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We evaluated the effect of resistant starch (RS) and resistant starch with wheat bran (RS+WB) on the colonic ammonia metabolism in healthy volunteers using the biomarker 15N-lactose ureide (15N-LU). Particularly, it was investigated whether this biomarker allowed to estimate differences in the site of fermentation. Ten volunteers were included in a placebo-controlled crossover study. They consumed in random order 2 x 15 g RS/day for 2 weeks and placebo for 2 weeks separated by 2 weeks wash-out. At baseline, on the first day of each intake period and after each intake period, they consumed a 15N-labelled test meal and collected all urine in different fractions for 48 h. In ten other volunteers, the effect of 2 x 15 g RS/day and of 2 x 15 g RS + 2 x 6 g WB was compared. These volunteers collected urine and feces for 72 h. 15N-content of urine and feces was measured using combustion-isotope ratio mass spectrometry. RS exerted a significant decrease in cumulative urinary 15N-excretion which was different from placebo. The effect was most pronounced in the 6-24 h urine fraction which suggest fermentation in the proximal colon. The effect of RS+WB on cumulative urinary 15N-excretion was not significantly different from the effect of RS. A less pronounced decrease in the 6-24 h fraction was observed suggesting less fermentation in the proximal colon whereas no indications for more distal fermentation were observed. Since about 80% of the cumulative urinary 15N was recovered within 24 h, it was concluded that the biomarker 15N-LU was useful to monitor processes in the proximal colon rather than in the distal colon. [ABSTRACT FROM AUTHOR]

This article discusses the sociology of religion in the Netherlands. The sociology of religion in the Netherlands actually did not take shape until after the second world war. Undoubtedly there were a few starts in the different denominations before 1940, but the actual development of the discipline cannot be conceptualized without constantly keeping the postwar situation in Holland in mind. In the political and hence also in the religious field, once can call the Netherlands of the interwar-period a petrified society. Pillarization was at its peak, as shown by the deadly grip in which the governing Christian parties held each other in parliament; they were totally dependent on one another. Christian coalition governments followed each other in rapid succession, especially in the critical thirties. In these, the names of the various ministers did not change, but only the names of the cabinets: First Cabinet Colijin, Second Cabinet Colijin and so forth. The three main churches: the Roman Catholic, the Dutch Reformed and the Free Reformed, kept silent, which was not too difficult for the first and the third, because they had actual links with the political parties of their members, but the Dutch Reformed church, as the classical Volkskirche was torn apart by its own discord and so did not speak.

Background and Hypothesis: Chronic kidney disease (CKD) patients are advised to limit their protein intake. A high protein diet is known to induce glomerular hyperfiltration, as well as hypertrophy of the remnant kidney, and glomerulosclerosis. Whether the diet causes changes in kidney tubule transport via gut microbiome metabolites is still unknown. We hypothesized that protein intake affects not only the intestinal generation and absorption, but also the kidney disposal of microbial amino acid metabolites., Methods: We combined data from animal models and human studies. 5/6th nephrectomy rats were administered a high (HP) or low-protein (LP) diet for 7 weeks. Plasma and urine concentration of the uremic toxins (UTs) indoxyl sulfate (IS), p-cresyl sulfate (PCS), and p-cresyl glucuronide (PCG) were measured. Their fractional excretion (FE) was calculated. The expression of kidney membrane transporters OAT1, OAT3, BCRP, OCT2 and MRP4 was analyzed. Differences in FE of UTs between individuals with higher and lower protein intake in two CKD cohorts were sought., Results: CKD rats on an HP diet showed increased plasma levels of PCS and PCG but not IS compared to rats on a LP diet. Conversely, urinary excretion and FE of IS were higher in the HP CKD group. BCRP, MRP4 and OCT2 were not influenced by the diet. OAT1 and OAT3 were upregulated in the HP CKD group. In two independent cohorts of CKD patients, individuals with a high dietary protein intake showed a significantly higher FE of IS., Conclusions: A HP diet leads to a higher generation and/or absorption of aminoacid-derived UT precursors in CKD rodent models and humans, most likely via gut microbiome modulation. We