Clinical features, management, and outcome of hemodialysis patients with SARS-CoV-2.

The aim of the study was to evaluate the clinical features of the patients on HD with COVID-19 and determine the prognostic factors. In this single-center prospective study, a total of 58 chronic renal failure patients on HD and diagnosed COVID-19 infection were enrolled in the study. The patients were divided into two groups according to their need for intensive care unit referral. Demographic features of the patients, clinical manifestations, laboratory data, treatments, and clinical outcome were evaluated. The mean age of 58 HD patients was 63.2 ± 13.8 (30-93) years and female-male ratio was 0.34. SARS-CoV2-PCR positivity rate was 32.8%. 85.2% of patients (n = 46) had bilateral lesions and 14.8% (n = 8) had unilateral one lesion in chest CT. The most common symptoms were fatigue (in 44 patients, 80%) and dyspnea (in 31 patients, 56.4%). The most common comorbidity was HT (in 37 patients, 67.3%). The patients who need intensive care and died were older (p = 0.015). We observed lower platelet and eosinophil counts, potassium levels, higher AST, troponin and CRP levels in the group of patients who need intensive care and died than the group who survived (p = 0.043, 0.005, 0.033, 0.007, 0.001, <0.001, respectively). 15.5% of the patients (n = 9) were transferred to intensive care unit. Among them, two were discharged with cure and seven patients died. Mortality rate was 12.1%. Older age, lower platelet and eosinophil counts and higher AST, troponin and CRP levels were prognostic risk factors in our HD patients who needed intensive care.

Expanding the Donor Pool: First Use of Hepatitis B Virus Nat Positive Solid Organ Allografts Into Seronegative Recipients.

OBJECTIVES: The aim of this study was to assess the 1-year safety and effectiveness of HBV Nucleic Acid Test positive (HBV NAT+) allografts in seronegative kidney transplant (KT) and liver transplant (LT) recipients. SUMMARY BACKGROUND DATA: Despite an ongoing organ shortage, the utilization of HBV NAT+ allografts into seronegative recipients has not been investigated. METHODS: From January 2017 to October 2020, a prospective cohort study was conducted among consecutive KT and LT recipients at a single institution. Primary endpoints were post-transplant HBV viremia, graft and patient survival. RESULTS: With median follow-up of 1-year, there were no HBV-related complications in the 89 HBV NAT+ recipients. Only 9 of 56 KTs (16.1%) and 9 of 33 LTs (27.3%) experienced post-transplant HBV viremia at a median of 185 (KT) and 269 (LT) days postoperatively. Overall, viremic episodes resolved to undetected HBV DNA after a median of 80 days of entecavir therapy in 16 of 18 recipients. Presently, 100% of KT recipients and 93.9% of LT recipients are HBV NAT- with median follow-up of 13 months, whereas 0 KT and 8 LT (24.2%) recipients are HBV surface antigen positive indicating chronic infection. KT and LT patient and allograft survival were not different between HBV NAT+ and HBV NAT- recipients (P > 0.05), whereas HBV NAT+ KT recipients had decreased waitlist time and pretransplant duration on dialysis (P < 0.01). CONCLUSIONS: This is the largest series describing the transplantation of HBV NAT+ kidney and liver allografts into HBV seronegative recipients without chronic HBV viremia or decreased 1-year patient and graft survival. Increasing the utilization of HBV NAT+ organs in nonviremic recipients can play a role in decreasing the national organ shortage.

Coronavirus Disease 2019 and Kidney Transplantation in Saudi Arabia: Outcomes and Future Opportunities.

