Toshiko Tokoro

Sympathetic overactivity and sudden cardiac death among hemodialysis patients with left ventricular hypertrophy

BACKGROUND We prospectively investigated whether cardiac autonomic imbalance is associated with sudden cardiac death (SCD) among a group of hemodialysis patients with left ventricular hypertrophy (LVH). METHODS In a prospective cohort study, we enrolled 196 asymptomatic patients on chronic hemodialysis who had LVH as determined by echocardiography and had undergone twenty-four-hour ambulatory Holter electrocardiography between dialysis sessions (males/females, 114/82; mean age, 65+/-12 years) to analyze heart rate variability. We calculated the percentage difference between adjacent NN intervals more than 50 ms (pNN50) and high-frequency component (HF, 0.15-0.40 Hz) as parameters of cardiac parasympathetic activity, and the low-frequency component (LF, 0.04-0.15 Hz)/HF component ratio as a parameter of sympathetic activity. RESULTS During 4.5+/-1.9-year follow-up, 21 patients who had undergone coronary revascularization within 60 days of enrollment were excluded from the analysis. Among the remaining 175 patients (male/female, 105/70; 66+/-12 years), SCD was recognized in 23 patients. On stepwise Cox hazard analysis, SCD was positively associated with age and LF/HF ratio, and tended to be inversely associated with pNN50. On Kaplan-Meier analysis, SCD-free survival rates at 5 years were 29.4% and 98.1% in patients with LF/HF ratios of 1.9 or more and below 1.9, respectively. CONCLUSIONS The presence of cardiac sympathetic overactivity may predict the occurrence of SCD in the asymptomatic hemodialysis patients with LVH.

Predominant tubulointerstitial nephritis in a patient with systemic lupus nephritis.

In most cases of systemic lupus erythematosus (SLE), glomerular lesions are the main renal complication. Although tubulointerstitial lesions are often associated with severe glomerular lesions, predominant or isolated tubulointerstitial injury in the presence of minimal glomerular abnormalities with SLE, so-called predominant tubulointerstitial lupus nephritis, is rare. Only ten cases are reported in the English literature. Herein, we describe the case of a 64-year-old man with SLE who presented with acute renal deterioration attributable to acute tubulointerstitial nephritis. Renal biopsy showed diffuse infiltration of inflammatory mononuclear cells in the interstitium and tubulitis without significant glomerular lesions. Immunofluorescence study revealed positive staining for IgG, C3, and C1q along the renal tubular basement membrane (TBM). Electron microscopy also showed electron-dense deposits in the TBM. Other causes of tubulointerstitial injury, such as drug use and infection, were ruled out. Taking these findings together with the presence of antitubular basement membrane antibody, predominant tubulointerstitial lupus nephritis was diagnosed. Treatment with oral corticosteroids for 6 weeks improved renal function. Even after tapering of the corticosteroid, renal function and serological markers of SLE activity have remained stable in this patient for more than 12 months.

Plasma S100A12 Level Is Associated with Cardiovascular Disease in Hemodialysis Patients

BACKGROUND AND OBJECTIVES S100A12 is an endogenous receptor ligand for advanced glycation end products. Cardiovascular disease remains a major cause of morbidity and mortality in patients with chronic kidney disease. In this study, we report cross-sectional data on 550 hemodialysis patients and assess the relationship between plasma S100A12 level and cardiovascular disease. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A cross-sectional study of 550 maintenance hemodialysis patients was conducted. We investigated the past history of cardiovascular disease and quantified the plasma level of S100A12 protein in all participants. RESULTS Plasma S100A12 level was higher in hemodialysis patients with cardiovascular disease (n=197; 33.8 ± 28.1 ng/ml) than in those without it (n=353; 20.2 ± 16.1 ng/ml; P<0.001). In multivariate logistic regression analysis, the plasma S100A12 level (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.13 to 1.44; P<0.001) was identified as an independent factor associated with the prevalence of cardiovascular disease. The other factors associated with the prevalence of cardiovascular diseases were the presence of diabetes mellitus (OR, 2.81; 95% CI, 1.79 to 4.41; P < 0.001) and high-sensitivity CRP level (OR, 1.02; 95% CI, 1.00 to 1.05; P=0.046). Furthermore, the plasma S100A12 level (OR, 1.30; 95% CI, 1.09 to 1.54; P=0.004) was significantly associated with cardiovascular disease even in hemodialysis patients without diabetes mellitus (n=348). CONCLUSIONS These results suggest that the plasma S100A12 protein level is strongly associated with the prevalence of cardiovascular disease in hemodialysis patients.

Total parathyroidectomy improves survival of hemodialysis patients with secondary hyperparathyroidism.