demonstrate that dietary protein intake modulates transcription and expression of OAT1 and OAT3, corroborating the existence of the remote sensing and signaling hypothesis. Dietary protein intake influences kidney physiology beyond glomerular filtration., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Rationale & Objective: Kidneys are vital for vitamin D metabolism, and disruptions in both production and catabolism occur in chronic kidney disease. Although vitamin D activation occurs in numerous tissues, the kidneys are the most relevant source of circulating active vitamin D. This study investigates extrarenal vitamin D activation and the impact of kidney transplantation on vitamin D metabolism in patients who are anephric., Study Design: Case series., Setting & Participants: Adult patients with previous bilateral nephrectomy (anephric) not receiving active vitamin D therapy evaluated at the time of (N=38) and 1 year after (n=25) kidney transplantation., Analytical Approach: Chromatography with tandem mass spectrometry was used to measure vitamin D metabolites. Activity of CYP24A1 [24,25(OH) 2 D/25(OH)D] and CYP27B1 [1α,25(OH) 2 D/25(OH)D] is expressed as metabolic ratios. Differences between time points were evaluated by paired t-test or Wilcoxon matched-pairs signed-rank test., Results: At time of transplantation, 1α,25(OH) 2 D was detectable in all patients (4-36pg/mL). There was a linear relationship between 25(OH)D and 1α,25(OH) 2 D levels (r=0.58, P<0.001), with 25(OH)D explaining 34% of the variation in 1α,25(OH) 2 D levels. There were no associations between 1α,25(OH) 2 D and biointact parathyroid hormone (PTH) or fibroblast growth factor 23 (FGF-23). One year after transplantation, 1α,25(OH) 2 D levels recovered (+205%), and CYP27B1 activity increased (+352%). Measures of vitamin D catabolism, 24,25(OH) 2 D and CYP24A1 activity increased 3- to 5-fold. Also, at 12 months after transplantation, 1α,25(OH) 2 D was positively correlated with PTH (ρ=0.603, P=0.04) but not with levels of 25(OH)D or FGF-23., Limitations: Retrospective, observational study design with a small cohort size., Conclusions: Low-normal levels of 1α,25(OH) 2 D was demonstrated in anephric patients, indicating production outside the kidneys. This extrarenal CYP27B1 activity may be more substrate driven than hormonally regulated. Kidney transplantation seems to restore kidney CYP27B1 and CYP24A1 activity, as evaluated by vitamin D metabolic ratios, resulting in both increased vitamin D production and catabolism. These findings may have implications for vitamin D supplementation strategies in the setting of kidney failure and transplantation., Plain-Language Summary: Vitamin D activation occurs in multiple tissues, but the kidneys are considered the only relevant source of circulating levels. This study investigates vitamin D activation outside the kidneys by measuring vitamin D metabolites in 38 patients without kidneys. Active vitamin D was detectable in all patients, indicating production outside of the kidneys. There was a strong relationship between active and precursor vitamin D levels, but no association with mineral metabolism hormones, indicating that vitamin D production was more substrate dependent than hormonally regulated. One year after kidney transplantation, active vitamin D levels increased 2-fold and breakdown products increased 3-fold, indicating that production and degradation of the hormone recovers after kidney transplantation. These findings are relevant for future research into vitamin D supplementation in kidney failure., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Rationale & Objective: Prior studies have demonstrated the diagnostic potential of urinary chemokines C-X-C motif ligand 9 (CXCL9) and CXCL10 for kidney transplant rejection. However, their benefit in addition to clinical information has not been demonstrated. We evaluated the diagnostic performance for detecting acute rejection of urinary CXCL9 and CXCL10 when integrated with clinical information., Study Design: Single-center prospective cohort study., Setting & Participants: We analyzed 1,559 biopsy-paired urinary samples from 622 kidney transplants performed between April 2013 and July 2019 at a single transplant center in Belgium. External validation was performed in 986 biopsy-paired urinary samples., Tests Compared: We quantified urinary CXCL9 (uCXCL9) and CXCL10 (uCXCL10) using an automated immunoassay platform and normalized the values to urinary creatinine. Urinary chemokines were incorporated into a multivariable model with routine clinical markers (estimated glomerular filtration rate, donor-specific antibodies, and polyoma viremia) (integrated