BACKGROUND Kidney transplant services all over the world were severely impacted by the coronavirus disease 2019 pandemic. The optimum management of kidney transplant recipients with coronavirus disease 2019 remains uncertain. MATERIAL AND METHODS We conducted a multicenter cohort study of kidney transplant recipients with coronavirus disease 2019 infection in Saudi Arabia. Multivariable Cox regression analysis was used to study predictors of graft and patient outcomes at 28 days after coronavirus disease 2019 diagnosis. RESULTS We included 130 kidney transplant recipients, with a mean age of 48.7(±14.4) years. Fifty-nine patients were managed at home with daily follow-up utilizing a dedicated clinic, while 71 (54.6%) required hospital admission. Acute kidney injury occurred in 35 (26.9%) patients. Secondary infections occurred in 38 (29.2%) patients. SARS-CoV-2 antibodies testing was carried out in 84 patients, of whom 70 tested positive for IgG and/or IgM. Fourteen patients died (10.8%). A multivariable Cox regression analysis showed that age, creatinine at presentation, acute kidney injury, and use of azithromycin were significantly associated with worse patient survival. Graft loss was associated with requiring renal replacement therapy and development of secondary infections. CONCLUSIONS Despite kidney transplant recipients with coronavirus disease 2019 infection having higher rate of hospital admission and mortality compared to the general population, a significant number of them can be managed using a telemedicine clinic. Most kidney transplant patients seem to mount an antibody response following coronavirus disease 2019 infection, and it remains to be seen if they will have a similar response to the incoming vaccines.

Longitudinal proteomic profiling of dialysis patients with COVID-19 reveals markers of severity and predictors of death.

End-stage kidney disease (ESKD) patients are at high risk of severe COVID-19. We measured 436 circulating proteins in serial blood samples from hospitalised and non-hospitalised ESKD patients with COVID-19 (n = 256 samples from 55 patients). Comparison to 51 non-infected patients revealed 221 differentially expressed proteins, with consistent results in a separate subcohort of 46 COVID-19 patients. Two hundred and three proteins were associated with clinical severity, including IL6, markers of monocyte recruitment (e.g. CCL2, CCL7), neutrophil activation (e.g. proteinase-3), and epithelial injury (e.g. KRT19). Machine-learning identified predictors of severity including IL18BP, CTSD, GDF15, and KRT19. Survival analysis with joint models revealed 69 predictors of death. Longitudinal modelling with linear mixed models uncovered 32 proteins displaying different temporal profiles in severe versus non-severe disease, including integrins and adhesion molecules. These data implicate epithelial damage, innate immune activation, and leucocyte-endothelial interactions in the pathology of severe COVID-19 and provide a resource for identifying drug targets.

COVID-19 varies from a mild illness in some people to fatal disease in others. Patients with severe disease tend to be older and have underlying medical problems. People with kidney failure have a particularly high risk of developing severe or fatal COVID-19. Patients with severe COVID-19 have high levels of inflammation, causing damage to tissues around the body. Many drugs that target inflammation have already been developed for other diseases. Therefore, to repurpose existing drugs or design new treatments, it is important to determine which proteins drive inflammation in COVID-19. Here, Gisby, Clarke, Medjeral-Thomas et al. measured 436 proteins in the blood of patients with kidney failure and compared the levels between patients who had COVID-19 to those who did not. This revealed that patients with COVID-19 had increased levels of hundreds of proteins involved in inflammation and tissue injury. Using a combination of statistical and machine learning analyses, Gisby et al. probed the data for proteins that might predict a more severe disease progression. In total, over 200 proteins were linked to disease severity, and 69 with increased risk of death. Tracking how levels of blood proteins changed over time revealed further differences between mild and severe disease. Comparing this data with a similar study of COVID-19 in people without kidney failure showed many similarities. This suggests that the findings may apply to COVID-19 patients more generally. Identifying the proteins that are a cause of severe COVID-19 ­ rather than just correlated with it ­ is an important next step that could help to select new drugs for severe COVID-19.

Sex Differences in Extrahepatic Outcomes After Antiviral Treatment for Hepatitis C.

