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Background. Data about vaccine efficacy in solid organ transplant patients are limited. We previously reported our initial observation of a 6.2% immunogenicity rate in kidney transplant recipients (KTRs) after administration of 1 dose of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine. We sought to report our observations of anti-SARS-CoV-2 antibody in KTRs after 2 doses of the SARS-CoV-2 mRNA vaccine. Methods. We identified 105 KTRs who received 2 doses of the Pfizer-BioNTech or Moderna mRNA-1273 vaccine per availability and had anti-SARS-CoV-2 labs obtained at least 2 wk following administration of the second dose. Antibody testing was performed using 3 clinically validated qualitative and semiquantitative assays. Results. KTRs had a 36.2% antibody response rate, whereas an age ≥68 years and a longer time from transplant were factors associated with antibody response. Conclusions. The low antibody response in KTRs may be associated with the immunosuppressive state. More data are needed to evaluate if KTRs may require higher vaccine doses or an additional booster dose to increase their ability to mount an immune response to the SARS-CoV-2 vaccine.

BackgroundSolid organ transplant (SOT) recipients are predicted to have worse COVID-19 outcomes due to their compromised immunity. However, this association remains uncertain because published studies have had small sample sizes and variability in chronic comorbidity adjustment.MethodsIn this retrospective cohort study conducted at a multihospital health system, we compared COVID-19 outcomes and survival up to 60 days following hospital admission in SOT recipients taking baseline immunosuppressants versus hospitalized control patients.ResultsThe study included 4,562 patients who were hospitalized with COVID-19 (108 SOT recipients and 4,454 controls) from 03/2020 to 08/2020. Mortality at 60 days was higher for SOT recipients (17% SOT vs 10% control; unadjusted odds ratio (OR) = 1.74, 95% confidence interval (CI) 1.04-2.91, P = 0.04). We then conducted a 1:5 propensity matched cohort analysis (100 SOT recipients; 500 controls) using age, sex, race, body mass index, hypertension, diabetes, chronic kidney disease, liver disease, admission month, and area deprivation index. Within 28 days of admission, SOT recipients had fewer hospital-free days (median; 17 SOT vs 21 control; OR = 0.64, 95%CI 0.46-0.90, P = 0.01) but had similar ICU-free days (OR = 1.20, 95%CI 0.72-2.00, P = 0.49) and ventilator-free days (OR = 0.91, 95%CI 0.53-1.57, P = 0.75). There was no statistically significant difference in 28-day mortality (9% SOT vs 12% control; OR = 0.76, 95%CI 0.36-1.57, P = 0.46) or 60-day mortality (16% SOT vs 14% control; OR = 1.15, 95%CI 0.64-2.08, P = 0.64).ConclusionsHospitalized SOT recipients appear to need additional days of hospital care but can achieve short-term mortality outcomes from COVID-19 that are similar to non-SOT recipients in a propensity matched cohort study.

Background. Orthostatic hypotension (OH) is a poorly understood complication of simultaneous pancreas–kidney (SPK) transplantation. We sought to determine the incidence, timing, and relationship of OH to rapid glycemic control in the early posttransplant period. Methods. This was a nonrandomized retrospective single-center review of 75 SPK and 19 kidney-alone (KA) recipients with type 1 diabetes (DM). Results. OH occurred in 57 (76%) SPK versus 2 (10%) KA recipients (odds ratio [OR] 61.72, 95% confidence interval [CI], 9.69-393.01; P < 0.001). The median onset of OH was 12 (interquartile range [IQR] 9–18) days posttransplant and resolved in 85% of SPK recipients after a median of 2.5 (IQR 1.2–6.3) months. Among SPK recipients, independent risk factors for OH were a shorter duration of DM (OR 0.85, 95% CI, 0.73-0.98; P = 0.03) and rapid glycemic control in the early posttransplant period (OR 1.13, 95% CI, 1.01-1.27; P = 0.04), as evidenced by a larger percent change in hemoglobin A1c (HbA1c) from transplant to month 3. OH patients had a higher median baseline HbA1c [8.3% (IQR 7.2–10.0) versus 7.1% (IQR 6.8–8.3); P = 0.07], lower median 3-month HbA1c [4.8% (IQR 4.6–5.2) versus 5.2% (IQR 5.0–5.4); P = 0.02], and a larger reduction in HbA1c over time as compared to recipients without OH (P < 0.01). Conclusions. Our results show that OH is more likely to occur following SPK versus KA transplantation and is strongly associated with rapid glucose normalization within the early posttransplant period.

