Prognosis of acute myocardial infarction in patients on hemodialysis stratified by Killip classification in the modern interventional era (focus on the prognosis of Killip class 1).

Cardiovascular events and death are more prevalent in hemodialysis (HD) patients than in the general population. However, a detailed prognostic risk stratification of HD patients with acute myocardial infarction (AMI) has not yet been performed in the modern interventional era. We examined 4509 AMI patients (89 AMI/HD and 4420 AMI/non-HD) from the Mie ACS registry and detailed prognostic analyses based on the Killip classification were performed (Cohort A). In addition, prognosis of Killip class1 AMI/HD was compared with those of 313 non-AMI/HD patients from the MIE-CARE HD study using propensity score-matching method (Cohort B). Primary endpoint was all-cause mortality for up to 2 years. All-cause death occurred in 13.0% of AMI/non-HD and 35.8% of AMI/HD during follow-up, and patients with Killip class 1 had lower 30-day and 2-year mortality than those with Killip class ≥ 2 in both AMI/non-HD and AMI/HD. Cox regression analyses identified that Killip class ≥ 2 was the strongest independent prognostic factor of 30-day mortality with a hazard ratio of 7.44 (p < 0.001), whereas both presence of HD and Killip class ≥ 2 were the independent prognostic factors of mortality for up to 2 years. In Cohort B, a propensity score-matching analysis revealed similar all-cause mortality rates between Killip class 1 AMI/HD and non-AMI/HD. In HD patients with Killip class 1 AMI, 30-day mortality was around 6%, and long-term mortality among 30-day survivors after AMI was comparable with the natural course of HD patients in the modern interventional era. Clinical trial registration: URL: https://www.umin.ac.jp/ctr/index-j.htm . UMIN000036020 and UMIN000008128.

Efficacy of xanthine oxidase inhibitor for chronic kidney disease patients with hyperuricemia.

BACKGROUND: Hyperuricemia is a known risk factor for end-stage renal disease. Although xanthine oxidase (XO) inhibitors are expected to protect the kidney function, evidence to this end is insufficient at present. METHODS: This study was a multi-center, open-labeled, randomized study conducted in Mie Prefecture in Japan. Patients were included if they were between 20 and 80 years old and had a serum uric acid (sUA) level ≥ 7.0 mg/dl with or without gout, estimated glomerular filtration rate (eGFR) of 15-60 ml/min/1.73 m2, and urinary protein creatinine ratio (uPCR) of 0.15-3.5 g/gCr. Patients were randomly assigned to a Topiroxostat or Febuxostat group, and the treatment target for the sUA level was < 6.0 mg/dl. The primary outcome was the change in the uPCR after 24 weeks. RESULTS: The change in the median uPCR after 24 weeks was not statistically significant after treatment in the Topiroxostat or Febuxostat group (0.05 g/gCr and - 0.04 g/gCr, respectively). However, the sUA levels decreased significantly in both groups (Topiroxostat group: 8.6 ± 1.1 at baseline to 6.0 ± 1.1 mg/dl at 24 weeks, Febuxostat group: 8.4 ± 1.1 mg/dl at baseline to 5.9 ± 1.3 mg/dl at 24 weeks). No significant change in the eGFR after 24 weeks was noted in either the Topiroxostat or Febuxostat group (- 0.04 ± 4.59 ml/min/1.73 m2 and 0.31 ± 4.70 ml/min/1.73 m2, respectively). CONCLUSIONS: In this study, XO inhibitors did not significantly reduce the uPCR in chronic kidney disease stage 3 and 4 patients with hyperuricemia.

Echocardiographic Assessment of Cardiac Structural and Functional Abnormalities in Patients With End-Stage Renal Disease Receiving Chronic Hemodialysis.

BACKGROUND: The aim of this study was to assess the echocardiographic characteristics of chronic hemodialysis (HD) patients with end-stage renal disease (ESRD) in a multicenter prospective cohort study.Methods and Results:Three hundred and fifteen patients with ESRD (67.9±10.6 years, 47.6% male) on chronic HD for ≥1 year were examined on transthoracic echocardiography, including Doppler-derived aortic valve area (AVA) measurement. Only 11.5% and 3.4% of all patients had normal left ventricular (LV) geometry and normal LV filling pattern, respectively. The majority of patients had aortic and mitral valvular calcification, and approximately 50% of all 315 patients had aortic valve narrowing with AVA <2.0 cm2. Patients were divided into 3 groups according to AVA index tertile: group 1, highest tertile; group 2, middle tertile; and group 3, lowest tertile. Group 3 was older, had a greater cardiothoracic ratio on chest X-ray, higher plasma brain natriuretic peptide and total LV afterload, and lower stroke volume index than the other 2 groups. Age and intact parathyroid hormone (PTH) level were independently associated with low AVA index. CONCLUSIONS: Patients with ESRD on chronic HD have a high prevalence of cardiac structural and functional abnormalities including calcified aortic sclerosis. High age and PTH were associated with aortic valve narrowing in these patients.

Hemodynamic and pathophysiological characteristics of intradialytic blood pressure elevation in patients with end-stage renal disease.