INTRODUCTION: Despite recognized differences in the rates of cardiovascular and renal disease between men and women in the general population, studies of the downstream effects of antiviral treatment for hepatitis C (HCV) have not investigated differences in outcomes based on sex. We analyzed sex differences in risk of acute coronary syndrome (ACS), end-stage renal disease (ESRD), and ischemic stroke by treatment and response in a large US-based multisite cohort of HCV patients. METHODS: Observation started at the HCV diagnosis date (untreated) or last antiviral treatment start (treated). Treatment selection bias was addressed using an inverse probability-weighting approach. We estimated the effect of treatment on the cumulative incidence of outcomes using the Fine-Gray method (subdistribution hazard ratios [sHR] and 95% confidence intervals [95% CI]). Death was a competing risk. RESULTS: Roughly 40% of 15,295 HCV patients were women. After controlling for other risk factors, sustained virological response (SVR) (interferon-based [IFN] or direct-acting antiviral [DAA]) significantly reduced risk of all outcomes, particularly among female patients. Female patients who achieved SVR after IFN-based treatment had significantly lower risk of ACS compared with male patients with SVR from either treatment type (sHR 0.45 [95% CI 0.35-0.59] vs 0.81 [95% CI 0.69-0.96, for DAA SVR] and sHR 0.72 [95% 0.62, 0.85, for IFN SVR]). Successful treatment seemed to be most protective against ESRD; female patients who achieved SVR were at 66%-68% lower risk than untreated patients (sHR 0.32 [95% CI 0.17-0.60 for DAA SVR] and 0.34 [95% CI 0.20-0.58 for IFN SVR]), whereas men were at 38%-42% lower risk (sHR 0.62 [95% CI 0.46-0.85 for DAA SVR] and 0.58 [95% CI 0.43-0.76 for IFN SVR]). IFN treatment failure significantly increased risk of all outcomes by 50%-100% among female patients. Compared with no treatment, female patients who experienced IFN treatment failure were at 63% increased risk of ACS (sHR 1.63 [95% CI 1.35-1.96]), almost twice the risk of ESRD (sHR 1.95 [95% CI 1.43-2.66]) and 51% increased risk of stroke (sHR 1.49 [95%CI 1.11-2.00]). DISCUSSION: SVR reduced the risk of extrahepatic complications, particularly in females. The significantly increased risk associated with IFN TF in women-a subset who represented roughly 10% of that group-underscores the importance of prioritizing these patients for DAA treatment irrespective of the fibrosis stage.

Clinical outcomes following DAA therapy in patients with HCV-related cirrhosis depend on disease severity.

BACKGROUND & AIMS: HCV-infected patients with cirrhosis achieve high sustained virological response (SVR) rates with direct-acting antivirals (DAAs) even after hepatic decompensation. We aimed to assess the clinical outcome following DAAs among patients with compensated and decompensated cirrhosis in relation to SVR and changes in model for end-stage liver disease (MELD) score. METHODS: Consecutive DAA-treated chronic HCV-infected patients with cirrhosis from 4 hepatology clinics were included. The primary endpoint in survival analyses was clinical disease progression, defined as liver failure, hepatocellular carcinoma, liver transplantation or death. RESULTS: In total, 868 patients were included with a median age of 59 (IQR 54-65) years; 719 (83%) with Child-Pugh A cirrhosis and 149 (17%) with Child-Pugh B/C cirrhosis. SVR was attained by 647 (90%) Child-Pugh A patients and 120 (81%) Child-Pugh B/C patients. During a median follow-up of 28 (IQR 20-36) months, 102 (14%) Child-Pugh A patients and 96 (64%) Child-Pugh B/C patients experienced clinical disease progression. SVR was independently associated with an improved event-free survival in patients with Child-Pugh A cirrhosis (adjusted hazard ratio [HR] 0.47; 95% CI 0.27-0.82, p = 0.007), but not in patients with Child-Pugh B/C cirrhosis (adjusted HR 1.23; 95% CI 0.67-2.26; p = 0.51). Twelve weeks post-DAAs, 28 (19%) patients with Child-Pugh B/C cirrhosis had ≥2-point MELD decline, but their 2-year event-free survival did not differ from those with a stable MELD (47.9%; 95% CI 28.7-67.1 vs. 48.9%; 95% CI 38.1-59.7, respectively, p = 0.99). CONCLUSIONS: Among patients with chronic HCV infection, DAA-induced SVR was associated with a reduced risk of clinical disease progression in patients with Child-Pugh A cirrhosis but not in patients with Child-Pugh B/C cirrhosis. In Child-Pugh B/C cirrhosis, a ≥2-point MELD decline did not translate into improved clinical outcome. LAY SUMMARY: Chronic HCV infection can be cured with antiviral therapy. In this study, we evaluated the long-term effects of antiviral therapy on liver-related complications in patients with cirrhosis. Our results suggest that patients with compensated cirrhosis who were cured of their HCV infection have a lower rate of complications. In contrast, the rate of complications was not related to virological cure among those with decompensated cirrhosis. While these patients seem to remain in need of liver transplantation, antiviral therapy may lower their priority on the liver transplantation waiting list.

