COVID-19 is a viral respiratory disease associated with neurologic complications such as encephalitis or stroke in a minority of patients. The wide variety of neurologic manifestations with often unclear etiology may confound diagnosis and management. We present a young man admitted following an 8-day onset of self-resolving episodes of left hemiplegia and hemifacial droop. Diagnostic work up for seizures and stroke was largely negative. “Intra-ictal” ECD-single-photon emission computerized tomography/computerized tomography was consistent with right middle cerebral artery ischemia. Subsequent diagnostic work up revealed positive COVID-19 screening and newly-elevated antiphospholipid antibodies. Antiepileptic medications were discontinued, and the patient was successfully treated as an outpatient with corticosteroids leading to resolution of symptoms.

Background: COVID-19 mortality disproportionately affects the Black population in the United States (US). To explore this association a cohort study was undertaken. Methods: We assembled a cohort of 505,992 patients receiving ambulatory care at Bronx Montefiore Health System (BMHS) between 1/1/18 and 1/1/20 to evaluate the relative risk of hospitalization and death in two time-periods, the pre-COVID time-period (1/1/20–2/15/20) and COVID time-period (3/1/20–4/15/20). COVID testing, hospitalization and mortality were determined with the Black and Hispanic patient population compared separately to the White population using logistic modeling. Evaluation of the interaction of pre-COVID and COVID time periods and race, with respect to mortality was completed. Findings: A total of 9,286/505,992 (1.8%) patients were hospitalized during either or both pre-COVID or COVID periods. Compared to Whites the relative risk of hospitalization of Black patients did not increase in the COVID period (p for interaction=0.12). In the pre- COVID period, compared to Whites, the odds of death for Blacks and Hispanics adjusted for comorbidity was statistically equivalent. In the COVID period compared to Whites the adjusted odds of death for Blacks was 1.6 (95% CI 1.2–2.0, p = 0.001). There was a significant increase in Black mortality risk from pre-COVID to COVID periods (p for interaction=0.02). Adjustment for relevant clinical and social indices attenuated but did not fully explain the observed difference in Black mortality. Interpretation: The BMHS COVID experience demonstrates that Blacks do have a higher mortality with COVID incompletely explained by age, multiple reported comorbidities and available metrics of sociodemographic disparity. Funding: N/A

BACKGROUNDReports from centers treating patients with coronavirus disease 2019 (COVID-19) have noted that such patients frequently develop AKI. However, there have been no direct comparisons of AKI in hospitalized patients with and without COVID-19 that would reveal whether there are aspects of AKI risk, course, and outcomes unique to this infection.METHODSIn a retrospective observational study, we evaluated AKI incidence, risk factors, and outcomes for 3345 adults with COVID-19 and 1265 without COVID-19 who were hospitalized in a large New York City health system and compared them with a historical cohort of 9859 individuals hospitalized a year earlier in the same health system. We also developed a model to identify predictors of stage 2 or 3 AKI in our COVID-19.RESULTSWe found higher AKI incidence among patients with COVID-19 compared with the historical cohort (56.9% versus 25.1%, respectively). Patients with AKI and COVID-19 were more likely than those without COVID-19 to require RRT and were less likely to recover kidney function. Development of AKI was significantly associated with male sex, Black race, and older age (>50 years). Male sex and age >50 years associated with the composite outcome of RRT or mortality, regardless of COVID-19 status. Factors that were predictive of stage 2 or 3 AKI included initial respiratory rate, white blood cell count, neutrophil/lymphocyte ratio, and lactate dehydrogenase level.CONCLUSIONSPatients hospitalized with COVID-19 had a higher incidence of severe AKI compared with controls. Vital signs at admission and laboratory data may be useful for risk stratification to predict severe AKI. Although male sex, Black race, and older age associated with development of AKI, these associations were not unique to COVID-19.

BackgroundPatients with ESKD who are on chronic hemodialysis have a high burden of comorbidities that may place them at increased risk for adverse outcomes when hospitalized with COVID-19. However, data in this unique patient population are limited. The aim of our study is to describe the clinical characteristics and short-term outcomes in patients on chronic hemodialysis who require hospitalization for COVID-19.MethodsWe performed a retrospective study of 114 patients on chronic hemodialysis who were hospitalized with COVID-19 at two major hospitals in the Bronx from March 9 to April 8, 2020 during the surge of SARS-CoV-2 infections in New York City. Patients were followed during their hospitalization through April 22, 2020. Comparisons in clinical characteristics and laboratory data were made between those who survived and those who experienced in-hospital death; short-term outcomes were reported.ResultsMedian age was 64.5 years, 61% were men, and 89% were black or Hispanic. A total of 102 (90%) patients had hypertension, 76 (67%) had diabetes mellitus, 63 (55%) had cardiovascular disease, and 30% were nursing-home residents. Intensive care unit (ICU) admission was required in 13% of patients, and 17% required mechanical ventilation. In-hospital death occurred in 28% of the cohort, 87% of those requiring ICU, and nearly 100% of those requiring mechanical ventilation. A large number of in-hospital cardiac arrests were observed. Initial procalcitonin, ferritin, lactate dehydrogenase, C-reactive protein, and lymphocyte percentage were associated with in-hospital death.ConclusionsShort-term mortality in patients on chronic hemodialysis who were hospitalized with COVID-19 was high. Outcomes in those requiring ICU and mechanical ventilation were poor, underscoring the importance of end-of-life discussions in patients with ESKD who are hospitalized with severe COVID-19 and the need for heightened awareness of acute cardiac events in the setting of COVID-19. Elevated inflammatory markers were associated with in-hospital death in patients with ESKD who were hospitalized with COVID-19.

