Early Effect of the Circular Model of Kidney Allocation in the United States.

BACKGROUND: In March 2021, the United States implemented a new kidney allocation system (KAS250) for deceased donor kidney transplantation (DDKT), which eliminated the donation service area-based allocation and replaced it with a system on the basis of distance from donor hospital to transplant center within/outside a radius of 250 nautical miles. The effect of this policy on kidney discards and logistics is unknown. METHODS: We examined discards, donor-recipient characteristics, cold ischemia time (CIT), and delayed graft function (DGF) during the first 9 months of KAS250 compared with a pre-KAS250 cohort from the preceding 2 years. Changes in discards and CIT after the onset of COVID-19 and the implementation of KAS250 were evaluated using an interrupted time-series model. Changes in allocation practices (biopsy, machine perfusion, and virtual cross-match) were also evaluated. RESULTS: Post-KAS250 saw a two-fold increase in kidneys imported from nonlocal organ procurement organizations (OPO) and a higher proportion of recipients with calculated panel reactive antibody (cPRA) 81%-98% (12% versus 8%; P<0.001) and those with >5 years of pretransplant dialysis (35% versus 33%; P<0.001). CIT increased (mean 2 hours), including among local OPO kidneys. DGF was similar on adjusted analysis. Discards after KAS250 did not immediately change, but we observed a statistically significant increase over time that was independent of donor quality. Machine perfusion use decreased, whereas reliance on virtual cross-match increased, which was associated with shorter CIT. CONCLUSIONS: Early trends after KAS250 show an increase in transplant access to patients with cPRA>80% and those with longer dialysis duration, but this was accompanied by an increase in CIT and a suggestion of worsening kidney discards.

Journal of family medicine and primary care- A five year bibliometric analysis from 2016 to 2020.

Aim: To conduct a five-year bibliometric analysis of the Journal of Family Medicine and Primary Care (J Family Med Prim Care) between 2016 and 2020. Setting and Design: This retrospective secondary data analysis was conducted in the Department of Conservative, Endodontics and Aesthetic Dentistry, Dental Institute, Rajendra Institute of Medical Sciences, Ranchi, Jharkhand and Rohilkhand Medical College and Hospital, Bareilly, UP. Material and Methods: The data of publications including research articles, review and case reports excluding editorials and letters to the editor, commentaries and invited articles published in the J Family Med Prim Care between 2016 and 2020 were downloaded from the journal website and analysed in terms of the bibliometric parameters. Results: The results revealed that the journal gave equal weightage to all types of articles. The total number of articles published between 2016 and 2020 was 2,426 out of which 1,666 articles were published from India and the remaining from other parts of the world. In India, the state of Delhi had the maximum publications while speciality Preventive and Social Medicine (22.42%) and General Medicine (23.12%) had the maximum articles. Moreover, between 2016 and 2020, J Family Med Prim Care had 2,132 citations of published articles and had 65 publications in 2020 about the Corona Virus Disease (COVID-19) pandemic. Conclusion: The issue numbers per year for J Family Med Prim Care has gradually increased over time. The publication is open for all fields of medical, dental sciences and allied sciences.

Impact of the COVID-19 pandemic on the kidney community: lessons learned and future directions.

The coronavirus disease 2019 (COVID-19) pandemic has disproportionately affected patients with kidney disease, causing significant challenges in disease management, kidney research and trainee education. For patients, increased infection risk and disease severity, often complicated by acute kidney injury, have contributed to high mortality. Clinicians were faced with high clinical demands, resource shortages and novel ethical dilemmas in providing patient care. In this review, we address the impact of COVID-19 on the entire spectrum of kidney care, including acute kidney injury, chronic kidney disease, dialysis and transplantation, trainee education, disparities in health care, changes in health care policies, moral distress and the patient perspective. Based on current evidence, we provide a framework for the management and support of patients with kidney disease, infection mitigation strategies, resource allocation and support systems for the nephrology workforce.

Previous SARS-CoV-2 infection or a third dose of vaccine elicited cross-variant neutralising antibodies in vaccinated solid-organ transplant recipients.

