision of continuous renal replacement therapy in the intensive care unit.

Sci Rep 2020 11 26;10(1):20616. Epub 2020 Nov 26.

Division of Nephrology, Bone and Mineral Metabolism, Department of Internal Medicine, University of Kentucky, Lexington, KY, USA.

Critically ill patients with requirement of continuous renal replacement therapy (CRRT) represent a growing intensive care unit (ICU) population. Optimal CRRT delivery demands continuous communication between stakeholders, iterative adjustment of therapy, and quality assurance systems. This Quality Improvement (QI) study reports the development, implementation and outcomes of a quality assurance system to support the provision of CRRT in the ICU. This study was carried out at the University of Kentucky Medical Center between September 2016 and June 2019. We implemented a quality assurance system using a step-wise approach based on the (a) assembly of a multidisciplinary team, (b) standardization of the CRRT protocol, (c) creation of electronic CRRT flowsheets, (d) selection, monitoring and reporting of quality metrics of CRRT deliverables, and (e) enhancement of education. We examined 34-month data comprising 1185 adult patients on CRRT (~ 7420 patient-days of CRRT) and tracked selected QI outcomes/metrics of CRRT delivery. As a result of the QI interventions, we increased the number of multidisciplinary experts in the CRRT team and ensured a continuum of education to health care professionals. We maximized to 100% the use of continuous veno-venous hemodiafiltration and doubled the percentage of patients using regional citrate anticoagulation. The delivered CRRT effluent dose (~ 30 ml/kg/h) and the delivered/prescribed effluent dose ratio (~ 0.89) remained stable within the study period. The average filter life increased from 26 to 31 h (p = 0.020), reducing the mean utilization of filters per patient from 3.56 to 2.67 (p = 0.054) despite similar CRRT duration and mortality rates. The number of CRRT access alarms per treatment day was reduced by 43%. The improvement in filter utilization translated into ~ 20,000 USD gross savings in filter cost per 100-patient receiving CRRT. We satisfactorily developed and implemented a quality assurance system for the provision of CRRT in the ICU that enabled sustainable tracking of CRRT deliverables and reduced filter resource utilization at our institution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-76785-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692557PMC
November 2020

The International Biomedical Workforce is Critical to Our Response to COVID-19 in the United States.

Mayo Clin Proc 2020 11 29;95(11):2336-2338. Epub 2020 Sep 29.

Division of Nephrology, Bone and Mineral Metabolism, Department of Internal Medicine, University of Kentucky, Lexington, KY.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mayocp.2020.09.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522644PMC
November 2020

International Medical Graduates in Nephrology: A Guide for Trainees and Programs.

Adv Chronic Kidney Dis 2020 07 2;27(4):297-304.e1. Epub 2020 Aug 2.

National Kidney Foundation, New York, NY.

A significant portion of the nephrology workforce has traditionally consisted of non-United States (US) citizen international medical graduates and international research trainees. Although international medical graduates are offered opportunities for training and professional growth that are beyond those available in their countries of origin, they typically encounter barriers to transition from training to practice and early-stage career development. In this article, we describe the exchange visitor and temporary worker visas granted to foreign trainees in the United States, focusing on the transition from training to nephrology practice and/or research. While we provide general recommendations on how to navigate this tedious and unpredictable process for both programs and trainees, consultation with immigration attorneys is indispensable for a successful outcome. Trainees are therefore encouraged to seek continuous support from their programs/sponsors and assistance from immigration representatives at their training institutions. We provide a positive message to emphasize that there are many pathways to arrive at the desired post-training destination.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.ackd.2020.05.003DOI Listing
July 2020

AKI Treated with Renal Replacement Therapy in Critically Ill Patients with COVID-19.

J Am Soc Nephrol 2021 01 16;32(1):161-176. Epub 2020 Oct 16.

Division of Nephrology, Kings County Hospital Center, New York City Health and Hospital Corporation, Brooklyn, New York.

Background: AKI is a common sequela of coronavirus disease 2019 (COVID-19). However, few studies have focused on AKI treated with RRT (AKI-RRT).

Methods: We conducted a multicenter cohort study of 3099 critically ill adults with COVID-19 admitted to intensive care units (ICUs) at 67 hospitals across the United States. We used multivariable logistic regression to identify patient-and hospital-level risk factors for AKI-RRT and to examine risk factors for 28-day mortality among such patients.

