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01 april 2023, Contains fulltext : 291123.pdf (Publisher’s version ) (Open Access), RATIONALE & OBJECTIVE: Mono-allelic variants in COL4A3 and COL4A4 (COL4A3/COL4A4) have been identified in a spectrum of glomerular basement membrane nephropathies, including thin basement membrane nephropathy and autosomal dominant Alport syndrome. With the increasing use of next generation sequencing, mono-allelic COL4A3/COL4A4 variants are detected more frequently, but phenotypic heterogeneity impedes counseling. We aimed to investigate the phenotypic spectrum, kidney biopsy results, and segregation patterns of patients with mono-allelic COL4A3/COL4A4 variants identified by whole exome sequencing. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: We evaluated clinical and pathologic characteristics of 17 Dutch index patients with mono-allelic variants in COL4A3/COL4A4 detected by diagnostic whole exome sequencing and 25 affected family members with variants confirmed by Sanger sequencing. RESULTS: Eight different mono-allelic COL4A3/COL4A4 variants were identified across members of 11 families, comprising 7 glycine substituted missense variants and 1 frameshift variant. All index patients had microscopic hematuria at clinical presentation (median age 43 years) and 14 had (micro)albuminuria/proteinuria. All family members showed co-segregation of the variant with at least hematuria. At end of follow-up of all 42 individuals (median age 54 years), 16/42 patients had kidney function impairment, of whom 6 had kidney failure. Reports of kidney biopsies of 14 patients described thin basement membrane nephropathy, focal segmental glomerulosclerosis, minimal change lesions, and Alport syndrome. Electron microscopy images of 7 patients showed a significantly thinner glomerular basement membrane compared with images of patients with idiopathic focal segmental glomerulosclerosis and other hereditary glomerular diseases. No genotype-phenotype correlations could be established. LIMITATIONS: Retrospective design, ascertainment bias toward severe kidney phenotypes, and familial

Het RIVM heeft in opdracht van het ministerie van Volksgezondheid, Welzijn en Sport een overzicht gemaakt van onderzoeken naar de hoeveelheid natrium (ofwel zout), kalium en jodium die Nederlanders binnenkrijgen. Het overzicht maakt duidelijk welke kennis ontbreekt, welk onderzoek nog nodig is en welke aanbevelingen er zijn voor beleid. Zo blijkt dat de Nederlandse bevolking de afgelopen jaren minder zout binnenkrijgt, maar nog steeds te veel. Te veel zout kan een hoge bloeddruk veroorzaken, wat een grotere kans geeft op hart- en vaatziekten. Het blijft daarom belangrijk dat de hoeveelheid die mensen per dag binnenkrijgen, blijft dalen. De Gezondheidsraad heeft bepaald dat mensen maximaal 6 gram zout per dag mogen binnenkrijgen. Volgens de meest recente meting is dat bij mannen nu 11 gram per dag, bij vrouwen 8 gram. De overheid heeft al verschillende maatregelen genomen, bijvoorbeeld fabrikanten stimuleren om de hoeveelheid zout in voedingsmiddelen te verlagen. Meer maatregelen en een betere uitvoering daarvan zijn nodig om de gewenste hoeveelheid te halen. Voor een goede bloeddruk is het belangrijk om genoeg kalium binnen te krijgen. Deze hoeveelheid is de afgelopen jaren gelijk gebleven en is voldoende. Mensen met nierfalen moeten er niet te veel van binnenkrijgen. Genoeg jodium is nodig voor een goede werking van de schildklier. In Nederland kregen mensen de afgelopen jaren minder jodium binnen maar het is tot nu toe nog net genoeg. Wel is het belangrijk dat deze hoeveelheid niet lager wordt, vooral bij vrouwen in de vruchtbare leeftijd. Jodium is belangrijk voor de ontwikkeling van de hersenen van het ongeboren kind. Het RIVM vindt het belangrijk te onderzoeken met welke maatregelen mensen nog minder zout binnenkrijgen. Deze maatregelen moeten wel in samenhang worden bekeken. Omdat jodium aan zout wordt toegevoegd, mag minder zout in voedingsmiddelen er bijvoorbeeld niet toe leiden dat mensen minder jodium binnenkrijgen. En omdat kalium vaak als vervanger van n

