Initial Experience With SARS-CoV-2-Neutralizing Monoclonal Antibodies in Kidney or Combined Kidney-Pancreas Transplant Recipients.

Background: Antiviral drugs have shown little impact in patient infected with acute respiratory coronavirus 2 (SARS-CoV-2). Especially for immunocompromised persons positive for SARS-CoV-2, novel treatments are warranted. Recently, the U.S. FDA has granted an emergency use authorization (EUA) to two monoclonal antibodies (mAb) targeting the viral spike protein: bamlanivimab and casivirimab and imdevimab. As per the EUA, all SARS-CoV-2 positive organ transplant recipients can receive mAb treatment. Patients and methods: We queried our center's transplant registry to identify SARS-CoV-2 infected recipients treated with single doses of either Bamlanivimab or casivirimab/imdevimab up to May 31, 2021. We analyzed clinical outcomes, renal function and virus-specific antibodies. The co-primary endpoints were hospitalization due to COVID-19 and SARS-CoV-2 RT-PCR negativity. Results: Thirteen patients at a median interval of 55 (IQR, 26-110) months from transplant were treated: 8 with bamlanivimab and 5 with casivirimab/imdevimab. In all, 4/13 (31%) patients were hospitalized at some time, while 11/13 (85%) achieved PCR negativity. 2/4 hospitalized patients received mAb as rescue treatment. Overall mortality was 23%, with one death attributable to transplant-associated lymphoma. All six patients infected with the B 1.1.7 variant were alive at last contact. Conclusion: mAb treatment appears effective when administered early to SARS-CoV-2-infected transplant recipients.

CytoSorb Rescue for COVID-19 Patients With Vasoplegic Shock and Multiple Organ Failure: A Prospective, Open-Label, Randomized Controlled Pilot Study.

OBJECTIVES: To investigate the effect of extracorporeal cytokine reduction by CytoSorb (CytoSorbents, Monmouth Junction, NJ) on COVID-19-associated vasoplegic shock. DESIGN: Prospective, randomized controlled pilot study. SETTING: Eight ICUs at three sites of the tertiary-care university hospital Charité-Universitätsmedizin Berlin. PATIENTS: COVID-19 patients with vasoplegic shock requiring norepinephrine greater than 0.2 µg/kg/min, C-reactive protein greater than 100 mg/L, and indication for hemodialysis. INTERVENTIONS: Randomization of 1:1 to receive CytoSorb for 3-7 days or standard therapy. To account for inadvertent removal of antibiotics, patients in the treatment group received an additional dose at each adsorber change. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was time until resolution of vasoplegic shock, estimated by Cox-regression. Secondary endpoints included mortality, interleukin-6 concentrations, and catecholamine requirements. The study was registered in the German Registry of Clinical Trials (DRKS00021447). From November 2020 to March 2021, 50 patients were enrolled. Twenty-three patients were randomized to receive CytoSorb and 26 patients to receive standard of care. One patient randomized to cytokine adsorption was excluded due to withdrawal of informed consent. Resolution of vasoplegic shock was observed in 13 of 23 patients (56.5%) in the CytoSorb and 12 of 26 patients (46.2%) in the control group after a median of 5 days (interquartile range [IQR], 4-5 d) and 4 days (IQR, 3-5 d). The hazard ratio (HR) for the primary endpoint, adjusted for the predefined variables age, gender, extracorporeal membrane oxygenation-therapy, or time from shock onset to study inclusion was HR, 1.23 (95% CI, 0.54-2.79); p = 0.63. The mortality rate was 78% in the CytoSorb and 73% in the control group (unadjusted HR, 1.17 [95% CI, 0.61-2.23]; p = 0.64). The effects on inflammatory markers, catecholamine requirements, and the type and rates of adverse events were similar between the groups. CONCLUSIONS: In severely ill COVID-19 patients, CytoSorb did not improve resolution of vasoplegic shock or predefined secondary endpoints.

Impact of Early Pancreatic Graft Loss on Outcome after Simultaneous Pancreas-Kidney Transplantation (SPKT)-A Landmark Analysis.

(1) Background: Simultaneous pancreas-kidney transplantation (SPKT) is a standard therapeutic option for patients with diabetes mellitus type I and kidney failure. Early pancreas allograft failure is a complication potentially associated with worse outcomes. (2) Methods: We performed a landmark analysis to assess the impact of early pancreas graft loss within 3 months on mortality and kidney graft survival over 10 years. This retrospective single-center study included 114 adult patients who underwent an SPKT between 2005 and 2018. (3) Results: Pancreas graft survival rate was 85.1% at 3 months. The main causes of early pancreas graft loss were thrombosis (6.1%), necrosis (2.6%), and pancreatitis (2.6%). Early pancreas graft loss was not associated with reduced patient survival (p = 0.168) or major adverse cerebral or cardiovascular events over 10 years (p = 0.741) compared to patients with functioning pancreas, after 3 months. Moreover, kidney graft function (p = 0.494) and survival (p = 0.461) were not significantly influenced by early pancreas graft loss. (4) Conclusion: In this study, using the landmark analysis technique, early pancreas graft loss within 3 months did not significantly impact patient or kidney graft survival over 10 years.

Intensive monitoring of post filter ionized calcium concentrations during CVVHD with regional citrate anticoagulation: A retrospective study.