Results: A total of 637 of 3099 patients (20.6%) developed AKI-RRT within 14 days of ICU admission, 350 of whom (54.9%) died within 28 days of ICU admission. Patient-level risk factors for AKI-RRT included CKD, men, non-White race, hypertension, diabetes mellitus, higher body mass index, higher d-dimer, and greater severity of hypoxemia on ICU admission. Predictors of 28-day mortality in patients with AKI-RRT were older age, severe oliguria, and admission to a hospital with fewer ICU beds or one with greater regional density of COVID-19. At the end of a median follow-up of 17 days (range, 1-123 days), 403 of the 637 patients (63.3%) with AKI-RRT had died, 216 (33.9%) were discharged, and 18 (2.8%) remained hospitalized. Of the 216 patients discharged, 73 (33.8%) remained RRT dependent at discharge, and 39 (18.1%) remained RRT dependent 60 days after ICU admission.

Conclusions: AKI-RRT is common among critically ill patients with COVID-19 and is associated with a hospital mortality rate of >60%. Among those who survive to discharge, one in three still depends on RRT at discharge, and one in six remains RRT dependent 60 days after ICU admission.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1681/ASN.2020060897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894677PMC
January 2021

Safety and Feasibility of Physical Rehabilitation and Active Mobilization in Patients Requiring Continuous Renal Replacement Therapy: A Systematic Review.

Crit Care Med 2020 11;48(11):e1112-e1120

Department of Internal Medicine, Division of Nephrology, Bone and Mineral Metabolism, University of Kentucky, Lexington, KY.

Objectives: To evaluate the safety and feasibility of physical rehabilitation and active mobilization in patients requiring continuous renal replacement therapy in the ICU.

Data Sources: Medline, CINAHL, PubMed, Pedro, and Cochrane Library were used to extract articles focused on physical activity and mobility in this population.

Study Selection: Research articles were included in this review if 1) included adult patients greater than or equal to 18 years old requiring continuous renal replacement therapy located in the ICU; 2) described physical rehabilitation, active mobilization, or physical activity deliverables; 3) reported data on patient safety and/or feasibility. The primary outcome was safety, defined as number of adverse events per total number of sessions.

Data Extraction: Five-hundred seven articles were evaluated based on title and abstract with reviewers selecting 46 to assess by full text. Fifteen observational studies were included for final analysis with seven studies focused solely on physical activity in patients requiring continuous renal replacement therapy.

Data Synthesis: Four-hundred thirty-seven adult ICU patients requiring continuous renal replacement therapy participated in some form of physical rehabilitation, physical activity, or active mobilization. Two major adverse events (hypotension event requiring vasopressor and continuous renal replacement therapy tube disconnection, pooled occurrence rate 0.24%) and 13 minor adverse events (pooled occurrence rate 1.55%) were reported during a total of 840 individual mobility or activity sessions. Intervention fidelity was limited by a low prevalence of higher mobility with only 15.5% of incidences occurring at or above level 5 of ICU Mobility Scale (transfer to chair, marching in place or ambulation away from bed, 122/715 reports). Feasibility in the provision of these interventions and/or continuous renal replacement therapy-specific deliverables was inconsistently reported.

Conclusions: Early rehabilitation and mobilization, specifically activity in and near the hospital bed, appears safe and mostly feasible in ICU patients requiring continuous renal replacement therapy. A cautious interpretation of these data is necessary due to limited aggregate quality of included studies, heterogeneous reporting, and overall low achieved levels of mobility potentially precluding the occurrence or detection of adverse events.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CCM.0000000000004526DOI Listing
November 2020

Characteristics and Outcomes of Individuals With Pre-existing Kidney Disease and COVID-19 Admitted to Intensive Care Units in the United States.

Am J Kidney Dis 2021 02 19;77(2):190-203.e1. Epub 2020 Sep 19.

Division of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA.

Rationale & Objective: Underlying kidney disease is an emerging risk factor for more severe coronavirus disease 2019 (COVID-19) illness. We examined the clinical courses of critically ill COVID-19 patients with and without pre-existing chronic kidney disease (CKD) and investigated the association between the degree of underlying kidney disease and in-hospital outcomes.

Study Design: Retrospective cohort study.

