Generation of potentially inhibitory autoantibodies to ADAMTS13 in coronavirus disease 2019.

It has recently been shown that von Willebrand factor (VWF) multimers contribute to immunothrombosis in Coronavirus disease 2019 (COVID-19). Since COVID-19 is associated with an increased risk of autoreactivity, the present study investigates, whether the generation of autoantibodies to ADAMTS13 contributes to this finding. In this observational prospective controlled multicenter study blood samples and clinical data of patients hospitalized for COVID-19 were collected from April to November 2020. The study included 156 individuals with 90 patients having confirmed COVID-19 of mild to critical severity. 30 healthy individuals and 36 critically ill ICU patients without COVID-19 served as controls. ADAMTS13 antibodies occurred in 31 (34.4%) COVID-19 patients. Antibodies occurred more often in critically ill COVID-19 patients (55.9%) than non-COVID-19 ICU patients and healthy controls (5.6% and 6.7%; p < 0.001), respectively. Generation of ADAMTS13 antibodies in COVID-19 was associated with lower ADAMTS13 activity (56.5%, interquartile range (IQR) 21.25 vs. 71.5%, IQR 24.25, p = 0.0041), increased disease severity (severe or critical in 90% vs. 62.3%, p = 0.019), and a trend to higher mortality (35.5% vs. 18.6%, p = 0.077). Median time to antibody development was 11 days after first positive SARS-CoV-2-PCR specimen. Gel analysis of VWF multimers resembled the constellation in patients with TTP. The present study demonstrates for the first time, that generation of ADAMTS13 antibodies is frequent in COVID-19, associated with lower ADAMTS13 activity and increased risk of an adverse disease course. These findings provide a rationale to include ADAMTS13 antibodies in the diagnostic workup of SARS-CoV-2 infections.

The Role of Innate Immune Cells in the Prediction of Early Renal Allograft Injury Following Kidney Transplantation.

Background: Despite recent advances and refinements in perioperative management of kidney transplantation (KT), early renal graft injury (eRGI) remains a critical problem with serious impairment of graft function as well as short- and long-term outcome. Serial monitoring of peripheral blood innate immune cells might be a useful tool in predicting post-transplant eRGI and graft outcome after KT. Methods: In this prospective study, medical data of 50 consecutive patients undergoing KT at the University Hospital of Leipzig were analyzed starting at the day of KT until day 10 after the transplantation. The main outcome parameter was the occurrence of eRGI and other outcome parameters associated with graft function/outcome. eRGI was defined as graft-related complications and clinical signs of renal IRI (ischemia reperfusion injury), such as acute tubular necrosis (ATN), delayed graft function (DGF), initial nonfunction (INF) and graft rejection within 3 months following KT. Typical innate immune cells including neutrophils, natural killer (NK) cells, monocytes, basophils and dendritic cells (myeloid, plasmacytoid) were measured in all patients in peripheral blood at day 0, 1, 3, 7 and 10 after the transplantation. Receiver operating characteristics (ROC) curves were performed to assess their predictive value for eRGI. Cutoff levels were calculated with the Youden index. Significant diagnostic immunological cutoffs and other prognostic clinical factors were tested in a multivariate logistic regression model. Results: Of the 50 included patients, 23 patients developed eRGI. Mean levels of neutrophils and monocytes were significantly higher on most days in the eRGI group compared to the non-eRGI group after transplantation, whereas a significant decrease in NK cell count, basophil levels and DC counts could be found between baseline and postoperative course. ROC analysis indicated that monocytes levels on POD 7 (AUC: 0.91) and NK cell levels on POD 7 (AUC: 0.92) were highly predictive for eRGI after KT. Multivariable analysis identified recipient age (OR 1.53 (95% CI: 1.003−2.350), p = 0.040), recipient body mass index > 25 kg/m2 (OR 5.6 (95% CI: 1.36−23.9), p = 0.015), recipient cardiovascular disease (OR 8.17 (95% CI: 1.28−52.16), p = 0.026), donor age (OR 1.068 (95% CI: 1.011−1.128), p = 0.027), <0.010), deceased-donor transplantation (OR 2.18 (95% CI: 1.091−4.112), p = 0.027) and cold ischemia time (CIT) of the renal graft (OR 1.005 (95% CI: 1.001−1.01), p = 0.019) as clinically relevant prognostic factors associated with increased eRGI following KT. Further, neutrophils > 9.4 × 103/µL on POD 7 (OR 16.1 (95% CI: 1.31−195.6), p = 0.031), monocytes > 1150 cells/ul on POD 7 (OR 7.81 (95% CI: 1.97−63.18), p = 0.048), NK cells < 125 cells/µL on POD 3 (OR 6.97 (95% CI: 3.81−12.7), p < 0.01), basophils < 18.1 cells/µL on POD 10 (OR 3.45 (95% CI: 1.37−12.3), p = 0.02) and mDC < 4.7 cells/µL on POD 7 (OR 11.68 (95% CI: 1.85−73.4), p < 0.01) were revealed as independent biochemical predictive variables for eRGI after KT. Conclusions: We show that the combined measurement of immunological innate variables (NK cells and monocytes on POD 7) and specific clinical factors such as prolonged CIT, increased donor and recipient age and morbidity together with deceased-donor transplantation were significant and specific predictors of eRGI following KT. We suggest that intensified monitoring of these parameters might be a helpful clinical tool in identifying patients at a higher risk of postoperative complication after KT and may therefore help to detect and­by diligent clinical management­even prevent deteriorated outcome due to IRI and eRGI after KT.

