Hirohisa Kawahara

Comparison of Percutaneous Coronary Intervention with Medication in the Treatment of Coronary Artery Disease in Hemodialysis Patients

It has been reported that percutaneous coronary intervention (PCI) is beneficial for coronary artery disease (CAD) among the general population. However, its effects in patients who are on hemodialysis (HD) remain unclear. A prospective cohort study was performed to clarify whether PCI has a therapeutic advantage over medical therapy among HD patients with CAD. A follow-up study to 5 yr was conducted among 259 HD patients with ischemic heart disease. Mean follow-up was 39 mo. Patients were divided into three groups: 122 patients without significant stenosis, 88 patients who had significant stenosis and were treated with PCI, and 49 patients who had significant stenosis and were treated with medication only. The primary end point was cardiac death, and the secondary end point was all-cause death. The results showed that the 5-yr cardiac survival rate was 41.6% in the medication group, 77.1% in the PCI group (P = 0.0006), and 84.5% in the nonstenosis group (P < 0.0001). The 5-yr all-cause survival rate was 19.3% in the medication group, 48.4% in the PCI group (P = 0.004), and 64.3% in the nonstenosis group (P < 0.0001). Even after adjustment for other risk factors, effects of PCI on the risk for cardiac and all-cause death remained significant and independent (odds ratio 0.14; 95% confidence interval 0.08 to 0.25, P = 0.0006; and odds ratio 0.37; 95% confidence interval 0.26 to 0.54, P = 0.0062, respectively). Results were consistent when the therapeutic effect of PCI or medication was analyzed using propensity-matched patients. These data suggested that PCI could improve the prognosis of HD patients with CAD. PCI would be recommended for HD patients with CAD.

Effects of Combination Treatment with Losartan and Trandolapril on Office and Ambulatory Blood Pressures in Non-Diabetic Renal Disease: A COOPERATE-ABP Substudy

Background: In the COOPERATE trial, the combination treatment of the angiotensin-II receptor blocker losartan and the angiotensin-converting-enzyme inhibitor trandolapril significantly retarded progression of non-diabetic kidney disease compared with each monotherapy. The benefit could be greatly attributable to the potent reduction of proteinuria, because the three treatment groups showed the same reductions of office blood pressure (OBP). Ambulatory blood pressure (ABP) is reported to be better than OBP in predicting progression of kidney disease. Methods: Ninety-two patients enrolled in the COOPERATE trial underwent 24-hour ABP monitoring at randomization and at month 6, year 1, year 2 and year 3 on randomized treatment. Results: Both OBP and ABP were similarly reduced among the three groups at all measurement points (p = NS) and throughout the whole study period (p = NS). No significant correlation between the change in 24-hour ABP and the change in proteinuria was seen (p = NS). A Cox-multivariable analysis showed that covariates affecting the renal outcomes (a doubling serum-Cr level and/or end-stage renal failure) were the change in proteinuria (hazard ratio 0.49, 95% CI 0.34–0.78, p = 0.01) and treatments (0.58, 0.45–0.99, 0.03), but not 24-hour ABP (0.98, 0.89–2.01, 0.17). Conclusion: The better renoprotective effect of the combination treatment is attributed to BP-independent mechanisms by more complete renin-angiotensin system blockade.

Low circulating CD34+ cell count is associated with poor prognosis in chronic hemodialysis patients

Circulating CD34-positive (CD34(+)) cells, a population that includes endothelial progenitor cells, are believed to contribute to vascular homeostasis. Here we determine the prognostic value of CD34(+) cell measurements in 216 chronic hemodialysis patients. A total of 43 cardiovascular events and 13 deaths occurred over an average 23 months follow-up in this cohort. A cutoff number for circulating CD34(+) cells was determined by receiver operating characteristic curve analysis to maximize the power of the CD34(+) cell count in predicting future cardiovascular events. Based on this, 93 patients were categorized as having low and 123 patients as having high numbers of CD34(+) cells, determined by flow cytometry at the time of enrollment. Both cumulative cardiovascular event-free survival and all-cause survival were significantly less in the group of patients with low numbers of CD34(+) cells. By multivariate analyses, a low level of circulating CD34(+) cells was an independent and significant predictor for both cardiovascular events and all-cause mortality. Our study shows that a reduced number of circulating CD34(+) cells is significantly associated with vascular risks and all-cause mortality in patients on chronic hemodialysis. These cells may be a useful biomarker.

