Use and Safety of Remdesivir in Kidney Transplant Recipients With COVID-19.

INTRODUCTION: Remdesivir has demonstrated antiviral activity against coronavirus, shortening the time to recovery in adults hospitalized with moderate/severe COVID-19. Severe adverse events such as acute kidney injury have been reported. Scant data are available on the use and safety of remdesivir in kidney transplant recipients. METHODS: We present a multicenter cohort study of 51 kidney transplant recipients with COVID-19 treated with remdesivir. Outcomes and safety were assessed. RESULTS: Mean age at diagnosis was 60 years, with a median time since kidney transplant of 4.5 years. Mean time since admission to remdesivir was 2 days. Twenty-eight patients (54.9%) required mechanical ventilation (19 noninvasive). Mortality was 18.9% and markedly higher if aged ≥65 years (45% vs. 3.2% in younger patients). Acute kidney injury was present in 27.7% of patients, but was diagnosed in 50% before treatment. No patients required remdesivir discontinuation because of adverse events. We did not find significant hepatoxicity or systemic symptoms resulting from the drug. CONCLUSION: In our cohort of kidney transplant recipients, remdesivir was well tolerated and safe in renal and hepatic toxicity, but randomized trials are needed to assess its efficacy.

The Impact of Age on Mortality in Chronic Haemodialysis Popu-Lation with COVID-19.

Age and chronic kidney disease have been described as mortality risk factors for coronavirus disease 2019 (COVID-19). Currently, an important percentage of patients in haemodialysis are elderly. Herein, we investigated the impact of age on mortality among haemodialysis patients with COVID-19. Data was obtained from the Spanish COVID-19 chronic kidney disease (CKD) Working Group Registry. From 18 March 2020 to 27 August 2020, 930 patients on haemodialysis affected by COVID-19 were included in the Registry. A total of 254 patients were under 65 years old and 676 were 65 years or older (elderly group). Mortality was 25.1% higher (95% CI: 22.2-28.0%) in the elderly as compared to the non-elderly group. Death from COVID-19 was increased 6.2-fold in haemodialysis patients as compared to the mortality in the general population in a similar time frame. In the multivariate Cox regression analysis, age (hazard ratio (HR) 1.59, 95% CI: 1.31-1.93), dyspnea at presentation (HR 1.51, 95% CI: 1.11-2.04), pneumonia (HR 1.74, 95% CI: 1.10-2.73) and admission to hospital (HR 4.00, 95% CI: 1.83-8.70) were identified as independent mortality risk factors in the elderly haemodialysis population. Treatment with glucocorticoids reduced the risk of death (HR 0.68, 95% CI: 0.48-0.96). In conclusion, mortality is dramatically increased in elderly haemodialysis patients with COVID-19. Our results suggest that this high risk population should be prioritized in terms of protection and vaccination.

Predictors of severe COVID-19 in kidney transplant recipients in the different epidemic waves: Analysis of the Spanish Registry.

SARS-CoV-2 infection has produced high mortality in kidney transplant (KT) recipients, especially in the elderly. Until December 2020, 1011 KT with COVID-19 have been prospectively included in the Spanish Registry and followed until recovery or death. In multivariable analysis, age, pneumonia, and KT performed ≤6 months before COVID-19 were predictors of death, whereas gastrointestinal symptoms were protective. Survival analysis showed significant increasing mortality risk in four subgroups according to recipient age and time after KT (age <65 years and posttransplant time >6 months, age <65 and time ≤6, age ≥65 and time >6 and age ≥65 and time ≤6): mortality rates were, respectively, 11.3%, 24.5%, 35.4%, and 54.5% (p < .001). Patients were significantly younger, presented less pneumonia, and received less frequently specific anti-COVID-19 treatment in the second wave (July-December) than in the first one (March-June). Overall mortality was lower in the second wave (15.1 vs. 27.4%, p < .001) but similar in critical patients (66.7% vs. 58.1%, p = .29). The interaction between age and time post-KT should be considered when selecting recipients for transplantation in the COVID-19 pandemic. Advanced age and a recent KT should foster strict protective measures, including vaccination.