Hepatitis C and Treatment in Patients with Chronic Kidney Disease.

Hepatitis C virus (HCV) is associated with increased mortality and morbidity in patients with chronic kidney disease (CKD). The early detection and treatment of Hepatitis C associated with kidney disease is paramount to preventing the progressive loss of kidney function. HCV treatment until the advent of direct acting anti-viral agents (DAAs) was limited to interferon and ribavirin. Interferon and ribavirin treatment resulted in only modest success but with frequent adverse events and poor tolerability. Furthermore, interferon and ribavirin could not be used in certain patient populations including those with advanced CKD, were on dialysis, or those who have received a kidney transplant. DAAs have now made treatment possible in these sub-groups with a sustained viral response (SVR) of 90-100% and minimal side effects. DAAs have helped increase transplant rates by allowing for the use of HCV positive kidneys in recipients who are HCV negative. Although the choice of DAAs should be carefully considered and based on patient characteristics, concomitant medications, and HCV genotype.

The impact of COVID-19 in hemodialysis patients: Experience in a hospital dialysis unit.

INTRODUCTION: COVID-19 is a very high transmission disease with a variable prognosis in the general population. Patients in hemodialysis therapy are particularly vulnerable to developing an infectious disease, but the incidence and prognosis of hemodialysis patients with COVID-19 is still unclear. The main objective is to describe the experience of our dialysis unit in preventing and controlling the spread of SARS-CoV-2 infection. METHODS: Preventive structural and organizational changes were applied to all patients and health care personnel in order to limit the risk of local transmission of SARS-CoV-2 infection. FINDINGS: The Nephrology department at Sant Joan Despí Moises Broggi Hospital-Consorci Sanitari Integral is a reference for two satellite hemodialysis centers caring for 156 patients. We combine our own hemodialysis maintenance program for 87 patients with hospitalized patients from peripheral hemodialysis centers. In this area, the reported incident rate of COVID-19 in these peripherical hemodialysis centers was 9.5% to 19.9% and the death rate 25% to 30.5%. In our hemodialysis program, the incidence rate was 5.7%. Three out of five required hospitalization (60%) and nobody died. DISCUSSION: Although the risk of local transmission of the disease was very high due to the increase in hemodialysis patients from peripheral centers admitted to hospital, the incidence rate of COVID-19 was very low in our own hemodialysis patients. We believe that the structural and organizational changes adopted early on and the diagnosis algorithm played an important role in minimizing the spread of the disease.

Coronavirus-associated kidney outcomes in COVID-19, SARS, and MERS: a meta-analysis and systematic review.

OBJECTIVES: A meta-analysis and systematic review was conducted on kidney-related outcomes of three recent pandemics: SARS, MERS, and COVID-19, which were associated with potentially fatal acute respiratory distress syndrome (ARDS). METHODS: A search of all published studies until 16 June 2020 was performed. The incidence/prevalence and mortality risk of acute and chronic renal events were evaluated, virus prevalence, and mortality in preexisting hemodialysis patients was investigated. RESULTS: A total of 58 eligible studies involving 13452 hospitalized patients with three types of coronavirus infection were included. The reported incidence of new-onset acute kidney injury (AKI) was 12.5% (95% CI: 7.6%-18.3%). AKI significantly increased the mortality risk (OR = 5.75, 95% CI 3.75-8.77, p < 0.00001) in patients with coronavirus infection. The overall rate of urgent-start kidney replacement therapy (urgent-start KRT) use was 8.9% (95% CI: 5.0%-13.8%) and those who received urgent-start KRT had a higher risk of mortality (OR = 3.43, 95% CI 2.02-5.85, p < 0.00001). Patients with known chronic kidney disease (CKD) had a higher mortality than those without CKD (OR = 1.97, 95% CI 1.56-2.49, p < 0.00001). The incidence of coronavirus infection was 7.7% (95% CI: 4.9%-11.1%) in prevalent hemodialysis patients with an overall mortality rate of 26.2% (95% CI: 20.6%-32.6%). CONCLUSIONS: Primary kidney involvement is common with coronavirus infection and is associated with significantly increased mortality. The recognition of AKI, CKD, and urgent-start KRT as major risk factors for mortality in coronavirus-infected patients are important steps in reducing future mortality and long-term morbidity in hospitalized patients with coronavirus infection.

