Publications by authors named "Pieter Evenepoel"

229 Publications

Bone health in ageing men.

Rev Endocr Metab Disord 2022 Jul 16. Epub 2022 Jul 16.

Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Herestraat 49, ON1bis box 902, 3000 , Leuven, Belgium.

Osteoporosis does not only affect postmenopausal women, but also ageing men. The burden of disease is projected to increase with higher life expectancy both in females and males. Importantly, osteoporotic men remain more often undiagnosed and untreated compared to women. Sex steroid deficiency is associated with bone loss and increased fracture risk, and circulating sex steroid levels have been shown to be associated both with bone mineral density and fracture risk in elderly men. However, in contrast to postmenopausal osteoporosis, the contribution of relatively small decrease of circulating sex steroid concentrations in the ageing male to the development of osteoporosis and related fractures, is probably only minor. In this review we provide several clinical and preclinical arguments in favor of a 'bone threshold' for occurrence of hypogonadal osteoporosis, corresponding to a grade of sex steroid deficiency that in general will not occur in many elderly men. Testosterone replacement therapy has been shown to increase bone mineral density in men, however data in osteoporotic ageing males are scarce, and evidence on fracture risk reduction is lacking. We conclude that testosterone replacement therapy should not be used as a sole bone-specific treatment in osteoporotic elderly men.
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http://dx.doi.org/10.1007/s11154-022-09738-5DOI Listing
July 2022

Vascular calcification of the abdominal aorta has minimal impact on lumbar spine bone density in patients with chronic kidney disease.

Bone 2022 09 1;162:116482. Epub 2022 Jul 1.

Department of Microbiology, Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, KU Leuven, Leuven, Belgium; Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium. Electronic address:

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http://dx.doi.org/10.1016/j.bone.2022.116482DOI Listing
September 2022

Lipid Profile Is Negatively Associated with Uremic Toxins in Patients with Kidney Failure-A Tri-National Cohort.

Toxins (Basel) 2022 06 16;14(6). Epub 2022 Jun 16.

Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, SE-17177 Stockholm, Sweden.

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.
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http://dx.doi.org/10.3390/toxins14060412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9231137PMC
June 2022

Clinical utility of bone turnover markers in patients with chronic kidney disease.

Curr Opin Nephrol Hypertens 2022 07 10;31(4):332-338. Epub 2022 Jun 10.

Department of Microbiology, Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, KU Leuven.

Purpose Of Review: The burden of fractures is very high in patients with chronic kidney disease (CKD). It is increasingly recognized that knowledge of bone turnover is of paramount importance in guiding mineral metabolism and osteoporosis therapy in CKD. Bone histomorphometry is the gold standard to assess bone turnover, but is seldomly performed in clinical practice. Bone turnover markers (BTMs) may be the long awaited noninvasive diagnostic that may help to close the therapeutic gap in patients with advanced CKD presenting with bone fragility.

Recent Findings: Mounting evidence indicates that BTMs may be useful in skeletal and nonskeletal risk stratification, in guiding mineral metabolism and osteoporosis therapy, and in monitoring the therapeutic response.

Summary: BTMs provide information that is complementary to other clinical tests. It may be envisioned that in the near future, the assessment of nonkidney cleared BTMs may become part of routine clinical evaluation and monitoring of bone health in CKD patients, integrated with clinical risk factors, imaging data and, eventually, bone histomorphometry. Panels of BTMs will likely be more informative than single markers, and the same might hold true for trends as opposed to single time point data.
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http://dx.doi.org/10.1097/MNH.0000000000000798DOI Listing
July 2022

Bone histomorphometry for the diagnosis of renal osteodystrophy: a call for harmonization of reference ranges.

Kidney Int 2022 Aug 25;102(2):431-434. Epub 2022 May 25.

Department of Microbiology, Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, Katholieke Universiteit Leuven, Belgium; Division of Nephrology, Department of Medicine, University Hospitals Leuven, Leuven, Belgium. Electronic address:

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http://dx.doi.org/10.1016/j.kint.2022.04.030DOI Listing
August 2022

Time for Revival of Bone Biopsy with Histomorphometric Analysis in Chronic Kidney Disease (CKD): Moving from Skepticism to Pragmatism.

Nutrients 2022 Apr 22;14(9). Epub 2022 Apr 22.

Policlinico San Martino, 16132 Genova, Italy.

Bone Biopsy (BB) with histomorphometric analysis still represents the gold standard for the diagnosis and classification of different forms of renal osteodystrophy. Bone biopsy is the only technique able to provide comprehensive information on all bone parameters, measuring static and dynamic parameters of turnover, cortical and trabecular microarchitecture, and mineralization defects. In nephrological practice, bone biopsy yields relevant indications to support therapeutic choices in CKD, heavily impacting the management and prognosis of uremic patients. Unfortunately, the use of bone biopsy has decreased; a lack of expertise in performing and interpreting, perceived procedure invasiveness and pain, and reimbursement issues have all contributed to this decline. Nevertheless, both bone biomarkers and instrumental images cannot be considered reliable surrogates for histological findings, being insufficiently accurate to properly evaluate underlying mineral and bone disorders. This is a multidisciplinary position paper from the Nephrology and Osteoporosis Italian Scientific Societies with the purpose of restating the role of bone biopsy in CKD patient management and of providing strong solutions to allow diffusion of this technique in Italy, but potentially also in other countries. The Italian approach through the optimization and standardization of bone biopsy procedure, the construction of the Italian Hub and Spoke network, and a request for adjustment and national homogenization of reimbursement to the Italian Health Ministry has led the way to implement bone biopsy and to improve CKD patient management and prognosis.
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http://dx.doi.org/10.3390/nu14091742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9103887PMC
April 2022

Parathyroidectomy Versus Calcimimetic: The Lower the PTH the Better?

J Clin Endocrinol Metab 2022 07;107(8):e3532-e3533

Department of Microbiology, Immunology and T ransplantation; Nephrology and Renal Transplantation Research Group, KU Leuven, 3000 Leuven, Belgium.