model). This model was then compared with the tissue diagnosis according to the Banff classification for acute rejection., Outcome: Acute rejection detected on kidney biopsy using the Banff classification., Results: Chemokines integrated with routine clinical markers had high diagnostic value for detection of acute rejection (n=150) (receiver operating characteristic area under the curve 81.3% [95% CI, 77.6-85.0]). The integrated model would help avoid 59 protocol biopsies per 100 patients when the risk for rejection is predicted to be below 10%. The performance of the integrated model was similar in the external validation cohort., Limitations: The cross-sectional nature obviates investigating the evolution over time and prediction of future rejection., Conclusions: The use of an integrated model of urinary chemokines and clinical markers for noninvasive monitoring of rejection could enable a reduction in the number of biopsies. Urinary chemokines may be useful noninvasive biomarkers whose use should be further studied in prospective randomized trials to clarify their role in guiding clinical care and the use of biopsies to detect rejection after kidney transplantation., Plain-Language Summary: Urinary chemokines CXCL9 and CXCL10 have been suggested to be good noninvasive biomarkers of kidney transplant rejection. However, defining a context of use and integration with clinical information is necessary before clinical implementation can begin. In this study, we demonstrated that urinary chemokines CXCL9 and CXCL10, together with clinical information, have substantial diagnostic accuracy for the detection of acute kidney transplant rejection. Application of urinary chemokines together with clinical information may guide biopsy practices following kidney transplantation and potentially reduce the need for kidney transplant biopsies., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Kidney transplantation is the most efficient renal replacement therapy. Current diagnostics for monitoring graft health are either invasive or lack precision. Metabolomics is an emerging discipline focused on the analysis of the small molecules involved in metabolism. Given the kidneys' central role in metabolic homeostasis and previous observations of altered metabolites correlating with restricted kidney graft function, metabolomics is highly promising for the discovery of novel biomarkers and the development of novel diagnostics. In this perspective, we summarize the known metabolic roles for the kidney, discuss biomarkers of graft health and immune status emerging from metabolomics research, and provide our perspective on how these and future findings can be integrated in clinical practice to enable precision diagnostics.

Chronic kidney disease (CKD)-mineral bone disorder (CKD-MBD) leads to fractures and cardiovascular disease. Observational studies suggest beneficial effects of dietary fiber on both bone and cardiovascular outcomes, but the effect of fiber on CKD-MBD is unknown. To determine the effect of fiber on CKD-MBD, we fed the Cy/+ rat with progressive CKD a casein-based diet of 0.7% phosphate with 10% inulin (fermentable fiber) or cellulose (non-fermentable fiber) from 22 weeks to either 30 or 32 weeks of age (~30% and ~15% of normal kidney function; CKD 4 and 5). We assessed CKD-MBD end points of biochemistry, bone quantity and quality, cardiovascular health, and cecal microbiota and serum gut-derived uremic toxins. Results were analyzed by two-way analysis of variance (ANOVA) to evaluate the main effects of CKD stage and inulin, and their interaction. The results showed that in CKD animals, inulin did not alter kidney function but reduced the increase from stage 4 to 5 in serum levels of phosphate and parathyroid hormone, but not fibroblast growth factor-23 (FGF23). Bone turnover and cortical bone parameters were similarly improved but mechanical properties were not altered. Inulin slowed progression of aorta and cardiac calcification, left ventricular mass index, and fibrosis. To understand the mechanism, we assessed intestinal microbiota and found changes in alpha and beta diversity and significant changes in several taxa with inulin, together with a reduction in circulating gut derived uremic toxins such as indoxyl sulfate and short-chain fatty acids. In conclusion, the addition of the fermentable fiber inulin to the diet of CKD rats led to a slowed progression of CKD-MBD without affecting kidney function, likely mediated by changes in the gut microbiota composition and lowered gut-derived uremic toxins. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research., (© 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.)