Overview The coronavirus disease 2019 (COVID-19) pandemic is unprecedented and information about the severe acute respiratory syndrome coronavirus 2 is evolving rapidly. New York is one of the epicenters of the COVID-19 outbreak in the United States, reporting >1000 confirmed cases as of March 17, 2020, and cases are escalating exponentially. The majority of cases are in Westchester County (n=220) and New York City (NYC; n=463), which includes Bronx (1). The local index patient case was a Westchester man who became ill on February 22, was not associated with a recent travel exposure to a country on the watch list (China, Iran, South Korea, and Italy), or known to have had direct contact with a COVID-19–confirmed patient. At the present time it is estimated that community-wide transmission accounts for 87% of confirmed cases. Nephrologists in the Bronx have been handicapped in managing patients with ESKD during the early weeks of the COVID-19 pandemic due to the limitations of available rapid testing for severe acute respiratory syndrome coronavirus 2. Montefiore Medical Center, located in the north Bronx in close proximity to Westchester, has been one of the main tertiary care hospitals in NYC caring for persons under investigation (PUIs) and for COVID-19–confirmed patients. Our nephrology division's clinical faculty care for approximately 850 patients with ESKD (approximately 800 on hemodialysis and approximately 50 on peritoneal dialysis) in 12 outpatient hemodialysis facilities (two Fresenius and 10 DaVita facilities) in the Bronx. We report our experience with caring for the ESKD population and patients who are hospitalized with AKI in the Bronx during the first 3 weeks of the local NYC COVID-19 pandemic. Outpatient Dialysis Population Strategies proposed for the prevention and management of COVID-19 transmission for patients with ESKD in the outpatient dialysis facilities have been dynamic. The American Society of Nephrology's (ASN's) Nephrologists Transforming Dialysis Safety (NTDS) website has been on the forefront of informing the nephrology community of the earliest and most updated guidance from the Centers for Disease Control and Prevention (CDC) about COVID-19 preparation and management of patients with ESKD in the outpatient dialysis setting (2,3). The NTDS's initial release of frequently asked questions for outpatient dialysis facilities based on CDC guidelines was on March 4, and the ASN and CDC provided an informational webinar on March 11, which is still available on the website (4). The most updated policies from the large dialysis organizations (LDOs), including DaVita and Fresenius, were distributed to medical directors and staff for the Bronx facilities on March 16. Table 1 provides a timeline of the COVID-19 pandemic in Westchester and NYC and illustrates the necessary adaptations to CDC recommendations and the LDOs' policies and procedures as the number of PUIs and confirmed COVID-19 cases increased in our region and as more information became available. Table 1 also illustrates the changing policies at Montefiore-affiliated outpatient hemodialysis facilities as guidelines and knowledge of the pandemic evolved. Table 1. - Timeline and evolution of COVID-19 outpatient hemodialysis management recommendations (CDC) and policy changes (CDC and LDOs) for Montefiore-affiliated facilities Recommendation March 3, 2020 March 7, 2020 March 17, 2020 All patients with confirmed COVID-19 in Westchester and New York City 2 82 1024 Affected geographic areas International travel to affected geographic areas within 14 d from National geographic areas Global spread China New Rochelle and New York City Now largely community transmission without known exposure Iran Washington State Italy Japan South Korea Sampling of specimens Upper respiratory nasopharyngeal swab and oropharyngeal swab Recommendation revised to a single upper respiratory nasopharyngeal swab Sputum if productive cough BAL or tracheal aspirate Laboratory testing locations Ship overnight to CDC or New York State Department of Health More local and commercial laboratories begin testing, but still very limited Restricted testing of patients who are hospitalized with severe symptoms only After negative influenza and respiratory viral panel Mask and isolation recommendations N95 mask or respirator Face masks are an acceptable alternative due to limited availability of N95 masks (unless aerosolized procedure planned) Airborne isolation Droplet isolation Policies specific for outpatient hemodialysis location Dialysis should not occur in an outpatient facility for a PUI unless an AIIR is available, preferably in an acute care hospital in an AIIR at this time Dialysis for PUIs may occur in outpatient hemodialysis facilities Maintain at least 6 feet of separation between masked, symptomatic PUIs and other patients in waiting areas and during dialysis treatment. Ideally, dialyze symptomatic PUIs in a separate room with the door closed. Hepatitis B isolation rooms should only be used if The patient is hepatitis B surface antigen positive or The facility has no patients on the census with hepatitis B infection who would require treatment in the isolation room If a separate room is not available, the masked PUI should be treated at a corner or end-of-row station, away from the main flow of traffic, and separated by at least 6 feet from the nearest patient (in all directions) Cohorting symptomatic PUIs, patients with confirmed COVID-19 requiring HD, and the HCP caring for them together In the section of the unit and/or on the same shift (the last shift of the day), separating symptomatic PUIs from COVID-19–confirmed cases by day Cohort into a designated COVID-19 facility EMS transportation of PUIs or patients with COVID-19 to health care facilities Recommendations are for EMS workers trained in infection control and use of PPE No information exists for non-EMS staff Use full PPE (N95 or face mask, eye protection, gowns, gloves) Notify facility in advance so infection control measures may be taken before arrival Patient should wear a face mask and be separated