In vitro and in vivo evidence that the switch from calcineurin to mTOR inhibitors may be a strategy for immunosuppression in Epstein-Barr virus-associated post-transplant lymphoproliferative disorder.

Post-transplant lymphoproliferative disorder is a life-threatening complication of immunosuppression following transplantation mediated by failure of T cells to control Epstein-Barr virus (EBV)-infected and transformed B cells. Typically, a modification or reduction of immunosuppression is recommended, but insufficiently defined thus far. In order to help delineate this, we characterized EBV-antigen-specific T cells and lymphoblastoid cell lines from healthy donors and in patients with a kidney transplant in the absence or presence of the standard immunosuppressants tacrolimus, cyclosporin A, prednisolone, rapamycin, and mycophenolic acid. Phenotypes of lymphoblastoid cell-lines and T cells, T cell-receptor-repertoire diversity, and T-cell reactivity upon co-culture with autologous lymphoblastoid cell lines were analyzed. Rapamycin and mycophenolic acid inhibited lymphoblastoid cell-line proliferation. T cells treated with prednisolone and rapamycin showed nearly normal cytokine production. Proliferation and the viability of T cells were decreased by mycophenolic acid, while tacrolimus and cyclosporin A were strong suppressors of T-cell function including their killing activity. Overall, our study provides a basis for the clinical decision for the modification and reduction of immunosuppression and adds information to the complex balance of maintaining anti-viral immunity while preventing acute rejection. Thus, an immunosuppressive regime based on mTOR inhibition and reduced or withdrawn calcineurin inhibitors could be a promising strategy for patients with increased risk of or manifested EBV-associated post-transplant lymphoproliferative disorder.

Effect of Nephrectomy After Allograft Failure on Inflammation, Erythropoiesis, Donor-Specific Antibodies, and Outcome of Re-Transplantation.