Background: Chronic kidney disease (CKD) patients exhibit a heightened cardiovascular (CV) risk which may be partially explained by increased medial vascular calcification. Although gut-derived uremic toxin trimethylamine N-oxide (TMAO) is associated with calcium-phosphate deposition, studies investigating phenylacetylglutamine's (PAG) pro-calcifying potential are missing., Methods: The effect of TMAO and PAG in vascular calcification was investigated using 120 kidney failure patients undergoing living-donor kidney transplantation (LD-KTx), in an observational, cross-sectional manner. Uremic toxin concentrations were related to coronary artery calcification (CAC) score, epigastric artery calcification score, and markers of established non-traditional risk factors that constitute to the 'perfect storm' that drives early vascular aging in this patient population. Vascular smooth muscle cells were incubated with TMAO or PAG to determine their calcifying effects in vitro and analyse associated pathways by which these toxins may promote vascular calcification., Results: TMAO, but not PAG, was independently associated with CAC score after adjustment for CKD-related risk factors in kidney failure patients. Neither toxin was associated with epigastric artery calcification score; however, PAG was independently, positively associated with 8-hydroxydeoxyguanosine. Similarly, TMAO, but not PAG, promoted calcium-phosphate deposition in vitro, while both uremic solutes induced oxidative stress., Conclusions: In conclusion, our translational data confirm TMAO's pro-calcifying effects, but both toxins induced free radical production detrimental to vascular maintenance. Our findings suggest these gut-derived uremic toxins have different actions on the vessel wall and therapeutically targeting TMAO may help reduce CV-related mortality in CKD., (© 2023 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Background: Studies on academic integrity reveal high rates of plagiarism and cheating among students. We have developed an online teaching tool, Integrity Games ( https://integgame.eu/ ), that uses serious games to teach academic integrity. In this paper, we test the impact of a soft intervention - a short quiz - that was added to the Integrity Games website to increase users' interest in learning about integrity. Based on general principles of behavioral science, our quiz highlighted the intricacy of integrity issues, generated social comparisons, and produced personalized advice. We expected that these interventions would create a need for knowledge and encourage participants to spend more time on the website., Methods: In a randomized controlled trial involving N = 405 students from Switzerland and France, half of the users had to take a short quiz before playing the serious games, while the other half could directly play the games. We measured how much time they spent playing the games, and, in a post-experimental survey, we measured their desire to learn about integrity issues and their understanding of integrity issues., Results: Contrary to our expectations, the quiz had a negative impact on time spent playing the serious games. Moreover, the quiz did not increase participants' desire to learn about integrity issues or their overall understanding of the topic., Conclusions: Our quiz did not have any measurable impact on curiosity or understanding of integrity issues, and may have had a negative impact on time spent on the Integrity games website. Our results highlight the difficulty of implementing behavioral insights in a real-world setting., Trial Registration: The study was preregistered at https://osf.io/73xty ., (© 2023. The Author(s).)

Background: Common genetic variants of the enzymes and efflux pump involved in tacrolimus disposition have been associated with calcineurin inhibitor nephrotoxicity, but their importance is unclear because of the multifactorial background of renal fibrosis. This study explores the pro-fibrotic response of tacrolimus exposure in relation to the differential capacity for tacrolimus metabolism in proximal tubule cells (PTCs) with a variable (pharmaco)genetic background., Methods: PTCs were obtained from protocol allograft biopsies with different combinations of CYP3A5 and ABCB1 variants and were incubated with tacrolimus within the concentration range found in vivo. Gene and protein expression, CYP3A5 and P-glycoprotein function, and tacrolimus metabolites were measured in PTC. Connective tissue growth factor (CTGF) expression was assessed in protocol biopsies of kidney allograft recipients., Results: PTCs produce CTGF in response to escalating tacrolimus exposure, which is approximately 2-fold higher in cells with the CYP3A5*1 and ABCB1 TT combination in vitro. Increasing tacrolimus exposure results in relative higher generation of the main tacrolimus metabolite {13-O-desmethyl tacrolimus [M1]} in cells with this same genetic background. Protocol biopsies show a larger increase in in vivo CTGF tissue expression over time in TT vs. CC/CT but was not affected by the CYP3A5 genotype., Conclusions: Tacrolimus exposure induces a pro-fibrotic response in a PTC model in function of the donor pharmacogenetic background associated with tacrolimus metabolism. This finding provides a mechanistic insight into the nephrotoxicity associated with tacrolimus treatment and offers opportunities for a tailored immunosuppressive treatment., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Kidney transplantation (KTx) is the preferred form of renal replacement therapy in chronic kidney disease (CKD) patients, owing to increased quality of life and reduced mortality when compared to chronic dialysis. Risk of cardiovascular disease is reduced after KTx; however, it is still a leading cause of death in this patient population. Thus, we aimed to investigate whether functional properties of the vasculature differed two years post-KTx (postKTx) compared to baseline (time of KTx). Using the EndoPAT device in 27 CKD patients undergoing living-donor KTx, we found that vessel stiffness significantly improved while endothelial function worsened postKTx vs. baseline. Furthermore, baseline serum indoxyl sulphate (IS), but not p-cresyl sulphate, was independently negatively associated with reactive hyperemia index, a marker of endothelial function, and independently positively associated with P-selectin postKTx. Finally, to better understand the functional effects of IS in vessels, we incubated human resistance arteries with IS overnight and performed wire myography experiments ex vivo. IS-incubated arteries showed reduced bradykinin-mediated endothelium-dependent relaxation compared to controls via reduced nitric oxide (NO) contribution. Endothelium-independent relaxation in response to NO donor sodium nitroprusside was similar between IS and control groups. Together, our data suggest that IS promotes worsened endothelial dysfunction postKTx, which may contribute to the sustained CVD risk.