as much as possible Family members and contacts should not ride if possible. If riding in the vehicle, they should wear a mask When possible, isolate the driver from the patient compartment and close windows. Ventilation should be in nonrecirculated mode If the vehicle is without an isolated driver compartment, outside air ventilation must be implemented Patient screening and use of face masks Before arrival Patients call ahead to facility or physician to prepare and triage in the facility Patients with fever or respiratory symptoms advised to call ahead to facility or physician to prepare and triage (possibly to an acute hospital setting) Infection prevention manager assists staff with patient screening Goal is to keep patients out of the acute hospital setting if medically stable and can be dialyzed as an outpatient Patients who have arrived to facility All patients are required to wear a mask regardless of symptoms Patients with symptoms should put on a face mask at check in Essential visitors Limit visitors to essential visitors All essential visitors are now screened and must wear a mask while in facility (LDO policy) Face mask not required unless there are respiratory symptoms Health care providers' face mask use HCPs required to wear a face mask All HCPs are required to wear a face mask at all times while in facility (LDO policy)a During catheter connection and disconnection or When caring for a PUI or patient positive for COVID-19a PPE use (eye protection, disposable gown, and nonsterile gloves) HCPs required to use full PPE HCPs providing direct patient care are now required to use full PPE from the first patient interaction in the waiting room to the treatment floor During catheter connection and disconnection or Remove PPE, except face mask, before entering medication room When caring for a PUI or patient with confirmed COVID-19 and Don new PPE upon leaving medication room Change PPE between PUIs or patients with COVID-19 (LDO policy) COVID-19, coronavirus disease 2019; CDC, Centers for Disease Control and Prevention; LDO, large dialysis organizations (DaVita Kidney Care and Fresenius Kidney Care); BAL, bronchoalveolar lavage; PUI, person under investigation; AIIR, airborne isolation room; HD, hemodialysis; HCP, health care provider; EMS, emergency medical services; PPE, personal protective equipment.aUntil the supply of N95 masks is restored. Early Actions Implemented in the First Week of March Distribution of Information to Patients. The NTDS poster on "COVID-19 awareness" and CDC posters on "cough etiquette" and "handwashing" were posted at the entrance of the facilities and in the lobby, both in Spanish and in English. Educational material was distributed to patients, families, and staff. More frequent antiseptic cleaning of chairs and door handles in the lobby was ordered and the provision of easy access to 60%–95% alcohol-based hand sanitizers was implemented in the waiting room. Use of the CDC's Patient Screening Questionnaire and Situation Guidelines. Initially, patients were advised to call ahead to the outpatient hemodialysis facility or call their nephrologist to report fever or respiratory symptoms so that they could be advised on whether to proceed to the hospital or be safely evaluated in the hemodialysis facility. The provider could then call the hospital staff to prepare for their arrival or the hemodialysis facility could prepare to screen them. For patients arriving at the outpatient facility, only those outpatients who were symptomatic were being formally screened and given a mask. Patients who met criteria for being a PUI were sent to the hospital and the provider called the hospital staff in advance. At this time, the recommendations were that it would be advisable to refer symptomatic PUIs to an acute hospital setting where hemodialysis could be performed in an airborne isolation room and where staff would use personal protective equipment (PPE), including an N95 mask. Those PUIs sent to the hospital would have a respiratory viral panel performed to test for both influenza A and B and for respiratory syncytial viral. Due to severe limitations on COVID-19 testing—where tests were initially sent to the CDC and were then performed by the New York State Department of Health with a 1–2 day time to result, this testing was reserved only for the moderate to severely ill PUIs. Revisions to Hemodialysis Situation Guidelines and Screening: Mid-March The revised CDC recommendations in this period were such that droplet isolation and use of face masks were acceptable, due to shortage of N95 masks, unless an aerosolized procedure was planned. This facilitated performing hemodialysis in the outpatient facility under the specific conditions outlined in Table 1. Hospitalization was reserved for the patients with ESKD who were the most ill and who required an acute level of care. A triage plan—coordinated by centralized infection prevention managers working with the dialysis staff and physician—was instrumental to determine the most appropriate setting to provide hemodialysis for PUIs who were asymptomatic, symptomatic, and COVID-19 confirmed, with the goal of avoiding unnecessary emergency department visits and hospitalizations. As the number of PUIs and confirmed patients with COVID-19 has grown, so has the need to expand outpatient screening to everyone. The revised screening policy at the two major LDOs now mandate that all patients, visitors, staff, physicians, and physician extenders entering the dialysis clinic must be screened for signs and symptoms of COVID-19 before admittance to the dialysis treatment floor. Policy for Use of PPE. Initially, only patients who arrived at the dialysis facility with fever or respiratory symptoms were asked to put on a mask before entering. Health care workers were only required to wear masks during catheter connection procedures or if they had a cough. Due to the rapid rise in COVID-19 cases, the LDOs soon intensified their PPE policy beyond that recommended by the CDC. The current revised policy is that all patients are required to wear a mask upon entry to