Settings & Participants: 4,264 critically ill patients with COVID-19 (143 patients with pre-existing kidney failure receiving maintenance dialysis; 521 patients with pre-existing non-dialysis-dependent CKD; and 3,600 patients without pre-existing CKD) admitted to intensive care units (ICUs) at 68 hospitals across the United States.

Predictor(s): Presence (vs absence) of pre-existing kidney disease.

Outcome(s): In-hospital mortality (primary); respiratory failure, shock, ventricular arrhythmia/cardiac arrest, thromboembolic events, major bleeds, and acute liver injury (secondary).

Analytical Approach: We used standardized differences to compare patient characteristics (values>0.10 indicate a meaningful difference between groups) and multivariable-adjusted Fine and Gray survival models to examine outcome associations.

Results: Dialysis patients had a shorter time from symptom onset to ICU admission compared to other groups (median of 4 [IQR, 2-9] days for maintenance dialysis patients; 7 [IQR, 3-10] days for non-dialysis-dependent CKD patients; and 7 [IQR, 4-10] days for patients without pre-existing CKD). More dialysis patients (25%) reported altered mental status than those with non-dialysis-dependent CKD (20%; standardized difference=0.12) and those without pre-existing CKD (12%; standardized difference=0.36). Half of dialysis and non-dialysis-dependent CKD patients died within 28 days of ICU admission versus 35% of patients without pre-existing CKD. Compared to patients without pre-existing CKD, dialysis patients had higher risk for 28-day in-hospital death (adjusted HR, 1.41 [95% CI, 1.09-1.81]), while patients with non-dialysis-dependent CKD had an intermediate risk (adjusted HR, 1.25 [95% CI, 1.08-1.44]).

Limitations: Potential residual confounding.

Conclusions: Findings highlight the high mortality of individuals with underlying kidney disease and severe COVID-19, underscoring the importance of identifying safe and effective COVID-19 therapies in this vulnerable population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.ajkd.2020.09.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501875PMC
February 2021

Outcomes of critically ill solid organ transplant patients with COVID-19 in the United States.

Am J Transplant 2020 11 15;20(11):3061-3071. Epub 2020 Sep 15.

Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA.

National data on patient characteristics, treatment, and outcomes of critically ill coronavirus disease 2019 (COVID-19) solid organ transplant (SOT) patients are limited. We analyzed data from a multicenter cohort study of adults with laboratory-confirmed COVID-19 admitted to intensive care units (ICUs) at 68 hospitals across the United States from March 4 to May 8, 2020. From 4153 patients, we created a propensity score matched cohort of 386 patients, including 98 SOT patients and 288 non-SOT patients. We used a binomial generalized linear model (log-binomial model) to examine the association of SOT status with death and other clinical outcomes. Among the 386 patients, the median age was 60 years, 72% were male, and 41% were black. Death within 28 days of ICU admission was similar in SOT and non-SOT patients (40% and 43%, respectively; relative risk [RR] 0.92; 95% confidence interval [CI]: 0.70-1.22). Other outcomes and requirement for organ support including receipt of mechanical ventilation, development of acute respiratory distress syndrome, and receipt of vasopressors were also similar between groups. There was a trend toward higher risk of acute kidney injury requiring renal replacement therapy in SOT vs. non-SOT patients (37% vs. 27%; RR [95% CI]: 1.34 [0.97-1.85]). Death and organ support requirement were similar between SOT and non-SOT critically ill patients with COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ajt.16280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460925PMC
November 2020

Fibroblast Growth Factor 23 and αKlotho in Acute Kidney Injury: Current Status in Diagnostic and Therapeutic Applications.

Nephron 2020 25;144(12):665-672. Epub 2020 Aug 25.

Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, Dallas, Texas, USA,

Fibroblast growth factor (FGF) 23 and αKlotho are circulating mineral regulatory substances that also have a very diverse range of actions. Acute kidney injury (AKI) is a state of high FGF23 and low αKlotho. Clinical association data for FGF23 are strong, but the basic pathobiology of FGF23 in AKI is rather sparse. Conversely, preclinical data supporting a pathogenic role of αKlotho in AKI are strong, but the human data are still being generated. This pair of substances can potentially serve as diagnostic and prognostic biomarkers. FGF23 blockade and αKlotho restoration can have prophylactic and therapeutic utility in AKI. The literature to date is briefly reviewed in this article.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000509856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708396PMC
August 2020

Klotho in Clinical Nephrology: Diagnostic and Therapeutic Implications.

