Considerable Variability Among Transplant Nephrologists in Judging Deceased Donor Kidney Offers

Introduction: Transplant clinicians may disagree on whether or not to accept a deceased donor kidney offer. We investigated the interobserver variability between transplant nephrologists regarding organ acceptance and whether the use of a prediction model impacted their decisions.Methods: We developed an observational online survey with 6 real-life cases of deceased donor kidneys offered to a waitlisted recipient. Per case, nephrologists were asked to estimate the risk of adverse outcome and whether they would accept the offer for this patient, or for a patient of their own choice, and how certain they felt. These questions were repeated after revealing the risk of adverse outcome, calculated by a validated prediction model. Results: Sixty Dutch nephrologists completed the survey. The intraclass correlation coefficient of their estimated risk of adverse outcome was poor (0.20, 95% confidence interval [CI] 0.08–0.62). Interobserver agreement of the decision on whether or not to accept the kidney offer was also poor (Fleiss kappa 0.13, 95% CI 0.129–0.130). The acceptance rate before and after providing the outcome of the prediction model was significantly influenced in 2 of 6 cases. Acceptance rates varied considerably among transplant centers. Conclusion: In this study, the estimated risk of adverse outcome and subsequent decision to accept a suboptimal donor kidney varied greatly among transplant nephrologists. The use of a prediction model could influence this decision and may enhance nephrologists’ certainty about their decision.</p

Adherence to preventive measures after SARS-CoV-2 vaccination and after awareness of antibody response in kidney transplant recipients in the Netherlands:a nationwide questionnaire study

BACKGROUND: Kidney transplant recipients (KTRs) were advised to tightly adhere to government recommendations to curb the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) because of a high risk of morbidity and mortality and decreased immunogenicity after vaccination. The aim of this study was to analyse the change in adherence to preventive measures after vaccination and awareness of antibody response, and to evaluate its effectiveness.METHODS: In this large-scale, national questionnaire study, questionnaires were sent to 3531 KTRs enrolled in the Dutch RECOVAC studies, retrospectively asking for adherence to nine preventive measures on a 5-point Likert scale before and after SARS-CoV-2 vaccination and after awareness of antibody response. Blood samples were collected 28 days after the second vaccination. Antibody response was categorised as non-responder (≤50 BAU/mL), low-responder (&gt;50 ≤ 300 BAU/mL) or high-responder (&gt;300 BAU/mL), and shared with participants as a correlate of protection. Participants of whom demographics on sex and age, blood samples and completed questionnaires were available, were included. Our study took place between February 2021 and January 2022. The primary outcome of adherence before and after vaccination was assessed between August and October 2021 and compared via the Wilcoxon signed rank sum test. Logistic regression analysis was performed to estimate the association between antibody response and non-adherence, and adherence on acquiring SARS-CoV-2 infection. This study is registered at ClinicalTrials.gov (NCT04841785).FINDINGS: In 2939 KTRs (83%) who completed the first questionnaire on adherence to preventive measures, adherence was higher before than after vaccination (4.56, IQR 4.11-4.78 and 4.22, IQR 3.67-4.67, p &lt; 0.001). Adherence after awareness of antibody response was analysed in 2399 KTRs (82%) of whom also blood samples were available, containing 949 non-responders, 500 low-responders and 950 high-responders. Compared to non-responders, low- and high-responders reported higher non-adherence. Higher adherence was associated with lower infection rates before and after vaccination (OR 0.67 [0.51-0.91], p = 0.008 and OR 0.48 [0.28-0.86], p = 0.010).INTERPRETATION: Adherence decreased after SARS-CoV-2 vaccination and in KTRs who were aware of a subsequent antibody response compared with those without. Preventive measures in this vulnerable group seem to be effective, regardless of vaccination status. This study starts a debate on sharing antibody results with the patient and future studies should elucidate whether decreased adherence in antibody responders is justified, also in view of future pandemics.FUNDING: The Netherlands Organization for Health Research and Development and the Dutch Kidney Foundation.</p

Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

Publisher Copyright: © 2019, The Author(s).Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.Peer reviewe

Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria

Improving outcomes for donation after circulatory death kidney transplantation: Science of the times

Contains fulltext : 221518.pdf (publisher's version ) (Open Access

Spectrum of retinal abnormalities in renal transplant patients using chronic low-dose steroids

Contains fulltext : 179619.pdf (Publisher’s version ) (Open Access

Didactical characteristics of Dutch websites about kidney transplantation targeted for kidney patients and living donors: An exploratory study