Objectives: The SARS-CoV-2 pandemic poses a great threat to global health, particularly in solid organ transplant recipients (SOTRs). A 3-dose mRNA vaccination protocol has been implemented for the majority of SOTRs, yet their immune responses are less effective compared to healthy controls (HCs). Methods: We analyzed the humoral immune responses against the vaccine strain and variants of concern (VOC), including the highly mutated-omicron variant in 113 SOTRs, of whom 44 had recovered from COVID-19 (recovered-SOTRs) and 69 had not contracted the virus (COVID-naïve). In addition, 30 HCs, 8 of whom had recovered from COVID-19, were also studied. Results: Here, we report that three doses of the mRNA vaccine had only a modest effect in eliciting anti-viral antibodies against all viral strains in the fully vaccinated COVID-naive SOTRs (n = 47). Only 34.0% of this group of patients demonstrated both detectable anti-RBD IgG with neutralization activities against alpha, beta, and delta variants, and only 8.5% of them showed additional omicron neutralizing capacities. In contrast, 79.5% of the recovered-SOTRs who received two doses of vaccine demonstrated both higher anti-RBD IgG levels and neutralizing activities against all VOC, including omicron. Conclusion: These findings illustrate a significant impact of previous infection on the development of anti-SARS-CoV-2 immune responses in vaccinated SOTRs and highlight the need for alternative strategies to protect a subset of a lesser-vaccine responsive population.

Increased Mortality Associated with Hypermagnesemia in Severe COVID-19 Illness.

Background: Although electrolyte abnormalities are common among patients with COVID-19, very little has been reported on magnesium homeostasis in these patients. Here we report the incidence of hypermagnesemia, and its association with outcomes among patients admitted with COVID-19. Methods: We retrospectively identified all patients with a positive test result for SARS-CoV-2 who were admitted to a large quaternary care center in New York City in spring 2020. Details of the patients' demographics and hospital course were obtained retrospectively from medical records. Patients were defined as having hypermagnesemia if their median magnesium over the course of their hospitalization was >2.4 mg/dl. Results: A total of 1685 patients hospitalized with COVID-19 had their magnesium levels checked during their hospitalization, and were included in the final study cohort, among whom 355 (21%) had hypermagnesemia. Patients who were hypermagnesemic had a higher incidence of shock requiring pressors (35% vs 27%, P<0.01), respiratory failure requiring mechanical ventilation (28% vs 21%, P=0.01), AKI (65% vs 50%, P<0.001), and AKI severe enough to require renal replacement therapy (18% vs 5%, P<0.001). In an adjusted multivariable model, hypermagnesemia was observed more commonly with increasing age, male sex, AKI requiring RRT, hyperkalemia, and higher CPK. Survival probability at 30 days was 34% for the patients with hypermagnesemia, compared with 65% for patients without hypermagnesemia. An adjusted multivariable time to event analysis identified an increased risk of mortality with older age, need for vasopressors, higher C-reactive protein levels, and hypermagnesemia (HR, 2.03; 95% CI, 1.63 to 2.54, P<0.001). Conclusions: In conclusion, we identified an association between hypermagnesemia among patients hospitalized with COVID-19 and increased mortality. Although the exact mechanism of this relationship remains unclear, hypermagnesemia potentially represents increased cell turnover and higher severity of illness, which is frequently associated with more severe forms of AKI.

Protocol for Local On-Site Dialysate Production for Continuous Renal Replacement Therapy during the COVID-19 Pandemic.

AKI frequently occurs in patients with COVID-19, and kidney injury severe enough to require RRT is a common complication among patients who are critically ill. During the surge of the pandemic, there was a high demand for dialysate for continuous RRT, and this increase in demand, coupled with vulnerabilities in the supply chain, necessitated alternative approaches, including internal production of dialysate. Using a standard hemodialysis machine and off-the-shelf supplies, as per Food and Drug Administration guidelines, we developed a method for on-site dialysate production that is adaptable and can be used to fill multiple bags at once. The use of a central reverse osmosis unit, dedicated hemodialysis machine, sterile bags with separate ports for fill and use, and frequent testing will ensure stability, sterility, and-therefore-safety of the produced dialysate. The dialysate made in house was tested and it showed both stability and sterility for at least 30 hours. This detailed description of our process for generating dialysate can serve as a guide for other programs experiencing similar vulnerabilities in the demand versus supply of dialysate.