Sympathetic activation: a potential link between comorbidities and COVID-19.

In coronavirus disease 2019 (COVID-19), higher morbidity and mortality are associated with age, male gender, and comorbidities, such as chronic lung diseases, cardiovascular pathologies, hypertension, kidney diseases, diabetes mellitus, and obesity. All of the above conditions are characterized by increased sympathetic discharge, which may exert significant detrimental effects on COVID-19 patients, through actions on the lungs, heart, blood vessels, kidneys, metabolism, and/or immune system. Furthermore, COVID-19 may also increase sympathetic discharge, through changes in blood gases (chronic intermittent hypoxia, hyperpnea), angiotensin-converting enzyme (ACE)1/ACE2 imbalance, immune/inflammatory factors, or emotional distress. Nevertheless, the potential role of the sympathetic nervous system has not yet been considered in the pathophysiology of COVID-19. In our opinion, sympathetic overactivation could represent a so-far undervalued mechanism for a vicious circle between COVID-19 and comorbidities.

Detection of SARS-CoV-2 in Hemodialysis Effluent of Patient with COVID-19 Pneumonia, Japan.

We report detection of severe acute respiratory syndrome coronavirus 2 RNA in hemodialysis effluent from a patient in Japan with coronavirus disease and prolonged inflammation. Healthcare workers should observe strict standard and contact precautions and use appropriate personal protective equipment when handling hemodialysis circuitry from patients with diagnosed coronavirus disease.

Co-infection with SARS-CoV-2 and parainfluenza virus in a hemodialysis patient: A case report.

BACKGROUND: In December 2019, the 2019 novel coronavirus disease (COVID-19) caused by SARS-CoV-2 emerged in China and now has spread to many countries. Limited data are available for hemodialysis patients with COVID-19. CASE PRESENTATION: We report a 66-year-old man with confirmed COVID-19 and parainfluenza virus infection in Wuhan. We describe the clinical characteristics, radiological findings, and treatment of the hemodialysis patient, including the patient's initial pneumonia at presentation with progression to acute respiratory distress syndrome (ARDS). DISCUSSION AND CONCLUSION: Our case underscores the possibility of SARS-CoV-2 co-infection with other pathogens in hemodialysis patients and the importance of early identification of COVID-19.

Increased systemic sST2 in patients with end stage renal disease contributes to milder liver damage during HCV infection.

INTRODUCTION: Hepatitis C Virus (HCV) is the leading cause of chronic liver disease and is a serious global health problem. Hepatitis C infection is highly prevalent in patients with end stage renal disease (ESRD), due to frequent exposure to blood and blood products, nosocomial transmission of HCV, and prolong hemodialysis duration. The aim of the study was to evaluate the influence of IL-33/ST2 signaling pathway on severity of the liver disease in ESRD HCV+ patients. METHODOLOGY: Blood samples from patients with end stage renal disease (ESRD) and hepatitis C infection (HCV), 20 patients with HCV infection, 20 patients with ESRD and 20 healthy control donor patients were taken for the examination of biochemical parameters, for the determination of the serum cytokine concentration, and for the molecular diagnostics of HCV. RESULTS: Systemic sST2 positively correlated with serum level of urea and creatinine, respectively. Serum sST2 was significantly increased in ESRD HCV+ patients in comparison to HCV+ group. sST2/IL-1, sST2/IL-4 and sST2/IL-23 ratios were significantly increased in serum of ESRD HCV+ patients in comparison to HCV+ patients. Significantly higher systemic level of sST2 and sST2/IL-1 and sST2/IL-4 ratios were measured in ESRD patients compared to non-ESRD patients. CONCLUSION: These results suggested that elevated level sST2, as the consequence of renal failure, causes less destruction of liver in HCV infection.