The molecular mechanisms underlying metabolic bone diseases, including renal osteodystrophy, are poorly understood. Transcriptomics are increasingly used to characterize biological molecular networks and prove promising in identifying therapeutic targets and biomarkers. A reliable method for obtaining sufficient amounts of high quality RNA from human bone biopsies is a prerequisite for the implementation of molecular diagnostics in clinical research and practice. The present study aimed to develop a simple and adequate method for isolating bone and bone marrow mRNA from transiliac bone biopsies. Several storage, separation, and extraction procedures were compared. The procedure was optimized in pig samples and subsequently validated in human samples. Appropriate amounts of mineralized bone and bone marrow mRNA of moderate to high quality were obtained from transiliac bone biopsies that were immersed in the stabilizing solution Allprotect Tissue Reagent at room temperature for up to 3 days prior to freezing. After thawing, bone marrow and mineralized bone were separated by a multistep centrifugation procedure and subsequently disrupted and homogenized by a bead crusher. Appropriate separation of mineralized bone and bone marrow was confirmed by discriminatory gene expression profiles., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Kidney transplant injury processes are associated with molecular changes in kidney tissue, primarily related to immune cell activation and infiltration. How these processes are reflected in the circulating immune cells, whose activation is targeted by strong immunosuppressants, is poorly understood. To study this, we analyzed the molecular alterations in 384 peripheral blood samples from four European transplant centers, taken at the time of a kidney allograft biopsy, selected for their phenotype, using RNA-sequencing. In peripheral blood, differentially expressed genes in 136 rejection and 248 no rejection samples demonstrated upregulation of glucocorticoid receptor and nucleotide oligomerization domain-like receptor signaling pathways. Pathways enriched in antibody-mediated rejection (ABMR) were strongly immune-specific, whereas pathways enriched in T cell-mediated rejection were less immune related. In polyomavirus infection, upregulation of mitochondrial dysfunction and interferon signaling pathways was seen. Next, we integrated the blood results with transcriptomics of 224 kidney allograft biopsies which showed consistently upregulated genes per phenotype in both blood and biopsy. In single-cell RNASeq (scRNASeq) analysis of seven kidney allograft biopsies, the consistently overexpressed genes in ABMR were mostly expressed by infiltrating leukocytes in the allograft. Similarly, in peripheral blood scRNASeq analysis, these genes were overexpressed in ABMR in immune cell subtypes. Furthermore, overexpression of these genes in ABMR was confirmed in independent cohorts in blood and biopsy. Thus, our results highlight the immune activation pathways in peripheral blood leukocytes at the time of kidney allograft pathology, despite the use of current strong immunosuppressants, and provide a framework for future therapeutic interventions., (Copyright © 2022 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Patients with kidney failure (KF) have a high incidence of cardiovascular (CV) disease, partly driven by insufficient clearance of uremic toxins. Recent investigations have questioned the accepted effects of adverse lipid profile and CV risk in uremic patients. Therefore, we related a panel of uremic toxins previously associated with CV morbidity/mortality to a full lipid profile in a large, tri-national, cross-sectional cohort. Total, high-density lipoprotein (HDL), non-HDL, low-density lipoprotein (LDL), and remnant cholesterol, as well as triglyceride, levels were associated with five uremic toxins in a cohort of 611 adult KF patients with adjustment for clinically relevant covariates and other patient-level variables. Univariate analyses revealed negative correlations of total, non-HDL, and LDL cholesterol with all investigated uremic toxins. Multivariate linear regression analyses confirmed independent, negative associations of phenylacetylglutamine with total, non-HDL, and LDL cholesterol, while indole-3 acetic acid associated with non-HDL and LDL cholesterol. Furthermore, trimethylamine-N-Oxide was independently and negatively associated with non-HDL cholesterol. Sensitivity analyses largely confirmed findings in the entire cohort. In conclusion, significant inverse associations between lipid profile and distinct uremic toxins in KF highlight the complexity of the uremic milieu, suggesting that not all uremic toxin interactions with conventional CV risk markers may be pathogenic.