the facility and throughout their treatment, regardless of risk or symptoms. All other essential visitors must wear a mask while in the facility. All health care providers are required to wear a face mask at all times, both on and off the treatment floor. All staff members providing direct patient care are now required to wear full PPE, including gowns, gloves, face shields or goggles, and surgical face masks, from the first patient interaction in the facility lobby to the treatment floor. In the medication preparation area, staff are required to only wear a surgical face mask and are expected to remove PPE (except face masks) before entry to the medication preparation area and then don new PPE (including gown, gloves, and face shield) upon leaving the medication preparation area and returning to the treatment floor. The obvious potential downside to these extreme measures is the risk of potentially competing with acute hospitals for the limited and rapidly shrinking supply of PPE. Plans for Outpatient Hemodialysis Provision for Patients with COVID-19. In the third week of March, the first patient requiring hemodialysis with confirmed COVID-19 presented at one of our Montefiore-affiliated outpatient LDO facilities for dialysis. The patient was dialyzed at the outpatient facility 2 days before when the patient was asymptomatic, screened negative, and denied fever, respiratory symptoms, recent travel, or other known exposure. The outpatient hemodialysis staff, patients, and visitors who may have been exposed to the virus are being evaluated to ascertain the level of exposure to determine if they meet criteria for a PUI, and are being closely monitored for fever (temperature taken twice daily, monitor for respiratory symptoms) for 14 days. One of the LDOs reported that six patients on hemodialysis in their United States facilities have been confirmed COVID-19 positive as of March 17 and were receiving hemodialysis in the acute hospital setting. Because we anticipate more patients on hemodialysis testing COVID-19 positive, Montefiore-affiliated LDO facilities plan to cohort patients with confirmed COVID-19 who are medically stable into designated COVID-19 units in the Bronx. The proposed plan is for symptomatic PUIs to be dialyzed on the last shift, separated from other patients, so as to allow for a proper environmental disinfection period. Ideally, PUIs should undergo rapid testing; however, local testing sites and laboratories were severely limited and, as of March 20, have been closed by the New York State Department of Health due to a severe shortage of test kits and PPE for the staff manning these testing sites. These patients may also dialyze at an allocated "COVID-19 facility," providing the symptomatic PUIs and those with confirmed COVID-19 dialyze on different days. The CDC has provided recommended guidelines for transport of a PUI or patient with documented COVID-19 to an acute hospital or outpatient hemodialysis facility, but this pertains to trained emergency medical services using appropriate PPE and environmental disinfection (5). The local department of health must closely monitor every patient with confirmed COVID-19, perform an evaluation of residence, and provide PPE for cohabitants. New Outpatient Hemodialysis Placement. Testing for COVID-19 would be invaluable for placing new patients requiring hemodialysis for admission into the appropriate outpatient facility, similarly to what is done for hepatitis B and tuberculosis screening. No such policy exists at this time. Patients Who Are Hospitalized Established Patients on Hemodialysis Presenting to the Acute Hospital Figure 1 is a flow diagram that illustrates the proposed plan for the management of patients on hemodialysis sent to the Montefiore emergency department with fever, respiratory symptoms, known travel, or known COVID-19 exposure as of the morning of March 20. This has been a dynamic decision process and adjustments have been made on an almost daily basis. As the number of patients with COVID-19 who require hospitalization has increased, it has been decided to now cohort all patients with COVID-19 (from three Montefiore-affiliated hospitals) to the Moses Campus hospital to conserve PPE and streamline protocols.Figure 1.: Management of ESKD for patients with coronavirus disease 2019 and persons under investigation in the emergency department. Early identification of suspect or confirmed COVID-19 patients and their risk level is determined immediatly upon screening prior to entering the emergency department. COVID-19 suspected or confirmed patients are then evaluated by the emergency department staff to further determine their clinical stability. Patients who require acute hospitalization are admitted to a COVID-19 or PUI floor, or to an intensive care unit. Stable patients are discharge with appropriate travel precautions and self-isolation. COVID-19, coronavirus disease 2019; CRRT, continuous RRT; HD, hemodialysis; PUI, person under investigation.Patients are immediately masked (if this has not already been done) and isolated. The evaluating emergency room providers wear full PPE during the screening process. Patients who are confirmed for COVID-19 are issued an orange tag (high risk) and clinical stability for discharge is determined. If stable, they are reassigned to a designated COVID-19 outpatient hemodialysis facility. A PUI receives a blue tag (intermediate risk) and undergoes further testing for COVID-19 and a respiratory viral pathogen panel. If a PUI is stable for discharge, they may be assigned to a PUI-designated last shift or isolation room at an outpatient hemodialysis facility until COVID-19 testing results become available. COVID-19 tests were initially sent to the CDC for processing, and then to the New York State Department of Health. As of now, Montefiore Laboratory has the capability to perform on-site, rapid COVID-19 testing in a limited quantity. Patients on hemodialysis who have either COVID-19 or PUI status that require urgent dialysis in the emergency department are treated in the isolation room, which is then disinfected