BACKGROUND Morbidity and mortality rates are high for patients returning to dialysis after renal graft failure. Keeping failed kidney transplants in situ with concomitant minimization or withdrawal of immunosuppression is standard of care in many transplant centers. It is unclear, however, whether the resulting allospecific immune response can cause a microinflammatory milieu. The present work investigated the impact of allograft nephrectomy on systemic inflammation, erythropoiesis, and donor-specific antibodies (DSA). MATERIAL AND METHODS We performed a retrospective analysis evaluating C-reactive protein (CRP), hemoglobin concentration (Hb), ferritin, iron substitution dosages, erythropoietin dosages, and DSA in 92 transplant recipients with allograft failure, of whom 49 did not (Group A) and 43 did undergo transplant nephrectomy (Group B). Blood samples and clinical data were obtained 3-6 months after returning to dialysis. We additionally assessed outcome of kidney re-transplantation in a 10-year follow-up. RESULTS There was no significant difference in Hb concentrations, ferritin concentrations, CRP concentrations, iron, and EPO substitution dosages between the 2 groups. Patients undergoing nephrectomy had a significantly higher prevalence of DSA (65.1% vs 38.8%, P<0.0001). In the 10-year follow-up, 3 patients (12%) of Group B and none in Group A had allograft failure after primary successful re-transplantation. CONCLUSIONS Keeping a kidney graft in situ after returning to dialysis did not lead to an increase in microinflammation. Although DSA develops in more than 50% of patients after an allograft nephrectomy, the outcome of a renal re-transplantation seems to be unaffected. Thus, both strategies are feasible options in kidney transplant recipients after return to dialysis.

Minimally invasive video-assisted parathyroidectomy (MIVAP) versus conventional parathyroidectomy for renal hyperparathyroidism: a retrospective multicenter study.

To compare minimally invasive video-assisted parathyroidectomy (MIVAP) versus conventional surgery for renal hyperparathyroidism (rHPT). Between 2006 and 2020, 53 patients underwent MIVAP and 182 underwent conventional parathyroidectomy for rHPT at the Kliniken Essen-Mitte and Knappschaftskrankenhaus Bochum, respectively. Two propensity score-matched groups were retrospectively analyzed: the MIVAP group (VG; n = 53) and the conventional group (CG; n = 53). To assess long-term results, the patients were questioned prospectively (VG; n = 17, and CG; n = 26). The VG had a smaller incision (2.8 vs. 4.8 cm), shorter operation duration (81.0 vs. 13.9 min), and shorter duration of stay (2.4 vs. 5.7 days) (p < 0.0001) but a smaller drop in parathyroid hormone (PTH) postoperatively (81.3 vs. 85.5%. p = 0.022) than the CG. The conversion rate was 9.4% (n = 5). The VG had better Patient Scar Assessment Scale (PSAS) scores (10.8 vs. 11.7 p = 0.001) but worse SF-12 health survey scores (38.7 vs. 45.8 for physical health and 46.7 vs. 53.4 for mental health) (p < 0.0001). The PTH level at follow-up was higher in the VG (162.7 vs. 59.1 ng/l, p < 0.0001). There were no differences in morbidity, number of removed parathyroid glands, disease persistence, late rHPT relapse and need for repeat surgery between groups. MIVAP was superior to conventional parathyroidectomy regarding aesthetic outcomes and cost effectiveness. Conventional surgery showed better control of PTH levels and health scores on follow-up than MIVAP, without any impact on rHPT relapse and need for repeat surgery.Trail registration number and date of registration: DRKS00022545 on 14.12.2020.

Impact of weather changes on hospital admissions for hypertension.

Blood pressure (BP) shows a seasonal variation with higher levels at lower temperatures. Many hypertensives, however, report on BP disturbances rather in association with acutely changing weather conditions than with absolute temperatures. To date, the impact of changing meteorological parameters on hypertensive episodes remains elusive. We performed a retrospective time series regression analysis on 203,703 patients in three hospitals in Germany between 2010 and 2018, of whom 7362 patients were admitted for hypertensive disease. Numbers of daily admissions for hypertension were associated with metereological data obtained from three nearby weather stations. Data comprised temperature (mean, maximal, minimal and range within 24 h), athmospheric pressure, and precipitation. Changes of these parameters were calculated over a two and three day period. There was an inverse correlation between maximal daily temperature and the number of admissions for hypertensive disease, which remained significant both after adjustment for seasonality and week day in a spline model and in a constrained distributed lag model. A decrease of maximal temperature by 5 °C was associated with a 3% increase of risk for admission for hypertension and vice versa. There were no significant effects of precipitation and athmospheric pressure on the number of admissions. With regard to all observed metereological parameters, neither the change within two, nor within three days was consistently associated with the number of daily admissions. High temperatures are associated with lower numbers of hypertensive episodes requiring hospital admission. In contrast to the subjective perception of many hypertensive patients, however, acutely changing weather conditions are not associated with a higher risk of hypertensive emergency.