RIVM rapport:Nederlanders eten gemiddeld te veel zout, verzadigd vet en suiker, vooral via bewerkte voedingsmiddelen. De Nederlandse overheid wil dat fabrikanten minder zout en suiker aan voedingsmiddelen toevoegen en bijvoorbeeld een deel van het verzadigd vet vervangen door onverzadigd vet. Zo krijgen mensen toch minder van deze stoffen binnen als zij dezelfde bewerkte voedingsmiddelen blijven eten. In 2022 start de Nationale Aanpak Productverbetering (NAPV). Deze aanpak is bedoeld om verbeteringen in de samenstelling van bewerkte voedingsmiddelen, die via eerdere afspraken in gang zijn gezet, te versnellen. Het doel is ook om productverbetering uit te breiden naar alle bewerkte voedingsmiddelen in verschillende kanalen: niet alleen in supermarkten maar bijvoorbeeld ook in restaurants. De bedoeling is dat fabrikanten de samenstelling van voedingsmiddelen zo veel mogelijk aanpassen. Hiervoor zijn nu per voedingsmiddelengroep grenswaarden opgesteld voor de hoeveelheid zout, verzadigd vet en/of suiker. Het RIVM heeft dat samen met het Voedingscentrum en de HAS Hogeschool gedaan. Per voedingsstof (zout, verzadigd vet, suiker) zijn er drie grenswaarden (laag, midden, hoog), op basis waarvan voedingsmiddelen zijn ingedeeld. Het ministerie van VWS heeft de doelen voor de productverbetering bepaald. Bijvoorbeeld dat minimaal vijftig procent van de voedingsmiddelen onder de laagste grenswaarde zit. De NAPV maakt het mogelijk dat voedingsmiddelen stapsgewijs verbeteren. Zo kunnen fabrikanten van voedingsmiddelen die al onder de hoogste grenswaarde zijn gekomen, eraan werken om ze onder de middelste grenswaarde te laten vallen. Het RIVM gaat de komende jaren de veranderingen in de samenstelling van voedingsmiddelen volgen en kijken of de doelen worden behaald. Het plan voor de nieuwe aanpak is een onderdeel van het Preventieakkoord. Via het Preventieakkoord werken verschillende organisaties eraan om het aantal mensen met (ernstig) overgewicht te laten dalen. Zo worden ook ziekten die daa, On average, Dutch people eat too much salt, saturated fat and sugar, particularly through their consumption of processed foods. To combat this, the Dutch government would like manufacturers to add less salt and sugar to foods and, for example, replace some of the saturated fat with unsaturated fat. That way, people consume less of these substances even if they keep eating the same processed foods. The National Approach to Product Improvement (Nationale Aanpak Productverbetering, NAPV in Dutch) is set to start in 2022. This approach is intended to speed up the improvements to processed food composition that are already under way due to previously made agreements, and to increase their scope to include all processed foods. Additionally, the approach aims to improve foods in more channels – not just in supermarkets, but in restaurants as well, for example. The intention is for manufacturers to adapt the composition of their food products as far as possible. Therefore, ceiling limits for quantities of salt, saturated fat and/or sugar have now been developed by RIVM together with the Netherlands Nutrition Centre and HAS University of Applied Sciences. There are three ceiling limits (low, middle, high) for each nutrient, with foods being classified in the appropriate band. The Ministry of Health, Welfare and Sport established the objectives for this product improvement effort. To take an example, at least fifty percent of foods must be below the lowest ceiling limit. This approach will enable step-by-step improvements to food. For instance, manufacturers of foods that have already met the requirements for the highest ceiling limit might strive to let these foods drop below the middle limit. Over the next few years, RIVM will be measuring the changes in the composition of foods, and monitoring whether the objectives are met. The plan for the new approach is part of the National Prevention Agreement. This Agreement sees various organisations working together on reducing ove