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http://dx.doi.org/10.1210/clinem/dgac211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9282264PMC
July 2022

Effects of an SGLT Inhibitor on the Production, Toxicity, and Elimination of Gut-Derived Uremic Toxins: A Call for Additional Evidence.

Toxins (Basel) 2022 03 15;14(3). Epub 2022 Mar 15.

Nephrology Division, NYU Langone Medical Center, New York, NY 10016, USA.

Sodium-glucose cotransporter (SGLT) inhibitors are a class of oral hypoglycemic agents, which, in recent years, have been shown to improve renal and cardiovascular outcomes in patients with diabetic and non-diabetic chronic kidney disease. There remains considerable debate regarding the potential glucose-independent mechanisms by which these benefits are conferred. SGLT inhibitors, to a variable extent, impair small intestinal glucose absorption, facilitating the delivery of glucose into the colon. This suppresses protein fermentation, and thus the generation of uremic toxins such as phenols and indoles. It is acknowledged that such a shift in gut microbial metabolism yields health benefits for the host. SGLT inhibition, in addition, may be hypothesized to foster the renal clearance of protein-bound uremic toxins. Altered generation and elimination of uremic toxins may be in the causal pathway between SGLT inhibition and improved cardiometabolic health. Present review calls for additional research.
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http://dx.doi.org/10.3390/toxins14030210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8954461PMC
March 2022

Contemporary kidney transplantation has a limited impact on bone microarchitecture.

Bone Rep 2022 Jun 7;16:101172. Epub 2022 Feb 7.

Department of Microbiology, Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, KU Leuven, Leuven, Belgium.

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%,  = 0.02) and number of patients with marrow fibrosis (41 to 0%,  < 0.001). By μCT, trabecular thickness (134 to 125 μM,  = 0.003) decreased slightly. Other parameters of bone volume and microarchitecture, including cortical thickness (729 to 713 μm,  = 0.73) and porosity (10.2 to 9.5%,  = 0.15), remained stable. We conclude that kidney transplantation with current immunosuppressive protocols has a limited impact on bone microarchitecture.
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http://dx.doi.org/10.1016/j.bonr.2022.101172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8851083PMC
June 2022

Prevalence, progression and implications of breast artery calcification in patients with chronic kidney disease.

Clin Kidney J 2022 Feb 5;15(2):295-302. Epub 2021 Oct 5.

Department of Nephrology and Renal Transplantation, University Hospitals Leuven and Laboratory of Nephrology, Department of Microbiology, Immunology, and Transplantation, KU Leuven, Leuven, Belgium.

Breast arterial calcification (BAC) is increasingly recognized as a specific marker of medial calcification. The present retrospective observational cohort study aimed to define the prevalence, progression rate, risk factors and clinical implications of BAC in chronic kidney disease (CKD) patients across stages of disease. The presence and extent of BAC were determined on mammograms in 310 females (58.7 ± 10.8 years, Caucasian) with CKD across various stages of disease [CKD G2-5D  = 132; transplant (Tx) recipients  = 178]. In a subset of 88 patients, repeat mammography was performed, allowing us to calculate the annualized BAC rate. Overall, BAC was observed in 34.7% of the patients. BAC prevalence (P = 0.02) and BAC score (P = 0.05) increased along the progression of CKD. In the overall cohort, patients with BAC were characterized by older age, more cardiovascular disease, more inflammation, higher pulse pressure and borderline higher prevalence of diabetes and were more often treated with a vitamin K antagonist (VKA). The BAC progression rate was significantly lower in Tx patients as compared with CKD G5D. Progressors were characterized by more inflammation, worse kidney function, higher BAC score and higher serum phosphate level (Tx only) at baseline and were more often treated with a VKA. Major adverse cardiovascular event-free survival was significantly worse in Tx patients with BAC. In conclusion, BAC is common among CKD patients, progresses at a slower pace in Tx patients as compared with CKD 5D and associates with dismal cardiovascular outcomes. BAC score, kidney function, serum phosphate at baseline and VKA usage seem to be important determinants of progression.
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http://dx.doi.org/10.1093/ckj/sfab178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8825218PMC
February 2022

Natural History of Bone Disease following Kidney Transplantation.

J Am Soc Nephrol 2022 03 19;33(3):638-652. Epub 2022 Jan 19.

Department of Microbiology, Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, KU Leuven, Leuven, Belgium

Background: Knowledge of the effect of kidney transplantation on bone is limited and fragmentary. The aim of this study was to characterize the evolution of bone disease in the first post-transplant year.

Methods: We performed a prospective, observational cohort study in patients referred for kidney transplantation under a steroid-sparing immunosuppressive protocol. Bone phenotyping was done before, or at the time of, kidney transplantation, and repeated at 12 months post-transplant. The phenotyping included bone histomorphometry, bone densitometry by dual-energy x-ray absorptiometry, and biochemical parameters of bone and mineral metabolism.

Results: Paired data were obtained for 97 patients (median age 55 years; 72% male; 21% of patients had diabetes). Bone turnover remained normal or improved in the majority of patients (65%). Bone histomorphometry revealed decreases in bone resorption (eroded perimeter, mean 4.6% pre- to 2.3% post-transplant; 0.001) and disordered bone formation (fibrosis, 27% pre- versus 2% post-transplant; <0.001). Whereas bone mineralization was normal in all but one patient pretransplant, delayed mineralization was seen in 15% of patients at 1 year post-transplant. Hypophosphatemia was associated with deterioration in histomorphometric parameters of bone mineralization. Changes in bone mineral density were highly variable, ranging from -18% to +17% per year. Cumulative steroid dose was related to bone loss at the hip, whereas resolution of hyperparathyroidism was related to bone gain at both spine and hip.

Conclusions: Changes in bone turnover, mineralization, and volume post-transplant are related both to steroid exposure and ongoing disturbances of mineral metabolism. Optimal control of mineral metabolism may be key to improving bone quality in kidney transplant recipients.