Predictors of impaired SARS-CoV-2 immunity in healthcare workers after vaccination with BNT162b2.

Healthcare workers are at substantially increased risk for infection with SARS-CoV-2. Successful vaccination constitutes a crucial prerequisite to protect this group during the pandemic. Since post vaccination antibody monitoring is not standard of care in all healthcare institutions, data on risk factors of impaired vaccine induced immune response are urgently required. Moreover, there are no data on cellular immune responses in humoral low responders so far. Anti-SARS-CoV-2 spike IgG was assessed after vaccination with BNT162b2 in 1386 employees of three hospitals of a German healthcare provider. Concentrations were compared to those of 45 convalescent employees. Vaccine-induced cellular immunity was measured in employees with reduced humoral response by assessment of frequencies of SARS-CoV-2-reactive CD4+ and CD8+ T cell. Anti-SARS-CoV-2 spike IgG were detected in 99.9% of 1386 healthcare workers after completed vaccination. The median antibody concentration was significantly higher after vaccination than after infection with SARS-CoV-2 (p = 0.0001). 10 subjects (0.7%) generated an IgG concentration < 100 IU/ml, and only two persons (0.1%, solid organ recipients) did not produce detectable antibodies at all. T cell responses of those subjects with submaximal or lacking humoral response were comparable to employees with maximal antibody titers. 50% of those individuals with impaired or lacking humoral immune response were on immunosuppression. Vaccination to SARS-CoV-2 with BNT162b2 is very effective in healthcare workers yielding a seroconversion rate of 99.9%. Immunosuppression is the most important risk factor of an impaired immune response. There was no case of vaccination failure without immunosuppression. Thus, post vaccination antibody monitoring is highly recommendable in those employees with immunosuppression.

Effect of plasma exchange on COVID-19 associated excess of von Willebrand factor and inflammation in critically ill patients.

Ubiquitous microthromboses in the pulmonary vasculature play a crucial role in the pathogenesis of COVID-19 associated acute respiratory distress syndrome (ARDS). Excess of Willebrand factor (vWf) with intravascular multimer formation was identified as a key driver of this finding. Plasma exchange (PLEX) might be a therapeutic option to restore the disbalance between vWf and ADAMTS13. We report the effects of PLEX on vWf, ADAMTS13, inflammatory cytokines and parameters of ventilation. We investigated 25 patients, who were on mechanical ventilation for COVID-19 pneumonia with ARDS at two German university hospitals. All patients received PLEX as an ultima ratio measure for refractory ARDS. VWf antigen (vWf:Ag), ADAMTS13 activity, a cytokine panel mirroring the inflammatory situation and clinical parameters were assessed before and after three to six PLEX therapies with fresh frozen plasma. Before the PLEX sequence there was an excessive release of vWf:Ag (425.4 ± 167.5%) and mildly reduced ADAMTS13 activity (49.7 ± 23.3%). After the PLEX series, there was a significant increase of ADAMTS13 activity to 62.4 ± 17.7% (p = 0.029) and a significant decrease of vWf:Ag to 336.1 ± 138.2% (p = 0.041) resulting in a 63% improvement of the ADAMT13/vWf:Ag ratio from 14.5 ± 10.0 to 23.7 ± 14.6, p = 0.024. Comparison of parameters before and after individual PLEX sessions (n = 35) revealed a mean reduction of vWf from 387.8 ± 165.1 to 213.2 ± 62.3% (p = 0.001) and an increase of ADAMTS13 activity from 60.4 ± 20.1 to 70.5 ± 14.0% (p = 0.001). Parallelly, monocyte chemotactic protein-1 and interleukin-18 decreased significantly (p = 0.034 each). Along the PLEX sequence lactate dehydrogenase (p = 0.001), C-reactive protein (p = 0.001), and positive end expiratory pressure (p = 0.01) significantly decreased accompanied by an improvement of Horovitz index (p = 0.001). PLEX restores the disbalance between ADAMTS13 and vWf:Ag, a driver of immunothrombosis. Moreover, it reduces the inflammatory state and is associated with a benefit of ventilation parameters. These findings render a further rationale to regard PLEX as a therapeutic option in severe COVID-19.

