Studying the short-term complications of kidney transplantation: from bed to bench

This thesis demonstrates that kidneys from DCD donors can be fully embraced, and that the perception of DCD kidney transplantation being inferior to DBD kidney transplantation – mainly motivated by concerns regarding high incidences of DGF and EGL – is no longer justified. One explanation for this phenomenon is that outcomes of transplanted DCD kidneys have improved over time, with a similar incidence of EGL following DBD and DCD kidney transplantation in the current era. Another explanation is that both donor types have different biological responses to DGF: whilst DGF severely impacts on DBD graft survival, DGF has no impact on DCD graft survival. This difference relates to donor type-specific regulation of resilience and pro-inflammatory pathways benefitting the DCD graft and its outcomes. As such, the persistent high incidence of DGF in DCD grafts should not be regarded an impediment toward the use of these donor kidneys.This thesis additionally explores a series of physiological and methodological contrasts between preclinical and clinical I/R injury, that all may contribute to the impaired translatability of preclinical studies in clinical practice. Awareness of these pitfalls may help to improve study designs in future research, bringing us one step closer towards bridging the translational gap.ABN Amro; Chiesi; ChipSoft; ETB-BISLIFE; LUMC Transplant Center; Nederlandse Transplantatie Vereniging; XVIVOLUMC / Geneeskund

Het Monitoring en Evaluatie Programma Zandwinning RWS LaMER 2007 en 2008 - 2012: overzicht, resultaten en evaluatie

Zandwinning en -transport kunnen potentieel leiden tot diverse effecten zoals verminderde productie van algen en schelpdieren door extra slib in de waterkolom en verstoring. Geschatte effecten van zandwinning volgens de MERren. Visuele verstoring van zeehonden en vogels: de dieren worden verstoord doordat ze de sleephopperzuiger zien en reageren door bv weg te vluchten en andere vormen van onrust wat kan resulteren in (tijdelijke) effecten op de conditie van het dier en zelfs voortplanting en populatiedynamica. Geluidverstoring van vissen, vogels en zeezoogdieren: geluid wordt geproduceerd tijdens het baggeren op de winlocatie en tijdens het varen, waarbij de geluidsbron zich verplaatst. Verstoringseffecten kunnen ook optreden door het geluid tijdens baggeren (zowel boven als onderwater). Dit heeft op hoofdlijnen het zelfde effect als visuele verstoring maar via een andere effectroute

Circumventing the crabtree effect in cell culture: a systematic review

Metabolic reprogramming and mitochondrial dysfunction are central elements in a broad variety of physiological and pathological processes. While cell culture established itself as a versatile technique for the elaboration of physiology and disease, studying metabolism using standard cell culture protocols is profoundly interfered by the Crabtree effect. This phenomenon refers to the adaptation of cultured cells to a glycolytic phenotype, away from aoxidative phosphorylation in glucose-containing medium, and questions the applicability of cell culture in certain fields of research. In this systematic review we aim to provide a comprehensive overview and critical appraisal of strategies reported to circumvent the Crabtree effect.Toxicolog

Preclinical models versus clinical renal ischemia reperfusion injury: a systematic review based on metabolic signatures

Despite decennia of research and numerous successful interventions in the preclinical setting, renal ischemia reperfusion (IR) injury remains a major problem in clinical practice, pointing toward a translational gap. Recently, two clinical studies on renal IR injury (manifested either as acute kidney injury or as delayed graft function) identified metabolic derailment as a key driver of renal IR injury. It was reasoned that these unambiguous metabolic findings enable direct alignment of clinical with preclinical data, thereby providing the opportunity to elaborate potential translational hurdles between preclinical research and the clinical context. A systematic review of studies that reported metabolic data in the context of renal IR was performed according to the PRISMA guidelines. The search (December 2020) identified 35 heterogeneous preclinical studies. The applied methodologies were compared, and metabolic outcomes were semi-quantified and aligned with the clinical data. This review identifies profound methodological challenges, such as the definition of IR injury, the follow-up time, and sampling techniques, as well as shortcomings in the reported metabolic information. In light of these findings, recommendations are provided in order to improve the translatability of preclinical models of renal IR injury.Transplant surger

Het Monitoring en Evaluatie Programma Zandwinning RWS LaMER 2007 en 2008 - 2012: overzicht, resultaten en evaluatie

Zandwinning en -transport kunnen potentieel leiden tot diverse effecten zoals verminderde productie van algen en schelpdieren door extra slib in de waterkolom en verstoring. Geschatte effecten van zandwinning volgens de MERren. Visuele verstoring van zeehonden en vogels: de dieren worden verstoord doordat ze de sleephopperzuiger zien en reageren door bv weg te vluchten en andere vormen van onrust wat kan resulteren in (tijdelijke) effecten op de conditie van het dier en zelfs voortplanting en populatiedynamica. Geluidverstoring van vissen, vogels en zeezoogdieren: geluid wordt geproduceerd tijdens het baggeren op de winlocatie en tijdens het varen, waarbij de geluidsbron zich verplaatst. Verstoringseffecten kunnen ook optreden door het geluid tijdens baggeren (zowel boven als onderwater). Dit heeft op hoofdlijnen het zelfde effect als visuele verstoring maar via een andere effectroute

