Background
Per- and polyfluorinated alkyl substances (PFAS) have received increasing scientific and political attention in recent years. Several thousand commercially produced compounds are used in ...numerous products and technical processes. Due to their extreme persistence in the environment, humans and all other life forms are, therefore, increasingly exposed to these substances. In the following review, PFAS will be examined comprehensively.
Results
The best studied PFAS are carboxylic and sulfonic acids with chain lengths of C4 to C14, particularly perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS). These substances are harmful to aquatic fauna, insects, and amphibians at concentrations of a few µg/L or less, accumulate in organisms, and biomagnify in food webs. Humans, as the final link in numerous food chains, are subjected to PFAS uptake primarily through food and drinking water. Several PFAS have multiple toxic effects, particularly affecting liver, kidney, thyroid, and the immune system. The latter effect is the basis for the establishment of a tolerable weekly dose of only 4.4 ng/kg body weight for the sum of the four representatives PFOA, PFOS, perfluorononanoic acid (PFNA) and perfluorohexane sulfonic acid (PFHxS) by the European Food Safety Authority (EFSA) in 2020. Exposure estimates and human biomonitoring show that this value is frequently reached, and in many cases exceeded. PFAS are a major challenge for analysis, especially of products and waste: single-substance analyses capture only a fragment of the large, diverse family of PFAS. As a consequence, sum parameters have gained increasing importance. The high mobility of per and polyfluorinated carboxylic and sulfonic acids makes soil and groundwater pollution at contaminated sites a problem. In general, short-chain PFAS are more mobile than long-chain ones. Processes for soil and groundwater purification and drinking water treatment are often ineffective and expensive. Recycling of PFAS-containing products such as paper and food packaging leads to carryover of the contaminants. Incineration requires high temperatures to completely destroy PFAS. After PFOA, PFOS and a few other perfluorinated carboxylic and sulfonic acids were regulated internationally, many manufacturers and users switched to other PFAS: short-chain representatives, per- and polyfluorinated oxo carboxylic acids, telomeric alcohols and acids. Analytical studies show an increase in environmental concentrations of these chemicals. Ultra-short PFAS (chain length C1–C3) have not been well studied. Among others, trifluoroacetic acid (TFA) is present globally in rapidly increasing concentrations.
Conclusions
The substitution of individual PFAS recognized as hazardous by other possibly equally hazardous PFAS with virtually unknown chronic toxicity can, therefore, not be a solution. The only answer is a switch to fluorine-free alternatives for all applications in which PFAS are not essential.
Background
Children presenting with proliferative lupus nephritis (LN) are treated with intensified immunosuppressive protocols. Data on renal outcome and treatment toxicity is scare.
Methods
...Twelve-month renal outcome and comorbidity were assessed in 79 predominantly Caucasian children with proliferative LN reported to the Lupus Nephritis Registry of the German Society of Paediatric Nephrology diagnosed between 1997 and 2015.
Results
At the time of diagnosis, median age was 13.7 (interquartile range 11.8–15.8) years; 86% showed WHO histology class IV, nephrotic range proteinuria was noted in 55%, and median estimated glomerular filtration rate amounted to 75 ml/min/1.73 m
2
. At 12 months, the percentage of patients with complete and partial remission was 38% and 41%, respectively. Six percent of patients were non-responders and 15% presented with renal flare. Nephrotic range proteinuria at the time of diagnosis was associated with inferior renal outcome (odds ratio 5.34, 95% confidence interval 1.26–22.62,
p
= 0.02), whereas all other variables including mode of immune-suppressive treatment (e.g., induction treatment with cyclophosphamide (IVCYC) versus mycophenolate mofetil (MMF)) were not significant correlates. Complications were reported in 80% of patients including glucocorticoid toxicity in 42% (Cushingoid appearance, striae distensae, cataract, or osteonecrosis), leukopenia in 37%, infection in 23%, and menstrual disorder in 20%. Growth impairment, more pronounced in boys than girls, was noted in 78% of patients.
Conclusions
In this cohort of juvenile proliferative LN, renal outcome at 12 months was good irrespectively if patients received induction treatment with MMF or IVCYC, but glucocorticoid toxicity was very high underscoring the need for corticoid sparing protocols.
