Facility-level CKD-MBD composite score and risk of adverse clinical outcomes among patients on hemodialysis

Block et al. BMC Nephrology (2016) 17:166 DOI 10.1186/s12882-016-0382-8 RESEARCH ARTICLE Open Access Facility-level CKD-MBD composite score and risk of adverse clinical outcomes among patients on hemodialysis Geoffrey A. Block1, Akeem A. Yusuf2, Mark D. Danese3, Heidi S. Wirtz4, Yan Hu2, Thy P. Do4, Kerry Cooper5, David T. Gilbertson2*, Brian D. Bradbury4 and Allan J. Collins2,6 Abstract Background: Patients receiving hemodialysis with values outside of target levels for parathyroid hormone (PTH: 150–600 pg/mL), calcium (Ca: 8.4–10.2 mg/dL), and phosphate (P: 3.5–5.5 mg/dL) are at elevated morbidity and mortality risk. We examined whether patients receiving care in dialysis facilities where greater proportions of patients have at least two values out of target have a higher risk of adverse clinical outcomes. Methods: The study cohort consisted of 39,085 prevalent hemodialysis patients in 1298 DaVita dialysis facilities as of September 1, 2009, followed from January 1, 2010, until an outcome, a censoring event, or December 31, 2010. We determined the quintile of the distribution across facilities of the proportion of patients with at least two of three parameters out of, or above, target over a 4-month baseline period. The primary composite outcome was cardiovascular hospitalization or death. Secondary outcomes included death, cardiovascular hospitalization, and parathyroidectomy. Poisson regression models were used to estimate the association of facility quintile with outcomes. Results: Facility quintile was associated with a 7 % increased risk of cardiovascular hospitalization or death (quintile 5 versus 1, RR 1.07, 95 % CI 1.01–1.13) using the out-of-target measure of exposure and a 12 % increased risk (RR 1.12, 95 % CI 1.06–1.19) using the above-target measure. No association was seen for death using either measure. Patients in facility quintiles 3–5 (versus 1) were at increased parathyroidectomy risk (RR ranged from 2.05, 95 % CI 1.10–3.82, for quintile 3 to 2.73, 95 % CI 1.50–4.98, for quintile 5). Conclusions: Facility level analysis of a large prevalent sample of US patients on hemodialysis demonstrates that patients in facilities with the least control of PTH, Ca, and P had the greatest risk of parathyroidectomy or the combination of cardiovascular hospitalization or death. Keywords: Chronic kidney disease-mineral bone disorder, End-stage renal disease, Hemodialysis Background Secondary hyperparathyroidism (SHPT) is associated with a variety of adverse skeletal and cardiovascular consequences in patients with chronic kidney disease (CKD). The term “chronic kidney disease-mineral bone disorder (CKD-MBD)” replaced the older term “renal osteodystrophy” to more clearly convey the broad spectrum of sequelae that accompany abnormalities in blood levels of parathyroid hormone (PTH), calcium, and phosphate, the * Correspondence: 2 Chronic Disease Research Group, Minneapolis Medical Research Foundation, 914 South Eighth St, Suite S4.210, Minneapolis, MN 55404, USA Full list of author information is available at the end of the article biochemical hallmarks of SHPT. Both highly elevated and very low concentrations of these biomarkers have consistently been associated with increased mortality risk; on the basis of these epidemiologic observations, international guidelines suggest target values for each. In addition, two recently published studies have shown that patients with uncontrolled SHPT and significant elevations of PTH, calcium, and phosphate levels may ultimately undergo surgical parathyroidectomy, the complications [1] of which have until recently been largely underappreciated [1]. Although most epidemiologic studies have investigated the prognostic importance of a single CKD-MBD value, two recent studies have focused on clinical outcomes © The Author(s). 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Block et al. BMC Nephrology (2016) 17:166 related to the joint distribution of all three. In the first, patients were categorized into one of 36 possible phenotypes of mutually exclusive combinations of PTH, calcium, and phosphate that represent most of the excess risk associated with CKD-MBD after adjustment for baseline risk of mortality and cardiovascular hospitalization [2]. The second reported an exhaustive examination of dichotomous combinations of all possible phenotypes reflecting simultaneous achievement of zero, one, two, or all three of the target values proposed by the Kidney Disease Improving Global Outcomes (KDIGO) workgroup on CKD-MBD [3, 4]. This study found that a dichotomous construct defined by two or more out-of-target or aboverange biomarkers accounted for more than 70 % of excess events (akin to sensitivity) while reducing the size of the at-risk population by at least 30 % (akin to specificity). While this was highly prognostic at the patient level, there is need to evaluate how prognostic such a simple definition is at the facility level. In the current investigation, we aimed to extend this conceptual framework to better understand how to operationalize the patient-level CKD-MBD composite score at the facility level. This approach can be used as a starting point for discussing facility-level metrics to define quality care in CKD-MBD rather than any single parameter of PTH, calcium, or phosphate. We examined whether patients receiving care in dialysis centers where greater proportions of patients have two or more values outside of the target range for PTH, calcium, and phosphate are at increased risk for clinically meaningful outcomes related to CKD-MBD, including cardiovascular hospitalization, mortality, parathyroidectomy, and a composite endpoint of all-cause mortality and cardiovascular hospitalization. Methods Data sources We merged two different data sources to conduct this study: the DaVita Clinical Data Warehouse and the United States Renal Data System (USRDS). Permission to merge these files was obtained from the project officers of the National Institute of Diabetes and Digestive and Kidney Diseases. We obtained laboratory data from the DaVita Clinical Data Warehouse and demographic, comorbidity, dialysis facility, hospitalization, and outcomes data from the USRDS database. Study population and design We derived the study cohort from the source population of all DaVita in-center hemodialysis facilities from September 1, 2009, through December 31, 2010, reflecting the most contemporar (...truncated)