Sporadic Creutzfeldt-Jakob disease (sCJD) has not been previously reported in patients with clotting disorders treated with fractionated plasma products. We report 2 cases of sCJD identified in the United Kingdom in patients with a history of extended treatment for clotting disorders; 1 patient had hemophilia B and the other von Willebrand disease. Both patients had been informed previously that they were at increased risk for variant CJD because of past treatment with fractionated plasma products sourced in the United Kingdom. However, both cases had clinical and investigative features suggestive of sCJD. This diagnosis was confirmed in both cases on neuropathologic and biochemical analysis of the brain. A causal link between the treatment with plasma products and the development of sCJD has not been established, and the occurrence of these cases may simply reflect a chance event in the context of systematic surveillance for CJD in large populations.

A patient with a heterozygous variant of Creutzfeldt-Jakob disease (CJD) with a methionine/valine genotype at codon 129 of the prion protein gene was recently reported. Using an ultrasensitive and specific protein misfolding cyclic amplification–based assay for detecting variant CJD prions in cerebrospinal fluid, we discriminated this heterozygous case of variant CJD from cases of sporadic CJD.

Variably protease-sensitive prionopathy (VPSPr) can occur in persons of all codon 129 genotypes in the human prion protein gene (PRNP) and is characterized by a unique biochemical profile when compared with other human prion diseases. We investigated transmission properties of VPSPr by inoculating transgenic mice expressing human PRNP with brain tissue from 2 persons with the valine-homozygous (VV) and 1 with the heterozygous methionine/valine codon 129 genotype. No clinical signs or vacuolar pathology were observed in any inoculated mice. Small deposits of prion protein accumulated in the brains of inoculated mice after challenge with brain material from VV VPSPr patients. Some of these deposits resembled microplaques that occur in the brains of VPSPr patients. Comparison of these transmission properties with those of sporadic Creutzfeldt-Jakob disease in the same lines of mice indicated that VPSPr has distinct biological properties. Moreover, we established that VPSPr has limited potential for human-to-human transmission.

Background. Acceptance of dual kidney transplantation (DKT) has proven difficult, due to surgical complexity and concerns regarding long-term outcomes. We herein present a standard technique for ipsilateral DKT and compare outcomes to single-kidney transplant (SKT) recipients. Methods. A retrospective single-center comparison of DKT and SKT performed between February 2007 and July 2013. Results. Of 516 deceased donor kidney transplants, 29 were DKT and 487 were SKT. Mean follow-up was 43 ± 67 months. DKT recipients were older and more likely than SKT recipients to receive an extended criteria graft (p

Ganciclovir-resistant cytomegalovirus (CMV) is associated with significant morbidity in solid organ transplant recipients. Management of ganciclovir-resistant CMV may be complicated by nephrotoxicity which is commonly observed with recommended therapies and/or rejection induced by “indirect” viral effects or reduction of immunosuppression. Herein, we report a series of four high serologic risk (donor CMV positive/recipient CMV negative) kidney transplant patients diagnosed with ganciclovir-resistant CMV disease. All patients initially developed “breakthrough” viremia while still receiving valganciclovir prophylaxis after transplant and were later confirmed to exhibit UL97 mutations after failing to eradicate virus on adequate dosages of valganciclovir. The patients were subsequently and successfully treated with reduced-dose (1-2 mg/kg) cidofovir and CMV-hyperimmune globulin, given in 2-week intervals. In addition, all patients exhibited stable renal function after completion of therapy, and none experienced acute rejection. The combination of reduced-dose cidofovir and CMV-hyperimmune globulin appeared to be a safe and effective regimen in patients with mild disease due to ganciclovir-resistant CMV.

The pharmacokinetics of tacrolimus are influenced by many factors, including genetic variability, acute infections, liver dysfunction, and interacting medications, which can result in elevated concentrations. The most appropriate management of acute tacrolimus toxicity has not been defined though case reports exist describing the therapeutic use of enzyme inducers to increase tacrolimus metabolism and decrease concentrations. We are reporting on the utilization of phenytoin to assist in decreasing tacrolimus concentrations in a case series of four solid organ transplant recipients with acute, symptomatic tacrolimus toxicity presenting with elevated serum creatinine, potassium, and tacrolimus trough concentrations greater than 30 ng/mL. All four patients had the potential causative agents stopped or temporarily held and were given 300 to 400 mg/day of phenytoin for two to three days. Within three days of beginning phenytoin, all four patients had a decrease in tacrolimus concentration to less than 15 ng/mL, a return to or near baseline creatinine concentration, and lack of phenytoin-related side effects. Therefore, phenytoin appears to be a safe and potentially beneficial treatment option in patients with symptomatic tacrolimus toxicity.