Graphical abstract
Autosomal recessive polycystic kidney disease (ARPKD) is a severe pediatric hepatorenal disorder with pronounced phenotypic variability. A substantial number of patients with early diagnosis reaches ...adulthood and some patients are not diagnosed until adulthood. Yet, clinical knowledge about adult ARPKD patients is scarce. Here, we describe forty-nine patients with longitudinal follow-up into young adulthood that were identified in the international ARPKD cohort study ARegPKD. Forty-five patients were evaluated in a cross-sectional analysis at a mean age of 21.4 (±3.3) years describing hepatorenal findings. Renal function of native kidneys was within CKD stages 1 to 3 in more than 50% of the patients. Symptoms of hepatic involvement were frequently detected. Fourteen (31%) patients had undergone kidney transplantation and six patients (13%) had undergone liver transplantation or combined liver and kidney transplantation prior to the visit revealing a wide variability of clinical courses. Hepatorenal involvement and preceding complications in other organs were also evaluated in a time-to-event analysis. In summary, we characterize the broad clinical spectrum of young adult ARPKD patients. Importantly, many patients have a stable renal and hepatic situation in young adulthood. ARPKD should also be considered as a differential diagnosis in young adults with fibrocystic hepatorenal disease.
The widespread use of manufactured nanomaterials (MN) increases the need for describing and predicting their environmental fate and behaviour. A number of recent reviews have addressed the scientific ...challenges in disclosing the governing processes for the environmental fate and behaviour of MNs, however there has been less focus on the regulatory adequacy of the data available for MN. The aim of this paper is therefore to review data, testing protocols and guidance papers which describe the environmental fate and behaviour of MN with a focus on their regulatory reliability and relevance. Given the often identified need for modification of OECD testing guidelines, the use of these cannot per se be assigned high regulatory adequacy. Though the specific test considerations will differ between conventional chemicals and MN, the ultimate endpoints of interest are similar. The water compartment must be considered as one of the main points of entry, facilitating dispersion of MN in the environment and establishing a link to the other environmental compartments such as soil, sediment, air, and biota. Once released to water various processes like dissolution, agglomeration, heteroagglomeration, sedimentation, interaction with natural organic matter, transformation and uptake by biota are processes of high relevance for the fate of MN in water. In the review it is found that the OECD draft test guidelines for dissolution and agglomeration will greatly assist in the generation of regulatory relevant and reliable data. Gaps do however exist in test methods for environmental fate, such as methods to estimate heteroagglomeration and the tendency for MNs to transform in the environment.
Background The objective of this initiative was to develop a treat-to-target (T2T) approach for the management of patients with Familial Mediterranean Fever (FMF), including the definition of a ...complex treatment target, and establish strategies that improve patient care and long-term outcome. Methods An initial set of statements as well as a flow chart visualising the proposed concept was developed. To adapt the preliminary statements to the current state of knowledge, a systematic literature search was performed and the modified statements were subject to a Delphi approach. To ensure the applicability of the statements in daily practice, an online survey was conducted among paediatric rheumatologists in Germany. In addition, data from the national AID-NET registry were analysed with respect to therapeutic response. Results This T2T initiative yielded a total of 26 statements guiding FMF management with respect to diagnosis, treatment targets, treatment strategies and monitoring. The online survey identified cut-off values for inflammatory markers indicating treatment intensification and appropriate measures in case of colchicine intolerance or non-adherence. The analysis of data derived from the national AID-NET showed that colchicine therapy was successfully terminated in 61% of patients (27 out of 44) with heterozygous MEFV mutations. Multidimensional treatment targets incorporating objective and subjective reported outcome measures were developed. These provide the basis for stratifying patients into the following treatment paths: continue colchicine, persisting attacks / inflammation, colchicine intolerance, persisting arthritis, colchicine reduction and adjustment/reduction of biologics. Conclusions The proposed consensus treatment plan for the management of FMF incorporates multidimensional targets allowing transparent treatment decisions, which will promote personalised disease management and increase adherence to therapy. Keywords: Children, Colchicine, Colchicine resistance, Disease activity, Familial Mediterranean Fever, interleukin-1 antagonists, Medication adherence, Treat-to-target
