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      Combinations of mineral and bone disorder markers and risk of death and hospitalizations in the international Dialysis Outcomes and Practice Patterns Study

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          Abstract

          Background

          Prior studies have developed a chronic kidney disease–mineral and bone disorder (CKD-MBD) composite score based on combinations of calcium (Ca), phosphorus (P) and parathyroid hormone (PTH) that have been shown to be associated with an increased risk of clinical outcomes in the USA. We examined this association in a contemporary, international cohort of hemodialysis patients.

          Methods

          We studied 19 313 patients surviving ≥12 months in the Dialysis Outcomes and Practice Patterns Study Phases 3–5 (2005–15) from Europe, Canada and the USA. The CKD-MBD composite score was defined as the number of markers above target levels (P, 3.5–5.5 mg/dL; Ca, 8.4–10.2 mg/dL; PTH, 150–600 pg/mL). Using Cox models, we estimated hazard ratios (HRs) for death and a composite event (death or hospitalization), contrasting MBD 2/3 (2–3 parameters above target) with MBD 0 (all in target), adjusted for a disease risk score (DRS).

          Results

          MBD 2/3 above target was observed in 10–14% of patients across regions and was associated with greater DRS-adjusted mortality {HR 1.41 [95% confidence interval (CI) 1.10–1.82]} and composite events [HR 1.23 (95% CI 1.10–1.38)] in the USA compared with MBD 0; the mortality association was stronger for patients ≥ 65 years of age [HR 1.82 (95% CI 1.28–2.58)] compared with patients <65 years of age [HR 1.11 (95% CI 0.80–1.55)]. HRs observed in Canada and Europe were generally consistent but weaker. Estimates for MBD 2/3 outside target (above or below) were slightly lower in all regions.

          Conclusions

          Simultaneous consideration of Ca, P and PTH may help in identifying patients on dialysis with a higher risk of major clinical outcomes related to CKD-MBD.

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          Most cited references23

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          KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD).

          (2009)
          The 2009 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline on the management of chronic kidney disease-mineral and bone disorder (CKD-MBD) is intended to assist the practitioner caring for adults and children with CKD stages 3-5, on chronic dialysis therapy, or with a kidney transplant. The guideline contains recommendations on evaluation and treatment for abnormalities of CKD-MBD. This disease concept of CKD-MBD is based on a prior KDIGO consensus conference. Tests considered are those that relate to the detection and monitoring of laboratory, bone, and cardiovascular abnormalities. Treatments considered are interventions to treat hyperphosphatemia, hyperparathyroidism, and bone disease in patients with CKD stages 3-5D and 1-5T. The guideline development process followed an evidence based approach and treatment recommendations are based on systematic reviews of relevant treatment trials. Recommendations for testing used evidence based on diagnostic accuracy or risk prediction and linked it indirectly with how this would be expected to achieve better outcomes for patients through better detection, evaluation or treatment of disease. Critical appraisal of the quality of the evidence and the strength of recommendations followed the GRADE approach. An ungraded statement was provided when a question did not lend itself to systematic literature review. Limitations of the evidence, especially the lack of definitive clinical outcome trials, are discussed and suggestions are provided for future research.
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            Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis.

            Cardiovascular disease is common in older adults with end-stage renal disease who are undergoing regular dialysis, but little is known about the prevalence and extent of cardiovascular disease in children and young adults with end-stage renal disease. We used electron-beam computed tomography (CT) to screen for coronary-artery calcification in 39 young patients with end-stage renal disease who were undergoing dialysis (mean [+/-SD] age, 19+/-7 years; range, 7 to 30) and 60 normal subjects 20 to 30 years of age. In those with evidence of calcification on CT scanning, we determined its extent. The results were correlated with the patients' clinical characteristics, serum calcium and phosphorus concentrations, and other biochemical variables. None of the 23 patients who were younger than 20 years of age had evidence of coronary-artery calcification, but it was present in 14 of the 16 patients who were 20 to 30 years old. Among those with calcification, the mean calcification score was 1157+/-1996, and the median score was 297. By contrast, only 3 of the 60 normal subjects had calcification. As compared with the patients without coronary-artery calcification, those with calcification were older (26+/-3 vs. 15+/-5 years, P<0.001) and had been undergoing dialysis for a longer period (14+/-5 vs. 4+/-4 years, P< 0.001). The mean serum phosphorus concentration, the mean calcium-phosphorus ion product in serum, and the daily intake of calcium were higher among the patients with coronary-artery calcification. Among 10 patients with calcification who underwent follow-up CT scanning, the calcification score nearly doubled (from 125+/-104 to 249+/-216, P=0.02) over a mean period of 20+/-3 months. Coronary-artery calcification is common and progressive in young adults with end-stage renal disease who are undergoing dialysis.
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              Cardiac calcification in adult hemodialysis patients. A link between end-stage renal disease and cardiovascular disease?