and requires a down period of 207 minutes before the room can be used. Hemodialysis Procedure for Patients with COVID-19 or PUIs Assigned to the Hospital Floor For patients with confirmed COVID-19 or PUIs who require hospitalization, the level of patient acuity dictates whether they require a critical care setting or may be closely monitored on the dedicated COVID-19–positive floor. Patients with COVID-19 and PUIs receive bedside hemodialysis in their room using a portable hemodialysis machine with portable reverse osmosis, which is hooked up to the walled hemodialysis plumbing unit. The efflux goes directly into the designated drain to prevent excess splash. Droplet precautions are maintained. The dialysis staff uses full PPE, including isolation gowns, masks (preferably N95 if available), appropriate eye protection, and gloves. The staff has been trained to don and doff their protective gear according to CDC protocols. The dialysis machine is cleaned and disinfected with 1:100 bleach wipes. The machines are not dedicated to any individual patient. The tubing and dialyzers are discarded in the red hazardous waste bins. Patients with COVID-19 or PUIs Assigned to the Critical Care Setting The nephrology team assesses the need for RRT and which modality is most appropriate. When in the patient room, full PPE is required. Limited medical staff exposure is advised and physical exam is performed only when necessary. Patients who receive continuous venovenous hemodialysis (CVVHD) require a dialysis catheter (untunneled or tunneled) for vascular access. The CVVHD effluent is directed into a dedicated drain to minimize splash and does not require any additional disinfection. CVVHD is performed by the critical care nursing staff wearing full PPE. Critical patients who receive intermittent hemodialysis are treated by the dialysis nursing staff in full PPE, as described previously. The dialysis nursing staff minimizes time in the patient room by sitting outside the glass partition as is possible. Intubation procedures are performed by the critical care team using the appropriate PPE including N95 masks. Patients with COVID-19 or PUIs with AKI Patients with AKI requiring RRT are triaged in the same manner as to whether they require intensive care or can be treated on the medical floor. An untunneled dialysis catheter is placed by either critical care, interventional radiology, or the nephrology team. If hemodynamically unstable, the patient is transferred to the intensive care unit (ICU) for either intermittent hemodialysis or CVVHD. If hemodynamically stable, the patient can be cohorted on a dedicated COVID-19 medical floor and receive bedside hemodialysis in their room. Hemodialysis nurses wear full PPE and minimize exposure time by sitting immediately outside of the doorway during the hemodialysis treatment. Planning meetings by the hospital and nephrology leadership have been ongoing to adapt to the rise in the number of patients with COVID-19. We have been able to increase our dialysis capacity on several dedicated COVID-19 floors by installing additional walled hemodialysis plumbing in the patient rooms. The goal is to try to further increase capacity by purchasing more hemodialysis machines and CVVHD machines; however, these supplies are in high demand. The major limiting factor is the number of rooms with hemodialysis plumbing on the COVID-19 cohort floors and the number of hemodialysis nursing staff available, because these individualized treatments in the patient's room require one-to-one nursing. A potential future option for the patients with AKI is to provide acute peritoneal dialysis; however, we have not implemented this yet. Montefiore Nephrology Service Census for COVID-19–Confirmed Cases As of March 20, the Montefiore Medical Center inpatient nephrology services have cared for 20 patients with confirmed COVID-19: seven were patients with ESKD on hemodialysis (five receiving bedside hemodialysis in their room and two receiving CVVHD in the ICU) and 13 were patients with AKI (six not requiring RRT, five receiving CVVHD in the ICU, and two receiving hemodialysis in the ICU). One of the patients in the ICU died after withdrawal of care, and one patient with AKI died. Discharge Planning for Patients with COVID-19 or PUIs Discharge planning for hospitalized patients with confirmed COVID-19 or PUIs on hemodialysis requires appropriate planning and allocation to the outpatient facility, as described above. As described previously, the CDC has provided recommended guidelines for transport of a PUI or patient with documented COVID-19 to an outpatient hemodialysis (5). The local department of health must monitor every patient with confirmed COVID-19, perform an evaluation of residence, and provide PPE for cohabitants before discharge. The NYC Department of Health does not require a negative COVID-19 test to discharge a patient from a health care facility. As per the NYC Department of Health, after discharge, a patient with confirmed COVID-19 or PUIs should self-isolate and remind their household contacts to self-monitor (6). Self-isolation for persons who are not hospitalized and have COVID-19 or are PUIs is recommended for 7 days after onset of illness and 72 hours after being consistently afebrile (without antipyretics) with resolving respiratory symptoms, as per the NYC Department of Health (6). If discharge occurs before this self-isolation period, it is recommended that patients with confirmed COVID-19 and PUIs dialyze at an allocated COVID-19 facility or PUI designated last shift. The duration required for placing a discharged PUI on a PUI designated last shift, or patient with confirmed COVID-19 at a COVID-19 outpatient hemodialysis facility may need to be for a longer period. Future guidelines are needed regarding the timing of patient discharge from a COVID-19 hemodialysis facility to their home facility, and should consider the utility of requiring a negative COVID-19 viral test result when testing becomes more widely available. Disclosures M. Coco and M. Mokrzycki have nothing to disclose. Funding None.