The effect of peritoneal dialysates with low–glucose degradation products on peritoneal membrane morphology is largely unknown, with functional relevancy predominantly derived from experimental ...studies. To investigate this, we performed automated quantitative histomorphometry and molecular analyses on 256 standardized peritoneal and 172 omental specimens from 56 children with normal renal function, 90 children with end-stage kidney disease at time of catheter insertion, and 82 children undergoing peritoneal dialysis using dialysates with low–glucose degradation products. Follow-up biopsies were obtained from 24 children after a median peritoneal dialysis of 13 months. Prior to dialysis, mild parietal peritoneal inflammation, epithelial-mesenchymal transition and vasculopathy were present. After up to six and 12 months of peritoneal dialysis, blood microvessel density was 110 and 93% higher, endothelial surface area per peritoneal volume 137 and 95% greater, and submesothelial thickness 23 and 58% greater, respectively. Subsequent peritoneal changes were less pronounced. Mesothelial cell coverage was lower and vasculopathy advanced, whereas lymphatic vessel density was unchanged. Morphological changes were accompanied by early fibroblast activation, leukocyte and macrophage infiltration, diffuse podoplanin presence, epithelial mesenchymal transdifferentiation, and by increased proangiogenic and profibrotic cytokine abundance. These transformative changes were confirmed by intraindividual comparisons. Peritoneal microvascular density correlated with peritoneal small-molecular transport function by uni- and multivariate analysis. Thus, in children on peritoneal dialysis neutral pH dialysates containing low–glucose degradation products induce early peritoneal inflammation, fibroblast activation, epithelial-mesenchymal transition and marked angiogenesis, which determines the PD membrane transport function.
Objective
Pediatric patients spend significant time on maintenance hemodialysis (HD) and traveling. They are often not capable of participating in sports activities. To assess the effects of exercise ...training during HD on dialysis efficacy in children and adolescents, we set up a multi-center randomized controlled trial (RCT).
Methods
Patients on HD, age 6 to 18 years, were randomized either to 3× weekly bicycle ergometer training or to no training during HD for 12 weeks. Change in single-pool Kt/V (spKt/V) was the primary outcome parameter.
Results
We randomized 54 patients of whom 45 qualified (23 in the intervention and 22 in the waiting control group, 14.5 ± 3.01 years, 32 male and 13 female) for the intention-to-treat (ITT) population. Only 26 patients finished study per-protocol (PP). Training was performed for an average of 11.96 weeks (0.14–13.14) at 2.08 ± 0.76 times per week and for a weekly mean of 55.52 ± 27.26 min. Single-pool Kt/V was similar in the intervention compared to the control group (1.70 0.33 vs. 1.79 0.55) at V0 and (1.70 0.36 vs. 1.71 0.51) at V1; secondary endpoints also showed no difference in both ITT and PP analysis. No significant adverse events were reported. No bleeding or needle dislocation occurred in 1670 training sessions.
Conclusions
Intradialytic bicycle training is safe, but does not improve dialysis efficacy and physical fitness. However, the study can be considered underpowered, particularly because of high dropout rates. Future studies need better strategies to increase motivation and compliance and other more effective/intensive exercise measures should be evaluated.
Trial registration
The trial was registered in
ClinicalTrials.Gov
(
Clinicaltrials.gov
identifier: NCT01561118) on March 22, 2012.
In continental plate interiors, ground surface movements are at the limit of the noise level and close to or below the accuracy of current geodetic techniques. Absolute gravity measurements are ...valuable to quantify slow vertical movements, as this instrument is drift free and, unlike GPS, independent of the terrestrial reference frame. Repeated absolute gravity (AG) measurements have been performed in Oostende (Belgian coastline) and at eight stations along a southwest‐northeast profile across the Belgian Ardennes and the Roer Valley Graben (Germany), in order to estimate the tectonic deformation in the area. The AG measurements, repeated once or twice a year, can resolve elusive gravity changes with a precision better than 3.7 nm/s2/yr (95% confidence interval) after 11 years, even in difficult conditions. After 8–15 years (depending on the station), we find that the gravity rates of change lie in the −3.1, 8.1 nm/s2/yr interval and result from a combination of anthropogenic, climatic, tectonic, and glacial isostatic adjustment (GIA) effects. After correcting for the GIA, the inferred gravity rates and consequently, the vertical land movements, reduce to zero within the uncertainty level at all stations except Jülich (because of man‐induced subsidence) and Sohier (possibly, an artifact because of the shortness of the time series at that station).
Key Points
Comprehensive investigation of very slow gravity changes
Assessing slow intraplate vertical land movements
Demonstrating the actual precision of repeated absolute gravity measurements
PDF
