Objective: This report describes three patients with Ebola virus disease who were treated in the United States and developed for severe critical illness and multiple organ failure secondary to Ebola virus infection. The patients received mechanical ventilation, renal replacement therapy, invasive monitoring, vasopressor support, and investigational therapies for Ebola virus disease.
Data Sources: Patient medical records from three tertiary care centers (Emory University Hospital, University of Nebraska Medical Center, and Texas Health Presbyterian Dallas Hospital).
Study Selection: Not applicable.
Data Extraction: Not applicable.
Data Synthesis: Not applicable.
Conclusion: In the severe form, patients with Ebola virus disease may require life-sustaining therapy, including mechanical ventilation and renal replacement therapy. In conjunction with other reported cases, this series suggests that respiratory and renal failure may occur in severe Ebola virus disease, especially in patients burdened with high viral loads. Ebola virus disease complicated by multiple organ failure can be survivable with the application of advanced life support measures. This collective, multicenter experience is presented with the hope that it may inform future treatment of patients with Ebola virus disease requiring critical care treatment.
HIV treatment with tenofovir alafenamide fumarate (TAF) has decreased renal toxicity compared with tenofovir disoproxil fumarate in clinical trials. We report the case of a patient with HIV/HCV coinfection who was started on a TAF-based HIV regimen and developed acute kidney injury that worsened with the addition of sofosbuvir-ledipasvir.
Saturated fatty acids like palmitate contribute to muscle atrophy in a number of conditions (e.g., type II diabetes) by altering insulin signaling. Akt is a key modulator of protein balance that inhibits the FoxO transcription factors (e.g., FoxO3) which selectively induce the expression of atrophy-inducing genes (atrogenes) in the ubiquitin-proteasome and autophagy-lysosome systems. Conversely, omega-3 polyunsaturated fatty acids have beneficial effects on insulin signaling and may preserve muscle mass. In an earlier report, the omega-3 fatty acid docosahexaenoic acid (DHA) protected myotubes from palmitate-induced atrophy; the mechanisms underlying the alterations in protein metabolism were not identified. This study investigated whether DHA prevents a palmitate-induced increase in proteolysis by restoring Akt/FoxO signaling. Palmitate increased the rate of protein degradation, while cotreatment with DHA prevented the response. Palmitate reduced the activation state of Akt and increased nuclear FoxO3 protein while decreasing its cytosolic level. Palmitate also increased the messenger RNAs (mRNAs) of two FoxO3 atrogene targets, the E3 ubiquitin ligase atrogin-1/MAFbx and the autophagy mediator Bnip3. DHA attenuated the effects of palmitate on Akt activation, FoxO3 localization and atrogene mRNAs. DHA, alone or in combination with palmitate and decreased the ratio of LC3B-II:LC3B-I protein as well as the rate of autophagosome formation, as indicated by reduced LC3B-II protein in the presence of 10 mmol/L methylamine, suggesting an independent effect of DHA on the macroautophagy pathway. These data indicate that palmitate induces myotube atrophy, at least in part, by activating multiple proteolytic systems and that DHA counters the catabolic effects of palmitate by restoring Akt/FoxO signaling.
Background:
Although older adults with predialysis chronic kidney disease are at higher risk for falls, the prognostic significance of a serious fall injury prior to dialysis initiation has not been well described in the end-stage renal disease population.
Methods:
We examined the association between a serious fall injury in the year prior to starting hemodialysis and adverse health outcomes in the year following dialysis initiation using a retrospective cohort study of U.S. Medicare beneficiaries . 67 years old who initiated dialysis in 2010.2012. Serious fall injuries were defined using diagnostic codes for falls plus an injury (fracture, joint dislocation, or head injury). Health outcomes, defined as time-to-event variables within the first year of dialysis, included four outcomes: a subsequent serious fall injury, hospital admission, post-acute skilled nursing facility (SNF) utilization, and mortality.
Results:
Among this cohort of 81,653 initiating hemodialysis, 2,958 (3.6%) patients had a serious fall injury in the year prior to hemodialysis initiation. In the first year of dialysis, 7.6% had a subsequent serious fall injury, 67.6% a hospitalization, 30.7% a SNF claim, and 26.1% died. Those with versus without a serious fall injury in the year prior to hemodialysis initiation were at higher risk (hazard ratio, 95% confidence interval) for a subsequent serious fall injury (2.65, 2.41.2.91), hospitalization (1.11, 1.06.1.16), SNF claim (1.40, 1.30.1.50), and death (1.14, 1.06.1.22).
Conclusions:
For older adults initiating dialysis, a history of a serious fall injury may provide prognostic information to support decision making and establish expectations for life after dialysis initiation.
