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Purpose Vaccination against Streptococcus pneumoniae is recommended in transplant recipients to reduce the morbidity and mortality from invasive pneumococcal disease. Previous studies indicate that transplant recipients can produce specific antibodies after vaccination with the 13-valent pneumococcal conjugate vaccine Prevenar 13 (PCV13) or the pneumococcal polysaccharide vaccine Pneumovax 23 (PPSV23). National guidelines recommend sequential vaccination with PCV13 followed by PPSV23 in kidney transplant patients. However, there are currently no data on the serological response in kidney transplant recipients, who received a sequential vaccination with PCV13 and PPSV23. Methods In the current study, we sequentially vaccinated 46 kidney transplant recipients with PCV13 and PPSV23 and determined global and serotype-specific anti-pneumococcal antibody responses in the year following vaccination. Results Serotype-specific and global anti-pneumococcal antibody concentrations were significantly higher compared to baseline. We observed that serotype-specific antibody responses varied by serotype (between 2.2- and 2.9-fold increase after 12 months). The strongest responses after 12 months were detected against the serotypes 9N (2.9-fold increase) and 14 (2.8-fold increase). Global antibody responses also varied with respect to immunoglobulin class. IgG2 revealed the highest increase (2.7-fold), IgM the lowest (1.7-fold). Sequential vaccination with both vaccines achieved higher antibody levels in comparison with a historical cohort studied at our institute, that was vaccinated with PCV13 alone. During the 12-months follow-up period, none of the patients developed pneumococcal-associated pneumonia or vaccination-related allograft rejection. Conclusion In conclusion, we strongly recommend sequential vaccination over single immunization in kidney transplant recipients.

Background Norovirus (NoV) infection frequently progresses to chronic disease after kidney transplant (KTx). This study aims to assess potential risk factors helping to determine patients at risk of chronic NoV infection and to analyse the effect of NoV on allograft outcome. Additionally, we assessed the effectiveness of intravenous immunoglobulin (IVIg) therapy for chronic NoV infection. Methods The study enrolled 60 KTx patients requiring hospitalization because of NoV infection. Clinical parameters, severity of NoV infection and potential risk factors were evaluated. Outcome parameters were clinical symptoms, rehospitalizations, persistent shedding of virus and effects on allograft function. Results Patients were divided into 2 groups: 29 had acute NoV infection only, 31 progressed to chronic NoV infection. Chronic NoV infection was defined as a recurrence of clinical symptoms plus redetection of NoV in stool. Lymphocyte-depleting induction therapy and diabetes mellitus were independent risk factors for chronic infection. For patients with chronic NoV infection, length of stay in hospital was significantly prolonged (p= 0.024). Allograft function remained impaired in the chronic NoV group 6 and 12 months after initial admission.IVIg was administered to 18 patients with chronic NoV infection. No further clinical symptoms of NoV infection occurred in 13 (72%) of these patients. However, NoV was still detectable in stool specimens from 10 (77%) of these patients. Conclusions Chronic NoV infection is associated with reduced allograft function. Administration of IVIg to patients with chronic NoV infection seems beneficial in achieving freedom from clinical symptoms, despite limited effects on shedding of virus.