Clinical Trial Registry Name And Registration Number: Evolution of Bone Histomorphometry and Vascular Calcification Before and After Renal Transplantation, NCT01886950.
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http://dx.doi.org/10.1681/ASN.2021081081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8975071PMC
March 2022

Diagnostic Accuracy of Noninvasive Bone Turnover Markers in Renal Osteodystrophy.

Am J Kidney Dis 2022 05 26;79(5):667-676.e1. Epub 2021 Oct 26.

Department of Microbiology, Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, KU Leuven, Belgium; Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Belgium. Electronic address:

Rationale & Objective: Bone biopsy remains the gold standard for diagnosing renal osteodystrophy as comparable noninvasive alternatives have yet to be established. This study investigated the diagnostic accuracy of biochemical markers of skeletal remodeling to predict bone turnover.

Study Design: Cross-sectional retrospective diagnostic test study.

Setting & Participants: Patients with chronic kidney disease glomerular filtration rate categories 4-5, including patients treated with dialysis (G4-G5D) and kidney transplant recipients with successful transiliac bone biopsies.

Tests Compared: Bone turnover as determined by bone histomorphometry was compared with the following biochemical markers: full-length (amino acids 1-84) "biointact" parathyroid hormone (PTH), bone-specific alkaline phosphatase (BsAP), intact procollagen type I N-terminal propeptide (PINP), and tartrate-resistant acid phosphatase isoform 5b (TRAP5b).

Outcome: Diagnostic performance was evaluated by area under the receiver operator characteristics curve (AUC), sensitivity, specificity, and negative and positive predictive values. Optimal diagnostic cutoffs were determined in an exploration cohort (n = 100) and validated in a separate cohort (n = 99).

Results: All biomarkers differed across categories of low 33 (17%), normal 109 (55%), and high 57 (29%) bone turnover. AUC values were in the range of 0.75-0.85. High negative predictive values (≥90%) were found for both high and low bone turnover, indicating the ability to rule out both conditions using the suggested biomarker cutoffs. The highest diagnostic performances were seen with combinations of biomarkers, with overall diagnostic accuracies of 90% for high turnover, and 78% for low turnover. Results were comparable for kidney transplant candidates and recipients in a sensitivity analysis.

Limitations: The single-center approach and heterogeneity of the study cohort are main limitations of this study.

Conclusions: We conclude that the diagnostic performance of biochemical markers of bone turnover is acceptable, with clinical utility in ruling out both high and low turnover bone disease.
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http://dx.doi.org/10.1053/j.ajkd.2021.07.027DOI Listing
May 2022

Hepatic and Vascular Vitamin K Status in Patients with High Cardiovascular Risk.

Nutrients 2021 Oct 1;13(10). Epub 2021 Oct 1.

Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6200 MD Maastricht, The Netherlands.

Vitamin K dependent proteins (VKDP), such as hepatic coagulation factors and vascular matrix Gla protein (MGP), play key roles in maintaining physiological functions. Vitamin K deficiency results in inactive VKDP and is strongly linked to vascular calcification (VC), one of the major risk factors for cardiovascular morbidity and mortality. In this study we investigated how two vitamin K surrogate markers, dephosphorylated-undercarboxylated MGP (dp-ucMGP) and protein induced by vitamin K absence II (PIVKA-II), reflect vitamin K status in patients on hemodialysis or with calcific uremic arteriolopathy (CUA) and patients with atrial fibrillation or aortic valve stenosis. Through inter- and intra-cohort comparisons, we assessed the influence of vitamin K antagonist (VKA) use, vitamin K supplementation and disease etiology on vitamin K status, as well as the correlation between both markers. Overall, VKA therapy was associated with 8.5-fold higher PIVKA-II (0.25 to 2.03 AU/mL) and 3-fold higher dp-ucMGP (843 to 2642 pM) levels. In the absence of VKA use, non-renal patients with established VC have dp-ucMGP levels similar to controls (460 vs. 380 pM), while in HD and CUA patients, levels were strongly elevated (977 pM). Vitamin K supplementation significantly reduced dp-ucMGP levels within 12 months (440 to 221 pM). Overall, PIVKA-II and dp-ucMGP showed only weak correlation (r ≤ 0.26) and distinct distribution pattern in renal and non-renal patients. In conclusion, VKA use exacerbated vitamin K deficiency across all etiologies, while vitamin K supplementation resulted in a vascular VKDP status better than that of the general population. Weak correlation of vitamin K biomarkers calls for thoughtful selection lead by the research question. Vitamin K status in non-renal deficient patients was not anomalous and may question the role of vitamin K deficiency in the pathogenesis of VC in these patients.
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http://dx.doi.org/10.3390/nu13103490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8539359PMC
October 2021

Promoter Variant, Water Transport, and Outcomes in Peritoneal Dialysis.

N Engl J Med 2021 10;385(17):1570-1580

From the Division of Nephrology, Cliniques Universitaires Saint-Luc (J.M., E.G., O.D.), and Institut de Recherche Expérimentale et Clinique (J.M., C.M., H.D., A.S., N.H., J.-L.B., E.G., O.D.) and Institut de Recherche Santé et Société, Faculty of Public Health (R.C.), UCLouvain, Brussels, the Division of Nephrology, Clinique Saint-Joseph, Liege (P.B.), and the Department of Microbiology, Immunology, and Transplantation, Nephrology and Renal Transplantation Research Group, KU Leuven (P.E., B.B.), and the Department of Nephrology, Dialysis, and Renal Transplantation, University Hospitals Leuven (P.E., B.B.), Leuven - all in Belgium; the Department of Nephrology, Shanghai Jiao Tong University School of Medicine and Renji Hospital, Shanghai, China (Z.Y.); the Faculty of Medicine and Health Sciences, Keele University, Keele, United Kingdom (Z.Y., M.L., S.D.); the Institute of Physiology, University of Zurich, Zurich (H.D., O.D.), and the Center for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne (T.C.) - both in Switzerland; the Department of Clinical Epidemiology, Leiden University Medical Center, Leiden (M.V., F.D.), the Division of Nephrology, Department of Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam (A.M.C., D.G.S., R.T.K.), and the Department of Surgery, University Medical Center Groningen, Groningen (A.M.C.) - all in the Netherlands; the Division of Nephrology, Hospital Universitario La Paz, and Instituto de Investigación Sanitaria La Paz, Red de Investigación Renal, Universidad Autonoma, Madrid (R.S., M.A.B.); and Institut National de la Transfusion Sanguine, Paris (P.R.).

