Coronary artery calcification in chronic kidney disease (CKD) and non-chronic kidney disease Mathew RO, et al. Kidney Int 2017;91:797-807.
Renagel in New Dialysis (RIND) Study Outcomes Use of sevelamer HCl is associated with decreased mortality Sevelamer HCl Calcium P = 0.016 Multivariable adjusted (age, race, gender, diabetes, history of atherosclerotic Block GA, et al.. Kidney Int. 2007;71(5):438-441. cardiovascular disease, C-reactive protein, albumin, Kt/V, and baseline CAC score).
Jamal SA, et al. Lancet. 2013;382(9900):1268.
Non-calcium-based phosphate binders on mortality in patients with CKD 22 % (relative risk 78, 95% CI 0.61-0.98) decrease in all-cause mortality among patients received non-calcium-based binders compared with calcium-based binders Favours non calcium Favours calcium base Jamal SA, et al. Lancet. 2013;382(9900):1268.
Non-calcium-based phosphate binders on coronary artery calcification in patients with CKD Longest follow-up point for each study (mean difference in Agatston score −95.26, 95% CI −146.68 to −43.84) Favours non calcium Favours calcium base Jamal SA, et al. Lancet. 2013;382(9900):1268.
Effect of Cinacalcet on Cardiovascular Disease in Patients Undergoing Dialysis ❖ 3883 patients with moderate-to-severe secondary hyperparathyroidism (median level of intact parathyroid hormone, 693 pg/mL who were undergoing hemodialysis to receive either cinacalcet or placebo Intention-to-Treat Analysis Lag-Censoring Analysis Censoring of data at 6 months after study-drug discontinuation yielded primary composite end points in the cinacalcet group as compared with placebo group (HR 0.85; 95% CI, 0.76 to 0.95) EVOLVE Trial Investigators, Chertow GM, et al.. N Engl J Med 2012; 367:2482.
Severity of CKD anemia is associated with decreased survival ❖ Retrospective analysis of the PROMIS database in British Columbia of patients with NDD-CKD stage 3-5 (GFR <60 ml/min/1.73 m2) referred to a nephrologist during May 1998 to October 2002 (N=3028) Hb at time of 1.00 nephrology referral Probability of survival 0.95 ≥13 g/dL 0.90 12–12.9 g/dL 0.85 0.80 Log-rank test: 11–11.9 g/dL P=0.0001 <10 g/dL 10–10.9 g/dL 0.75 0.70 0 3 6 9 12 15 18 21 24 27 31 33 37 Months from Hb result CKD = chronic kidney disease; GFR = glomerular ltration rate; Hb = hemoglobin; NDD-CKD = non-dialysis dependent-chronic kidney disease; PROMIS = Patient Registration and Outcome Management Information System. Levin A et al. Nephrol Dial Trans. 2006;21:370–377. fi
Pathophysiology of the cardiorenal anemia syndrome Besarab A, et al. The Oncologist 2009; 14 (suppl1): 22–33
Erythropoietin Therapy and Left Ventricular Mass Index in CKD and ESRD Patients: A Meta-Analysis Severe anemia conventional Hb targets for EPO therapy are associated with a reduction in LVMi Baseline severe anemia Baseline moderate anemia severe anemia at baseline (<10 g/dl), when given EPO using a lower target level (Hb < 12 g/dl or Hct < 36%) Parfrey PS, et al. Clin J Am Soc Nephrol 2009;4:755-62.
Increased risk of mortality and CV events with ESAs at higher Hb targets in patients with CKD anemia NHCT1 CHOIR3 CREATE4 TREAT5 • 1265 patients with DD-CKD with CHF or ischemic • 1432 patients with NDD-CKD (eGFR 15-50 mL/min/ • 603 patients with NDD-stage 3/4 CKD (eGFR 15-35 • 4038 patients with T2DM NDD-CKD (eGFR 20-60 heart disease 1.73 m2) mL/min/1.73 m2) mL/min/1.73 m2) • high Hb (14 g/dL) vs • high Hb (13.5 g/dL) vs • high Hb (13-15 g/dL) vs • high Hb (13 g/dL; ESA) vs low Hb (10 g/dL)a low Hb (11.3 g/dL)a low Hb (10.5-11.5 g/dL) low Hb (9 g/dL; placebo + rescue ESA) With higher targets Increased risk of death/non-fatal MI Increased risk of death/MI/hCHF/ Trend of increased risk of Increased risk of fatal or non-fatal stroke mortalityc strokec RR 1.28 HR 1.34 RR 1.48 HR 1.92 (95% CI 1.069-1.56) (95% CI 1.03-1.74; p=0.03) (95% CI 0.87-2.52)6 (95% CI 1.38-2.68; p<0.001) • Open-label, prospective • Open-label, prospective • Open-label, parallel-group • Randomized, double-blind, placebo-controlled • 1° composite EP: Death, non-fatal MI • 1° composite EP: Death, MI, stroke, CHF • 1° composite EP: CV eventsb • 1° composite EPs: (1) Death, MI or hospitalization for MI, • Median follow-up: 14 months2 • Median follow-up: 16 months • Mean duration: 3 years stroke, CHF; (2) death or end-stage renal disease • Median follow-up: 29.1 months aStudy was terminated early; bSudden death, MI, acute heart failure, stroke, transient ischemic attack, angina pectoris resulting in hospitalization for ≥24 hours or prolongation of hospitalization, complication of peripheral vascular disease (amputation or necrosis), or cardiac arrhythmia resulting in hospitalization for ≥24 hours; cSecondary EP. CHF = congestive heart failure; CHOIR = Correction of Hemogloblin and Outcomes in Renal Insu ciency; CKD = chronic kidney disease; CREATE = Cardiovascular Risk Reduction by Early Anemia Treatment with Epoetin Beta; DD, dialysis-dependent; eGFR = estimated glomerular ltration rate; EP = endpoint; ESA = erythropoiesis-stimulating agent; Hb = hemoglobin; hCHF = hospitalization for CHF; HCT = hematocrit; HD = hemodialysis; HR = hazard ratio; MI = myocardial infarction; NDD = nondialysis-dependent; NHCT = Normal Hematocrit Cardiac Trial; RR = risk ratio; T2DM = Type 2 diabetes mellitus; TREAT = Trial to Reduce Cardiovascular Events with Aranesp Therapy . 1. Epogen Prescribing Information, Amgen Inc, July 2018; 2. Besarab A et al. N Engl J Med. 1998;339:584–590; 3. Singh A et al. N Engl J Med. 2006;355:2085–2098; 4. Drüeke T et al. N Engl J Med. 2006;355:2071–2084; 5. Pfe er M et al. N Engl J Med. 2009;361:2019–2032; 6. Phrommintikul A et al. Lancet. 2007;369:381-388. ffififf
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