Malina Grube,1 Frank Weber,2 Anna Lena Kahl,3 Andreas Kribben,1 Nils Mülling,1 Walter Reinhardt1 1Department of Nephrology, University Hospital Essen, Essen, Germany; 2Department of General-, Visceral- and Transplantation Surgery, Section of Endocrine Surgery, University Hospital Essen, Essen, Germany; 3Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, Essen, GermanyCorrespondence: Nils MüllingDepartment of Nephrology, University Hospital Essen, Hufelandstr. 55, Essen, 45147, GermanyEmail nils.muelling@uk-essen.deBackground: The period after parathyroidectomy (PTx) in dialysis patients is characterized by periods of severe hypocalcemia. This study aims to investigate the effect of high doses of active vitamin D immediately after PTx on the development of hypocalcemia.Materials and Methods: We retrospectively reviewed 111 patients with secondary hyperparathyroidism receiving subtotal PTx between 2010 and 2019. A high dose group “HDG” (n = 67) receiving 12 μg alfacalcidol in combination with 8.550 mg calcium acetate per day, which was then adapted according to lab values, was compared with a low dose group “LDG” (n = 44) receiving up to 4 μg alfacalcidol per day. The laboratory values were recorded up to ten weeks postoperatively.Results: The assumed drops in parathyroid hormone (PTH) and calcium were observed in both groups after PTx. We observed significantly lower calcium values in the LDG between days 4 and 18 postoperatively than in the HDG (p < 0.001). The proportion of severe hypocalcemia after PTx (total calcium < 1.5 mmol/l) in the HDG was 8.5% on day 1 and 47% on day 4 in the LDG. Intravenous calcium requirements were significantly lower in the HDG (7.6%) than in the LDG (45.7%; p = 0.001).Conclusion: The period after PTx in dialysis patients is characterized by an expected drop in PTH and calcium within the first days. Ongoing high turnover is observed in the 2nd and 3rd week after PTx. Administering high doses of alfacalcidol combined with calcium acetate diminishes the episodes of severe hypocalcemia and the need for intravenous calcium.Keywords: secondary hyperparathyroidism, hungry bone disease, parathyroidectomy, vitamin D, dialysis, CKD stage 5

Introduction High inflammation parameters like C-reactive protein and low albumin levels are considered as risk factors in CKD stage 5 patients. Due to dynamic changes in these parameters, there is evidence of an association between their variation and mortality in hemodialysis patients. Methods We retrospectively analyzed 153 patients on chronic hemodialysis. Dialysis-specific biochemical parameters were measured at three-month intervals over a 42-month period. Fluctuations were calculated as the percentage change in two subsequent measurements. Results Median age was 70 years. 41.10% of the patients died over the study period. Higher fluctuation rates in albumin and CRP were significantly associated with a higher mortality rate. Regression analysis revealed that only the fluctuations in albumin proved to be a predictive variable for the end point "death." If the fluctuation in albumin increases by 1%, the mortality risk rises by 22%. Conclusion Fluctuations in albumin are of predictive importance in patients on chronic hemodialysis.

Understanding the mechanisms and impact of booster vaccinations can facilitate decisions on vaccination programmes. This study shows that three doses of the same synthetic peptide vaccine eliciting an exclusive CD8+ T cell response against one SARS-CoV-2 Spike epitope protected all mice against lethal SARS-CoV-2 infection in the K18-hACE2 transgenic mouse model in the absence of neutralizing antibodies, while only a second vaccination with this T cell vaccine was insufficient to provide protection. The third vaccine dose of the single T cell epitope peptide resulted in superior generation of effector-memory T cells in the circulation and tissue-resident memory T (TRM) cells, and these tertiary vaccine-specific CD8+ T cells were characterized by enhanced polyfunctional cytokine production. Moreover, fate mapping showed that a substantial fraction of the tertiary effector-memory CD8+ T cells developed from remigrated TRM cells. Thus, repeated booster vaccinations quantitatively and qualitatively improve the CD8+ T cell response leading to protection against otherwise lethal SARS-CoV-2 infection.SummaryA third dose with a single T cell epitope-vaccine promotes a strong increase in tissue-resident memory CD8+ T cells and fully protects against SARS-CoV-2 infection, while single B cell epitope-eliciting vaccines are unable to provide protection.

ZUSAMMENFASSUNGIn den letzten Jahren ist die telemedizinische Betreuung von Heimdialysepatienten besonders in der Peritonealdialyse zunehmend eingesetzt worden. Insbesondere die Übersicht von strukturierten Daten zu geplanten und tatsächlichen Behandlungen ermöglicht ein proaktiveres Patientenmanagement. Durch dieses Vorgehen werden häufiger Anpassungen des Therapieregimes vorgenommen, was wiederum weniger nächtliche Alarme und weniger persönliche Vorstellungen in der Ambulanz zur Folge hat.