Predicting the impact of the third wave of COVID-19 in India using hybrid statistical machine learning models: A time series forecasting and sentiment analysis approach.

BACKGROUND: Since January 2020, India has faced two waves of COVID-19; preparation for the upcoming waves is the primary challenge for public health sectors and governments. Therefore, it is important to forecast future cumulative confirmed cases to plan and implement control measures effectively. METHODS: This study proposed a hybrid autoregressive integrated moving average (ARIMA) and Prophet model to predict daily confirmed and cumulative confirmed cases. The built-in auto.arima function was first used to select the optimal hyperparameter values of the ARIMA model. Then, the modified ARIMA model was used to find the best fit between the test and forecast data to find the best model parameter combinations. Articles, blog posts, and news stories from virologists, scientists, and health experts related to the third wave of COVID-19 were gathered using the Python web scraping package Beautiful Soup. Their opinions (sentiments) toward the potential third wave were analyzed using natural language processing (NLP) libraries. RESULTS: A spike in daily confirmed and cumulative confirmed cases was predicted in India in the next 180 days based on past time series data. The results were validated using various analytical tools and evaluation metrics, producing a root mean square error (RMSE) of 0.14 and a mean absolute percentage error (MAPE) of 0.06. The NLP processing results revealed negative sentiments in most articles and blogs, with few exceptions. CONCLUSION: The findings of this study suggest that there will be more active cases in the upcoming days. The proposed models can forecast future daily confirmed and cumulative confirmed cases. This study will help the country and states plan appropriate public health measures for the upcoming waves of COVID-19.

COVID-19-Associated Mortality among Kidney Transplant Recipients and Candidates in the United States.

BACKGROUND AND OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has had a profound effect on transplantation activity in the United States and globally. Several single-center reports suggest higher morbidity and mortality among candidates waitlisted for a kidney transplant and recipients of a kidney transplant. We aim to describe 2020 mortality patterns during the COVID-19 pandemic in the United States among kidney transplant candidates and recipients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using national registry data for waitlisted candidates and kidney transplant recipients collected through April 23, 2021, we report demographic and clinical factors associated with COVID-19-related mortality in 2020, other deaths in 2020, and deaths in 2019 among waitlisted candidates and transplant recipients. We quantify excess all-cause deaths among candidate and recipient populations in 2020 and deaths directly attributed to COVID-19 in relation to prepandemic mortality patterns in 2019 and 2018. RESULTS: Among deaths of patients who were waitlisted in 2020, 11% were attributed to COVID-19, and these candidates were more likely to be male, obese, and belong to a racial/ethnic minority group. Nearly one in six deaths (16%) among active transplant recipients in the United States in 2020 was attributed to COVID-19. Recipients who died of COVID-19 were younger, more likely to be obese, had lower educational attainment, and were more likely to belong to racial/ethnic minority groups than those who died of other causes in 2020 or 2019. We found higher overall mortality in 2020 among waitlisted candidates (24%) than among kidney transplant recipients (20%) compared with 2019. CONCLUSIONS: Our analysis demonstrates higher rates of mortality associated with COVID-19 among waitlisted candidates and kidney transplant recipients in the United States in 2020.

Elevated Neutrophil Gelatinase-Associated Lipocalin Is Associated With the Severity of Kidney Injury and Poor Prognosis of Patients With COVID-19.