BACKGROUND AND AIMS To compare the prognosis of chronic hemodialysis patients with or without parathyroidectomy. METHODS Among 158 chronic hemodialysis patients who underwent total parathyroidectomy between July 1998 and April 2009, 88 patients were matched with 88 controls for sex, age, underlying disease and prior dialysis history. Then a retrospective evaluation of their prognosis was performed over a median observation period of 4.41 years. RESULTS The overall survival rate was 90.4% in the parathyroidectomy group and 67.4% in the control group. The cardiovascular death-free survival rate was 94.6% in the parathyroidectomy group and 76.3% in the control group. During observation, intact parathyroid hormone was measured every 6 months, and its average serum level was 37 ± 92 ng/L in the total parathyroidectomy group versus 274 ± 233 ng/L in the control group (p=0.0001). The total parathyroidectomy group had a significantly lower corrected calcium level and higher serum albumin level. Multivariate analysis revealed that parathyroidectomy, atrial fibrillation and serum albumin were significant factors for both total and cardiovascular mortality. CONCLUSION Total parathyroidectomy was associated with better survival, probably due to decreased cardiovascular mortality.

Oral Nicorandil to Reduce Cardiac Death After Coronary Revascularization in Hemodialysis Patients: A Randomized Trial

BACKGROUND Survival after invasive coronary revascularization is worse in patients with chronic kidney disease than in patients without chronic kidney disease. We examined whether oral administration of nicorandil, a hybrid nitrate and adenosine triphosphate-sensitive potassium channel opener, could improve outcome after coronary revascularization in hemodialysis patients. STUDY DESIGN Open-labeled prospective randomized trial. SETTING & PARTICIPANTS Maintenance hemodialysis patients who underwent percutaneous coronary artery intervention and had complete coronary revascularization (absence of both restenosis and de novo coronary lesion) at coronary arteriography 6 months later. Enrollment occurred between January 1, 2002, and December 31, 2004. INTERVENTIONS Treatment with or without oral administration of nicorandil, 15 mg/d. OUTCOMES & MEASUREMENTS The primary end point was cardiac death (sudden cardiac death or death from acute myocardial infarction or congestive heart failure). The secondary end point was all-cause death. End-point adjudication was performed masked to the intervention. RESULTS 129 patients (91 men, 38 women) with a mean age of 66 +/- 9 (SD) years. During a 2.7 +/- 1.5-year follow-up, 26 died of cardiac events (acute myocardial infarction, 6; congestive heart failure, 5; sudden cardiac death, 15), and 12 died of noncardiac causes. Cardiac death-free survival rates were greater in the nicorandil group than in the control group (P = 0.009; at 3 years, 86.6% in the nicorandil group and 70.7% in the control group). All-cause death-free survival rates were also greater in the nicorandil group than in the control group (P = 0.01; at 3 years, 79.2% in the nicorandil group versus 60.5% in the control group). Additional percutaneous coronary artery intervention was performed in 6 participants in the nicorandil group and 2 participants in the control group. No serious side effects of nicorandil were reported during the course of the study. LIMITATIONS Small sample size and open-label design. CONCLUSIONS Oral administration of nicorandil may reduce cardiac death and improve the survival of hemodialysis patients after coronary revascularization.

'Takotsubo' cardiomyopathy in a maintenance hemodialysis patient.

Abstract:  An 84‐year‐old woman undergoing maintenance hemodialysis presented with chest discomfort lasting several days and electrocardiographic abnormalities. She had stopped smoking 2 weeks earlier and was experiencing irritability. Upon admission, electrocardiography showed ST‐segment elevation in leads I, II, aVF, and V2‐6 and an abnormal Q wave in leads II, III, and aVF. Ultrasound cardiography showed left ventricular anteroapical akinesia and basal hyperkinesia. The chest discomfort disappeared without specific therapy. During hospital days 1–5, the ST‐segment elevation gradually improved. Giant negative T waves then developed. The left ventricular asynergy resolved by day 8. Radionuclide imaging with iodine‐123‐beta‐methyl‐p‐iodophenyl pentadecanoic acid, but not with technetium‐99 m‐sestamibi, showed an apical defect. Elective coronary angiography showed no stenosis. ‘Takotsubo’ cardiomyopathy was diagnosed. After discharge, the patient continued regular dialysis without cardiac symptoms. We concluded that endogenously activated sympathetic nerve action in hemodialysis patients, especially those under emotional or physical stress, might be a causative factor for Takotsubo cardiomyopathy.

Clinical Potential of Nicorandil to Inhibit Major Cardiac Events in Hemodialysis Patients with Suspected Myocardial Ischemia

Background/Aims: We examined whether nicorandil, which is a hybrid of an adenosine triphosphate-sensitive potassium channel opener and a nitrate, could inhibit major adverse cardiac events (MACE) in maintenance hemodialysis patients with suspected myocardial ischemia. Methods: We enrolled 148 asymptomatic patients on maintenance hemodialysis, who had exhibited potential myocardial ischemia as assessed by myocardial fatty acid imaging. The end-point was MACE including cardiac death and non-fatal acute myocardial infarction. A propensity-matched analysis was performed. Results: Over a mean duration of follow-up of 2.8 ± 1.6 years in the 82 propensity-matched patients (41 in the nicorandil group and 41 in the non-nicorandil group), we observed 17 cardiac deaths and 12 cases of nonfatal myocardial infarction. The incidence of MACE was lower (p = 0.0365) in the nicorandil group (10/41, 24.4%) than in the non-nicorandil group (19/41, 46.3%). On stepwise Cox hazard analysis, MACE was significantly inhibited by administration of nicorandil (hazard risk, 0.387; 95% CI 0.178–0.842; p = 0.0168). Kaplan-Meier survival estimates revealed that MACE-free survival rates at 3 years were 80.5 and 58.5% in patients with and without nicorandil, respectively. Conclusions: Oral administration of nicorandil may offer new potential for the inhibition of MACE in hemodialysis patients.