Urinary soluble CD163 as a biomarker of disease activity and relapse in antineutrophil cytoplasm antibody-associated glomerulonephritis.

BACKGROUND: Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis is a chronic relapsing and remitting autoimmune disease. Urinary soluble CD163 (usCD163) has been proposed as a biomarker of active renal vasculitis. We aimed to assess the potential usefulness of usCD163 for diagnosing renal relapse in patients with ANCA-associated glomerulonephritis. METHODS: One hundred and fifty-six samples from 47 patients with ANCA-associated glomerulonephritis belonging to two different cohorts (incident and prevalent) and 20 healthy controls were studied. Patients from the incident cohort were prospectively followed up, and usCD163 concentrations were measured every 3 months. Renal relapses were identified and changes in usCD163 concentrations were analysed. RESULTS: Normalized usCD163 concentrations were elevated at disease onset in all patients with active renal vasculitis, with a median concentration of 601 ng/mmol (interquartile range 221-1404 ng/mmol). On the other hand, usCD163 concentrations were undetectable among control patients with renal vasculitis in remission. Except for non-responders, usCD163 concentrations progressively decreased in all patients after treatment. In the presence of vasculitis relapse, there was a consistent increase in usCD163 concentrations, compared with previous values. The area under the receiver-operating characteristic curve of absolute and relative changes in usCD163 concentrations to identify relapse of ANCA-associated glomerulonephritis was 0.96 [95% confidence interval (CI) 0.91-1.00; P = 0.001] and 0.95 (95% CI 0.90-1.00; P = 0.001), respectively. Sensitivity and specificity for a relative increase of 20%, or an absolute increase of 20 ng/mmol, in usCD163 concentrations were 100% for both, and 89.3% and 87.5%, respectively. Urinary sCD163 concentrations significantly correlated with Birmingham Vasculitis Activity Score scores at Month 6 (r = 0.737; P = 0.006) and Month 12 (r = 0.804; P = 0.005). CONCLUSIONS: usCD163 represents an accurate biomarker for the detection of active renal vasculitis and relapse. Its close association with disease activity provides additional information for monitoring treatment response.

Use of tocilizumab in kidney transplant recipients with COVID-19.

Acute respiratory distress syndrome associated with coronavirus infection is related to a cytokine storm with large interleukin-6 (IL-6) release. The IL-6-receptor blocker tocilizumab may control the aberrant host immune response in patients with coronavirus disease 2019 (COVID-19) . In this pandemic, kidney transplant (KT) recipients are a high-risk population for severe infection and showed poor outcomes. We present a multicenter cohort study of 80 KT patients with severe COVID-19 treated with tocilizumab during hospital admission. High mortality rate was identified (32.5%), related with older age (hazard ratio [HR] 3.12 for those older than 60 years, P = .039). IL-6 and other inflammatory markers, including lactic acid dehydrogenase, ferritin, and D-dimer increased early after tocilizumab administration and their values were higher in nonsurvivors. Instead, C-reactive protein (CRP) levels decreased after tocilizumab, and this decrease positively correlated with survival (mean 12.3 mg/L in survivors vs. 33 mg/L in nonsurvivors). Each mg/L of CRP soon after tocilizumab increased the risk of death by 1% (HR 1.01 [confidence interval 1.004-1.024], P = .003). Although patients who died presented with worse respiratory situation at admission, this was not significantly different at tocilizumab administration and did not have an impact on outcome in the multivariate analysis. Tocilizumab may be effective in controlling cytokine storm in COVID-19 but randomized trials are needed.