Clin J Am Soc Nephrol 2020 12 22;16(1):162-176. Epub 2020 Jul 22.

Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, Dallas, Texas.

αKlotho (called Klotho here) is a membrane protein that serves as the coreceptor for the circulating hormone fibroblast growth factor 23 (FGF23). Klotho is also cleaved and released as a circulating substance originating primarily from the kidney and exerts a myriad of housekeeping functions in just about every organ. The vital role of Klotho is shown by the multiorgan failure with genetic deletion in rodents, with certain features reminiscent of human disease. The most common causes of systemic Klotho deficiency are AKI and CKD. Preclinical data on Klotho biology have advanced considerably and demonstrated its potential diagnostic and therapeutic value; however, multiple knowledge gaps exist in the regulation of Klotho expression, release, and metabolism; its target organs; and mechanisms of action. In the translational and clinical fronts, progress has been more modest. Nonetheless, Klotho has potential clinical applications in the diagnosis of AKI and CKD, in prognosis of progression and extrarenal complications, and finally, as replacement therapy for systemic Klotho deficiency. The overall effect of Klotho in clinical nephrology requires further technical advances and additional large prospective human studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2215/CJN.02840320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792642PMC
December 2020

A narrative review of pharmacologic de-resuscitation in the critically ill.

J Crit Care 2020 10 6;59:156-162. Epub 2020 Jul 6.

University of Kentucky College of Medicine, Department of Internal Medicine, Division of Nephrology, Bone and Mineral Metabolism, 740 South Limestone, Lexington, Kentucky 40536, United States of America. Electronic address:

Despite evidence highlighting harms of fluid overload, minimal guidance exists on counteraction via utilization of diuretics in the de-resuscitation phase. While diuretics have been shown to decrease net volume and improve clinical outcomes in the critically ill, a lack of standardization surrounding selection of diuretic regimen or monitoring of de-resuscitation exists. Current monitoring parameters of de-resuscitation often rely on clinical signs of fluid overload, end organ recovery and other biochemical surrogate markers which are often deemed unreliable. The majority of evidence suggests that achieving a net-negative fluid balance within 72 h after shock resolution may be of benefit; however, approaches to such goal are uncertain. Loop diuretics are a widely available type of diuretic for removal of volume in patients with sufficient kidney function, with the potential for adjunct diuretics in special circumstances. At present, administration of diuretics within the broad critically ill population fails to find uniformity and often efficacy. Given the lack of randomized controlled trials in this susceptible population, we aim to provide a thorough therapeutic understanding of diuretic pharmacotherapy which is necessary in order to achieve desired goal of fluid balance and improve overall outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcrc.2020.07.004DOI Listing
October 2020

Timing of Initiation of Renal-Replacement Therapy in Acute Kidney Injury.

