SARS-CoV-2 Vaccination in Kidney Transplant Recipients-Stratified Analysis of the Humoral Immune Response.

Kidney transplant recipients are at increased risk of SARS-CoV-2 infection and a more severe course of COVID-19. Methods: We conducted a quantitative serologic testing of antibodies specific for the wild type of SARS-CoV-2 and the Omicron variant of concern before and after a third-dose vaccination, either mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) in a cohort of 103 stable kidney transplant recipients (median [range] age, 58 [22-84] y, 57 men [55.3%]). Results: Third-dose vaccination increased the seroconversion rate from 57.3% to 71.8%. However, despite a marked rise of the antibody concentrations after the booster, 55.4% and 11.6% only formed neutralizing antibodies against the SARS-CoV-2 wild type and Omicron, respectively. Treatment with mycophenolic acid/mycophenolate mofetil (in strata of the dose quartiles), advanced age, and' above all' impaired renal function (eGFR <60 mL/min) adversely influenced the humoral immunity regarding seroconversion and inhibition of the wild type of SARS-CoV-2. Conclusions: Apart from immunosuppressive therapy, the humoral vaccination response is largely affected by nonmodifiable factors in kidney transplant recipients. With the currently leading and clinically easier Omicron variant, this puts into perspective the strategy to significantly enhance the protective efficacy of the available vaccines by reducing or temporarily stopping proliferation inhibitors, not least considering the inherent rejection risk with a possible deterioration of graft function.

Significance of an additional unenhanced scan in computed tomography angiography of patients with suspected acute aortic syndrome.

AIM: To assess potential benefits of an additional unenhanced acquisition in computed tomography angiography (CTA) in patients with suspected acute aortic syndrome (AAS). METHODS: A total of 103 aortic CTA (non-electrocardiography-gated, 128 slices) performed due to suspected AAS were retrospectively evaluated for acute aortic dissection (AAD), intramural hematoma (IMH), or penetrating aortic ulcer (PAU). Spiral CTA protocol consisted of an unenhanced acquisition and an arterial phase. If AAS was detected, a venous phase (delay, 90 s) was added. Images were evaluated for the presence and extent of AAD, IMH, PAU, and related complications. The diagnostic benefit of the unenhanced acquisition was evaluated concerning detection of IMH. RESULTS: Fifty-six (30% women; mean age, 67 years; median, 68 years) of the screened individuals had AAD or IMH. A triphasic CT scan was conducted in 76.8% (n = 43). 56% of the detected AAD were classified as Stanford type A, 44% as Stanford type B. 53.8% of the detected IMH were classified as Stanford type A, 46.2% as Stanford type B. There was no significant difference in the involvement of the ascending aorta between AAD and IMH (P = 1.0) or in the average age between AAD and IMH (P = 0.548), between Stanford type A and Stanford type B in general (P = 0.650) and between Stanford type A and Stanford type B within the entities of AAD and IMH (AAD: P = 0.785; IMH: P = 0.146). Only the unenhanced acquisitions showed a significant density difference between the adjacent lumen and the IMH (P = 0.035). Subadventitial hematoma involving the pulmonary trunk was present in 5 patients (16%) with Stanford A AAD. The difference between the median radiation exposure of a triphasic (2737 mGy*cm) compared to a biphasic CT scan (2135 mGy*cm) was not significant (P = 0.135). CONCLUSION: IMH is a common and difficult to detect entity of AAS. An additional unenhanced acquisition within an aortic CTA protocol facilitates the detection of IMH.

Effects of Dopamine Donor Pretreatment on Graft Survival after Kidney Transplantation: A Randomized Trial.

BACKGROUND AND OBJECTIVES: Donor dopamine improves initial graft function after kidney transplantation due to antioxidant properties. We investigated if a 4 µg/kg per minute continuous dopamine infusion administered after brain-death confirmation affects long-term graft survival and examined the exposure-response relationship with treatment duration. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Five-year follow-up of 487 renal transplant patients from 60 European centers who had participated in the randomized, multicenter trial of dopamine donor pretreatment between 2004 and 2007 (ClinicalTrials.gov identifier: NCT00115115). RESULTS: Follow-up was complete in 99.2%. Graft survival was 72.6% versus 68.7% (P=0.34), and 83.3% versus 80.4% (P=0.42) after death-censoring in treatment and control arms according to trial assignment. Although infusion times varied substantially in the treatment arm (range 0-32.2 hours), duration of the dopamine infusion and all-cause graft failure exhibited an exposure-response relationship (hazard ratio, 0.96; 95% confidence interval [95% CI], 0.92 to 1.00, per hour). Cumulative frequency curves of graft survival and exposure time of the dopamine infusion indicated a maximum response rate at 7.10 hours (95% CI, 6.99 to 7.21), which almost coincided with the optimum infusion time for improvement of early graft function (7.05 hours; 95% CI, 6.92 to 7.18). Taking infusion time of 7.1 hours as threshold in subsequent graft survival analyses indicated a relevant benefit: Overall, 81.5% versus 68.5%; P=0.03; and 90.3% versus 80.2%; P=0.04 after death-censoring. CONCLUSIONS: We failed to show a significant graft survival advantage on intention-to-treat. Dopamine infusion time was very short in a considerable number of donors assigned to treatment. Our finding of a significant, nonlinear exposure-response relationship disclosed a threshold value of the dopamine infusion time that may improve long-term kidney graft survival.

When is contrast-enhanced sonography preferable over conventional ultrasound combined with Doppler imaging in renal transplantation?

Conventional ultrasound in combination with colour Doppler imaging is still the standard diagnostic procedure for patients after renal transplantation. However, while conventional ultrasound in combination with Doppler imaging can diagnose renal artery stenosis and vein thrombosis, it is not possible to display subtle microvascular tissue perfusion, which is crucial for the evaluation of acute and chronic allograft dysfunctions. In contrast, real-time contrast-enhanced sonography (CES) uses gas-filled microbubbles not only to visualize but also to quantify renal blood flow and perfusion even in the small renal arterioles and capillaries. It is an easy to perform and non-invasive imaging technique that augments diagnostic capabilities in patients after renal transplantation. Specifically in the postoperative setting, CES has been shown to be superior to conventional ultrasound in combination with Doppler imaging in uncovering even subtle microvascular disturbances in the allograft perfusion. In addition, quantitative perfusion parameters derived from CES show predictive capability regarding long-term kidney function.