The impact of pain on the course of ADL functioning in patients with dementia

Item does not contain fulltextBACKGROUND: Understanding if and how pain influences activities of daily living (ADL) in dementia is essential to improving pain management and ADL functioning. This study examined the relationship between the course of pain and change in ADL functioning, both generally and regarding specific ADL functions. METHODS: Participants were Dutch nursing home residents (n = 229) with advanced dementia. ADL functioning was assessed with the Katz ADL scale, and pain with the Dutch version of the Pain Assessment Checklist for Seniors with Limited Ability to Communicate (PACSLAC-D). Changes of PACSLAC-D and Katz ADL scores were computed based on the difference in scores between baseline, 3-month and 6-month follow-up. Multivariate linear regression models were used to assess the relationships between change in pain score, change in total ADL score and specific ADL item scores during follow-up. RESULTS: At baseline, residents had a median ADL score of 18 (interquartile range 13-22, range 6-24) and 48% of the residents were in pain (PACSLAC-D ≥ 4). Residents with pain were more ADL dependent than residents without pain. A change in pain score within the first 3 months was a significant predictor for a decline in ADL functioning over the 6-month follow-up (B = 0.10, SE = 0.05, P = 0.045), and specifically, a decline on the items 'transferring' over the 6-month follow-up and 'feeding' during the first 3 months of follow-up. CONCLUSIONS: Pain is associated with ADL functioning cross-sectionally, and a change in pain score predicts a decline in ADL functioning, independent of dementia severity. Awareness of (changes in) ADL activities is clearly important and might result in both improved recognition of pain and improved pain management

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

The use of kidneys donated after circulatory death (DCD) remains controversial due to concerns with regard to high incidences of early graft loss, delayed graft function (DGF), and impaired graft survival. As these concerns are mainly based on data from historical cohorts, they are prone to time-related effects and may therefore not apply to the current timeframe. To assess the impact of time on outcomes, we performed a time-dependent comparative analysis of outcomes of DCD and donation after brain death (DBD) kidney transplantations. Data of all 11,415 deceased-donor kidney transplantations performed in The Netherlands between 1990-2018 were collected. Based on the incidences of early graft loss, two eras were defined (1998-2008 [n = 3,499] and 2008-2018 [n = 3,781]), and potential time-related effects on outcomes evaluated. Multivariate analyses were applied to examine associations between donor type and outcomes. Interaction tests were used to explore presence of effect modification. Results show clear time-related effects on posttransplant outcomes. The 1998-2008 interval showed compromised outcomes for DCD procedures (higher incidences of DGF and early graft loss, impaired 1-year renal function, and inferior graft survival), whereas DBD and DCD outcome equivalence was observed for the 2008-2018 interval. This occurred despite persistently high incidences of DGF in DCD grafts, and more adverse recipient and donor risk profiles (recipients were 6 years older and the KDRI increased from 1.23 to 1.39 and from 1.35 to 1.49 for DBD and DCD donors). In contrast, the median cold ischaemic period decreased from 20 to 15 hours. This national study shows major improvements in outcomes of transplanted DCD kidneys over time. The time-dependent shift underpins that kidney transplantation has come of age and DCD results are nowadays comparable to DBD transplants. It also calls for careful interpretation of conclusions based on historical cohorts, and emphasises that retrospective studies should correct for time-related effects.Transplant surger

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

The use of kidneys donated after circulatory death (DCD) remains controversial due to concerns with regard to high incidences of early graft loss, delayed graft function (DGF), and impaired graft survival. As these concerns are mainly based on data from historical cohorts, they are prone to time-related effects and may therefore not apply to the current timeframe. To assess the impact of time on outcomes, we performed a time-dependent comparative analysis of outcomes of DCD and donation after brain death (DBD) kidney transplantations. Data of all 11,415 deceased-donor kidney transplantations performed in The Netherlands between 1990-2018 were collected. Based on the incidences of early graft loss, two eras were defined (1998-2008 [n = 3,499] and 2008-2018 [n = 3,781]), and potential time-related effects on outcomes evaluated. Multivariate analyses were applied to examine associations between donor type and outcomes. Interaction tests were used to explore presence of effect modification. Results show clear time-related effects on posttransplant outcomes. The 1998-2008 interval showed compromised outcomes for DCD procedures (higher incidences of DGF and early graft loss, impaired 1-year renal function, and inferior graft survival), whereas DBD and DCD outcome equivalence was observed for the 2008-2018 interval. This occurred despite persistently high incidences of DGF in DCD grafts, and more adverse recipient and donor risk profiles (recipients were 6 years older and the KDRI increased from 1.23 to 1.39 and from 1.35 to 1.49 for DBD and DCD donors). In contrast, the median cold ischaemic period de