Clinical features of patients with coronavirus disease 2019 from a designated hospital in Beijing, China.

Clinical and laboratory data on patients with coronavirus disease 2019 (COVID-19) in Beijing, China, remain extremely limited. In this study, we summarized the clinical characteristics of patients with COVID-19 from a designated hospital in Beijing. In total, 55 patients with laboratory-confirmed SARS-CoV-2 infection in Beijing 302 Hospital were enrolled in this study. Demographic data, symptoms, comorbidities, laboratory values, treatments, and clinical outcomes were all collected and retrospectively analyzed. A total of 15 (27.3%) patients had severe symptoms, the mean age was 44.0 years (interquartile range [IQR], 34.0-56.0), and the median incubation period was 7.5 days (IQR, 5.0-11.8). A total of 26 (47.3%) patients had exposure history in Wuhan of less than 2 weeks, whereas 20 (36.4%) patients were associated with familial clusters. Also, eighteen (32.7%) patients had underlying comorbidities including hypertension. The most common symptom of illness was fever (45; 81.8%); 51 (92.7%) patients had abnormal findings on chest computed tomography. Laboratory findings showed that neutrophil count, percentage of lymphocyte, percentage of eosinophil, eosinophil count, erythrocyte sedimentation rate, albumin, and serum ferritin are potential risk factors for patients with a poor prognosis. A total of 26 patients (47.3%) were still hospitalized, whereas 29 (52.7%) patients had been discharged. Compared with patients in Wuhan, China, the symptoms of patients in Beijing are relatively mild. Older age, more comorbidities, and more abnormal prominent laboratory markers were associated with a severe condition. On the basis of antiviral drugs, it is observed that antibiotics treatment, appropriate dosage of corticosteroid, and gamma globulin therapy significantly improve patients' outcomes. Early identification and timely medical treatment are important to reduce the severity of patients with COVID-19.

COVID-19 in kidney transplant recipients.

There is minimal information on coronavirus disease 2019 (COVID-19) in immunocompromised individuals. We have studied 10 patients treated at 12 adult care hospitals. Ten kidney transplant recipients tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by polymerase chain reaction, and 9 were admitted. The median age was 57 (interquartile range [IQR] 47-67), 60% were male, 40% Caucasian, and 30% Black/African American. Median time from transplant to COVID-19 testing was 2822 days (IQR 1272-4592). The most common symptom was fever, followed by cough, myalgia, chills, and fatigue. The most common chest X-ray and computed tomography abnormality was multifocal patchy opacities. Three patients had no abnormal findings. Leukopenia was seen in 20% of patients, and allograft function was stable in 50% of patients. Nine patients were on tacrolimus and a mycophenolic antimetabolite, and 70% were on prednisone. Hospitalized patients had their antimetabolite agent stopped. All hospitalized patients received hydroxychloroquine and azithromycin. Three patients died (30%), and 5 (50%) developed acute kidney injury. Kidney transplant recipients infected with COVID-19 should be monitored closely in the setting of lowered immunosuppression. Most individuals required hospitalization and presenting symptoms were similar to those of nontransplant individuals.

[Managing patients in dialysis and with kidney transplant infected with Covid-19].

We are in the midst of a health emergency that is totally new for us all and that requires a concerted effort, especially when it comes to safeguarding patients on hemodialysis, and kidney transplant recipients. Brescia is currently a very active cluster of infections (2918 cases on the 17/03/2020), second only to Bergamo. The way our structure is organised has allowed us to treat nephropathic patients directly within the Nephrology Unit, following of course a great deal of reshuffling; at the moment, we are treating 21 transplanted patients and 17 on hemodialysis. This has led us to adopt a systematic approach to handling this emergency, not only in managing inpatients, but also in researching the new disease. Our approach is mirrored in the guidelines attached to this article, originally intended for internal use only but potentially very useful to our colleagues, as they face the same exact problems. We have also started collecting data on our positive patients with the aim of understanding better the functioning of this disease and how best to manage it. If anyone is interested, we ask you to please get in touch with us, so we can coordinate our efforts.