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Contains fulltext : 249325.pdf (Publisher’s version ) (Open Access)

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Item does not contain fulltext, We report a 53-year-old man who presented with acute renal failure. His medical history revealed a spondyloarthropathy, for which secukinumab was started recently, and a monoclonal gammopathy of unknown significance. Kidney function deteriorated despite the withdrawal of secukinumab and dialysis was started. In the serum, type 1 cryoglobulins were present and a kidney biopsy showed ischaemic glomeruli, with thrombosis of the larger interlobular arteries. Other causes of thrombotic microangiopathy were excluded. Bone marrow immunophenotyping showed 1% monoclonal plasma cells. A diagnosis of monoclonal gammopathy of renal significance was made. Haematological treatment resulted in haematological and renal response.

Contains fulltext : 252055.pdf (Publisher’s version ) (Open Access), The International IgA Nephropathy (IgAN) Prediction Tool is the preferred method in the 2021 KDIGO guidelines to predict, at the time of kidney biopsy, the risk of a 50% drop in estimated glomerular filtration rate or kidney failure. However, it is not known if the Prediction Tool can be accurately applied after a period of observation post-biopsy. Using an international multi-ethnic derivation cohort of 2,507 adults with IgAN, we updated the Prediction Tool for use one year after biopsy, and externally validated this in a cohort of 722 adults. The original Prediction Tool applied at one-year without modification had a coefficient of variation (R(2)) of 55% and 54% and four-year concordance (C statistic) of 0.82 but poor calibration with under-prediction of risk (integrated calibration index (ICI) 1.54 and 2.11, with and without race, respectively). Our updated Prediction Tool had a better model fit with higher R(2) (61% and 60%), significant increase in four-year C-statistic (0.87 and 0.86) and better four-year calibration with lower ICI (0.75 and 0.35). On external validation, the updated Prediction Tool had similar R(2) (60% and 58%) and four-year C-statistics (both 0.85) compared to the derivation analysis, with excellent four-year calibration (ICI 0.62 and 0.56). This updated Prediction Tool had similar prediction performance when used two years after biopsy. Thus, the original Prediction Tool should be used only at the time of biopsy whereas our updated Prediction Tool can be used for risk stratification one or two years post-biopsy.

Item does not contain fulltext, We have developed an artificial neural network prediction model for end-stage kidney disease (ESKD) in patients with primary immunoglobulin A nephropathy (IgAN) using a retrospective cohort of 948 patients with IgAN. Our tool is based on a two-step procedure of a classifier model that predicts ESKD, and a regression model that predicts development of ESKD over time. The classifier model showed a performance value of 0.82 (area under the receiver operating characteristic curve) in patients with a follow-up of five years, which improved to 0.89 at the ten-year follow-up. Both models had a higher recall rate, which indicated the practicality of the tool. The regression model showed a mean absolute error of 1.78 years and a root mean square error of 2.15 years. Testing in an independent cohort of 167patients with IgAN found successful results for 91% of the patients. Comparison of our system with other mathematical models showed the highest discriminant Harrell C index at five- and ten-years follow-up (81% and 86%, respectively), paralleling the lowest Akaike information criterion values (355.01 and 269.56, respectively). Moreover, our system was the best calibrated model indicating that the predicted and observed outcome probabilities did not significantly differ. Finally, the dynamic discrimination indexes of our artificial neural network, expressed as the weighted average of time-dependent areas under the curve calculated at one and two years, were 0.80 and 0.79, respectively. Similar results were observed over a 25-year follow-up period. Thus, our tool identified individuals who were at a high risk of developing ESKD due to IgAN and predicted the time-to-event endpoint. Accurate prediction is an important step toward introduction of a therapeutic strategy for improving clinical outcomes.