Background: Variability in ultrafiltration influences prescriptions and outcomes in patients with kidney failure who are treated with peritoneal dialysis. Variants in , the gene that encodes the archetypal water channel aquaporin-1, may contribute to that variability.

Methods: We gathered clinical and genetic data from 1851 patients treated with peritoneal dialysis in seven cohorts to determine whether variants were associated with peritoneal ultrafiltration and with a risk of the composite of death or technique failure (i.e., transfer to hemodialysis). We performed studies in cells, mouse models, and samples obtained from humans to characterize an variant and investigate mitigation strategies.

Results: The common promoter variant rs2075574 was associated with peritoneal ultrafiltration. Carriers of the TT genotype at rs2075574 (10 to 16% of patients) had a lower mean (±SD) net ultrafiltration level than carriers of the CC genotype (35 to 47% of patients), both in the discovery phase (506±237 ml vs. 626±283 ml, P = 0.007) and in the validation phase (368±603 ml vs. 563±641 ml, P = 0.003). After a mean follow-up of 944 days, 139 of 898 patients (15%) had died and 280 (31%) had been transferred to hemodialysis. TT carriers had a higher risk of the composite of death or technique failure than CC carriers (adjusted hazard ratio, 1.70; 95% confidence interval [CI], 1.24 to 2.33; P = 0.001), as well as a higher risk of death from any cause (24% vs. 15%, P = 0.03). In mechanistic studies, the rs2075574 risk variant was associated with decreases in promoter activity, aquaporin-1 expression, and glucose-driven osmotic water transport. The use of a colloid osmotic agent mitigated the effects of the risk variant.

Conclusions: A common variant in was associated with decreased ultrafiltration and an increased risk of death or technique failure among patients treated with peritoneal dialysis. (Funded by the Swiss National Science Foundation and others.).
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http://dx.doi.org/10.1056/NEJMoa2034279DOI Listing
October 2021

Patterns of renal osteodystrophy 1 year after kidney transplantation.

Nephrol Dial Transplant 2021 11;36(11):2130-2139

Department of Microbiology, Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, KU Leuven, Leuven, Belgium.

Background: Renal osteodystrophy is considered common, but is not well characterized in contemporary kidney transplant recipients. This study reports extensively on bone phenotype by bone histomorphometry, bone densitometry and novel bone biomarkers 1 year after kidney transplantation.

Methods: A transiliac bone biopsy and dual-energy X-ray absorptiometry scans were performed in 141 unselected kidney transplant recipients in this observational cohort study. Blood and 24-h urine samples were collected simultaneously.

Results: The median age was 57 ± 11 years, 71% were men and all were of Caucasian ethnicity. Bone turnover was normal in 71% of patients, low in 26% and high in just four cases (3%). Hyperparathyroidism with hypercalcaemia was present in 13% of patients, of which only one had high bone turnover. Delayed bone mineralization was detected in 16% of patients, who were characterized by hyperparathyroidism (137 versus 53 ρg/mL), a higher fractional excretion of phosphate (40 versus 32%) and lower levels of phosphate (2.68 versus 3.18 mg/dL) and calcidiol (29 versus 37 ng/mL) compared with patients with normal bone mineralization. Osteoporosis was present in 15-46% of patients, with the highest prevalence at the distal skeleton. The proportion of osteoporotic patients was comparable across categories of bone turnover and mineralization.

Conclusions: The majority of kidney transplant recipients, including patients with osteoporosis, have normal bone turnover at 1-year post-transplant. Low bone turnover is seen in a substantial subset, while high bone turnover is rare. Vitamin D deficiency and hypophosphataemia represent potential interventional targets to improve bone health post-transplant.
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http://dx.doi.org/10.1093/ndt/gfab239DOI Listing
November 2021

Strategies for asymmetrical triacetate dialyser heparin-free effective haemodialysis: the SAFE study.

Clin Kidney J 2021 Aug 28;14(8):1901-1907. Epub 2020 Nov 28.

Division of Nephrology, UZ Leuven, Leuven, Belgium.

Background: In haemodialysis, maintaining patency of the extracorporeal circuit requires the use of anticoagulants. Although (low molecular weight) heparins are the mainstay, these are not well tolerated in all patients. Alternative approaches include saline infusion, citrate-containing dialysate, regional citrate anticoagulation or the use of heparin-coated membranes. Asymmetric cellulose triacetate (ATA) dialysers have a low degree of platelet contact activation and might be an alternative to heparin-coated dialysers. The aim of this study was to test the clotting propensity of ATA when used without systemic anticoagulation.

Methods: We performed a Phase II pilot study in maintenance dialysis patients. The 'Strategies for Asymmetrical Triacetate dialyzer heparin-Free Effective hemodialysis' (SAFE) study was a two-arm open-label crossover study. In Arm A, patients were dialysed using 1.9 m ATA membranes in combination with a citrate-containing dialysate (1 mM). In Arm B, the ATA membrane was combined with high-volume predilution haemodiafiltration (HDF) without any other anticoagulation. The primary endpoint was the success rate to complete 4 h of haemodialysis without preterm clotting. Secondary endpoints included time to clotting and measures of dialysis adequacy.

Results: We scheduled 240 dialysis sessions (120/arm) in 20 patients. Patients were randomized 1:1 to start with Arm A or B. All patients crossed to the other arm halfway through the study. A total of 232 (96.7%) study treatments were delivered. Overall, 23 clotting events occurred, 7 in Arm A and 16 in Arm B. The success rate in Arm A (ATA + citrate-containing dialysate) was 90.8/94.0% [intention to treat (ITT)/as treated]. The success rate in Arm B (ATA + predilution HDF) was 83.3/86.2% (ITT/as treated). Time to clotting was borderline significantly better in Arm A (Mantel-Cox log rank P = 0.05).