Low-density lipoprotein apheresis is associated with removal of SARS-CoV-2 antibodies.

BACKGROUND: Low-density lipoprotein apheresis is not specific to lipoproteins but removes immunoglobulins as well. It remains elusive, whether protective SARS-CoV-2 antibodies after vaccination from COVID-19 are eliminated as well. METHODS: A cross-sectional case-control study on 55 patients undergoing weekly lipoprotein apheresis and 21 patients with comparable comorbidities and epidemiology not undergoing apheresis. SARS-CoV-2 IgG was assessed in all patients prior to apheresis and in 38 patients both before and after apheresis. RESULTS: SARS-CoV-2 IgG concentrations before a session of lipoprotein apheresis were comparable to control patients not undergoing apheresis(1727 IU/ml, IQR 365-2500) vs. 1652 IU/ml,(IQR408.8-2500), p = 0.78). SARS-CoV-2 IgG concentrations were reduced by lipoprotein apheresis from 1656 IU/ml(IQR 540.5-2500) prior to 1305 IU/ml (IQR 449-2500) afterwards(p < 0.0001). CONCLUSION: Lipoprotein apheresis removes SARS-CoV-2 IgG. The average elimination rate was 21.2%. In the present population of patients undergoing apheresis once weekly, however, the elimination did not lead to inferior concentrations compared to patients not undergoing lipoprotein apheresis.

Challenges Associated with Pancreas and Kidney Retransplantation-A Retrospective Analysis.

Simultaneous pancreas and kidney transplantation (SPK) is an accepted treatment for diabetic patients with renal failure, and is associated with increased survival and quality of life for recipients. There are only a few publications on the outcomes of simultaneous pancreas-kidney retransplantation (Re-SPK) after previous SPK and the loss of function of both grafts. A total of 55 patients with type 1 diabetes mellitus underwent pancreas retransplantation at our center between January 1994 and March 2021. Twenty-four of these patients underwent Re-SPK after a previous SPK. All 24 operations were technically feasible. Patient survival rate after 3 months, 1 year, and 5 years was 79.2%, 75%, and 66.7%, respectively. The causes of death were septic arterial hemorrhage (n = 3), septic multiorgan failure (n = 2), and was unknown in one patient. Pancreas and kidney graft function after 3 months, 1 year, and 5 years were 70.8% and 66.7%, 66.7% and 62.5%, and 45.8% and 54.2%, respectively. Relaparotomy was performed in 13 out of 24 (54.2%) patients. The results of our study show that Re-SPK, after previously performed SPK, is a technical and immunological challenge, associated with a significantly increased mortality and complication rate; therefore, the indication for Re-SPK should be very strict. Careful preoperative diagnosis is indispensable.

Impact of Histidine-Tryptophan-Ketoglutarate Versus University of Wisconsin Solution on the Outcome of Pancreas Transplant With Cold Ischemic Time ≥12 Hours: A Retrospective Study.