An increase in systolic blood pressure (SBP) after hemodialysis (intradialytic-HTN) is associated with adverse outcomes in patients on regular hemodialysis. However, the hemodynamic and Doppler echocardiographic characteristics of intradialytic-HTN and its impact on clinical outcomes are unclear. A retrospective analysis of 84 patients (45 men, 70±9 years) stratified into three groups on the basis of SBP response from pre- to post-hemodialysis: GHTN (intradialytic-HTN, SBP increase 10 mm Hg), GDROP<15 mm Hg (SBP drop <15 mm Hg), and GDROP15 mm Hg (SBP drop 15 mm Hg). Hemodynamic and echocardiographic assessments were performed pre- and post-hemodialysis, and patients were followed for 41±17 months. GHTN had higher blood glucose and lower baseline SBP, serum potassium and total cholesterol. Cardiothoracic ratio was smaller, and peak early diastolic mitral annular velocity (E') was lower in GHTN. During hemodialysis, SBP and diastolic blood pressure increased only in GHTN. After hemodialysis, left ventricular (LV) filling pressure (E/E' ratio) decreased only in GDROP15 mm Hg, resulting in a higher E/E' ratio in GHTN than GDROP15 mm Hg. Multivariate logistic regression analysis revealed a positive correlation between blood glucose and intradialytic-HTN, whereas cardiothoracic ratio, pre-hemodialysis SBP and the change in E/E' ratio with hemodialysis were negatively related to intradialytic-HTN. During follow-up, GHTN had more cardiovascular deaths than GDROP15 mm Hg (P=0.03). Multivariate Cox regression analysis showed that lower serum potassium and previous coronary artery disease, but not intradialytic-HTN, were associated with cardiovascular deaths. A higher LV afterload and elevated filling pressures after hemodialysis, indicative of increased cardiovascular stiffening and impaired diastolic filling, may contribute in part to an increased cardiovascular burden in patients with intradialytic-HTN.

Kidney-protective effects of azelnidipine versus a diuretic in combination with olmesartan in hypertensive patients with diabetes and albuminuria: a randomized study.

BACKGROUND: A thiazide diuretic used in combination with benazepril is superior to amlodipine plus benazepril in reducing albuminuria in hypertensive patients with diabetes. However, calcium channel blockers have diverse characteristics. Thus, we investigated whether combining an angiotensin receptor blocker with either azelnidipine or a thiazide diuretic produced similar reductions in albuminuria in hypertensive diabetic patients for the same levels of blood pressure achieved. METHODS: Hypertensive patients with type 2 diabetes and albuminuria (30-600 mg/g creatinine) under antihypertensive treatment (mean age 67.0±7.6 years) were instructed to stop all antihypertensive treatment and take a combination of olmesartan (20 mg/day) and amlodipine (5 mg/day) for 3 months (run-in period). Then, patients were randomly assigned to receive either olmesartan plus azelnidipine (16 mg/day; n=71) or olmesartan plus trichlormethiazide (1 mg/day; n=72) for an additional 6 months. The primary end point was urinary excretion of albumin at 6 months after randomization. RESULTS: At the time of randomization, urinary albumin was 116.0 and 107.8 mg/g creatinine (geometric mean) in the azelnidipine and diuretic arms, respectively, and was reduced to a similar extent [79.8 (95% confidence interval 66.4-96.0) and 89.7 (74.6-107.7) mg/g creatinine, respectively, after adjustment for baseline values]. Blood pressure did not differ between the two groups throughout the study period. CONCLUSIONS: Azelnidipine is equally effective as a thiazide diuretic in reducing urinary albumin when used in combination with olmesartan.

Short-term effects of low-dose tolvaptan on hemodynamic parameters in patients with chronic heart failure.

BACKGROUND: We evaluated the short-term effects of low-dose tolvaptan treatment on hemodynamic parameters in patients with chronic heart failure (HF). METHODS: We studied 22 patients (69 ± 10 years) with chronic HF and excess fluid retention despite receiving appropriate medical therapy, including loop and/or thiazide diuretics. The therapeutic effects of low-dose (7.5mg) once-daily tolvaptan on hemodynamics associated with changes in fluid balance and neurohumoral activations were investigated after a seven day treatment period. RESULTS: After the treatment period, body weight decreased (-2.7 ± 2.3 kg) associated with increases in daily urine output. Whereas plasma arginine-vasopressin levels, serum aldosterone concentration, and plasma renin activity mildly increased, plasma levels of B-type natriuretic peptide and atrial natriuretic peptide significantly decreased after tolvaptan treatment. Serum electrolytes were not adversely affected by tolvaptan treatment. Although cardiac index and systemic vascular resistance index remained unchanged, mean pulmonary artery wedge pressure (22 ± 7 mmHg vs. 17 ± 7 mmHg, p<0.05), mean right atrial pressure (12 ± 5 mmHg vs. 9 ± 5 mmHg, p<0.05), mean pulmonary artery pressure (32 ± 9 mmHg vs. 25 ± 7 mmHg, p<0.05), and pulmonary vascular resistance index (332 ± 207 dynes/cm(-5)/m(2) vs. 245 ± 110 dynes/cm(-5)/m(2), p<0.05) significantly decreased after tolvaptan treatment. The extent of the reduction in pulmonary vascular resistance index after tolvaptan treatment strongly correlated with baseline values. CONCLUSIONS: Short-term treatment with low-dose tolvaptan improved hemodynamic parameters and correlated with significant fluid removal in patients with chronic HF.