Contains fulltext : 225968.pdf (Publisher’s version ) (Closed access), Immunosuppression in IgA nephropathy (IgAN) should be reserved for patients at high-risk of disease progression, which KDIGO guidelines determine based solely on proteinuria 1g or more/day. To investigate if treatment decisions can be more accurately accomplished using individualized risk from the International IgAN Prediction Tool, we simulated allocation of a hypothetical immunosuppression therapy in an international cohort of adults with IgAN. Two decision rules for treatment were applied based on proteinuria of 1g or more/day or predicted risk from the Prediction Tool above a threshold probability. An appropriate decision was defined as immunosuppression allocated to patients experiencing the primary outcome (50% decline in eGFR or ESKD) and withheld otherwise. The net benefit and net reduction in treatment are the proportion of patients appropriately allocated to receive or withhold immunosuppression, adjusted for the harm from inappropriate decisions, calculated for all threshold probabilities from 0-100%. Of 3299 patients followed for 5.1 years, 522 (15.8%) experienced the primary outcome. Treatment allocation based solely on proteinuria of 1g or more/day had a negative net benefit (was harmful) because immunosuppression was increasingly allocated to patients without progressive disease. Compared to using proteinuria, treatment allocation using the Prediction Tool had a larger net benefit up to 23.4% (95% confidence interval 21.5-25.2%) and a larger net reduction in treatment up to 35.1% (32.3-37.8%). Thus, allocation of immunosuppression to high-risk patients with IgAN can be substantially improved using the Prediction Tool compared to using proteinuria.

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Importance Although IgA nephropathy (IgAN) is the most common glomerulonephritis in the world, there is no validated tool to predict disease progression. This limits patient-specific risk stratification and treatment decisions, clinical trial recruitment, and biomarker validation. Objective To derive and externally validate a prediction model for disease progression in IgAN that can be applied at the time of kidney biopsy in multiple ethnic groups worldwide. Design, Setting, and Participants We derived and externally validated a prediction model using clinical and histologic risk factors that are readily available in clinical practice. Large, multi-ethnic cohorts of adults with biopsy-proven IgAN were included from Europe, North America, China, and Japan. Main Outcomes and Measures Cox proportional hazards models were used to analyze the risk of a 50% decline in estimated glomerular filtration rate (eGFR) or end-stage kidney disease, and were evaluated using the R2D measure, Akaike information criterion (AIC), C statistic, continuous net reclassification improvement (NRI), integrated discrimination improvement (IDI), and calibration plots. Results The study included 3927 patients; mean age, 35.4 (interquartile range, 28.0-45.4) years; and 2173 (55.3%) were men. The following prediction models were created in a derivation cohort of 2781 patients: a clinical model that included eGFR, blood pressure, and proteinuria at biopsy; and 2 full models that also contained the MEST histologic score, age, medication use, and either racial/ethnic characteristics (white, Japanese, or Chinese) or no racial/ethnic characteristics, to allow application in other ethnic groups. Compared with the clinical model, the full models with and without race/ethnicity had better R2D (26.3% and 25.3%, respectively, vs 20.3%) and AIC (6338 and 6379, respectively, vs 6485), significant increases in C statistic from 0.78 to 0.82 and 0.81, respectively (ΔC, 0.04; 95% CI, 0.03-0.04 and ΔC, 0.03

Women in top positions of academia are underrepresented, which contributes to gender inequality and a loss of new perspectives and talent in the workforce. This second wave of a two-wave longitudinal study (one year in between measurements) aims to identify processes that stimulate the career advancement of (female) academics over time. It is hypothesized that a feminine organizational culture and Family Supportive Supervisor Behaviour (FSSB) play an essential role in the ambitions and intentions to leave of academics, by stimulating academics’ work engagement and work life balance. In order to examine this, an online follow-up questionnaire was sent to assistant professors at a large Dutch university. A matching procedure based on unique codes matched data of two waves to one particular participant (N = 205), enabling longitudinal statistical analyses. Results indicate a causal pathway wherein FSSB causes general ambition one year later through increased work engagement. Furthermore, results indicate a causal pathway wherein a feminine organizational culture or FSSB cause the ambition to become a full professor, through increased work life balance. Unexpectedly, while examining whether the effects of these processes are stronger for women, the current data do not reveal any significant gender differences. Implications of these findings and recommendations for future research are further discussed.