It is important to the general nephrology community to find noninvasive methods to diagnose metabolic bone disease, whether in patients receiving dialysis or renal transplant. Undiagnosed renal bone disease can lead to debilitating fractures that are many times more common than in the general population (1–3). Renal transplant recipients have underlying renal osteodystrophy that develops pretransplantation and is mainly due to loss of control of bone and mineral metabolism. Diagnosis of renal osteodystrophy relies on an understanding of the normal and pathologic microarchitecture of bone. Mineralized histology of bone biopsies is the gold standard for determination of microarchitecture. The diagnostic spectrum obtained from it spans from low turnover (adynamic) to high turnover (hyperparathyroid) bone disease. In addition to adynamic bone where cellular activity is essentially at a standstill, low turnover disease may include mineralization defect, where bone is replaced with excess unmineralized osteoid. High turnover histology typically shows an exuberance of cellular activity with increased osteoblasts, osteoclasts, and peritrabecular fibrosis. The bone biopsy can give static information on trabecular number, thickness, microfractures, spatial configuration, and connectivity—all parameters that speak to bone strength and metabolic capacity. In addition, the bone biopsy can give information on dynamic parameters such as bone formation rate, a measure of new bone formed, the amount of new bone made, the rate at which the new bone is mineralized, and the activation frequency or estimate of bone remodeling (4,5). However, bone histology has fallen out of favor in part because of its invasiveness and technical difficulty in acquisition, processing, and interpretation. Noninvasive imaging methods have largely replaced mineralized bone histology and have made clinical assessment of bone status a universal standard of practice. In addition to offering a more global view of the physical status of bone than the small sample in a biopsy, these methods can also yield some of the information obtained from mineralized bone histology. The two techniques currently best suited to be partial surrogates for mineralized bone histology are dual-energy x-ray absorptiometry (DXA) and quantitative computed tomography in its various forms (central, peripheral, high resolution, and micro computed tomography). However, these methods have their limitations. Even in their most advanced forms, they cannot give critical measurements obtained from histology. DXA measures bone mineral density and has been validated across women in the general nonrenal population to predict fracture risk and to generate treatment paradigms on the basis of the derived T-score (6). In general, a T-score of −2.5 (SD from normal in the normal 30-year-old woman) is considered osteoporotic and is associated with increased fracture risk. However, bone mineral density as measured by DXA, important in the diagnosis of osteoporosis, cannot distinguish between underlying high or low turnover bone disease: it only measures mineral content. This is not surprising because DXA contains little of the spatial or cellular information detected by bone histology. DXA does not correlate with bone histology or histomorphometric analysis of bone activity. In fact, the Kidney Disease Outcomes Quality Initiative does not recommend its routine use in patients who are prerenal transplant (7). The shortcomings of DXA compared with mineralized histology in the diagnosis of renal bone disease are best illustrated in studies of patients receiving renal transplant. Here, osteodystrophy takes on more and different significance because bone architecture is altered beyond what is already present in renal failure by the added stressors of transplantation. These include the addition of antirejection medications (calcineurin inhibitors and steroids especially), changes in mineral metabolism (because electrolytes are in constant flux as allograft function stabilizes), and normal age-related changes. In the days before steroid minimization for prevention of allograft rejection, it was not unusual to see a significant decrease in bone mineral density (BMD) in the first 6 months post-transplant (8). Few studies have compared BMD with histomorphometry. A cross-sectional study of bone histomorphometry in women receiving transplant with normal renal function reported high and low bone turnover, with BMD T-scores in the osteoporotic range. Hip BMD but not vertebral BMD correlated with cortical and trabecular histomorphometry (9). Bone histomorphometry done in a cross-sectional study of renal transplant recipients, both men and women, who were postrenal transplant for a varying number of years, showed mainly low bone turnover and low bone volume; however, no BMD data were presented (10). In a study on the use of the intravenous bisphosphonate pamidronate to prevent bone loss, we showed that vertebral BMD decreased significantly in the control group as compared with the treated group, whereas most of the patients in both groups developed adynamic bone disease. However, this study did not compare bone histology with BMD readings (11). In a subsequent study on men and women receiving transplant, on steroid minimization, and randomized for use of the popular oral bisphosphonate risedronate, we found that baseline BMD was in the healthy or osteopenic range of T-scores and that it did not change over the course of the 12-month study in either group. Bone histomorphometry showed lower bone turnover with osteomalacia in the treated men and preserved trabecular thickness in the treated women. Of interest, neither T-scores nor BMD at any site correlated with any histomorphometric measures, and BMD could not predict bone disease (12). This may imply that we cannot reliably diagnose transplant bone disease on the basis of BMD alone. High resolution peripheral quantitative computed tomography (HR-pQCT) scanning is a new and still experimental imaging technique that yields more detailed information than any previous noninvasive technique. It is derived from clinically