COVID-19: clinical course and outcomes of 36 hemodialysis patients in Spain.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia emerged in Wuhan, China in December 2019. Unfortunately, there is a lack of evidence about the optimal management of novel coronavirus disease 2019 (COVID-19), and even less is available in patients on maintenance hemodialysis therapy than in the general population. In this retrospective, observational, single-center study, we analyzed the clinical course and outcomes of all maintenance hemodialysis patients hospitalized with COVID-19 from March 12th to April 10th, 2020 as confirmed by real-time polymerase chain reaction. Baseline features, clinical course, laboratory data, and different therapies were compared between survivors and nonsurvivors to identify risk factors associated with mortality. Among the 36 patients, 11 (30.5%) died, and 7 were able to be discharged within the observation period. Clinical and radiological evolution during the first week of admission were predictive of mortality. Among the 36 patients, 18 had worsening of their clinical status, as defined by severe hypoxia with oxygen therapy requirements greater than 4 L/min and radiological worsening. Significantly, 11 of those 18 patients (61.1%) died. None of the classical cardiovascular risk factors in the general population were associated with higher mortality. Compared to survivors, nonsurvivors had significantly longer dialysis vintage, increased lactate dehydrogenase (490 U/l ± 120 U/l vs. 281 U/l ± 151 U/l, P = 0.008) and C-reactive protein levels (18.3 mg/dl ± 13.7 mg/dl vs. 8.1 mg/dl ± 8.1 mg/dl, P = 0.021), and a lower lymphocyte count (0.38 ×103/µl ± 0.14 ×103/µl vs. 0.76 ×103/µl ± 0.48 ×103/µl, P = 0.04) 1 week after clinical onset. Thus, the mortality among hospitalized hemodialysis patients diagnosed with COVID-19 is high. Certain laboratory tests can be used to predict a worsening clinical course.

The new marker YKL-40, a molecule related to inflammation, is associated with cardiovascular events in stable haemodialysis patients.

BACKGROUND: YKL-40 is a glycoprotein associated with inflammatory conditions, including atherosclerosis and endothelial dysfunction. The objective was to analyse serum YKL-40 levels in a haemodialysis population and explore their association with dialysis dosing measures, inflammation, body composition and development of cardiovascular (CV) events. METHODS: We performed a prospective study of 78 chronic haemodialysis patients enrolled in 2013 and followed up until 2018. At baseline, serum YKL-40, inflammatory and nutrition markers and body composition were assessed. During a median follow-up of 43 (interquartile range 24-66) months, CV events were recorded. RESULTS: The mean age of patients was 62 ± 16 years and 66% were men. The mean YKL-40 was 207 ± 106 ng/dL. Higher YKL-40 levels were associated with lower Kt/V urea, convective volume, serum albumin and prealbumin and with higher troponin T. During follow-up, 50% developed CV events. Cox analysis showed an association between CV events and YKL-40, diabetes, hypertension, C-reactive protein, lower prealbumin, ß2-microglobulin, glycosylated haemoglobin and troponin T values. The multivariate Cox analysis confirmed an independent association between CV events and YKL-40 {hazard ratio [HR] 1.067 [95% confidence interval (CI) 1.009-1.211]; P: 0.042}, troponin T [HR 1.037 (95% CI 1.009-1.683); P: 0.007], lower prealbumin [HR 0.827 (95% CI 0.224-0.988); P: 0.009] and diabetes [HR 2.103 (95% CI 1.554-3.172); P: 0.008]. Kaplan-Meier confirmed the association between CV events and YKL-40 (log rank 7.28; P = 0.007). CONCLUSIONS: YKL-40 is associated with CV events in haemodialysis patients. Higher dialysis dose and convective volume are associated with lower serum YKL-40 levels.