INTRODUCTION: Loss of kidney function is a common feature of COVID-19 infection, but serum creatinine (SCr) is not a sensitive or specific marker of kidney injury. We tested whether molecular biomarkers of tubular injury measured at hospital admission were associated with acute kidney injury (AKI) in those with COVID-19 infection. METHODS: This is a prospective cohort observational study consisting of 444 consecutive patients with SARS-CoV-2 enrolled in the Columbia University emergency department (ED) at the peak of the pandemic in New York (March 2020-April 2020). Urine and blood were collected simultaneously at hospital admission (median time: day 0, interquartile range: 0-2 days), and urine biomarkers were analyzed by enzyme-linked immunosorbent assay (ELISA) and a novel dipstick. Kidney biopsies were probed for biomarker RNA and for histopathologic acute tubular injury (ATI) scores. RESULTS: Admission urinary neutrophil gelatinase-associated lipocalin (uNGAL) level was associated with AKI diagnosis (267 ± 301 vs. 96 ± 139 ng/ml, P < 0.0001) and staging; uNGAL levels >150 ng/ml had 80% specificity and 75% sensitivity to diagnose AKI stages 2 to 3. Admission uNGAL level quantitatively associated with prolonged AKI, dialysis, shock, prolonged hospitalization, and in-hospital death, even when admission SCr level was not elevated. The risk of dialysis increased almost 4-fold per SD of uNGAL independently of baseline SCr, comorbidities, and proteinuria (odds ratio [OR] [95% CI]: 3.59 [1.83-7.45], P < 0.001). In the kidneys of those with COVID-19, NGAL mRNA expression broadened in parallel with severe histopathologic injury (ATI). Conversely, low uNGAL levels at admission ruled out stages 2 to 3 AKI (negative predictive value: 0.95, 95% CI: 0.92-0.97) and the need for dialysis (negative predictive value: 0.98, 95% CI: 0.96-0.99). Although proteinuria and urinary (u)KIM-1 were implicated in tubular injury, neither was diagnostic of AKI stages. CONCLUSION: In the patients with COVID-19, uNGAL level was quantitatively associated with histopathologic injury (ATI), loss of kidney function (AKI), and severity of patient outcomes.

Post-acute COVID-19 syndrome.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic, which has resulted in global healthcare crises and strained health resources. As the population of patients recovering from COVID-19 grows, it is paramount to establish an understanding of the healthcare issues surrounding them. COVID-19 is now recognized as a multi-organ disease with a broad spectrum of manifestations. Similarly to post-acute viral syndromes described in survivors of other virulent coronavirus epidemics, there are increasing reports of persistent and prolonged effects after acute COVID-19. Patient advocacy groups, many members of which identify themselves as long haulers, have helped contribute to the recognition of post-acute COVID-19, a syndrome characterized by persistent symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms. Here, we provide a comprehensive review of the current literature on post-acute COVID-19, its pathophysiology and its organ-specific sequelae. Finally, we discuss relevant considerations for the multidisciplinary care of COVID-19 survivors and propose a framework for the identification of those at high risk for post-acute COVID-19 and their coordinated management through dedicated COVID-19 clinics.

Renal Considerations in COVID-19: Biology, Pathology, and Pathophysiology.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged into a worldwide pandemic of epic proportion. Beyond pulmonary involvement in coronavirus disease 2019 (COVID-19), a significant subset of patients experiences acute kidney injury. Patients who die from severe disease most notably show diffuse acute tubular injury on postmortem examination with a possible contribution of focal macro- and microvascular thrombi. Renal biopsies in patients with proteinuria and hematuria have demonstrated a glomerular dominant pattern of injury, most notably a collapsing glomerulopathy reminiscent of findings seen in human immunodeficiency virus (HIV) in individuals with apolipoprotein L-1 (APOL1) risk allele variants. Although various mechanisms have been proposed for the pathogenesis of acute kidney injury in SARS-CoV-2 infection, direct renal cell infection has not been definitively demonstrated and our understanding of the spectrum of renal involvement remains incomplete. Herein we discuss the biology, pathology, and pathogenesis of SARS-CoV-2 infection and associated renal involvement. We discuss the molecular biology, risk factors, and pathophysiology of renal injury associated with SARS-CoV-2 infection. We highlight the characteristics of specific renal pathologies based on native kidney biopsy and autopsy. Additionally, a brief discussion on ancillary studies and challenges in the diagnosis of SARS-CoV-2 is presented.

Challenges of Clinical Research Administration During the COVID-19 Pandemic.