Objective: The aim was to explore the origin, content topics, teaching modes (instruction, interaction, and assessment), and corresponding social-epistemological dimensions (choices in knowledge transfer vs. knowledge building, and individual vs. group learning) of web-based information on kidney transplantation targeted for patients and living donors. Methods: Dutch websites on kidney transplantation were retrieved using the search engine Google.nl. From 24 websites, 250 webpages were examined on origin, content topics, teaching modes, and corresponding social-epistemological dimensions. Results: The majority of the websites had a professional organization as origin (20/24). The number and distribution of content topics varied among the websites. Of the 16 different teaching modes found, 11 were instructional, 4 were interactional, and 1 assessment mode was found. The websites offered almost exclusively teaching modes on individual and passive learning, whereas group learning and interactive knowledge building was hardly encountered. Conclusion: The diversity in teaching modes and social-epistemological dimensions of Dutch websites on kidney transplantation targeted for patients and living donors is limited. The websites only provided a partial view on kidney transplantation; information regarding contact with others, e.g. support, was limited. A more balanced availability of teaching approaches and content topics is desirable to fit with the didactical goals to make well-considered health decisions

Circulating Markers of Endothelial Dysfunction Interact With Proteinuria in Predicting Mortality in Renal Transplant Recipients

BACKGROUND: Proteinuria is associated with endothelial dysfunction (ED) and increased mortality. We investigated whether urinary protein excretion (UPE) is correlated with markers of ED and whether these markers affect the association of proteinuria with mortality in renal transplant recipients (RTR). METHODS: Six hundred four RTR with a functioning graft for more than 1 year were included. RTR were divided according to UPE: less than 0.3, 0.3 to 1.0, and more than 1.0 g/24 hr. Soluble intercellular adhesion molecule type 1 (sICAM-1) and soluble vascular cellular adhesion molecule type 1 (sVCAM-1) were measured using ELISA. RESULTS: UPE (0.2 [0.0-0.5] g/24 hr), sICAM-1 (603 (514-721) ng/mL), and sVCAM-1 (952 [769-1196] ng/mL) were measured at 6.0 (2.6-11.4) years posttransplant. During follow-up for 5.3 (4.7-5.7) years, 94 (16%) RTR died. UPE was correlated with sVCAM-1 (standardized beta=0.13, P=0.001) but not with sICAM-1 (standardized beta=0.04, P=0.3). RTR with UPE more than 1.0 g/24 hr and high sICAM-1 (hazard ratio=4.7, 95% confidence interval 2.3-9.7, P<0.0001) or sVCAM-1 (hazard ratio=4.2, 95% confidence interval 2.0-8.6, P=0.0001) concentrations were at increased risk for death, whereas RTR with UPE more than 1.0 g/24 hr and low concentrations of sICAM-1 and sVCAM-1 were not. CONCLUSIONS: In RTR, UPE is correlated with sVCAM-1 but not with sICAM-1. Furthermore, RTR with proteinuria and high concentrations of sICAM-1 or sVCAM-1 have an increased risk for death, compared with RTR without proteinuria, whereas this is not the case in RTR with proteinuria but low concentrations of sICAM-1 and sVCAM-1. These results suggest that ED plays a role in the association of proteinuria with mortality after renal transplantation

Equivalent Long-term Transplantation Outcomes for Kidneys Donated After Brain Death and Cardiac Death: Conclusions From a Nationwide Evaluation

Background: Despite growing waiting lists for renal transplants, hesitations persist with regard to the use of deceased after cardiac death (DCD) renal grafts. We evaluated the outcomes of DCD donations in The Netherlands, the country with the highest proportion of DCD procedures (42.9%) to test whether these hesitations are justified. Methods: This study included all procedures with grafts donated after brain death (DBD) (n = 3611) and cardiac death (n = 2711) performed between 2000 and 2017. Transplant outcomes were compared by Kaplan Meier and Cox regression analysis, and factors associated with short (within 90 days of transplantation) and long-term graft loss evaluated in multi-variable analyses. Findings: Despite higher incidences of early graft loss (+50%) and delayed graft function (+250%) in DCD grafts, 10-year graft and recipient survival were similar for the two graft types (Combined 10-year graft survival: 73.9% (95% CI: 72.5–75.2), combined recipient survival: 64.5% (95 CI: 63.0–66.0%)). Long-term outcome equivalence was explained by a reduced impact of delayed graft function on DCD graft survival (RR: 0.69 (95% CI: 0.55–0.87), p < 0.001). Mid and long-term graft function (eGFR), and the impact of incident delayed graft function on eGFR were similar for DBD and DCD grafts. Interpretation: Mid and long term outcomes for DCD grafts are equivalent to DBD kidneys. Poorer short term outcomes are offset by a lesser impact of delayed graft function on DCD graft survival. This nation-wide evaluation does not justify the reluctance to use of DCD renal grafts. A strong focus on short-term outcome neglects the superior recovery potential of DCD grafts. Keywords: Kidney transplantation, Donation after cardiac death, Donation after brain death, Outcome, Graft survival, Delayed graft functio