Autonomic Dysfunction in Hemodialysis Patients with Persistent Hypotension

To investigate autonomic mechanisms underlying persistent hypotension in long-term hemodialysis patients, high-frequency (HF, > 0.15 Hz) and low-frequency (LF, 0.04-0.15 Hz) components of heart rate variability and plasma noradrenaline were analyzed in 10 persistently hypotensive hemodialysis patients (group H), 11 normotensive patients (group N) and 10 healthy controls (group C). The HF amplitude, an index of cardiac parasympathetic activity, and LF-to-HF ratio, an index of sympathetic predominance, were in the order of groups C > N > H (p < 0.01). While the HF amplitude decreased with standing in all three groups (p < 0.05 for all), the LF-to-HF ratio increased only in groups N and C (p < 0.05 for both) but not in group H. Conversely, plasma noradrenaline level was in the order of groups C < N < H (p < 0.001). Furthermore, while the LF-to-HF ratio correlated positively with the plasma noradrenaline level in group C (r = 0.73, p < 0.01), it correlated negatively in group H (r = 0.69, p < 0.05). These results indicate that an impairment in both parasympathetic and sympathetic functions exists in hemodialysis patients with persistent hypotension, and that the apparent sympathetic dysfunction could result from a reduction in cardiovascular responsiveness to sympathetic stimulation.

Angiotensin-Converting Enzyme Inhibitor and Anemia in a Patient Undergoing Hemodialysis

We have observed a polycythemic patient with poly-cystic kidney disease (PCKD) and hypertension who was treated with enalapril maleate, which is a long-acting angiotensinconverting enzyme inhibitor (ACEI). In this patient, we studied the suppression of erythropoietin (Ep) synthesis by an ACEI. A 51-year-old man first noted the abdominal tumor in 1978. Included in his family history was the fact that his elder brother and elder sister had PCKD, which is characterized by autosomal dominant heredity and progressive renal failure. He consulted a physician for the abdominal tumor in 1978, and he was discovered to have multiple bilateral renal cysts without hepatic or pancreatic cysts. The diagnosis of PCKD was based on family history and computertomographic (CT) findings. In October 1984, he was transferred to our hospital for treatment of chronic renal failure (CRF). He was diagnosed as having end-stage CRF and operated upon for an arteriovenous fistula. His renal function slowly deteriorated. In April 1985, he started hemodialysis (HD) therapy. After HD treatment, his condition improved rapidly and his hematocrit (Ht) increased (18–25%). In 1988, Ht exceeded 40%. Because renal tumor with secondary polycythemia is well known [1], he was examinated by CT. There was no difference between the prior study and the follow-up study, which revealed multiple renal cysts occupying the renal parenchyma and no evidence of a malignant tumor. As the cencentration of Ep was 86.6 mU/ml and no renal tumor was found, we concluded that the polycythemia was caused by PCKD per se.

Loss of Fractal Heart Rate Dynamics in Depressive Hemodialysis Patients

Objective: To assess the relationship between depression, reduced heart rate (HR) variability, and altered HR dynamics among patients with end-stage renal disease who are receiving hemodialysis (HD) therapy. Methods: We analyzed the 24-hour electrocardiograms of 119 outpatients receiving chronic HD. HR variability was quantified with the standard deviation of normal-to-normal R-R intervals, the triangular index, and the powers of the high- (HF), low- (LF), very-low (VLF), and ultra-low frequency (ULF) components. Nonlinear HR dynamics was assessed with the short-term (α1) and long-term (α2) scaling exponents of the detrended fluctuation analysis and approximate entropy. The depression level was assessed using the Beck Depression Inventory, Second Edition (BDI-II). HR variability and dynamics measurements were compared by gender, diabetes, and depression with adjustment for age and serum albumin concentration. Results: Most indices of HR variability and dynamics were negatively correlated with age, serum albumin concentration, depression score, and were lower in women and patients with diabetes. The α2 was inversely associated with these variables. Depressed men had significantly lower HF, LF, VLF, and marginally lower ULF than nondepressed persons after adjustment for diabetes and other covariates; no difference in depression was observed in women. The α2 showed marginally significant difference in depression independent from gender and diabetes. Conclusions: Among the patients who received HD, depression is associated with reduced HR variability and loss of fractal HR dynamics. However, the influence of depression on HR variability may vary by gender and physiological backgrounds. Further prospective studies are necessary to confirm their association with poor prognosis. CHD = coronary heart disease; HR = heart rate; DFA = detrended fluctuation analysis; ApEn = approximate entropy; HD = hemodialysis; ESRD = end-stage renal disease; NKC = Nagoya Kidney Center; AMI = acute myocardial infarction; ECG = electrocardiography; PCR = protein catabolic rate; SDNN = standard deviation of normal-to-normal R-R intervals; HF = high-frequency band; LF = low-frequency band; VLF = very-low-frequency band; ULF = ultra-low-frequency band; SD = standard deviation; mNN = mean normal-to-normal R-R intervals; BDI = Beck Depression Inventory; DSM = Diagnostic and Statistical Manual of Mental Disorders; ANCOVA = analysis of covariance; GLM = general linear model.