OBJECTIVES: Histidine-tryptophan-ketoglutarate and University of Wisconsin solutions are currently used for pancreas graft preservation. Our hypothesis was whether the use of histidine-tryptophan-ketoglutarate solution is associated with worse pancreas graft survival than University of Wisconsin solution, in general and after prolonged cold ischemic time of ≥12 hours. MATERIALS AND METHODS: This retrospective study investigated the impact of static cold storage in histidine-tryptophan-ketoglutarate (n = 133) versus University of Wisconsin (n = 107) solution on outcomes of 240 pancreas transplant procedures. Patient and graft survival rates were compared after 1, 3, and 5 years in both groups. Serum lipase, amylase, and C-reactive protein levels and incidence of surgical complications were evaluated at postoperative week 1. A subgroup analysis of 96 grafts (52 with histidine-tryptophanketoglutarate/44 with University of Wisconsin) with pancreas graft cold ischemic time ≥12 hours was also performed. RESULTS: At mean follow-up of 75.2 ± 9.9 months, both groups demonstrated comparable short- and long-term patient survival. Overall, pancreas graft survival was slightly better in the histidine-tryptophan-ketoglutarate group (Kaplan-Meier analysis, log-rank P = .013). However, the subgroup analysis of grafts with cold ischemic time ≥12 hours showed slightly better pancreatic graft survival in the University of Wisconsin group, although not significantly (log-rank P = .95). Serum lipase and C-reactive protein levels at postoperative week 1 were higher in the histidinetryptophan-ketoglutarate group. Surgical complications were comparable. Multivariable Cox regression analysis identified neither solution as a risk factor affecting patient and graft survival. CONCLUSIONS: Although a direct comparison between histidine-tryptophan-ketoglutarate and University of Wisconsin showed better pancreas graft survival with histidine-tryptophan-ketoglutarate, the multivariable analysis showed that the perfusion solution does not significantly influence patient and graft survival. However, in the analysis of transplants with cold ischemic time ≥12 hours, pancreas graft survival was slightly better in the University of Wisconsin group, although not significantly.

Feasibility of non-invasive measurement of central blood pressure and arterial stiffness in shock.

BACKGROUND: Patients in haemodynamic shock are in need for an intensive care treatment. Invasive haemodynamic monitoring is state of the art for these patients. However, evolved, non-invasive blood pressure monitoring devices offer advanced functions like the assessment of central blood pressure and arterial stiffness. We analysed the feasibility of two oscillometric blood pressure devices in patients with shock. METHODS: We performed a monocentre prospective study, enrolling 57 patients admitted to the intensive care unit (ICU), due to septic and/or cardiogenic shock. We assessed invasive and non-invasive peripheral and central blood pressure <24 hours and 48 hours after admission on the ICU. Additional haemodynamic parameters such as pulse wave velocity (PWV), augmentation pressure and augmentation index were obtained through Mobil-o-Graph PWA (IEM) and SphygmoCor XCEL (AtCor Medical). RESULTS: A complete haemodynamic assessment was successful in all patients (48) with the Mobil-o-Graph 24 hours PWA and in 29 patients with the SphygmoCor XCEL (P = .001), when cases of death or device malfunction were excluded. Reasons for failure were severe peripheral artery disease, haemodynamic instability, oedema and agitation. Invasive blood pressure showed a sufficient correlation with both devices; however, large differences between invasive and non-invasive techniques were recorded in Bland-Altmann analysis (P < .05 for all parameters). PWV differed between the two devices. CONCLUSION: Non-invasive peripheral blood pressure measurement remains a rescue technique. However, non-invasive assessment of arterial stiffness and central blood pressure is possible in patients with septic or cardiogenic shock. Further studies are required to assess their clinical significance for patients in shock.

Biopsy findings after detection of de novo donor-specific antibodies in renal transplant recipients: a single center experience.