Conclusion: ATA dialysers have a low clotting propensity and both predilution HDF and a citrate-containing dialysate resulted in high rates of completed dialysis sessions.
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http://dx.doi.org/10.1093/ckj/sfaa228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323132PMC
August 2021

European hemodialysis patient satisfaction with phosphate binders is associated with serum phosphorus levels: the Dialysis Outcomes and Practice Patterns Study.

Clin Kidney J 2021 Aug 11;14(8):1886-1893. Epub 2021 Jun 11.

Arbor Research Collaborative for Health, Ann Arbor, MI, USA.

Background: Hemodialysis (HD) patients are commonly prescribed phosphate binders (PBs) to manage serum phosphorus levels, as hyperphosphatemia is strongly associated with poorer survival. Nonadherence with the PB prescription is associated with elevated serum phosphorus levels. We studied associations between patient satisfaction with their PB and serum phosphorus levels and mortality rates.

Methods: Adult HD patients in Germany, Italy, Spain and the UK in the Dialysis Outcomes and Practice Patterns Study were administered a survey instrument in late 2017. Patients were asked about their satisfaction with their PBs, as measured through three questions (difficulty, inconvenience and dissatisfaction) on a 5-point Likert scale, with each dichotomized into average worst versus good responses. These were used as predictors in linear regression models of continuous serum phosphorus levels and in Cox proportional hazards models of mortality, with adjustments for demographics, comorbidities and laboratory values.

Results: Patients having greater difficulty, inconvenience and dissatisfaction with their PB had higher serum phosphorus levels in adjusted models {+0.21 mg/dL [95% confidence interval (CI) ±0.23], +0.30 (±0.21) and 0.36 (±0.22), respectively}, and higher odds of having serum phosphorus levels ≥6.0 mg/dL. Measures of dissatisfaction were also associated with an elevated risk of mortality, with adjusted hazard ratios of 2.2 (95% CI 1.3-3.6), 1.6 (1.0-2.6) and 1.7 (1.1-2.7), respectively; this association was not strongly affected by adjustment for baseline serum phosphorous level.

Conclusions: Self-reported difficulty, inconvenience and dissatisfaction in taking one's prescribed PBs were associated with elevated serum phosphorus levels and serum phosphorus levels above clinically meaningful thresholds. While the mechanism for the association with mortality is unclear, patient-reported satisfaction should be considered when attempting to manage patient serum phosphorus levels.
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http://dx.doi.org/10.1093/ckj/sfab098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323136PMC
August 2021

Static histomorphometry allows for a diagnosis of bone turnover in renal osteodystrophy in the absence of tetracycline labels.

Bone 2021 11 18;152:116066. Epub 2021 Jun 18.

Department of Microbiology, Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, KU Leuven, Belgium; Department of Medicine, Division of Nephrology, University Hospitals Leuven, Belgium. Electronic address:

A bone biopsy with prior tetracycline labeling is the gold standard to diagnose renal osteodystrophy. In cases of missing tetracycline labels, it is still paramount to gain clinically relevant information from the extracted bone sample, by evaluating the static histomorphometry. This study investigates the diagnostic performance of static histomorphometry for the evaluation of high and low bone turnover. Transiliac bone biopsies taken pre- or post- kidney transplantation, of sufficient quality for a full histomorphometric analysis were included (n = 205). The cohort was randomly split to provide separate exploration and validation subsets. Diagnostic performance was evaluated by area under the receiver operator characteristics curve (AUC). All histomorphometric parameters were significantly different across categories of low (24%), normal (60%), and high (16%) bone turnover, and all were significant predictors of both high and low bone turnover (AUC 0.71-0.84). Diagnostic performance was very good for high turnover, as a combination of static parameters resulted in negative and positive predictive values (NPV and PPV) of 80% and 96%, respectively. For low turnover, the combined model resulted in PPV of 71% and NPV of 82%. We conclude that in the absence of tetracycline labels, static histomorphometry provide an acceptable alternative for a diagnosis of bone turnover in renal osteodystrophy.
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http://dx.doi.org/10.1016/j.bone.2021.116066DOI Listing
November 2021

Effect of Dietary Inulin Supplementation on the Gut Microbiota Composition and Derived Metabolites of Individuals Undergoing Hemodialysis: A Pilot Study.

J Ren Nutr 2021 Sep 11;31(5):512-522. Epub 2021 Jun 11.

Division of Nutritional Sciences, University of Illinois, Urbana, Illinois; Department of Kinesiology and Community Health, University of Illinois, Urbana, Illinois. Electronic address:

Objective: The prebiotic fiber inulin has been studied in individuals undergoing hemodialysis (HD) due to its ability to reduce gut microbiota-derived uremic toxins. However, studies examining the effects of inulin on the gut microbiota and derived metabolites are limited in these patients. We aimed to assess the impact of a 4-week supplementation of inulin on the gut microbiota composition and microbial metabolites of patients on HD.

Design And Methods: In a randomized, double-blind, placebo-controlled, crossover study, twelve HD patients (55 ± 10 y, 50% male, 58% Black American, BMI 31.6 ± 8.9 kg/m, 33% diabetes mellitus) were randomized to consume inulin [10 g/d for females; 15 g/d for males] or maltodextrin [6 g/d for females; 9 g/d for males] for 4 weeks, with a 4-week washout period. We assessed the fecal microbiota composition, fecal metabolites (short-chain fatty acids (SCFA), phenols, and indoles), and plasma indoxyl sulfate and p-cresyl sulfate.