Depression, alexithymia and long-term mortality in chronic hemodialysis patients.

Background: Depression increases the risk of mortality in hemodialysis patients. Alexithymia, a disorder of affect regulation, has also been reported to be associated with mortality risk in the general population. We conducted a prospective study to estimate the independent impact of depression and alexithymia on long-term mortality. Methods: A total of 230 hemodialysis outpatients, with a mean age of 56.3 ± 9.6 years, completed a batch of self-report measures including the Beck Depression Inventory-II (BDI-II), the 20-item Toronto Alexithymia Scale (TAS-20) and the 36-item Short Form Health Survey (SF-36). Survival status was confirmed every 6 months for up to 5 years. The presence of depression and alexithymia was defined by a BDI-II score of ≧14 and a TAS-20 score of ≧61, respectively. Results: During the follow-up period, 27 deaths were confirmed. Both depression and alexithymia were associated with an increased risk for all-cause mortality; the age- and sex-adjusted hazard ratio for depression was 2.36 (95% CI: 1.08–5.15; p = 0.03) and that for alexithymia was 4.29 (95% CI: 1.95–9.42; p < 0.001). Depression lost its statistical significance after controlling for alexithymia, whereas alexithymia remained significant even after adjusting for the baseline depression, health status (the summary scores of the SF-36), marital status and clinical covariates (multivariate adjusted hazard ratio = 3.62; 95% CI: 1.32–9.93; p = 0.01). Conclusions: Alexithymia is a strong independent risk factor for all-cause mortality in hemodialysis patients.

Immersing Feet in Carbon Dioxide-enriched Water Prevents Expansion and Formation of Ischemic Ulcers after Surgical Revascularization in Diabetic Patients with Critical Limb Ischemia

OBJECTIVE We investigated the effect of immersion of feet in CO2-enriched water for preventing expansion and formation of ischemic ulcer in critical limb ischemia of diabetic patients after surgical revascularization. MATERIALS AND METHODS Eligible patients were allocated CO2 group (CO2 immersion plus standard care) or control group (standard care alone) and were followed up for 3 months after surgical revascularization. The end point is defined as an expansion of a target ulcer (more than 101% of original size) or the formation of new ulcers during the follow-up period. RESULTS Fifty-nine patients out of originally enrolled 66 patients with type II diabetes were included in intention-to-treat population. The cumulative prevention rate for ischemic ulcer after 3 months was 97.1% in the CO2 group, while, in the control group, it was 77.8%, i.e., significantly lower than the CO2 group (P = 0.012, log-rank test). The transcutaneous oxygen pressure increased significantly only in the CO2 group, from 56 ± 14 to 63 ± 15 mmHg (P < 0.01, Wilcoxon signed rank test), in 3 months. CONCLUSION These results suggest that addition of CO2 immersion to standard care of critical limb ischemia in diabetic patients improves early postoperative outcome after vascular surgery.

Blood Flow Analysis of the Head and Lower Limbs by the Laser Doppler Blood Flowmeter During LDL Apheresis

Abstract:  The presence of peripheral arterial disease substantially increases the risk for both morbidity and mortality among end‐stage renal disease patients. Low‐density lipoprotein (LDL) apheresis has been also applied for the treatment of peripheral arterial disease to reduce LDL levels, resulting in the improvement of the blood flow to the ischemic limbs. In this study, we investigated the continuous changes of the tissue blood flows in the lower limbs and head during LDL‐apheresis treatment by a non‐invasive method (the non‐invasive continuous monitoring method (NICOMM) system). In this study, the tissue blood flow in both the head and lower limbs showed a significantly enhancement from before to after treatment. The tissue blood flow in the lower limbs showed a significantly larger improvement than that in the head. The short‐term effects of LDL apheresis were confirmed by using the NICOMM system; thus, this system will be useful for the determination of the appropriate schedule of LDL apheresis for long‐term effectiveness.

Dual blockade of the renin-angiotensin system in chronic renal disease: to do or not to do.

The renin-angiotensin-aldosterone system has an important role in the progression of both diabetic and nondiabetic nephropathy. Angiotensin-converting enzyme inhibitors and angiotensin-II receptor blocker can effectively retard or halt this progression. However, their renoprotective effect is not enough, because approximately 20% of patients have a progressive course to endstage renal disease. There is now clear evidence that combination therapy of two agents is more antiproteinuric and, likely renoprotective, than each agent alone. However, several critical issues should be addressed before recommending it as standard treatment in chronic renal disease.