Enfermedad invasiva por Streptococcus pyogenes: cambios en la incidencia y factores pronósticos / Invasive disease due to Streptococcus pyogenes: Changes in incidence and prognostic factors

Introducción: La enfermedad invasiva por Streptococcus del grupo A (EISGA) es una infección grave en niños, habiéndose comunicado un aumento de incidencia en los últimos años. Objetivo: Evaluar las características y evolución de la EISGA en niños y determinar cambios en la incidencia o gravedad. Material y métodos: Estudio retrospectivo de niños ≤ 16 años evaluados en un hospital terciario pediátrico de Madrid y diagnosticados de EISGA (junio 2005-julio 2013). Se analizó la epidemiología, clínica, microbiología y tratamiento, evaluándose cambios a lo largo del periodo estudiado y parámetros asociados a gravedad. Resultados: Se incluyeron 55 niños con EISGA; 33 (60%) mujeres, con una mediana de 48,5 (20,5-88,9) meses. Los síndromes clínicos más frecuentes fueron celulitis/absceso subcutáneo (21,8%), absceso ORL (20%), neumonía (16,4%), infección osteoarticular (16,4%) y mastoiditis (12,7%). La incidencia de EISGA (casos/105 urgencias/año) aumentó de 5,6 (4,2-7,2) entre junio 2005-mayo 2009 a 18,9 (15,1-26) entre junio 2009-mayo 2013; p = 0,057. El 63,6% (n = 35) y el 18,2% (n = 10) de los pacientes precisaron cirugía e ingreso en UCIP, respectivamente. Los niños en UCIP fueron más pequeños (26,5 vs. 52,6 meses; p = 0,116), presentaron proteína C reactiva más elevada (24,5 vs. 10,7 mg/dl; p < 0,001) y mayor frecuencia de neumonía (60 vs. 7%; p < 0,001). En el análisis multivariante solo la proteína C reactiva fue factor de riesgo de ingreso en UCIP (OR: 1,14 [1,004-1,286]; p = 0,04). No hubo secuelas. Conclusiones: Se objetivó un aumento de la incidencia de EISGA en niños en nuestro medio, siendo la menor edad, la presencia de neumonía y la proteína C reactiva elevada los parámetros asociados a gravedad en esta serie

Introduction: Invasive group A streptococcal disease (iGASD) is a serious infection in children. Several studies have shown an increased incidence in the past years. Objective: To evaluate the characteristics and outcome of iGASD in children, and to determine changes in incidence or severity. Material and methods: A retrospective study was conducted on children ≤ 16 years evaluated in a tertiary paediatric hospital in Madrid, and diagnosed with iGASD (June 2005-July 2013). An analysis was made of the demographics, symptomatology, microbiology, and treatment. The changes throughout the period studied were evaluated, as well as parameters associated with disease severity. Results: The study included a total of 55 children with iGASD, with 33 (60%) females, and a median age of 48.5 (20.5-88.9) months. The most frequent clinical syndromes were cellulitis/subcutaneous abscess (21.8%), ENT abscess (20%), pneumonia (16.4%), osteoarticular infection (16.4%), and mastoiditis (12.7%). The incidence of iGASD (cases/105 emergencies/year) increased from 5.6 (4.2-7.2) between June 2005-May 2009 to 18.9 (15.1-26) between June 2009-May 2013; P = .057. Surgery and admission to PICU was required by 35 (63.6%) and 10 (18.2%) patients, respectively. Children in PICU were younger (26.5 vs 52.6 months, P = .116), had a higher C-reactive protein (24.5 vs 10.7 mg/dl, P < .001) and higher frequency of pneumonia (60 vs 7%, P < .001). In the multivariate analysis, only C-reactive protein was a risk factor for admission to PICU (OR: 1.14 [1.004-1.286], P = .04). There were no sequelae. Conclusions: An increased incidence of iGASD was observed in the children in this study. Lower age, pneumonia, and higher C-reactive protein were associated with disease severity in this series

Obesity and chronic kidney disease progression-the role of a new adipocytokine: C1q/tumour necrosis factor-related protein-1.