N Engl J Med 2020 07;383(3):240-251

From the Department of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta and Alberta Health Services, Edmonton (S.M.B.), the Division of Nephrology (R.W.), St. Michael's Hospital and the University of Toronto, Li Ka Shing Knowledge Institute (R.W., B.R.C., O.M.S., K.E.T.), Department of Medicine (R.W., O.M.S.), and Applied Health Research Centre (B.R.C., K.E.T.), St. Michael's Hospital, the Dalla Lana School of Public Health (K.E.T.), the Institute of Health Policy, Management, and Evaluation (R.W., B.R.C.), University of Toronto, and the Department of Critical Care Medicine, Sunnybrook Health Sciences Centre and the University of Toronto (N.K.J.A.), Toronto, the Department of Medicine, Université de Sherbrooke and Centre de Recherche du Centre Hospitalier Universitaire (CHU) de Sherbrooke, Sherbrooke, QC (F.L.), the Division of Critical Care, Juravinski Hospital, McMaster University, Hamilton, ON (B.R.), and the Division of Nephrology, London Health Sciences Centre, London, ON (M.W.) - all in Canada; the Department of Intensive Care, Austin Hospital and Royal Melbourne Hospital, School of Medicine, University of Melbourne, Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University (R.B., A.D.N.), Melbourne, VIC, and the George Institute for Global Health, Concord Clinical School, Faculty of Medicine, University of Sydney, Sydney (M.P.G., A.Y.W.) - both in Australia; the Institute of Primary Health Care, University of Bern, Bern (B.R.C.), and the Department of Critical Care Medicine, CHU Vaudois, Lausanne (A.G.S.) - both in Switzerland; Hôpital Louis Mourier (D.D.) and Université Léonard de Vinci (S.G.), INSERM Unité UMR S1155, Sorbonne Université and Université de Paris, Paris, Hôpital Avicenne, Bobigny (S.G.), and Hôpital Universitaire François Mitterrand, Lipness Team, INSERM Research Center Lipids, Nutrition, Cancer-Unité Mixte de Recherche 1231 and Laboratoire d'Excellence LipSTIC, Centre d'Investigation Clinique-Epidemiologie Clinique, CHU Dijon-Bourgogne, and INSERM Centre d'Investigation Clinique 1432, Université de Bourgogne, Dijon (J.-P.Q.) - all in France; the Department of Critical Care Medicine, Peking Union Medical College Hospital, Beijing (B.D.), and the Department of Critical Care Medicine, Zhongda Hospital Southeast University, Nanjing (H.Q.) - both in China; the Department of Intensive Care, University of Ghent, Ghent, Belgium (E.A.H.); the Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, Innsbruck, Austria (M.J.); Vita Salute San Raffaele University and IRCCS San Raffaele Scientific Institute, Milan (G.L.); the Divisions of Nephrology and Critical Care Medicine, University of California, San Francisco, San Francisco (K.D.L.); the Wellcome-Wolfson Institute for Experimental Medicine, Queen's University, and the Regional Intensive Care Unit, Royal Victoria Hospital, Belfast (D.F.M.), and King's College London, Guy's and St. Thomas' Hospital, London (M.O.) - both in the United Kingdom; the Cardiothoracic and Vascular Intensive Care Unit, Auckland City Hospital, Auckland (S.P.M.), and the Medical Research Institute of New Zealand (S.P.M.) and the Intensive Care Unit, Wellington Regional Hospital and Medical Research Institute of New Zealand (P.Y.), Wellington - both in New Zealand; the Division of Nephrology, Bone and Mineral Metabolism, University of Kentucky, Lexington (J.A.N.); University College Dublin Clinical Research Centre at St. Vincent's University Hospital, Dublin (A.D.N.); the Division of Nephrology, University of Pittsburgh, and Veterans Affairs Pittsburgh Healthcare System, Pittsburgh (P.M.P.); the Department of Intensive Care, University of Helsinki, and Helsinki University Hospital, Helsinki (V.P., S.V.); Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil (F.T.); and the Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, Germany (A.Z.).

Background: Acute kidney injury is common in critically ill patients, many of whom receive renal-replacement therapy. However, the most effective timing for the initiation of such therapy remains uncertain.

Methods: We conducted a multinational, randomized, controlled trial involving critically ill patients with severe acute kidney injury. Patients were randomly assigned to receive an accelerated strategy of renal-replacement therapy (in which therapy was initiated within 12 hours after the patient had met eligibility criteria) or a standard strategy (in which renal-replacement therapy was discouraged unless conventional indications developed or acute kidney injury persisted for >72 hours). The primary outcome was death from any cause at 90 days.

Results: Of the 3019 patients who had undergone randomization, 2927 (97.0%) were included in the modified intention-to-treat analysis (1465 in the accelerated-strategy group and 1462 in the standard-strategy group). Of these patients, renal-replacement therapy was performed in 1418 (96.8%) in the accelerated-strategy group and in 903 (61.8%) in the standard-strategy group. At 90 days, death had occurred in 643 patients (43.9%) in the accelerated-strategy group and in 639 (43.7%) in the standard-strategy group (relative risk, 1.00; 95% confidence interval [CI], 0.93 to 1.09; P = 0.92). Among survivors at 90 days, continued dependence on renal-replacement therapy was confirmed in 85 of 814 patients (10.4%) in the accelerated-strategy group and in 49 of 815 patients (6.0%) in the standard-strategy group (relative risk, 1.74; 95% CI, 1.24 to 2.43). Adverse events occurred in 346 of 1503 patients (23.0%) in the accelerated-strategy group and in 245 of 1489 patients (16.5%) in the standard-strategy group (P<0.001).