Prognosis of Hepatocellular Carcinoma after Hepatectomy in Patients with Renal Dysfunction

We evaluated the effect of renal dysfunction on the prognosis of hepatocellular carcinoma in 224 patients who underwent hepatic resection. Survival was compared between patients with (57 patients) and without renal dysfunction (116 patients), using a creatinine clearance ≤70 ml/min as the cut-off value. There were no significant differences with respect to other preoperative characteristics, operative findings, or histology between the two groups. There was also no difference in survival between the two groups after hepatic resection. However, among 132 patients with a solitary tumor measuring ≤5 cm in greatest dimension, the disease-free and overall survival rates of 36 patients with renal dysfunction were significantly worse after resection than those of the patients without renal dysfunction (p = 0.04 and p = 0.0003, respectively). By multivariate analysis, renal dysfunction was an independent factor indicating a poor prognosis for disease-free and overall survival after resection of small solitary tumors (p = 0.0401 and p = 0.0031, respectively). Renal dysfunction did not affect the overall prognosis after resection of hepatocellular carcinoma, but it worsened the prognosis of patients with small solitary lesions.

Clinical potential of oral nicorandil to improve myocardial fatty acid metabolism after percutaneous coronary intervention in hemodialysis patients.

Background/Aims: The assessment of myocardial fatty acid metabolism impairment by single-photon emission computed tomography (SPECT) using 123I-β-methyliodophenyl-pentadecanoic acid (BMIPP) might predict the risk of cardiac death in hemodialysis patients. We investigated the potential of oral nicorandil to improve myocardial fatty acid metabolism after percutaneous coronary intervention (PCI) in this population. Methods: We evaluated 128 hemodialysis patients who had obtained coronary revascularization by PCI (90 men and 38 women, 66 ± 9 years). Participants for the analysis were randomly assigned to either the nicorandil (n = 63) or control group (n = 65). BMIPP SPECT was performed every year after coronary revascularization by PCI. Uptake on SPECT was graded in 17 segments on a 5-point scale (0, normal; 4, absent) and assessed as BMIPP summed scores (SS). Results: The incidence of cardiac death was lower (p = 0.004) in the nicorandil group (7/63, 11.1%) than in the control group (21/65, 32.3%) during a mean follow-up of 2.7 ± 1.4 years. BMIPP SS reduction rates improved in the nicorandil group compared with the control group from 3 years of administration. In Kaplan-Meier analyses, free survival rate of cardiac death was higher in patients with a ≥20% BMIPP SS reduction rate as compared with those with a <20% BMIPP SS reduction rate (p = 0.0001). In multiple logistic analysis, oral administration of nicorandil was associated with ≥20% reduction rates of BMIPP SS (odds ratio 2.823, p = 0.011). Conclusion: Long-term oral administration of nicorandil may improve impaired myocardial fatty acid metabolism after coronary revascularization by PCI in hemodialysis patients.

Oral nicorandil for prevention of cardiac death in hemodialysis patients without obstructive coronary artery disease: a propensity-matched patient analysis.

Background/Aims: We examined the potential of oral administration of nicorandil for protecting against cardiac death in hemodialysis patients without obstructive coronary artery disease. Methods: This study was based on a cohort study of 155 hemodialysis patients with angiographic absence of obstructive coronary lesions, with analysis performed in 100 propensity-matched patients (54 men and 46 women, 64 ± 10 years), including 50 who received oral administration of nicorandil (15 mg/day, nicorandil group) and 50 who did not (control). The efficacy of nicorandil in preventing cardiac death was investigated. Results: Over a mean follow-up period of 5.3 ± 1.9 years, we observed 25 cardiac deaths among 100 propensity-matched patients, including 6 due to acute myocardial infarction, 11 due to heart failure, and 8 due to sudden cardiac death. The incidence of cardiac death was lower (p < 0.001) in the nicorandil group (4/50, 8%) than in the control (21/50, 42%). On multivariate Cox hazard analysis, cardiac death was inversely associated with oral nicorandil (hazard ratio, 0.123; p = 0.0002). On Kaplan-Meier analysis, cardiac death-free survival rates at 5 years were higher in the nicorandil group than in the control group (91.4 vs. 66.4%). Conclusion: Oral nicorandil may inhibit cardiac death of hemodialysis patients without obstructive coronary artery disease.