              We sought to determine clinical and laboratory correlates of calcification of the coronary arteries (CAs), aorta and mitral and aortic valves in adult subjects with end-stage renal disease (ESRD) receiving hemodialysis. Vascular calcification is known to be a risk factor for ischemic heart disease in non-uremic individuals. Patients with ESRD experience accelerated vascular calcification, due at least in part to dysregulation of mineral metabolism. Clinical correlates of the extent of calcification in ESRD have not been identified. Moreover, the clinical relevance of calcification as measured by electron-beam tomography (EBT) has not been determined in the ESRD population. We conducted a cross-sectional analysis of 205 maintenance hemodialysis patients who received baseline EBT for evaluation of vascular and valvular calcification. We compared subjects with and without clinical evidence of atherosclerotic vascular disease and determined correlates of the extent of vascular and valvular calcification using multivariable linear regression and proportional odds logistic regression analyses. The median coronary artery calcium score was 595 (interquartile range, 76 to 1,600), values consistent with a high risk of obstructive coronary artery disease in the general population. The CA calcium scores were directly related to the prevalence of myocardial infarction (p < 0.0001) and angina (p < 0.0001), and the aortic calcium scores were directly related to the prevalence of claudication (p = 0.001) and aortic aneurysm (p = 0.02). The extent of coronary calcification was more pronounced with older age, male gender, white race, diabetes, longer dialysis vintage and higher serum concentrations of calcium and phosphorus. Total cholesterol (and high-density lipoprotein and low-density lipoprotein subfractions), triglycerides, hemoglobin and albumin were not significantly related to the extent of CA calcification. Only dialysis vintage was significantly associated with the prevalence of valvular calcification. Coronary artery calcification is common, severe and significantly associated with ischemic cardiovascular disease in adult ESRD patients. The dysregulation of mineral metabolism in ESRD may influence vascular calcification risk.
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                Author and article information

                Journal
                Clin Kidney J
                Clin Kidney J
                ckj
                Clinical Kidney Journal
                Oxford University Press
                2048-8505
                2048-8513
                December 2020
                08 November 2019
                08 November 2019
                : 13
                : 6
                : 1056-1062
                Affiliations
                [1 ] Arbor Research Collaborative for Health , Ann Arbor, MI, USA
                [2 ] Center for Observational Research , Amgen, Thousand Oaks, CA, USA
                [3 ] Department of Internal Medicine, University of Michigan , Ann Arbor, MI, USA
                [4 ] DaVita Clinical Research , Minneapolis, MN, USA
                [5 ] Vanderbilt University Medical Center , Nashville, TN, USA
                Author notes
                Correspondence and offprint requests to: Douglas S. Fuller; E-mail: Doug.Fuller@ 123456ArborResearch.org
                Article
                sfz112
                10.1093/ckj/sfz112
                7769536
                33391749
                398b7743-ed55-4371-b24e-7a8684afffdd
                © The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 10 April 2019
                : 30 July 2019
                Page count
                Pages: 7
                Funding
                Funded by: Amgen, DOI 10.13039/100002429;
                Categories
                Original Articles
                AcademicSubjects/MED00340

                Nephrology
                calcium,ckd-mbd,dopps,hemodialysis,parathyroid hormone,phosphorus
                Nephrology
                calcium, ckd-mbd, dopps, hemodialysis, parathyroid hormone, phosphorus

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