Conclusions: Among critically ill patients with acute kidney injury, an accelerated renal-replacement strategy was not associated with a lower risk of death at 90 days than a standard strategy. (Funded by the Canadian Institutes of Health Research and others; STARRT-AKI ClinicalTrials.gov number, NCT02568722.).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMoa2000741DOI Listing
July 2020

Preparedness of Kidney Replacement Therapy in the Critically Ill During COVID-19 Surge.

Kidney Int Rep 2020 Jul 7;5(7):961-964. Epub 2020 Jun 7.

Department of Internal Medicine, Division of Nephrology, University of Alabama at Birmingham, Birmingham, Alabama, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ekir.2020.05.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275991PMC
July 2020

Serum Klotho in Living Kidney Donors and Kidney Transplant Recipients: A Meta-Analysis.

J Clin Med 2020 Jun 12;9(6). Epub 2020 Jun 12.

Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA.

α-Klotho is a known anti-aging protein that exerts diverse physiological effects, including phosphate homeostasis. Klotho expression occurs predominantly in the kidney and is significantly decreased in patients with chronic kidney disease. However, changes in serum klotho levels and impacts of klotho on outcomes among kidney transplant (KTx) recipients and kidney donors remain unclear. A literature search was conducted using MEDLINE, EMBASE, and Cochrane Database from inception through October 2019 to identify studies evaluating serum klotho levels and impacts of klotho on outcomes among KTx recipients and kidney donors. Study results were pooled and analyzed utilizing a random-effects model. Ten cohort studies with a total of 431 KTx recipients and 5 cohort studies with a total of 108 living kidney donors and were identified. After KTx, recipients had a significant increase in serum klotho levels (at 4 to 13 months post-KTx) with a mean difference (MD) of 243.11 pg/mL (three studies; 95% CI 67.41 to 418.81 pg/mL). Although KTx recipients had a lower serum klotho level with a MD of = -234.50 pg/mL (five studies; 95% CI -444.84 to -24.16 pg/mL) compared to healthy unmatched volunteers, one study demonstrated comparable klotho levels between KTx recipients and eGFR-matched controls. Among kidney donors, there was a significant decrease in serum klotho levels post-nephrectomy (day 3 to day 5) with a mean difference (MD) of -232.24 pg/mL (three studies; 95% CI -299.41 to -165.07 pg/mL). At one year following kidney donation, serum klotho levels remained lower than baseline before nephrectomy with a MD of = -110.80 pg/mL (two studies; 95% CI 166.35 to 55.24 pg/mL). Compared to healthy volunteers, living kidney donors had lower serum klotho levels with a MD of = -92.41 pg/mL (two studies; 95% CI -180.53 to -4.29 pg/mL). There is a significant reduction in serum klotho levels after living kidney donation and an increase in serum klotho levels after KTx. Future prospective studies are needed to assess the impact of changes in klotho on clinical outcomes in KTx recipients and living kidney donors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm9061834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355868PMC
June 2020

Adipose-Derived Inflammatory and Coagulant Mediators in Patients With Sepsis.

Shock 2021 May;55(5):596-606

Aging and Critical Care Research Laboratory, University of Kentucky, Lexington, Kentucky.

Abstract: Results from preclinical sepsis studies using rodents are often criticized as not being reproducible in humans. Using a murine model, we previously reported that visceral adipose tissues (VAT) are highly active during the acute inflammatory response, serving as a major source of inflammatory and coagulant mediators. The purpose of this study was to determine whether these findings are recapitulated in patients with sepsis and to evaluate their clinical significance. VAT and plasma were obtained from patients undergoing intra-abdominal operations with noninflammatory conditions (control), local inflammation, or sepsis. In mesenteric and epiploic VAT, gene expression of pro-inflammatory (TNFα, IL-6, IL-1α, IL-1β) and pro-coagulant (PAI-1, PAI-2, TSP-1, TF) mediators was increased in sepsis compared with control and local inflammation groups. In the omentum, increased expression was limited to IL-1β, PAI-1, and PAI-2, showing a depot-specific regulation. Histological analyses showed little correlation between cellular infiltration and gene expression, indicating a resident source of these mediators. Notably, a strong correlation between PAI-1 expression in VAT and circulating protein levels was observed, both being positively associated with markers of acute kidney injury (AKI). In another cohort of septic patients stratified by incidence of AKI, circulating PAI-1 levels were higher in those with versus without AKI, thus extending these findings beyond intra-abdominal cases. This study is the first to translate upregulation of VAT mediators in sepsis from mouse to human. Collectively, the data suggest that development of AKI in septic patients is associated with high plasma levels of PAI-1, likely derived from resident cells within VAT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SHK.0000000000001579DOI Listing
May 2021

COVID-19: Nephrology preparedness checklist.