Rationale & Objective: Non-Hispanic Black and Hispanic patients present with kidney failure at younger ages than White patients. Younger patients are also more likely to receive transplants and home dialysis than in-center hemodialysis (ICHD), but it is unknown whether racial and ethnic disparities in treatment differ by age. We compared use of kidney replacement therapies between racial and ethnic groups among patients with incident kidney failure overall and by age. Study Design: Retrospective cohort study. Setting & Participants: 830,402 US adult (age >21 years) patients initiating kidney failure treatment during the period of 2011-2018. Exposures: Patient race and ethnicity (non-Hispanic Black, non-Hispanic White, Hispanic, or other) and age group (22-44, 45-64, 65-74, or 75-99 years). Outcome: Treatment modality (transplant, peritoneal dialysis [PD], home hemodialysis [HHD], or ICHD) as of day 90 of treatment. Analytical Approach: Differences in treatment modalities were quantified for patient subgroups defined by race and ethnicity and by age. Log-binomial regression models were fit to estimate adjusted risk ratios. Results: 81% of patients were treated with ICHD, 3.0% underwent transplants (85% preemptive, 57% living-donor), 10.5% were treated with PD, and 0.7% were treated with HHD. Absolute disparities in treatment were most pronounced among patients aged 22-44 years. Compared with non-Hispanic White patients, whose percentages of treatment with transplant, PD, and HHD were 10.9%, 19.0%, and 1.2%, respectively, non-Hispanic Black patients were less commonly treated with each modality (unadjusted percentages, 1.8%, 13.8%, and 0.6%, respectively), as were Hispanic patients (4.4%, 16.9%, and 0.5%, respectively; all differences P < 0.001). After adjustment, the largest relative disparities were observed for transplant among the 22-44–year age group; compared with non-Hispanic White patients, the adjusted risk ratios for non-Hispanic Black and Hispanic patients were 0.21 (95% CI, 0.19-0.23) and 0.47 (95% CI, 0.43, 0.51), respectively. Limitations: Race and ethnicity data not self-reported. Conclusions: Among adults with incident kidney failure, racial and ethnic disparities in transplant and home dialysis use are most pronounced among the youngest adult patient age group.
Chaperone-mediated autophagy (CMA) is a lysosomal proteolytic pathway in which cytosolic substrate proteins contain specific chaperone recognition sequences required for degradation and are translocated directly across the lysosomal membrane for destruction. CMA proteolytic activity has a reciprocal relationship with macroautophagy: CMA is most active in cells in which macroautophagy is least active. Normal renal proximal tubular cells have low levels of macroautophagy, but high basal levels of CMA activity. CMA activity is regulated by starvation, growth factors, oxidative stress, lipids, aging, and retinoic acid signaling. The physiological consequences of changes in CMA activity depend on the substrate proteins present in a given cell type. In the proximal tubule, increased CMA results from protein or calorie starvation and from oxidative stress. Overactivity of CMA can be associated with tubular lysosomal pathology and certain cancers. Reduced CMA activity contributes to protein accumulation in renal tubular hypertrophy, but may contribute to oxidative tissue damage in diabetes and aging. Although there are more questions than answers about the role of high basal CMA activity, this remarkable feature of tubular protein metabolism appears to influence a variety of chronic diseases.
Efforts to build muscle by increased protein feeding in hemodialysis patients have been thwarted by parallel increases in both muscle protein synthesis and degradation. The evidence suggests that muscle cells replace older proteins in response to feeding rather than using new proteins to drive muscle cell hypertrophy. This review presents the hypothesis that protein feeding provides an opportunity for muscle to accelerate proteolysis of proteins which have been damaged by oxidation, nitrosylation and/or glycosylation and to replace damaged mitochondria that contribute to oxidative stress. Increases in proteolysis with feeding are driven by insulin resistance and the increased oxidative stress of mitochondrial respiration. Oxidized proteins and organelles are excellent substrates for degradation by the proteasome, macroautophagy, and chaperone-mediated autophagy: these systems of proteolysis seem to be activated by oxydatiative stress. Replacement of oxidized and other damaged proteins may be a benefit of protein feeding in hemodialysis, but alternative strategies, including exercise, will be required to build muscle.
Background: The usage of nursing home (NH) services is a marker of frailty among older adults. Although the Centers for Medicare & Medicaid Services (CMS) revised the Medical Evidence Report Form CMS-2728 in 2005 to include data collection on NH institutionalization, the validity of this item has not been reported.