used quantitative computed tomography methods and improves resolution of bone trabecular structure and volume, but only on thin or small specimens or parts of the body. It has very low resolution compared with microscopy (82 µm as compared with <1 µm for light microscopy) (13) and does not give cellular, biochemical, or compositional information. Nonetheless, it has yielded useful information on bone microarchitecture (14,15). Trabecular bone score (TBS) is a new, clinically applicable approach to bone evaluation that can generate a measure of the potential to fracture in trabecular bone by recalculating DXA images (16). This is the first technique to directly add a clinical component to an otherwise purely structural evaluation. Whereas DXA measures total mineral content and derives a score (T-score) from this, TBS extracts spatial information from DXA images using grayscale textural analysis and thereby quantifies trabecular microarchitecture. There have been studies that show improved fracture prediction by TBS over DXA T-scores alone in the general population (17), and other retrospective studies that suggest that TBS scores predict fractures in renal transplant recipients (18). A recent cross-sectional study examined transiliac bone biopsy specimens from patients with idiopathic osteoporosis and fractures. It compared TBS obtained by spinal DXA to trabecular parameters of the bone biopsies as assessed by micro computed tomography. A significant correlation was found between TBS and the micro computed tomography images. However, TBS was not compared with the actual histomorphometry of the bone biopsy specimen (19). In the study published in this issue of the Clinical Journal of the American Society of Nephrology, Luckman et al. compared morphometric parameters derived from HR-pQCT with TBS parameters derived from DXA (20). A series of renal transplant recipients had been studied over the years with serial HR-pQCT and DXA (14,15). In a post hoc analysis, TBS was applied and correlated with DXA and HR-pQCT. Most of the patients had healthy DXA T-scores (>−1.0) pre- and post-transplant, which would imply a lower fracture risk over time. TBS analysis redefined fracture risk with at least 50% risk at any time point. TBS correlated with BMD, as expected because both are derived from DXA. TBS also correlated with HR-pQCT with respect to trabecular measurements of thickness, density, stiffness, and failure load. However, there were no incident or prevalent fractures reported during the study period, so the actual significance of the TBS prediction remains uncertain. At this time, it is still unclear whether the TBS can be useful as a noninvasive tool in the management of bone disease in patients receiving renal transplant. TBS may correlate with other imaging methods but it has not been validated with underlying bone histology and activity so that treatment decisions remain empirical. We are still looking, after many years of new methodology, laboratory tests, and examinations, for that noninvasive way to diagnose renal bone disease on which to base our treatments. For now, the bone biopsy remains the gold standard. Disclosures None.

BACKGROUND:With the development of all oral, interferon-free directly acting antiviral (DAA) medications, treatment of hepatitis C virus (HCV) infection in renal transplant recipients is possible, but limited data exists on its safety and efficacy. METHODS:We performed a retrospective cohort analysis of patients transplanted at our center with HCV who have been started on DAAs. Primary endpoints included sustained virologic response as defined as negative viral load at 12 weeks postcompletion of therapy and allograft function. RESULTS:A total of 31 patients met inclusion criteria. The most commonly used regimen was sofosbuvir and ledipasvir (n = 21). Of the treated patients, 100% had undetectable viral load at the completion of therapy. Of the 31 patients treated, 30 (97%) achieved sustained virologic response. Both graft and patient survivals at most recent follow-up was 100%. There was no significant change in glomerular filtration rate (GFR) before or after therapy (64.2 ± 16.5 mL/min per body surface area before vs. 58.9 ± 17.5 mL/min per body surface area after therapy; P = 0.22); however, 3 patients now have GFR less than 20. A total of 6 (19.3%) of 31 patients had worsening proteinuria during or shortly after therapy. Patients with more than 500 mg/g of proteinuria at the start of treatment were significantly more likely to develop worsening proteinuria than those with less than 500 mg/g of proteinuria at the start of therapy (P < 0.001). Retrospective review of 20 untreated HCV patients did not demonstrate worsening allograft function and proteinuria during a median follow-up time of 1386 days (range, 332-6254). CONCLUSIONS:Our preliminary data demonstrate that DAAs can be used safely and effectively in patients after kidney transplantation. Patients with proteinuria or lower GFR should be monitored more closely.

Patients with CKD stages 4 and 5 experience biochemical derangements associated with CKD-mineral bone disorder. Some of the key abnormalities are hyperparathyroidism, hyperphosphatemia, hypocalcemia, and metabolic acidosis. We review the available treatments for these conditions and the evidence behind the treatments. We conclude that there is greater evidence for treating hyperphosphatemia than hyperparathyroidism. Treatment of metabolic acidosis in small clinical trials appears to be safe. We caution the reader about side effects associated with some of these treatments that differ in patients with CKD Stages 4 and 5 compared with patients on dialysis. The use of cinacalcet has been associated with hyperphosphatemia in patients with functioning kidneys. Activated vitamin D therapy has been associated with elevated creatinine levels, which may or may not be a reflection of true decrement in kidney function. Finally, the use of non-calcium-containing phosphate binders may be associated with improved clinical outcomes in patients; however, many more clinical trials are needed in this important area of medicine.