Results: At baseline, factors that explained the gut microbiota variability included BMI category and type of phosphate binder prescribed. Inulin increased the relative abundance of the phylum Verrucomicrobia and its genus Akkermansia (P interaction = 0.045). Inulin and maltodextrin resulted in an increased relative abundance of the phylum Bacteroidetes and its genus Bacteroides (P time = 0.04 and 0.03, respectively). Both treatments increased the fecal acetate and propionate (P time = 0.032 and 0.027, respectively), and there was a trend toward increased fecal butyrate (P time = 0.06). Inulin did not reduce fecal p-cresol or indoles, or plasma concentrations of p-cresyl sulfate or indoxyl sulfate.

Conclusions: A 4-week supplementation of inulin did not lead to major shifts in the fecal microbiota and gut microbiota-derived metabolites. This may be due to high variability among participants and an unexpected increase in fecal excretion of SCFA with maltodextrin. Larger studies are needed to determine the effects of prebiotic fibers on the gut microbiota and clinical outcomes to justify their use in patients on HD.
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http://dx.doi.org/10.1053/j.jrn.2020.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403151PMC
September 2021

Differentiating the causes of adynamic bone in advanced chronic kidney disease informs osteoporosis treatment.

Kidney Int 2021 09 5;100(3):546-558. Epub 2021 Jun 5.

Division of Nephrology, University Hospitals Leuven, Leuven, Belgium. Electronic address:

Patients with chronic kidney disease (CKD) have an increased fracture risk because of impaired bone quality and quantity. Low bone mineral density predicts fracture risk in all CKD stages, including advanced CKD (CKD G4-5D). Pharmacological therapy improves bone mineral density and reduces fracture risk in moderate CKD. Its efficacy in advanced CKD remains to be determined, although pilot studies suggest a positive effect on bone mineral density. Currently, antiresorptive agents are the most commonly prescribed drugs for the prevention and therapy of osteoporosis. Their use in advanced CKD has been limited by the lack of large clinical trials and fear of causing kidney dysfunction and adynamic bone disease. In recent decades, adynamic bone disease has evolved as the most predominant form of renal osteodystrophy, commonly associated with poor outcomes, including premature mortality and progression of vascular calcification. Evolving evidence indicates that reduction of bone turnover by parathyroidectomy or pharmacological therapies, such as calcimimetics and antiresorptive agents, are not associated with premature mortality or accelerated vascular calcification in CKD. In contrast, chronic inflammation, oxidative stress, malnutrition, and diabetes can induce low bone turnover and associate with poor prognosis. Thus, the conditions causing suppression of bone turnover rather than the low bone turnover per se may account for the perceived association with outcomes. Anabolic treatment, in contrast, has been suggested to improve turnover and bone mass in patients with advanced CKD and low bone turnover; however, uncertainty about safety even exceeds that of antiresorptive agents. Here, we critically review the pathophysiological concept of adynamic bone disease and discuss the effect of low bone turnover on the safety and efficacy of anti-osteoporosis pharmacotherapy in advanced CKD.
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http://dx.doi.org/10.1016/j.kint.2021.04.043DOI Listing
September 2021

Secondary hyperparathyroidism, weight loss, and longer term mortality in haemodialysis patients: results from the DOPPS.

J Cachexia Sarcopenia Muscle 2021 08 1;12(4):855-865. Epub 2021 Jun 1.

Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara, Japan.

Background: Wasting is a common complication of kidney failure that leads to weight loss and poor outcomes. Recent experimental data identified parathyroid hormone (PTH) as a driver of adipose tissue browning and wasting, but little is known about the relations among secondary hyperparathyroidism, weight loss, and risk of mortality in dialysis patients.

Methods: We included 42,319 chronic in-centre haemodialysis patients from the Dialysis Outcomes and Practice Patterns Study phases 2-6 (2002-2018). Linear mixed models were used to estimate the association between baseline PTH and percent weight change over 12 months, adjusting for country, demographics, comorbidities, and labs. Accelerated failure time models were used to assess 12 month weight loss as a mediator between baseline high PTH and mortality after 12 months.

Results: Baseline PTH was inversely associated with 12 month weight change: 12 month weight loss >5% was observed in 21%, 18%, 18%, 17%, 15%, and 14% of patients for PTH ≥600 pg/mL, 450-600, 300-450, 150-300, 50-150, and <50 pg/mL, respectively. In adjusted analyses, 12 month weight change compared with PTH 150-299 pg/mL was -0.60%, -0.12%, -0.10%, +0.15%, and +0.35% for PTH ≥600, 450-600, 300-450, 50-150, and <50 pg/mL, respectively. This relationship was robust regardless of recent hospitalization and was more pronounced in persons with preserved appetite. During follow-up after the 12 month weight measure [median, 1.0 (interquartile range, 0.6-1.7) years; 6125 deaths], patients with baseline PTH ≥600 pg/mL had 11% [95% confidence interval (CI), 9-13%] shorter lifespan, and 18% (95% CI, 14-23%) of this effect was mediated through weight loss ≥2.5%.

Conclusions: Secondary hyperparathyroidism may be a novel mechanism of wasting, corroborating experimental data, and, among chronic dialysis patients, this pathway may be a mediator between elevated PTH levels and mortality. Future research should determine whether PTH-lowering therapy can limit weight loss and improve longer term dialysis outcomes.
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http://dx.doi.org/10.1002/jcsm.12722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350219PMC
August 2021

Functional vitamin K insufficiency, vascular calcification and mortality in advanced chronic kidney disease: A cohort study.

PLoS One 2021 24;16(2):e0247623. Epub 2021 Feb 24.

Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.