BACKGROUND: Obesity is a risk factor for incident chronic kidney disease (CKD) in the general population. C1q/tumour necrosis factor-related protein 1 (CTRP1) is a new adipokine with multiple vascular and metabolic effects and may modulate the association between obesity and vascular diseases. The aim of the study is to explore potential links between obesity, CTRP1 levels and CKD progression. METHODS: Patients with Stages 3 and 4 CKD without previous cardiovascular events were enrolled and divided into two groups according to body mass index (BMI). Demographic, clinical and analytical data and CTRP1 levels were collected at baseline. During follow-up, renal events [defined as dialysis initiation, serum creatinine doubling or a 50% decrease in estimated glomerular filtration rate (Modification of Diet in Renal Disease)] were registered. RESULTS: A total of 71 patients with CKD were divided into two groups: 25 obese (BMI >30 kg/m2) and 46 non-obese. CTRP1 in plasma at baseline was higher in obese patients [median (interquartile range) 360 (148) versus 288 (188) ng/mL, P = 0.041]. No significant association was found between CTRP1 levels and CKD stage, presence of diabetes, aldosterone and renin levels, or blood pressure. Obese patients had higher systolic blood pressure (P = 0.018) and higher high-sensitivity C-reactive protein (P = 0.019) and uric acid (P = 0.003) levels, without significant differences in the percentage of diabetic patients or albuminuria. During a mean follow-up of 65 months, 14 patients had a renal event. Patients with CTRP1 in the lowest tertile had more renal events, both in the overall sample (log rank: 5.810, P = 0.016) and among obese patients (log rank: 5.405, P = 0.020). Higher CTRP1 levels were associated with slower renal progression (hazard ratio 0.992, 95% confidence interval 0.986-0.998; P = 0.001) in a model adjusted for obesity, aspirin, albuminuria and renal function. CONCLUSIONS: CTRP1 levels are higher in obese than in non-obese patients with CKD. High CTRP1 levels may have a renal protective role since they were associated with slower kidney disease progression. Interventional studies are needed to explore this hypothesis.

[Invasive disease due to Streptococcus pyogenes: Changes in incidence and prognostic factors]. / Enfermedad invasiva por Streptococcus pyogenes: cambios en la incidencia y factores pronósticos.

INTRODUCTION: Invasive group A streptococcal disease (iGASD) is a serious infection in children. Several studies have shown an increased incidence in the past years. OBJECTIVE: To evaluate the characteristics and outcome of iGASD in children, and to determine changes in incidence or severity. MATERIAL AND METHODS: A retrospective study was conducted on children≤16 years evaluated in a tertiary paediatric hospital in Madrid, and diagnosed with iGASD (June 2005-July 2013). An analysis was made of the demographics, symptomatology, microbiology, and treatment. The changes throughout the period studied were evaluated, as well as parameters associated with disease severity. RESULTS: The study included a total of 55 children with iGASD, with 33 (60%) females, and a median age of 48.5 (20.5-88.9) months. The most frequent clinical syndromes were cellulitis/subcutaneous abscess (21.8%), ENT abscess (20%), pneumonia (16.4%), osteoarticular infection (16.4%), and mastoiditis (12.7%). The incidence of iGASD (cases/105 emergencies/year) increased from 5.6 (4.2-7.2) between June 2005-May 2009 to 18.9 (15.1-26) between June 2009-May 2013; P=.057. Surgery and admission to PICU was required by 35 (63.6%) and 10 (18.2%) patients, respectively. Children in PICU were younger (26.5 vs 52.6 months, P=.116), had a higher C-reactive protein (24.5 vs 10.7mg/dl, P<.001) and higher frequency of pneumonia (60 vs 7%, P<.001). In the multivariate analysis, only C-reactive protein was a risk factor for admission to PICU (OR: 1.14 [1.004-1.286], P=.04). There were no sequelae. CONCLUSIONS: An increased incidence of iGASD was observed in the children in this study. Lower age, pneumonia, and higher C-reactive protein were associated with disease severity in this series.