Cardiovascular complications are the leading causes of morbidity and mortality in patients with end-stage renal disease. The risk profile very often contributes to their death while on the waiting list. Most studies have been carried out in older patients with end-stage renal disease, reflecting the general dialysis population. The aim of this study was to analyze the risk profile in young patients with advanced chronic kidney disease on the kidney transplant waiting list.This was a retrospective, single-center study of 748 patients on the kidney transplant waiting list at the University Hospital Essen, Germany. Clinical and laboratory parameters were collected between 2015 and 2016.Of 748 patients (62% male), the median age was 48 years. Hypertension, coronary heart disease, and diabetes mellitus were the leading comorbidities, and their frequency rose significantly with age. Their median laboratory values did not differ significantly depending on age except for albumin. Hyperuricemia was quite common in our population with a prevalence of about 75% in women and 50% in men throughout all age groups. A total of 26.6% of the patients between 18 and 35 years of age had advanced anemia (hemoglobin 10 g/dL), and thus they were affected most frequently. Elevated C-reactive protein serum levels were observed in 37.2% of the patients. Regarding the lipid profile, we observed that HDL cholesterol was within the normal range in only among 51.9% of men and 44.3% of women.Cardiovascular risk factors are quite common in our cohort and affect young patients similarly.

ZUSAMMENFASSUNGDie Digitalisierung des Gesundheitswesens und auch der Nephrologie in Deutschland schreitet schnell voran. Nahezu täglich werden neue Teilprozesse in der Versorgung digitalisiert. Dabei können telemedizinische Ansätze die Betreuung von Heimdialysen und chronisch Nierenkranken verbessern. Die praktische Umsetzung ist allerdings im Hinblick auf die Datenschutzgrundverordnung, ärztliche Schweigepflicht, Medizinprodukteverordnung und einer vielschichtigen Gemengelage von Bedürfnissen sowie Rechten von Patienten, Ärzte und Industrie komplex.

Background: Calcineurin-inhibitors (CNI) are used in renal transplant patients (RTX) to prevent rejection. CNI mainly suppress T-cell mediated immunity but very little is known about the impact of long-term treatment with CNI on T-cell function. Objective: We investigated the immunological effects of long-term CNI intake in RTX patients in comparison to short-term CNI administration in healthy controls (HC). Methods: Blood was drawn from 30 RTX patients with long-term CNI treatment. In addition, blood was sampled from HC with short-term CNI treatment (four dosages) before the first and 2 hours after the last CsA intake. T-cells were analyzed for cytokine production, proliferation, and CD25 expression. Results: Short-term CNI reduced T-cell derived IL-2 and IFNγ as well as T-cell proliferation in HC. IFNγ was not suppressed in patients with long-term CNI treatment. IL-2 production, CD25 expression, and T-cell proliferation were enhanced in long-term CNI patients. Conclusion: Suppression of IFNγ/IL-2 and T-cell proliferation is weaker during long-term CNI treatment in patients compared to short-term treatment in healthy subjects. Enhanced CD25 expression may lower the threshold for T-cell activation during long-term CNI treatment.

Purpose The relationship between proteinuria and thyroid function remains controversial in patients with chronic kidney disease (CKD). We prospectively investigated the association between kidney and thyroid function in thyroid antibody-negative patients through all CKD stages. Methods We enrolled 184 nondialysis patients (mean age: 63.1 ± 16.9 years) without previous thyroid disease or thyroid-specific antibodies. Kidney function was assessed by estimating the glomerular filtration rate (eGFR) classified according KDIGO (CKD G1–5). Kidney damage was assessed by albuminuria (albumin-to-creatinine ratio, ACR) and classified as mild, moderate, or severe (ACR1: Results rT3 concentrations correlated negatively with albuminuria (r = −0.286, p p r = 0.289, p r = 0.196, p r = 0.408, p r = 0.390, p Conclusions In thyroid antibody-negative patients presenting advanced CKD (stages 4 and 5), even severe kidney protein loss failed to influence thyroid hormone status. However, albuminuria severity correlated negatively with rT3, which was significantly lower in patients with albuminuria in the nephrotic range.