Apelin exists in many isoforms, both in the circulation and in specific tissues. Apelin peptides have a short half-life but preservation before measurement is scarcely studied. Reproducible mass spectrometry methods to specifically measure a broad range of apelinergic peptide isoforms are currently lacking. A sample protocol to conserve apelinergic peptides in the preanalytical phase and a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method to measure apelinergic isoforms was developed. Apelin was measured in plasma. For validation, human embryonic kidney (HEK) cells transfected with cDNA for preproapelin were used. Results were compared with a validated radioimmunoassay (RIA) method. Acidifying plasma to pH 2.5 improves post-sampling stability of apelin. HPLC-MS/MS was unable to detect apelin isoforms in plasma of healthy volunteers (n = 16) and chronic kidney disease patients (n = 4). RIA could detect apelin in concentrations between 71 and 263 fmol/l in 10 healthy volunteers. An optimized preanalytical protocol was developed. A sensitive and specific HPLC-MS/MS method failed to detect apelin in human plasma. Apelin-36 was detected in HEK cells transfected with cDNA for preproapelin. Currently, RIA with relatively selective antibodies is the best alternative for the measurement of apelin but novel sensitive and specific methods are needed., (© 2022. The Author(s).)

Despite the critical role of cytokines in allograft rejection, the relation of peripheral blood cytokine profiles to clinical kidney transplant rejection has not been fully elucidated. We assessed 28 cytokines through multiplex assay in 293 blood samples from kidney transplant recipients at time of graft dysfunction. Unsupervised hierarchical clustering identified a subset of patients with increased pro-inflammatory cytokine levels. This patient subset was hallmarked by a high prevalence (75%) of donor-specific anti-human leukocyte antigen antibodies (HLA-DSA) and histological rejection (70%) and had worse graft survival compared to the group with low cytokine levels (HLA-DSA in 1.7% and rejection in 33.7%). Thirty percent of patients with high pro-inflammatory cytokine levels and HLA-DSA did not have histological rejection. Exploring the cellular origin of these cytokines, we found a corresponding expression in endothelial cells, monocytes, and natural killer cells in single-cell RNASeq data from kidney transplant biopsies. Finally, we confirmed secretion of these cytokines in HLA-DSA-mediated cross talk between endothelial cells, NK cells, and monocytes. In conclusion, blood pro-inflammatory cytokines are increased in kidney transplant patients with HLA-DSA, even in the absence of histology of rejection. These observations challenge the concept that histology is the gold standard for identification of ongoing allo-immune activation after transplantation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Van Loon, Lamarthée, Barba, Claes, Coemans, de Loor, Emonds, Koshy, Kuypers, Proost, Senev, Sprangers, Tinel, Thaunat, Van Craenenbroeck, Schols and Naesens.)

Bone microarchitecture is an important component of bone quality and disturbances may reduce bone strength and resistance to trauma. Kidney transplant recipients have an excess risk of fractures, and bone loss affecting both trabecular and cortical bone compartments have been demonstrated after kidney transplantation. The primary aim of this study was to investigate the impact of kidney transplantation on trabecular and cortical bone microarchitecture, assessed by histomorphometry and micro computed tomography (μCT). Iliac crest bone biopsies, analyzed by bone histomorphometry and μCT, were performed at time of kidney transplantation and 12 months post-transplantation in an unselected cohort of 30 patients. Biochemical markers of mineral metabolism and bone turnover were measured at both time-points. At 12 months post-transplantation, bone turnover was low in 5 (17%) and normal in 25 (83%) patients. By histomorphometry, bone remodeling normalized, with decreases in eroded perimeters (4.0 to 2.1%, p  = 0.02) and number of patients with marrow fibrosis (41 to 0%, p  < 0.001). By μCT, trabecular thickness (134 to 125 μM, p  = 0.003) decreased slightly. Other parameters of bone volume and microarchitecture, including cortical thickness (729 to 713 μm, p  = 0.73) and porosity (10.2 to 9.5%, p  = 0.15), remained stable. We conclude that kidney transplantation with current immunosuppressive protocols has a limited impact on bone microarchitecture., Competing Interests: PE reports personal fees from Amgen and Vifor-FMC. Remaining authors have no conflicts of interest to declare., (© 2022 The Authors. Published by Elsevier Inc.)