Patients with chronic kidney disease (CKD) suffer from vitamin K deficiency and are at high risk of vascular calcification (VC) and premature death. We investigated the association of functional vitamin K deficiency with all-cause mortality and whether this association is modified by the presence of VC in CKD stage 5 (CKD G5). Plasma dephosphorylated-uncarboxylated matrix Gla-protein (dp-ucMGP), a circulating marker of functional vitamin K deficiency, and other laboratory and clinical data were determined in 493 CKD G5 patients. VC was assessed in subgroups by Agatston scoring of coronary artery calcium (CAC) and aortic valve calcium (AVC). Backward stepwise regression did not identify dp-ucMGP as an independent determinant of VC. During a median follow-up of 42 months, 93 patients died. Each one standard deviation increment in dp-ucMGP was associated with increased risk of all-cause mortality (sub-hazard ratio (sHR) 1.17; 95% confidence interval, 1.01-1.37) adjusted for age, sex, cardiovascular disease, diabetes, body mass index, inflammation, and dialysis treatment. The association remained significant when further adjusted for CAC and AVC in sub-analyses (sHR 1.22, 1.01-1.48 and 1.27, 1.01-1.60, respectively). In conclusion, functional vitamin K deficiency associates with increased mortality risk that is independent of the presence of VC in patients with CKD G5.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247623PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904143PMC
August 2021

Traditional and Non-traditional Risk Factors for Osteoporosis in CKD.

Calcif Tissue Int 2021 04 14;108(4):496-511. Epub 2021 Feb 14.

Nephrology and Renal Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.

Osteoporosis is a state of bone fragility with reduced skeletal resistance to trauma, and consequently increased risk of fracture. A wide range of conditions, including traditional risk factors, lifestyle choices, diseases and their treatments may contribute to bone fragility. It is therefore not surprising that the multi-morbid patient with chronic kidney disease (CKD) is at a particularly high risk. CKD is associated with reduced bone quantity, as well as impaired bone quality. Bone fragility in CKD is a composite of primary osteoporosis, accumulation of traditional and uremia-related risk factors, assaults brought on by systemic disease, and detrimental effects of drugs. Some risk factors are modifiable and represent potential targets for intervention. This review provides an overview of the heterogeneity of bone fragility in CKD.
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http://dx.doi.org/10.1007/s00223-020-00786-0DOI Listing
April 2021

Data Sharing Under the General Data Protection Regulation: Time to Harmonize Law and Research Ethics?

Hypertension 2021 04 15;77(4):1029-1035. Epub 2021 Feb 15.

Urologie 24, Nuremberg, and Department of Urology, Friedrich-Alexander University of Erlangen, Germany (B.J.S-D).

The General Data Protection Regulation (GDPR) became binding law in the European Union Member States in 2018, as a step toward harmonizing personal data protection legislation in the European Union. The Regulation governs almost all types of personal data processing, hence, also, those pertaining to biomedical research. The purpose of this article is to highlight the main practical issues related to data and biological sample sharing that biomedical researchers face regularly, and to specify how these are addressed in the context of GDPR, after consulting with ethics/legal experts. We identify areas in which clarifications of the GDPR are needed, particularly those related to consent requirements by study participants. Amendments should target the following: (1) restricting exceptions based on national laws and increasing harmonization, (2) confirming the concept of broad consent, and (3) defining a roadmap for secondary use of data. These changes will be achieved by acknowledged learned societies in the field taking the lead in preparing a document giving guidance for the optimal interpretation of the GDPR, which will be finalized following a period of commenting by a broad multistakeholder audience. In parallel, promoting engagement and education of the public in the relevant issues (such as different consent types or residual risk for re-identification), on both local/national and international levels, is considered critical for advancement. We hope that this article will open this broad discussion involving all major stakeholders, toward optimizing the GDPR and allowing a harmonized transnational research approach.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.16340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968961PMC
April 2021

Non-oxidized parathyroid hormone (PTH) measured by current method is not superior to total PTH in assessing bone turnover in chronic kidney disease.

Kidney Int 2021 05 8;99(5):1173-1178. Epub 2021 Jan 8.

Department of Clinical Chemistry, CHU de Liège, Université de Liège, Liège, Belgium; Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium. Electronic address:

Parathyroid hormone (PTH) is a key regulator of bone turnover but can be oxidized in vivo, which impairs biological activity. Variable PTH oxidation may account for the rather poor correlation of PTH with indices of bone turnover in chronic kidney disease. Here, we tested whether non-oxidized PTH is superior to total PTH as a marker of bone turnover in 31 patients with kidney failure included from an ongoing prospective observational bone biopsy study and selected to cover the whole spectrum of bone turnover. Receiver Operating Characteristic (ROC) curves, Spearman correlation and regression analysis of non-oxidized PTH, total PTH and bone turnover markers (bone-specific alkaline phosphatase, procollagen N-terminal pro-peptide and tartrate-resistant acid phosphatase 5b) were used to assess the capability of non-oxidized PTH vs. total PTH to discriminate low from non-low and high from non-high bone turnover, as assessed quantitatively by bone histomorphometry. Serum levels of non-oxidized PTH and total PTH were strongly and significantly correlated. Histomorphometric parameters of bone turnover and the circulating bone turnover markers showed similar correlation coefficients with non-oxidized PTH and total PTH. The area under the ROC (AUROC) values for discriminating between low/non-low turnover for non-oxidized PTH and total PTH were significant and comparable (0.82 and 0.79, respectively). For high/non-high turnover the AUROCs were also significant and of the same magnitude (0.76 and 0.80, respectively). Thus, measuring non-oxidized PTH using the currently available method provides no added value compared to total PTH as an indicator of bone turnover in patients with kidney failure.
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http://dx.doi.org/10.1016/j.kint.2020.12.024DOI Listing
May 2021

Bone evaluation in paediatric chronic kidney disease: clinical practice points from the European Society for Paediatric Nephrology CKD-MBD and Dialysis working groups and CKD-MBD working group of the ERA-EDTA.

Nephrol Dial Transplant 2021 02;36(3):413-425

Department of Paediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School Children's Hospital, Hannover, Germany.