Previous research has demonstrated that an error management culture in which errors are discussed and analysed, can stimulate learning from errors and many other positive consequences, such as a higher quality of service and better performance. But how do we create and stimulate an error management culture within financial organisations? Based on previous research, the current study examined the relations between leadership error management, tone at the top error management, error policy, error management culture, and learning from errors within the financial sector. In order to study this, an online survey was conducted by the AFM among employees from thirteen different financial organisations (N = 436). Results demonstrated that the behaviour of direct supervisors and the top regarding errors positively related to learning from errors, both directly and indirectly through error management cultures. As expected, if direct supervisors and the top focused on error management and set the right example, more errors were openly shared and discussed within financial organisations, and more was learned from errors. Other interesting findings showed that managerial staff on average scored higher on constructs than the non-managerial staff, and some organisations scored better than others. Although error policy could not be analysed due to insufficient reliability, this study gave organisations more insight into their error management. Moreover, this study offers opportunities for financial organisations to stimulate error management cultures and learning from errors by implementing error management among direct supervisors and higher management.

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Contains fulltext : 174822.pdf (Publisher’s version ) (Open Access), In normal glomeruli, parietal epithelial cells (PECs) line the inside of Bowman's capsule and form an inconspicuous sheet of flat epithelial cells in continuity with the proximal tubular epithelial cells (PTECs) at the urinary pole and with the podocytes at the vascular pole. PECs, PTECs and podocytes have a common mesenchymal origin and are the result of divergent differentiation during embryogenesis. Podocytes and PTECs are highly differentiated cells with well-established functions pertaining to the maintenance of the filtration barrier and transport, respectively. For PECs, no specific function other than a structural one has been known until recently. Possible important functions for PECs in the fate of the glomerulus in glomerular disease have now become apparent: (1) PECs may be involved in the replacement of lost podocytes; (2) PECs form the basis of extracapillary proliferative lesions and subsequent sclerosis in glomerular disease. In addition to the acknowledgement that PECs are crucial in glomerular disease, knowledge has been gained regarding the molecular processes driving the phenotypic changes and behavior of PECs. Understanding these molecular processes is important for the development of specific therapeutic approaches aimed at either stimulation of the regenerative function of PECs or inhibition of the pro-sclerotic action of PECs. In this review, we discuss recent advances pertaining to the role of PECs in glomerular regeneration and disease and address the major molecular processes involved.

De Autoriteit Financiële Markten (AFM), toezichthouder op de financiële sector, heeft als speerpunt dat financiële organisaties het klantbelang centraal (KBC) stellen, om duurzaam financieel welzijn te creëren. KBC is een uiting van integer gedrag. In het huidige onderzoek is, onder adviseurs en bemiddelaars in de financiële sector, onderzocht of een ethische organisatiecultuur samenhangt met KBC, betrokkenheid en bevlogenheid. Daarbij is gekeken naar de mediërende rol van ethische spanning in het verband tussen ethische organisatiecultuur en KBC en is gekeken naar de modererende rol van morele identiteit op alle drie de verbanden. Hiervoor is een online vragenlijst uitgezet onder medewerkers van verschillende organisaties van adviseurs en bemiddelaars (N = 182). In lijn met de verwachtingen hangt ethische organisatiecultuur samen met KBC, betrokkenheid en bevlogenheid. Ten tweede is niet gebleken dat het verband tussen ethische organisatiecultuur en KBC wordt gemedieerd door ethische spanning. Ten derde is niet gebleken dat morele identiteit de verschillende verbanden modereert, hoewel morele identiteit wel samenhangt met meer KBC en betrokkenheid. Dit biedt steun voor zowel het clean barrels als good apples perspectief. Op basis van dit onderzoek wordt aangeraden om aan te sturen op een ethische organisatiecultuur door zowel toezichthouder als organisatie zelf om KBC, betrokkenheid en bevlogenheid te bevorderen.