Cocaine is abused worldwide as a recreational drug. It is a potent activator of the sympathetic nervous system leading to intense vasoconstriction, endothelial dysfunction, oxidative stress, platelet activation and decrease in prostaglandins E2 and prostacyclin. Cocaine can lead to widespread systemic adverse effects such as stroke, myocardial infarction, arterial dissection, vascular thrombosis and rhabdomyolysis. In human and rat kidneys, cocaine has been associated with glomerular, tubular, vascular and interstitial injury. It is not uncommon to diagnose cocainerelated acute kidney injury (AKI), malignant hypertension and chronic kidney disease. Cocaine abuse can lead to AKI by rhabdomyolysis, vasculitis, infarction, thrombotic microangiopathy and malignant hypertension. It is reported that 50-60% of people who use both cocaine and heroin are at increased risk of HIV, hepatitis and additional risk factors that can cause kidney diseases. While acute interstitial nephritis (AIN) is a known cause of AKI, an association of AIN with cocaine is unusual and seldom reported. We describe a patient with diabetes mellitus, hypertension and chronic hepatitis C, who presented with AKI. Urine toxicology was positive for cocaine and a kidney biopsy was consistent with AIN. Illicit drugs such as cocaine or contaminants may have caused AIN in this case and should be considered in the differential diagnosis of causes of AKI in a patient with substance abuse. We review the many ways that cocaine adversely impacts on kidney function.

Bisphosphonates may prevent or treat the bone loss promoted by the immunosuppressive regimens used in renal transplantation. Risedronate is a commonly used third-generation amino-bisphosphonate, but little is known about its effects on the bone health of renal transplant recipients. We randomly assigned 42 new living-donor kidney recipients to either 35 mg of risedronate weekly or placebo for 12 months. We obtained bone biopsies at the time of renal transplant and after 12 months of protocol treatment. Treatment with risedronate did not affect bone mineral density (BMD) in the overall cohort. In subgroup analyses, it tended to preserve BMD in female participants but did not significantly affect the BMD of male participants. Risedronate did associate with increased osteoid volume and trabecular thickness in male participants, however. There was no evidence for the development of adynamic bone disease. In summary, further study is needed before the use of prophylactic bisphosphonates to attenuate bone loss can be recommended in renal transplant recipients.

Activation of the renin-angiotensin system (RAS) followed by increased inflammatory cytokines may be important in the pathogenesis of chronic allograft dysfunction. As many renal transplant recipients show chronic changes on biopsy within the first year, early RAS blockade with angiotensin converting enzyme inhibitor (ACEI) could be beneficial. However, it remains unclear that early ACEI use is safe. We conducted a prospective, randomized, placebo-controlled trial to assess the safety of enalapril 5 mg during the early post-transplant period. Subjects took the study medication for six months. Primary endpoints were serum potassium (K) > 5.9 mEq/L and 30% increase in baseline creatinine. A total of 53 subjects were randomized, and of them, 27 received the study drug. Twenty-nine subjects, 14 ACEI and 15 controls, completed the six-month protocol without reaching an endpoint. Patients on ACEI had higher K and higher BUN at six months. Serum creatinine, hematocrit, and urinary protein were not different. There was no difference in urinary TGF-beta 1. Twenty-four subjects reached study endpoints. When the common clinical endpoints of elevated creatinine and hyperkalemia were combined, ACEI group had significantly increased endpoints vs. control (10/13, 77% vs. 5/11, 45%, p < 0.05). We conclude that ACEI use in the early post-transplant period can be safe but patients must be carefully selected and monitored for elevations in serum creatinine and potassium. Whether early ACEI is beneficial in preserving allograft function requires further study.

BACKGROUND AND OBJECTIVES:Elevated alkaline phosphatase (AlkPhos) and phosphate levels are associated with cardiovascular morbidity and mortality in patients receiving dialysis. A retrospective cohort study was conducted to test these associations in outpatients with an estimated GFR > or =60 ml/min/1.73 m(2). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:Patients with serum AlkPhos and phosphate levels measured between 2000 and 2002 (n = 10,743) at Montefiore Medical Center (MMC) clinics were followed through September 11, 2008 (median 6.8 years). Mortality data were obtained via Social Security Administration records (n = 949 deaths). Hospitalization data were obtained from MMC records. RESULTS:The mean age was 51 years, 64% were women, 22% were white, 26% were non-Hispanic black, 16% were Hispanic, 13% had a diagnosis of hypertension, 9% had diabetes mellitus, and 8% had cardiovascular disease at baseline. AlkPhos and phosphate were independently associated with mortality and cardiovascular-related hospitalization after multivariable adjustment. Comparing patients in the highest (> or =104 U/L) versus lowest quartile of AlkPhos (< or =66 U/L), the adjusted hazard ratio (HR) for mortality was 1.65 (P trend across quartiles <0.001). For the highest compared with the lowest quartile of serum phosphate (> or =3.8 mg/dl versus < or =3.0 mg/dl), the adjusted HR for mortality was 1.29 (P trend across quartiles = 0.008). High AlkPhos but not phosphate levels were also associated with all-cause, infection-related, and fracture-related hospitalization. CONCLUSIONS:Higher levels of serum AlkPhos and phosphate were associated with increased mortality and cardiovascular-related hospitalization in an inner-city clinic population. Further studies are needed to elucidate mechanisms underlying these associations.

The patient with chronic renal disease who has a fracture remains a unique management challenge. Opinions on treatment abound, but without adequate evidence to back them up.