Mineral and bone disorder (MBD) is widely prevalent in children with chronic kidney disease (CKD) and is associated with significant morbidity. CKD may cause disturbances in bone remodelling/modelling, which are more pronounced in the growing skeleton, manifesting as short stature, bone pain and deformities, fractures, slipped epiphyses and ectopic calcifications. Although assessment of bone health is a key element in the clinical care of children with CKD, it remains a major challenge for physicians. On the one hand, bone biopsy with histomorphometry is the gold standard for assessing bone health, but it is expensive, invasive and requires expertise in the interpretation of bone histology. On the other hand, currently available non-invasive measures, including dual-energy X-ray absorptiometry and biomarkers of bone formation/resorption, are affected by growth and pubertal status and have limited sensitivity and specificity in predicting changes in bone turnover and mineralization. In the absence of high-quality evidence, there are wide variations in clinical practice in the diagnosis and management of CKD-MBD in childhood. We present clinical practice points (CPPs) on the assessment of bone disease in children with CKD Stages 2-5 and on dialysis based on the best available evidence and consensus of experts from the CKD-MBD and Dialysis working groups of the European Society for Paediatric Nephrology and the CKD-MBD working group of the European Renal Association-European Dialysis and Transplant Association. These CPPs should be carefully considered by treating physicians and adapted to individual patients' needs as appropriate. Further areas for research are suggested.
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http://dx.doi.org/10.1093/ndt/gfaa210DOI Listing
February 2021

Discrepancies between bioimpedance spectroscopy devices in haemodialysis patients.

Clin Kidney J 2020 Oct 22;13(5):906-908. Epub 2019 Oct 22.

Department of Immunology and Microbiology, Laboratory of Nephrology and Renal Transplantation, Katholieke Universiteit Leuven, Leuven, Belgium.

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http://dx.doi.org/10.1093/ckj/sfz147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577755PMC
October 2020

European Consensus Statement on the diagnosis and management of osteoporosis in chronic kidney disease stages G4-G5D.

Nephrol Dial Transplant 2021 01;36(1):42-59

Bone and Mineral Research Unit (ISPA) (REDinREN), Hospital Universitario Central Asturias, Oviedo University, Spain.

Controlling the excessive fracture burden in patients with chronic kidney disease (CKD) Stages G4-G5D remains an impressive challenge. The reasons are 2-fold. First, the pathophysiology of bone fragility in patients with CKD G4-G5D is complex and multifaceted, comprising a mixture of age-related (primary male/postmenopausal), drug-induced and CKD-related bone abnormalities. Second, our current armamentarium of osteoporosis medications has not been developed for, or adequately studied in patients with CKD G4-G5D, partly related to difficulties in diagnosing osteoporosis in this specific setting and fear of complications. Doubts about the optimal diagnostic and therapeutic approach fuel inertia in daily clinical practice. The scope of the present consensus paper is to review and update the assessment and diagnosis of osteoporosis in patients with CKD G4-G5D and to discuss the therapeutic interventions available and the manner in which these can be used to develop management strategies for the prevention of fragility fracture. As such, it aims to stimulate a cohesive approach to the management of osteoporosis in patients with CKD G4-G5D to replace current variations in care and treatment nihilism.
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http://dx.doi.org/10.1093/ndt/gfaa192DOI Listing
January 2021

The risk of medically uncontrolled secondary hyperparathyroidism depends on parathyroid hormone levels at haemodialysis initiation.

Nephrol Dial Transplant 2021 01;36(1):160-169

Arbor Research Collaborative for Health, Ann Arbor, MI, USA.

Background: Optimal parathyroid hormone (PTH) control during non-dialysis chronic kidney disease (ND-CKD) might decrease the subsequent risk of parathyroid hyperplasia and uncontrolled secondary hyperparathyroidism (SHPT) on dialysis. However, the evidence for recommending PTH targets and therapeutic strategies is weak for ND-CKD. We evaluated the patient characteristics, treatment patterns and PTH control over the first year of haemodialysis (HD) by PTH prior to HD initiation.

Methods: We studied 5683 incident HD patients from 21 countries in Dialysis Outcomes and Practice Patterns Study Phases 4-6 (2009-18). We stratified by PTH measured immediately prior to HD initiation and reported the monthly prescription prevalence of active vitamin D and calcimimetics over the first year of HD and risk of PTH >600 pg/mL after 9-12 months on HD.

Results: The 16% of patients with PTH >600 pg/mL prior to HD initiation were more likely to be prescribed active vitamin D and calcimimetics during the first year of HD. The prevalence of PTH >600 pg/mL 9-12 months after start of HD was greater for patients who initiated HD with PTH >600 (29%) versus 150-300 (7%) pg/mL (adjusted risk difference: 19%; 95% confidence interval : 15%, 23%). The patients with sustained PTH >600 pg/mL after 9-12 months on HD were younger, more likely to be black, and had higher serum phosphorus and estimated glomerular filtration rates at HD initiation.

Conclusions: Increased PTH before HD start predicted a higher PTH level 9-12 months later, despite greater use of active vitamin D and calcimimetics. More targeted PTH control during ND-CKD may influence outcomes during HD, raising the need for PTH target guidelines in these patients.
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http://dx.doi.org/10.1093/ndt/gfaa195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771977PMC
January 2021

Uremic Toxins and Vascular Calcification-Missing the Forest for All the Trees.

Toxins (Basel) 2020 09 29;12(10). Epub 2020 Sep 29.

Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6229 ER Maastricht, The Netherlands.

The cardiorenal syndrome relates to the detrimental interplay between the vascular system and the kidney. The uremic milieu induced by reduced kidney function alters the phenotype of vascular smooth muscle cells (VSMC) and promotes vascular calcification, a condition which is strongly linked to cardiovascular morbidity and mortality. Biological mechanisms involved include generation of reactive oxygen species, inflammation and accelerated senescence. A better understanding of the vasotoxic effects of uremic retention molecules may reveal novel avenues to reduce vascular calcification in CKD. The present review aims to present a state of the art on the role of uremic toxins in pathogenesis of vascular calcification. Evidence, so far, is fragmentary and limited with only a few uremic toxins being investigated, often by a single group of investigators. Experimental heterogeneity furthermore hampers comparison. There is a clear need for a concerted action harmonizing and standardizing experimental protocols and combining efforts of basic and clinical researchers to solve the complex puzzle of uremic vascular calcification.
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http://dx.doi.org/10.3390/toxins12100624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599869PMC
September 2020
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