Impact of Continuous Deterioration of Kidney Function 6 to 8 Months After Percutaneous Coronary Intervention for Acute Coronary Syndrome Naohiko Nemoto, MD, PhDa,*, Masaki Iwasaki, MDb, Mami Nakanishi, MDa, Tadashi Araki, MDa, Makoto Utsunomiya, MDa, Masaki Hori, MDa, Nobutaka Ikeda, MD, PhDa, Kunihiko Makino, MD, PhDa, Hideki Itaya, MD, PhDa, Raisuke Iijima, MD, PhDa, Hidehiko Hara, MD, PhDa, Takuro Takagi, MDa, Nobuhiko Joki, MD, PhDb, Kaoru Sugi, MD, PhDa, and Masato Nakamura, MD, PhDa Preprocedural chronic kidney disease and contrast-induced acute kidney injury are predictors of in-hospital death and long-term mortality. However, neither the time course of kidney function after percutaneous coronary intervention (PCI) nor the relation between the time course of kidney function and prognosis has been adequately studied. We studied 531 patients who underwent PCI for acute coronary syndrome. The continuous deterioration of kidney function (CDKF) was defined as a >25% increase in serum creatinine level or serum creatinine >0.5 mg/dl above baseline at 6 to 8 months after PCI. CDKF was observed in 87 patients (16.4%). Independent risk factors for CDKF were contrast-induced acute kidney injury, preprocedural hemoglobin level, and proteinuria. Patients with CDKF exhibited significant higher 5-year mortality rate than patients without CDKF (25% vs 9.4%, log-rank p [ 0.0006). Independent risk factors for 5-year mortality were age >75 year, anemia, New York Heart Association class III or IV, low ejection fraction, and CDKF. CDKF is associated with an increased risk of all-cause mortality of 5 years in patients with acute coronary syndrome undergoing PCI. Ó 2014 Elsevier Inc. All rights reserved. (Am J Cardiol 2014;113:1647e1651)
Chronic kidney disease (CKD) is associated with cardiovascular events, such as acute coronary syndrome (ACS) and heart failure, as well as all-cause mortality.1e5 It has also been demonstrated that contrast-induced acute kidney injury (CI-AKI) that occurs after percutaneous coronary intervention (PCI) is an independent risk factor for short- and longterm mortality.3,6e8 These relations have been studied from the perspective of patient prognosis and have been referred to as cardiorenal syndrome.9 The relation between the worsening of renal dysfunction during hospitalization and the long-term outcome in patients with ACS undergoing PCI is well known.10 However, the time course of kidney function after discharge has not been adequately investigated, and the relation between the continuous deterioration of kidney function (CDKF) after discharge and mortality remains unknown. Therefore, we evaluated the prognosis of kidney dysfunction after discharge and long-term mortality in patients with ACS undergoing PCI.
Divisions of aCardiovascular Medicine and bNephrology, Toho University Ohashi Medical Center, Tokyo, Japan. Manuscript received December 17, 2013; revised manuscript received and accepted February 24, 2014. The authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. See page 1651 for disclosure information. *Corresponding author: Tel: (þ81) 3 3468 1251; fax: (þ81) 3 3468 1269. E-mail address: [email protected] (N. Nemoto). 0002-9149/14/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjcard.2014.02.019
Methods From January 2001 to October 2005, a total of 648 patients with ACS underwent PCI in our institution. Patients with endstage renal failure requiring dialysis (n ¼ 30), patients who died within 6 to 8 months after PCI (n ¼ 49), and patients who failed to have serum creatinine (Cr) level measured at 6 to 8 months after PCI (n ¼ 38) were excluded. The remaining 531 patients were divided into 2 groups: those with CDKF (CDKF group, n ¼ 444) and those without CDKF (non-CDKF group, n ¼ 87; Figure 1). The demographic and clinical characteristics of the patients were recorded on admission. Information regarding the laboratory parameters, pharmacologic data, and interventional therapies was obtained from the patient’s electronic medical charts. On admission, venous blood samples and urine samples were obtained before administration of any medications. These samples were tested using an automatic clinical chemistry analyzer (LABOSPECT 008; Hitachi, Tokyo, Japan). The Cr, total cholesterol, and high- and low-density lipoprotein levels were determined using enzymatic methods. The definition of ACS was based on the current guidelines.11 CDKF was defined as an absolute Cr increase of 0.5 mg/dl or a relative increase in Cr 25% above baseline from 6 to 8 months after PCI. CI-AKI was defined as an absolute Cr increase of 0.5 mg/dl or a relative increase in Cr 25% above baseline within 48 hours after PCI. The estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease formula,12 with coefficients modified for Japanese patients13: eGFR (ml$minute1$1.73 m2) ¼ 194 serum Cr 1.094 age0.287 (0.739 if female). CKD was defined as an eGFR www.ajconline.org