Methods: There were 27,913 patients ≥ 75 years of age with incident end-stage renal disease (ESRD) in 2006, which constituted our analysis cohort. We determined the accuracy of the CMS-2728 using a matched cohort that included the CMS Minimum Data Set (MDS) 2.0, often employed as a "gold standard" metric for identifying patients receiving NH care. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the CMS-2728 NH item. Next, we compared characteristics and mortality risk by CMS-2728 and MDS NH status agreement.
Results: The sensitivity, specificity, PPV and NPV of the CMS-2728 for NH status were 33%, 97%, 80% and 79%, respectively. Compared to those without the MDS or CMS-2728 NH indicator (No MDS/No 2728), multivariable adjusted hazard ratios (95% confidence interval) for mortality associated with NH status were 1.55 (1.46-1.64) for MDS/2728, 1.48 (1.42-1.54) for MDS/No 2728, and 1.38 (1.25-1.52) for No MDS/2728. NH utilization was more strongly associated with mortality than other CMS-2728 items in the model.
Conclusions: The CMS-2728 underestimated NH utilization among older adults with incident ESRD. The potential for misclassification may have important ramifications for assessing prognosis, developing advanced care plans and providing coordinated care.
Background: End-stage kidney disease patients on dialysis are particularly susceptible to COVID-19 infection due to comorbidities, age, and logistic constraints of dialysis making social distancing difficult. We describe our experience with hospitalized dialysis patients with COVID-19 and factors associated with mortality. Methods: From March 1, 2020, to May 31, 2020, all dialysis patients admitted to 4 Emory Hospitals and tested for COVID-19 were identified. Sociodemographic information and clinical and laboratory data were obtained from the medical record. Death was defined as an in-hospital death or transfer to hospice for end-of-life care. Patients were followed until discharge or death. Results: Sixty-four dialysis patients with COVID-19 were identified. Eighty-four percent were African-American. The median age was 64 years, and 59% were males. Four patients were on peritoneal dialysis, and 60 were on hemodialysis for a median time of 3.8 years, while 31% were obese. Fever (72%), cough (61%), and diarrhea (22%) were the most common symptoms at presentation. Thirty-three percent required admission to intensive care unit, and 23% required mechanical ventilation. The median length of stay was 10 days, while 11 patients (17%) died during hospitalization and 17% were discharged to a temporary rehabilitation facility. Age >65 years (RR 13.7, CI: 1.9-100.7), C-reactive protein >100 mg/dL (RR 8.3, CI: 1.1-60.4), peak D-dimer >3,000 ng/mL (RR 4.3, CI: 1.03-18.2), bilirubin >1 mg/dL (RR 3.9, CI: 1.5-10.4), and history of peripheral vascular disease (RR 3.2, CI: 1.2-9.1) were associated with mortality. Dialysis COVID-19-infected patients were more likely to develop thromboembolic complications than those without COVID-19 (RR 3.7, CI: 1.3-10.1). Conclusion: In a predominantly African-American population, the mortality of end-stage kidney disease patients admitted with COVID-19 infection was 17%. Age, C-reactive protein, D-dimer, bilirubin, and history of peripheral vascular disease were associated with worse survival.
Background.
The current surge of coronavirus 2019 (COVID-19) cases in certain parts of the country has burdened the healthcare system, limiting access to tertiary centers for many. As a result, COVID-19-positive Solid Organ Transplant (SOT) recipients are increasingly being managed by local healthcare providers. It is crucial for community providers to understand disease severity and know if COVID-19-impacted SOT recipients have a different clinical course compared with COVID-19-negative SOT recipients with a similar presentation.
Methods.
We conducted a retrospective analysis on SOT recipients suspected to have COVID-19 infection tested during March 14, 2020–April 30, 2020. Patients were followed from time of testing to May 31, 2020.
Results.
One hundred sixty SOT recipients underwent testing: 22 COVID-19 positive and 138 COVID-19 negative. COVID-19-positive patients were more likely to have rapid progression of symptoms (median 3 vs 6 d, P = 0.002), greater hospitalizations (78% vs 64%, P < 0.017), and need for intensive care unit care (45% vs 17%, P < 0.001) Severe COVID-19 infection was not observed in patients on Belatacept for immunosuppression (30% vs 87%,P = 0.001). COVID- 19 positive patients in the intensive care unit were more likely to have multifocal opacities on radiological imaging in comparison to those admitted to the medical floor (90% vs 11%). Survival probability was similar in both cohorts.
Conclusion.
COVID-19-infected SOT recipients have a propensity for rapid clinical decompensation. Local providers need to be work closely with transplant centers to appropriately triage and manage COVID-19 SOT recipients in the community.