Clin Nephrol 2020 07;94(1):14-17

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5414/CN110225DOI Listing
July 2020

Continuous Versus Intermittent Infusion of Vancomycin and the Risk of Acute Kidney Injury in Critically Ill Adults: A Systematic Review and Meta-Analysis.

Crit Care Med 2020 06;48(6):912-918

Department of Internal Medicine, University of Kentucky College of Medicine, Lexington, KY.

Objectives: Critically ill patients routinely receive vancomycin as empiric antibiotic therapy. A continuous infusion administration strategy may be superior to intermittent infusion by minimizing peak concentrations and variability thereby optimizing safety. We performed a systematic review and meta-analysis to investigate the impact of vancomycin infusion strategy on acute kidney injury in critically ill adults.

Data Sources: A systematic search of MEDLINE, CINAHL, Web of Science, International Pharmaceutical Abstracts, and Google Scholar was undertaken.

Study Selection: We included randomized controlled trials and observational studies evaluating acute kidney injury in critically ill adults comparing vancomycin administered by intermittent and continuous infusion. Secondary outcomes included mortality and pharmacokinetic target attainment.

Data Extraction: Eleven studies were identified for analysis with baseline demographics, endpoints, protocol definitions, and outcomes extracted.

Data Synthesis: When compared with intermittent infusion, continuous infusion was associated with a reduction in acute kidney injury in critically ill adults (odds ratio, 0.47; 95% CI, 0.34-0.65) and a 2.6 greater odds of pharmacokinetic target attainment (odds ratio, 2.63; 95% CI, 1.52-4.57). No difference in mortality was observed (odds ratio, 1.04; 95% CI, 0.80-1.35).

Conclusions: When administered via a continuous infusion, vancomycin is associated with a 53% reduction in the odds of acute kidney injury and a 2.6-fold higher odds of pharmacokinetic target attainment when compared with intermittent infusion without influencing overall mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CCM.0000000000004326DOI Listing
June 2020

Performance of soluble Klotho assays in clinical samples of kidney disease.

Clin Kidney J 2020 Apr 16;13(2):235-244. Epub 2019 Jul 16.

Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, MA, USA.

Background: Soluble Klotho has multiple systemic salutary effects. In animals, both acute and chronic kidney disease models display systemic Klotho deficiency. As such, there is considerable interest in investigating soluble Klotho as a biomarker in patients with different types and severity of kidney diseases. Unfortunately, there remains uncertainty regarding the best method to measure soluble Klotho in human serum samples.

Methods: Using human serum samples obtained from several clinical cohorts with a wide range of kidney function, we measured soluble Klotho using a commercial enzyme-linked immunosorbent assay (ELISA) as well as with an immunoprecipitation-immunoblot (IP-IB) assay utilizing a synthetic antibody with high affinity and specificity for Klotho. Recovery of spiking with a known amount of exogenous Klotho was tested. A subset of samples was analyzed with and without the addition of a protease inhibitor cocktail at the time of collection or after the first freeze-thaw cycle to determine if these maneuvers influenced performance.

Results: The IP-IB assay was superior to the ELISA at recovery of exogenous Klotho (81-115% versus 60-81%) across the spectrum of kidney function. Klotho measurements by IP-IB were highly correlated with estimated glomerular filtration rate (eGFR) ( = 0.80, P < 0.001) in comparison with the commercial ELISA, which exhibited minimal correlation with eGFR ( = 0.18, P = 0.12). Use of a protease inhibitor cocktail neither improved nor impaired performance of the IP-IB assay; however, subsequent freeze-thaw cycle resulted in a significant reduction in Klotho recovery and dissipated the correlation between Klotho levels and eGFR. With the ELISA, the use of protease inhibitor cocktail resulted in an increase in intrasubject variability.

Conclusions: The IP-IB assay is preferable to the commercial ELISA to measure soluble Klotho concentrations in never-thawed serum samples of humans with varying severity of kidney disease. However, due to the labor-intensive nature of the IP-IB assay, further research is needed to secure an assay suitable for high-throughput work.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ckj/sfz085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147321PMC
April 2020