1648
The American Journal of Cardiology (www.ajconline.org)
Figure 1. Enrollment criteria and study flow. CDKF was defined as an increase in absolute Cr level of 0.5 mg/dl or a relative increase in Cr 25% above baseline from 6 to 8 months after PCI. Table 1 Baseline clinical characteristics of patients Variable
Men Age (yrs) Age 75 yrs Body mass index (kg/m2) Hypertension Diabetes mellitus Dyslipidemia* Total cholesterol (mg/dl) High-density lipoprotein cholesterol (mg/dl) Triglyceride (mg/dl) Low-density lipoprotein cholesterol (mg/dl) Smoker CKD (3)† Glomerular filtration rate (ml/min) Serum Cr value (mg/dl) Serum Cr value 1.5 mg/dl Proteinuria CI-AKI Target vessels Ejection fraction (%) Low ejection fraction (40%) New York Heart Association class III or IV Hemoglobin (g/dl) Anemia (men
Chronic kidney disease (CKD) is associated with cardiovascular events, such as acute coronary syndrome (ACS) and heart failure, as well as all-cause mortality.1e5 It has also been demonstrated that contrast-induced acute kidney injury (CI-AKI) that occurs after percutaneous coronary intervention (PCI) is an independent risk factor for short- and longterm mortality.3,6e8 These relations have been studied from the perspective of patient prognosis and have been referred to as cardiorenal syndrome.9 The relation between the worsening of renal dysfunction during hospitalization and the long-term outcome in patients with ACS undergoing PCI is well known.10 However, the time course of kidney function after discharge has not been adequately investigated, and the relation between the continuous deterioration of kidney function (CDKF) after discharge and mortality remains unknown. Therefore, we evaluated the prognosis of kidney dysfunction after discharge and long-term mortality in patients with ACS undergoing PCI.
Divisions of aCardiovascular Medicine and bNephrology, Toho University Ohashi Medical Center, Tokyo, Japan. Manuscript received December 17, 2013; revised manuscript received and accepted February 24, 2014. The authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. See page 1651 for disclosure information. *Corresponding author: Tel: (þ81) 3 3468 1251; fax: (þ81) 3 3468 1269. E-mail address: [email protected] (N. Nemoto). 0002-9149/14/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjcard.2014.02.019
Methods From January 2001 to October 2005, a total of 648 patients with ACS underwent PCI in our institution. Patients with endstage renal failure requiring dialysis (n ¼ 30), patients who died within 6 to 8 months after PCI (n ¼ 49), and patients who failed to have serum creatinine (Cr) level measured at 6 to 8 months after PCI (n ¼ 38) were excluded. The remaining 531 patients were divided into 2 groups: those with CDKF (CDKF group, n ¼ 444) and those without CDKF (non-CDKF group, n ¼ 87; Figure 1). The demographic and clinical characteristics of the patients were recorded on admission. Information regarding the laboratory parameters, pharmacologic data, and interventional therapies was obtained from the patient’s electronic medical charts. On admission, venous blood samples and urine samples were obtained before administration of any medications. These samples were tested using an automatic clinical chemistry analyzer (LABOSPECT 008; Hitachi, Tokyo, Japan). The Cr, total cholesterol, and high- and low-density lipoprotein levels were determined using enzymatic methods. The definition of ACS was based on the current guidelines.11 CDKF was defined as an absolute Cr increase of 0.5 mg/dl or a relative increase in Cr 25% above baseline from 6 to 8 months after PCI. CI-AKI was defined as an absolute Cr increase of 0.5 mg/dl or a relative increase in Cr 25% above baseline within 48 hours after PCI. The estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease formula,12 with coefficients modified for Japanese patients13: eGFR (ml$minute1$1.73 m2) ¼ 194 serum Cr 1.094 age0.287 (0.739 if female). CKD was defined as an eGFR www.ajconline.org
1648
The American Journal of Cardiology (www.ajconline.org)
Figure 1. Enrollment criteria and study flow. CDKF was defined as an increase in absolute Cr level of 0.5 mg/dl or a relative increase in Cr 25% above baseline from 6 to 8 months after PCI. Table 1 Baseline clinical characteristics of patients Variable
Men Age (yrs) Age 75 yrs Body mass index (kg/m2) Hypertension Diabetes mellitus Dyslipidemia* Total cholesterol (mg/dl) High-density lipoprotein cholesterol (mg/dl) Triglyceride (mg/dl) Low-density lipoprotein cholesterol (mg/dl) Smoker CKD (3)† Glomerular filtration rate (ml/min) Serum Cr value (mg/dl) Serum Cr value 1.5 mg/dl Proteinuria CI-AKI Target vessels Ejection fraction (%) Low ejection fraction (40%) New York Heart Association class III or IV Hemoglobin (g/dl) Anemia (men