BACKGROUND In the midst of COVID-19, where health systems are severely overloaded, and arriving at hospitals and clinics poses risks for chronic condition patients, the need for telemedicine rises. This study examines readiness and potential barriers for telemedicine adoption among a specific sector of physicians. Chronic kidney disease (CKD) is a growing medical and economic problem worldwide. Digital strategies provide opportunities for more effective and efficient CKD management, especially when clinic-treated dialysis patients require treatment at the hospital, and when general practitioners consult nephrologists. OBJECTIVE This study aimed to identify both the current status and the needs, expectations and concerns of nephrologists in the context of digitization, which is a necessary step toward adoption of telemedicine, even partially. METHODS N=128 members of a professional nephrologists’ association participated in an online survey, conducted through “Lime Survey”. Members were contacted by the association via email. Participation was voluntary and anonymous. RESULTS Nephrology consultation between departments and organizations, occurs mostly by phone. Online consultation, and patient-management software would facilitate coordination reducing data-procurement efforts. However, nephrologists expressed concerns, e.g. that they would issue improper recommendations if they did not examine the patient in person, at the clinic. On a more procedural note, the survey showed that almost all nephrologists (more than 90%) are currently unable to discern clear remuneration regulations. Nephrologists need more health policy support and framework conditions for the technical implementation of digitization. Currently, the nephrologists are mainly typing input manually to enter information into the practice management system – they are not using more advanced, time-saving means, such as voice-to-text data transfer. The vast majority of respondents use Internet-related information sources several times a day, mostly to search for diagnostic and therapeutic standards. CONCLUSIONS Nephrologists are ambivalent about digitization. They perceive improved coordination between different departments as an opportunity but have doubts about the feasibility of integration into everyday practice. To allow for broader adoption of digitization practices, training, resources, and systems’ support are required. This can save patients’ and doctors’ time, reduce medical errors, and improve care.

Calcineurin-inhibitors (CNI) are used in renal transplant patients (RTX) to prevent rejection. CNI mainly suppress T-cell mediated immunity but very little is known about the impact of long-term treatment with CNI on T-cell function.We investigated the immunological effects of long-term CNI intake in RTX patients in comparison to short-term CNI administration in healthy controls (HC).Blood was drawn from 30 RTX patients with long-term CNI treatment. In addition, blood was sampled from HC with short-term CNI treatment (four dosages) before the first and 2 hours after the last CsA intake. T-cells were analyzed for cytokine production, proliferation, and CD25 expression.Short-term CNI reduced T-cell derived IL-2 and IFNγ as well as T-cell proliferation in HC. IFNγ was not suppressed in patients with long-term CNI treatment. IL-2 production, CD25 expression, and T-cell proliferation were enhanced in long-term CNI patients.Suppression of IFNγ/IL-2 and T-cell proliferation is weaker during long-term CNI treatment in patients compared to short-term treatment in healthy subjects. Enhanced CD25 expression may lower the threshold for T-cell activation during long-term CNI treatment.

IMPORTANCE: Although current guidelines suggest the use of regional citrate anticoagulation (which involves the addition of a citrate solution to the blood before the filter of the extracorporeal dialysis circuit) as first-line treatment for continuous kidney replacement therapy in critically ill patients, the evidence for this recommendation is based on few clinical trials and meta-analyses. OBJECTIVE: To determine the effect of regional citrate anticoagulation, compared with systemic heparin anticoagulation, on filter life span and mortality. DESIGN, SETTING, AND PARTICIPANTS: A parallel-group, randomized multicenter clinical trial in 26 centers across Germany was conducted between March 2016 and December 2018 (final date of follow-up, January 21, 2020). The trial was terminated early after 596 critically ill patients with severe acute kidney injury or clinical indications for initiation of kidney replacement therapy had been enrolled. INTERVENTIONS: Patients were randomized to receive either regional citrate anticoagulation (n = 300), which consisted of a target ionized calcium level of 1.0 to 1.40 mg/dL, or systemic heparin anticoagulation (n = 296), which consisted of a target activated partial thromboplastin time of 45 to 60 seconds, for continuous kidney replacement therapy. MAIN OUTCOMES AND MEASURES: Coprimary outcomes were filter life span and 90-day mortality. Secondary end points included bleeding complications and new infections. RESULTS: Among 638 patients randomized, 596 (93.4%) (mean age, 67.5 years; 183 [30.7%] women) completed the trial. In the regional citrate group vs systemic heparin group, median filter life span was 47 hours (interquartile range [IQR], 19-70 hours) vs 26 hours (IQR, 12-51 hours) (difference, 15 hours [95% CI, 11 to 20 hours]; P