In early 2020, clinicians and researchers rushed to understand the SARS-CoV-2 virus and how to go about treating and preventing it. Caring for patients while simultaneously learning about a disease not seen before created challenges on several levels. Much of the spotlight was on the researchers doing this critical work; however, these narratives remind us of the enormous effort and commitment shown by IRB members and research administrators responsible for research infrastructure. Despite the sense of urgency and obligation to plan and conduct clinical research during the pandemic, IRBs guaranteed that researchers still adhered to the core ethical principles that protect the rights and welfare of human subjects so that critical research could continue. Many themes emerge in these stories, including the need for flexibility in processes for both staff and research participants and the perception that IRB members serve as "research gatekeepers." With approaches to clinical research evolving, the SARS-CoV-2 pandemic may be the catalyst needed to make sustainable improvements to our research processes, roles, and goals.

Perspectives on COVID-19 vaccination among kidney and pancreas transplant recipients living in New York City.

PURPOSE: Solid organ transplant recipients are at increased risk of morbidity and mortality from coronavirus disease 2019 (COVID-19), but limited vaccine access and vaccine hesitancy can complicate efforts for expanded vaccination. We report patient perspectives and outcomes from a vaccine outreach initiative for a vulnerable population of transplant recipients living in New York City. METHODS: This was a retrospective review of qualitative perspectives from a COVID-19 vaccine outreach initiative. In the outreach effort, kidney and pancreas transplant recipients under care at the transplant center at NewYork-Presbyterian Hospital were initially contacted electronically with educational material about vaccination followed by telephone outreach to eligible unvaccinated patients. Calls were used to schedule vaccine appointments for patients who agreed, answer questions, and assess attitudes and concerns for patients not yet ready to be vaccinated, with conversational themes recorded. RESULTS: Of the 1,078 patients living in the 5 New York City boroughs who had not reported receiving COVID-19 vaccination, 320 eligible patients were contacted by telephone. Of these, 210 patients were scheduled for vaccination at our vaccine site (including 13 who agreed to vaccination after initially declining), while 110 patients were either not ready or not interested in being vaccinated. The total number of patients willing to be vaccinated was 554 when also including those already vaccinated. Unwillingness to be vaccinated was associated with younger age (median age of 47 vs 60 years, P < 0.001), Black race (P = 0.004), and residence in Bronx or Brooklyn counties (P = 0.018) or a zip code with a medium level of poverty (P = 0.044). The most common issues raised by patients who were ambivalent or not interested in vaccination were regarding unknown safety of the vaccines in general, a belief that there was a lack of data about the vaccines in transplant recipients, and a lack of trust in the scientific process underlying vaccine development, with 34% of the patients contacted expressing vaccine hesitancy overall. CONCLUSION: Our qualitative summary identifies determinants of COVID-19 vaccine hesitancy in a diverse transplant patient population, supporting the need for transplant centers to implement tailored interventions to increase vaccine acceptance in this vulnerable population.

Outcomes of COVID-19 in solid organ transplant recipients: A matched cohort study.

Whether solid organ transplant (SOT) recipients are at increased risk of poor outcomes due to COVID-19 in comparison to the general population remains uncertain. In this study, we compared outcomes of SOT recipients and non-SOT patients hospitalized with COVID-19 in a propensity score matched analysis based on age, race, ethnicity, BMI, diabetes, and hypertension. After propensity matching, 117 SOT recipients and 350 non-SOT patients were evaluated. The median age of SOT recipients was 61 years, with a median time from transplant of 5.68 years. The most common transplanted organs were kidney (48%), followed by lung (21%), heart (19%), and liver (10%). Overall, SOT recipients were more likely to receive COVID-19 specific therapies and to require ICU admission. However, mortality (23.08% in SOT recipients vs. 23.14% in controls, P = .21) and highest level of supplemental oxygen (P = .32) required during hospitalization did not significantly differ between groups. In this propensity matched cohort study, SOT recipients hospitalized with COVID-19 had similar overall outcomes as non-SOT recipients, suggesting that chronic immunosuppression may not be an independent risk factor for poor outcomes in COVID-19.