BACKGROUND: De novo donor-specific antibodies (DSA) are associated with an increased risk of antibody-mediated rejection and a substantial reduction of allograft survival. We hypothesized that detection of DSA should prompt a biopsy even in the absence of proteinuria and loss of estimated glomerular filtration rate (eGFR). However, data on a population without proteinuria or loss of kidney function is scant, and this is the main novelty of our study design. METHODS: Single center retrospective analysis on biopsy findings after detection of de novo DSA. One-hundred-thirty-two kidney and pancreas-kidney transplant recipients were included. Eighty-four of these patients (63.6%) underwent allograft biopsy. At the time of biopsy n = 50 (59.5%) had a protein/creatinine ratio (PCR) > 300 mg/g creatinine and/or a loss of eGFR ≥ 10 ml/min in the previous 12 months, whereas 40.5% did not. Diagnosis of rejection was performed according to Banff criteria. RESULTS: Seventy-seven (91.7%) of the biopsies had signs of rejection (47.6% antibody mediated rejection (ABMR), 13.1% cellular, 20.2% combined, 10.7% borderline). Among subjects without proteinuria or loss of eGFR ≥ 10 ml/min/a (n = 34), 29 patients (85.3%) showed signs of rejection (44.1% antibody mediated (ABMR), 14.7% cellular, 11.8% combined, 14.7% borderline). CONCLUSION: The majority of subjects with de novo DSA have histological signs of rejection, even in the absence of proteinuria and deterioration of graft function. Thus, it appears reasonable to routinely perform an allograft biopsy after the detection of de novo DSA.

Coronavirus Disease 2019 Associated Risk Score, Behavior, and Symptom Prevalence in German Transplant Recipients.

BACKGROUND: Transplant recipients are prone to developing severe infections because of immunosuppression. Therefore, studying the manifestation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in transplant recipients is of particular importance. METHODS: One hundred twelve transplant patients consecutively visiting the outpatient department of 2 German transplant centers were included in this study after providing written informed consent. The patients were interviewed about coronavirus disease 2019 (COVID-19) symptoms and history. Nasopharyngeal swabs were analyzed by SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR). SARS-CoV-2 IgG and IgA were measured concomitantly in patient sera by enzyme-linked immunosorbent assay. RESULTS: The risk of severe COVID-19 according to 2 recent scores differed among the analyzed patients. All patients were well educated about their presumed higher risk of a severe COVID-19 and described performing self-isolation wherever possible. Nevertheless, 20 patients reported contact with someone suspected of having COVID-19 or who tested positive shortly thereafter (18%). Despite this relatively high exposure, no clinically relevant case of COVID-19 was reported. Though SARS-CoV-2 IgG and IgA were found in 3 patients (3%); 2 patients were asymptomatic and only 1 had mild COVID-19 symptoms and positive RT-PCR 4 weeks earlier. There were no occult SARS-CoV-2 infections, as demonstrated by negative PCR tests. CONCLUSION: Despite the high exposure level, the incidence of COVID-19 remained very low. Because of the differences in COVID-19 risk, balancing risk exposure and quality of life should be recommended.

Psychological Responses to the Coronavirus Disease 2019 Pandemic in Renal Transplant Recipients.

BACKGROUND: Renal transplant recipients are at increased risk for an adverse course of coronavirus disease 2019 (COVID-19), most likely due to immunosuppression and the high level of cardiovascular comorbidity. Many transplant recipients are aware of these facts. The psychological effects of this knowledge, however, remain elusive. METHODS: Cross-sectional study on 62 renal transplant recipients. Fifty cardiovascular outpatients without immunosuppression and 55 healthy subjects served as control. We performed a focused psychological assessment during the pandemic (April 2020) and compared the data with a time 6 months before. Additionally, an intergroup analysis was performed for the data during the pandemic. The analysis was performed by means of a questionnaire derived from KPD-38. We extracted 5 questions focusing on the parameters "life satisfaction" and perceived "action competence." Life satisfaction score ranged from 2 to 8, and the score for action competence from 5 to 20. RESULTS: Both life satisfaction and perceived action competence were significantly lower during the pandemic than 6 months before in all the 3 groups (P < .005 each). During the pandemic median levels of life satisfaction did not significantly differ between the 3 groups (transplant recipients 6, interquartile range [IQR] 4-7; cardiovascular patients 5, IQR: 4-6; healthy controls 6, IQR 5-7; Kruskal-Wallis P > .05). In contrast, the perceived action competence was higher in healthy subjects (15, IQR 12-17) than in both renal transplant recipients (13, IQR 10-15) and cardiovascular patients (13, IQR 8-14, Kruskal-Wallis P = .0003). CONCLUSION: The COVID-19 pandemic has negative effects on life satisfaction and perceived action competence in renal transplant recipients, cardiovascular patients without immunosuppression, and healthy subjects. The effects on life satisfaction in transplant recipients did not differ from nonimmunocompromised patients or healthy controls. In contrast, the feeling of reduced action competence exceeded healthy controls, most likely due to a subjective need for stricter social distancing to avoid infection.