BACKGROUND: The aim of the present study was to assess the predictive value of post-filter ionized calcium (pfCa) levels for filter-clotting during continuous veno-venous hemodialysis (CVVHD) with regional citrate anticoagulation (RCA). METHODS: Retrospective analysis of a database derived from 6 intensive care units (ICU) at a university hospital. During the 3-year period 1070 patients were treated with RCA-CVVHD with a citrate starting dose of 4 mmol/L blood and a target-range for pfCa of 0.25-0.35 mmol/L. RESULTS: The pfCa concentrations at RCA-CVVHD initiation were within the target range in 69.7% of patients. Within 12 h the fraction of patients with pfCa above target-range decreased significantly from 13.1% to 7.8% (p < .001). There was no significant difference in filter survival between patients with a pfCa initially below, within, or above the target-range (83.7%, 89.5% and 90.4%; p = .228) and no significant correlation between the last pfCa and the incidence of filter clotting (rho 0.018, p = .572 and -0.054, p = .104; respectively). CONCLUSIONS: CVVHD with a citrate starting dose of 4 mmol/L blood resulted in a pfCa within target in the majority of patients. The observation that pfCa was not associated with the incidence of circuit clotting suggests that less frequent measurements of pfCA might be safe.

Assessment of the Kidney Donor Profile Index in a European cohort.

Background: Recently, transplant societies have had to change their allocation policies to counter global organ shortages. However, strategies differ significantly and long-term outcomes and cross-regional applicability remain to be evaluated. Methods: Therefore, we retrospectively analysed the Kidney Donor Profile Index (KDPI) of 987 adult kidney transplants at our centre using data from the Organ Procurement and Transplantation Network (OPTN) as a reference. Results: In our cohort, the median KDPI was 66%, with a higher proportion of >85% KDPI kidneys compared with the US cohort (32.3% versus 9.2%). Among elderly patients (≥65 years of age), 62% received >95% KDPI kidneys, which were primarily allocated within the Eurotransplant Senior Program (ESP). After 10 years, the rate of death-censored graft survival was 70.5%. Recipients of >85% KDPI kidneys were significantly older, demonstrating higher mortality, poorer graft survival and lower estimated glomerular filtration rate. Patients receiving ≥99% KDPI kidneys had a satisfactory 5-year death-censored graft survival (72.9%). The 5-year survival rate of patients living with a functioning graft exceeded the matched OPTN data in the whole KDPI range, despite a higher proportion of elderly recipients. Multivariate analysis revealed KDPI as an independent risk factor for graft loss (hazard ratio 1.14/10%, P < 0.001), although C-statistics of 0.62 indicated limited discriminative ability for individuals. Conclusion: The analysis demonstrated KDPI as a potentially useful tool for donor quality assessment in a European cohort. Most importantly, our analysis revealed acceptable outcomes even for very high KDPI kidneys.

Hyperlactatemia, Lactate Kinetics and Prediction of Citrate Accumulation in Critically Ill Patients Undergoing Continuous Renal Replacement Therapy With Regional Citrate Anticoagulation.

OBJECTIVES: Citrate accumulation is a major complication of regional citrate anticoagulation during continuous renal replacement therapy. We studied the prediction of citrate accumulation during continuous veno-venous hemodialysis with regional citrate anticoagulation by initial lactate concentrations and lactate kinetics. DESIGN: A retrospective follow-up analysis from a cohort of critically ill patients. SETTING: Mixed medical-surgical ICUs at a university hospital. PATIENTS: All adult patients with acute kidney injury and treated with regional citrate anticoagulation-continuous veno-venous hemodialysis during a 3-year period (n = 1,070) were included in this retrospective study and screened for metabolic signs of citrate accumulation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The frequency of citrate accumulation during the first 48 hours of therapy was 2.26%. In patients with initial normal lactate (< 2.2 mmol/L), elevated lactate (≥ 2.2 to < 4 mmol/L), or severe hyperlactatemia (≥ 4 mmol/L), the frequency of citrate accumulation was 0.77%, 2.70%, and 6.33%, respectively. Receiver operating characteristics-area under the curve of initial lactate concentration was 0.789 for the prediction of citrate accumulation. Optimal cutoff from receiver operating characteristics (2.39 mmol/L) showed strong negative prediction (99.28%), but weak positive prediction (5.21%). The slope intercept of lactate kinetics over 48 hours was positive and significantly higher in patients with citrate accumulation compared to those without (+0.2 vs -0.006 mmol/L/hr; p < 0.001). In patients with initial severe hyperlactatemia (≥ 4 mmol/L), the median calculated lactate clearance at 6, 12, and 18 hours was 24.0%, 48.1%, and 59.4% in the nonaccumulation group. These clearance rates were significantly higher at each time-point compared to patients with citrate accumulation (-9.8%, -20.5%, and 2.3%, respectively; p < 0.001 for each time-point). The highest receiver operating characteristics-area under the curve for citrate accumulation was observed for 12-hour values of lactate clearance (area under the curve = 0.839; 95% CI, 0.751-0.927) with an optimal cut-off value of 24.3%. CONCLUSIONS: Risk of citrate accumulation during regional citrate anticoagulation in a well-selected cohort of patients is low even in case of initial severe hyperlactatemia. Lactate kinetics rather than initially elevated lactate concentration should be considered in assessing the risk of citrate accumulation.