Rachel W Kubiak1, Leila R Zelnick2, Andy N Hoofnagle3, Charles E Alpers4, Christi M Terry5, Yan-Ting Shiu5, Alfred K Cheung5, Ian H de Boer2, Cassianne Robinson-Cohen2, Michael Allon6, Laura M Dember7, Harold I Feldman8, Jonathan Himmelfarb2, Thomas S Huber9, Prabir Roy-Chaudhury10, Miguel A Vazquez11, John W Kusek12, Gerald J Beck13, Peter B Imrey14, Bryan Kestenbaum2. 1. Kidney Research Institute, University of Washington, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA. Electronic address: rwkubiak@uw.edu. 2. Kidney Research Institute, University of Washington, Seattle, WA, USA. 3. Department of Laboratory Medicine, University of Washington, Seattle, WA, USA. 4. Department of Pathology, University of Washington, Seattle, WA, USA. 5. Division of Nephrology & Hypertension, University of Utah and Veterans Affairs Salt Lake City Healthcare System, Salt Lake City, UT, USA. 6. Department of Vascular Surgery, University of Alabama, Birmingham, AL, USA. 7. Renal, Electrolyte & Hypertension Division, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. 8. Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. 9. Division of Vascular Surgery and Endovascular Therapy, University of Florida College of Medicine, Gainesville, FL, USA. 10. Division of Nephrology and the University of Arizona Kidney Disease Program, University of Arizona, Tucson, AZ, USA. 11. Division of Nephrology, University of Texas Southwestern, Dallas, TX, USA. 12. National Institutes of Diabetes and Digestive and Kidney Diseases, Division of Kidney, Urologic & Hematologic Diseases, Bethesda, MD, USA. 13. Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA. 14. Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA; Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA.
Abstract
BACKGROUND: The arteriovenous fistula (AVF) is central to haemodialysis treatment, but up to half of surgically created AVF fail to mature. Chronic kidney disease often leads to mineral metabolism disturbances that may interfere with AVF maturation through adverse vascular effects. This study tested associations between mineral metabolism markers and vein histology at AVF creation and unassisted and overall clinical AVF maturation. METHODS: Concentrations of fibroblast growth factor 23, parathyroid hormone, calcium, phosphate, and vitamin D metabolites: 1,25(OH)2D, 24,25(OH)2D, 25(OH)D, and bioavailable 25(OH)D were measured in pre-operative serum samples from 562 of 602 participants in the Haemodialysis Fistula Maturation Study, a multicentre, prospective cohort study of patients undergoing surgical creation of an autologous upper extremity AVF. Unassisted and overall AVF maturation were ascertained for 540 and 527 participants, respectively, within nine months of surgery or four weeks of dialysis initiation. Study personnel obtained vein segments adjacent to the portion of the vein used for anastomosis, which were processed, embedded, and stained for measurement of neointimal hyperplasia, calcification, and collagen deposition in the medial wall. RESULTS: Participants in this substudy were 71% male, 43% black, and had a mean age of 55 years. Failure to achieve AVF maturation without assistance occurred in 288 (53%) participants for whom this outcome was determined. In demographic and further adjusted models, mineral metabolism markers were not significantly associated with vein histology characteristics, unassisted AVF maturation failure, or overall maturation failure, other than a biologically unexplained association of higher 24,25(OH)2D with overall failure. This exception aside, associations were non-significant for continuous and categorical analyses and relevant subgroups. CONCLUSIONS: Serum concentrations of measured mineral metabolites were not substantially associated with major histological characteristics of veins in patients undergoing AVF creation surgery, or with AVF maturation failure, suggesting that efforts to improve AVF maturation rates should increase attention to other processes such as vein mechanics, anatomy, and cellular metabolism among end stage renal disease patients.
BACKGROUND: The arteriovenous fistula (AVF) is central to haemodialysis treatment, but up to half of surgically created AVF fail to mature. Chronic kidney disease often leads to mineral metabolism disturbances that may interfere with AVF maturation through adverse vascular effects. This study tested associations between mineral metabolism markers and vein histology at AVF creation and unassisted and overall clinical AVF maturation. METHODS: Concentrations of fibroblast growth factor 23, parathyroid hormone, calcium, phosphate, and vitamin D metabolites: 1,25(OH)2D, 24,25(OH)2D, 25(OH)D, and bioavailable 25(OH)D were measured in pre-operative serum samples from 562 of 602 participants in the Haemodialysis Fistula Maturation Study, a multicentre, prospective cohort study of patients undergoing surgical creation of an autologous upper extremity AVF. Unassisted and overall AVF maturation were ascertained for 540 and 527 participants, respectively, within nine months of surgery or four weeks of dialysis initiation. Study personnel obtained vein segments adjacent to the portion of the vein used for anastomosis, which were processed, embedded, and stained for measurement of neointimal hyperplasia, calcification, and collagen deposition in the medial wall. RESULTS:Participants in this substudy were 71% male, 43% black, and had a mean age of 55 years. Failure to achieve AVF maturation without assistance occurred in 288 (53%) participants for whom this outcome was determined. In demographic and further adjusted models, mineral metabolism markers were not significantly associated with vein histology characteristics, unassisted AVF maturation failure, or overall maturation failure, other than a biologically unexplained association of higher 24,25(OH)2D with overall failure. This exception aside, associations were non-significant for continuous and categorical analyses and relevant subgroups. CONCLUSIONS: Serum concentrations of measured mineral metabolites were not substantially associated with major histological characteristics of veins in patients undergoing AVF creation surgery, or with AVF maturation failure, suggesting that efforts to improve AVF maturation rates should increase attention to other processes such as vein mechanics, anatomy, and cellular metabolism among end stage renal diseasepatients.
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