Lessons for the clinical nephrologist: recurrence of nephrotic syndrome induced by SARS-CoV-2.

SARS-CoV-2 is characterized by a multiorgan tropism including the kidneys. Recent autopsy series indicated that SARS-CoV-2 can infect both tubular and glomerular cells. Whereas tubular cell infiltration may contribute to acute kidney injury, data on a potential clinical correlative to glomerular affection is rare. We describe the first case of nephrotic syndrome in the context of COVID-19 in a renal transplant recipient. A 35 year old male patient received a kidney allograft for primary focal segmental glomerulosclerosis (FSGS). Three months posttransplant a recurrence of podocytopathy was successfully managed by plasma exchange, ivIG, and a conversion from tacrolimus to belatacept (initial proteinuria > 6 g/l decreased to 169 mg/l). Six weeks later he was tested positive for SARS-CoV-2 and developed a second increase of proteinuria (5.6 g/l). Renal allograft biopsy revealed diffuse podocyte effacement and was positive for SARS-CoV-2 in RNA in-situ hybridation indicating a SARS-CoV-2 associated recurrence of podocytopathy. Noteworthy, nephrotic proteinuria resolved spontaneously after recovering from COVID-19. The present case expands the spectrum of renal involvement in COVID-19 from acute tubular injury to podocytopathy in renal transplant recipients. Thus, it may be wise to test for SARS-CoV-2 prior to initiation of immunosuppression in new onset glomerulopathy during the pandemic.

Vaccination Against Urinary Tract Infection After Renal Transplantation.

BACKGROUND: Recurrent urinary tract infections (UTIs) increase mortality and reduce graft survival after renal transplantation. Because current prophylactic strategies such as methionine, cranberry juice, and antibiotics fail to sufficiently prevent recurrent infections in a substantial number of patients, there is a clinical need for alternative approaches. The present work describes first experiences with an immunization strategy against bacterial strains after kidney transplantation. METHODS: We performed a retrospective single-center analysis of an immunization approach against 10 strains of inactivated bacteria (StroVac). A total of 14 renal transplant recipients with 3 or more UTI episodes/year underwent immunization with 3 subcutaneous injections of inactivated bacteria (follow-up 12 months before to 12 months after immunization). These patients were compared to 14 renal transplant patients without immunization who were matched for number of UTIs and time after transplantation (24 months follow-up). We compared the UTI incidence and potential side effects, including development of de novo donor-specific antibodies (DSA). RESULTS: The immunization significantly decreased the incidence of UTIs from 3.4 ± 1.3 to 0.9 ± 1.0 by 74.9%. The incidence did not change from year 1 to year 2 of the observation period in the control group. Immunization was tolerated well, without any clinical complaints. There were no de novo DSAs in the first year after immunization. CONCLUSIONS: Immunization against inactivated bacterial strains substantially reduced the incidence of UTIs without eliciting any safety concerns in this small cohort of renal transplant recipients. This strategy may be a helpful expansion of our preventive measures in patients with recurrent UTIs.