Yoshitaka Kumada

Long-term outcome of percutaneous transluminal angioplasty in chronic haemodialysis patients with peripheral arterial disease

BACKGROUND Chronic haemodialysis patients are at an increased risk of peripheral artery disease (PAD). Although percutaneous transluminal angioplasty (PTA) has become a widely used therapeutic intervention for PAD, its outcome in haemodialysis patients remains poorly understood. The aim of this study was to clarify the long-term outcome of PTA as a primary treatment for PAD in haemodialysis patients. METHODS Consecutive 118 haemodialysis patients with 205 lesions and 108 non-haemodialysis patients with 143 lesions who underwent successful PTA as a first-choice therapeutic option for PAD were enrolled. Outcome measures included primary patency, limb salvage and survival. RESULTS Incidence of diabetes, history of coronary artery disease and femoropopliteal lesion were significantly more frequent in haemodialysis patients (P = 0.008, 0.005 and 0.0001, respectively), but critical limb ischaemia and TransAtlantic Inter-Society Consensus (TASC) lesion types occurred with comparable frequency in both groups. No patients had in-hospital complications. The 5-year primary patency, limb salvage and survival rates were significantly lower in haemodialysis patients (P = 0.01, 0.029 and 0.0024, respectively). On Cox multivariate analysis, haemodialysis was strongly predictive of amputation and all-cause death, but not of restenosis. In haemodialysis patients, TASC C+D lesion and ulceration/gangrene were independent predictors for restenosis and amputation. CONCLUSIONS The long-term outcome after PTA may be fully acceptable in haemodialysis patients who are at the highest risk of cardiovascular disease. PTA is a useful therapeutic strategy in haemodialysis patients with PAD, but PTA for TASC C+D lesions remains controversial.

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.

Clinical outcome after infrapopliteal bypass surgery in chronic hemodialysis patients with critical limb ischemia

OBJECTIVE Lower extremity bypass surgery has been widely performed to treat critical limb ischemia (CLI) in patients on hemodialysis (HD). However, the clinical outcome still remains unclear. We investigated the limb salvage rate after infrapopliteal bypass surgery in HD patients with CLI. METHODS From April 2006 to January 2013, 226 patients with 236 limbs who electively underwent bypass surgery for treatment of CLI due to infrapopliteal disease were enrolled. Patients were grouped by those who were on HD (n = 177) and those who were not (n = 49). They were monitored for 5 years or until December 2013 if the follow-up period was <5 years. Amputation-free survival, defined as freedom from major amputation or all-cause death, was primarily evaluated. Incidence of reintervention was also analyzed. RESULTS Ulcer/gangrene was present in 206 patients (91.2%), and 233 limbs (98.7%) were treated using autogenous vein. Age was younger (67 ± 9 vs 72 ± 9 years; P = .0011) and ulcer/gangrene was more prevalent (93.8% vs 81.6%, P = .0080) in HD patients than in non-HD patients. During the follow-up period (median, 28 months), 33 (14.6%) major amputations and 28 reinterventions (12.4%) occurred, and 65 patients (28.8%) died. The 5-year amputation-free survival rate was significantly lower in HD patients than in non-HD patients (43.6% vs 78.8%, P = .0033), and the adjusted hazard ratio (HR) for amputation or death for HD patients was 2.36 (95% confidence interval [CI], 1.13-4.92; P = .022). Compared with non-HD patients, the status of HD was similarly an independent risk of major amputation (72.4% vs 92.5%; adjusted HR, 4.36; 95% CI, 1.04-18.3; P = .045) and mortality (56.9% vs 83.2%; adjusted HR, 2.81; 95% CI, 1.30-6.09; P = .0085). However, freedom from reintervention was comparable between the two groups (84.3% vs 86.8%; P = .89). In HD patients, body mass index (HR, 0.86; 95% CI, 0.76-0.96; per 1 kg/m(2) increase; P = .014) and C-reactive protein (HR, 1.06; 95% CI, 1.01-1.11; P = .014) independently predicted major amputation. Elevated C-reactive protein levels were also associated with death (HR, 1.04; 95% CI, 1.01-1.09; P = .047). CONCLUSIONS The clinical outcome after infrapopliteal bypass surgery was poorer in HD patients with CLI compared with non-HD patients. Malnutrition or chronic inflammation was associated with poor outcome in HD patients with CLI due to infrapopliteal occlusive disease.

Nitinol stenting improves primary patency of the superficial femoral artery after percutaneous transluminal angioplasty in hemodialysis patients: A propensity-matched analysis

BACKGROUND Although percutaneous transluminal angioplasty (PTA) has become a common therapeutic standard for peripheral artery disease (PAD), high restenosis rates in the superficial femoral artery (SFA) remain a major problem. Nitinol stent implantation is reported to reduce restenosis in SFA after PTA in the general population; however, little is known about whether the nitinol stent improves primary patency after PTA in hemodialysis patients who are at higher risk of revascularization failure. The aim of this study was to clarify the effects of nitinol stent implantation for primary patency in SFA after PTA in hemodialysis patients with PAD. METHODS Eighty consecutive hemodialysis patients (167 SFA lesions) who underwent PTA with nitinol stents from January 2006 to January 2008 were compared with 64 hemodialysis patients (128 SFA lesions) who received stainless steel stents in the preceding 2 years. In the follow-up study to 2 years, incidence of restenosis, amputation, and all-cause mortality were analyzed. End points between the groups were examined with the Kaplan-Meier and log-rank methods. Prognostic values for end points were calculated by a Cox univariate analysis and Cox multivariable regression models. To statistically minimize the differences in each stent group, a propensity-matched analysis was also performed using the model including male gender, age, diabetes, hypertension, hyperlipidemia, smoking, incidence of ulcer/gangrene, and TransAtlantic Inter-Society Consensus (TASC) type C+D. RESULTS The 2-year primary patency rate was 58% in the nitinol group vs 42% in the stainless steel group (hazard ratio [HR], 0.58; 95% confidence interval [CI], 0.39-0.84; P = .0045), despite a higher prevalence of TASC C+D lesion in the nitinol group (68% vs 49%, P = .0014). In 108 lesions matched after propensity score analysis, the primary patency for 2 years was 64% in the nitinol group vs 42% in the stainless steel group (HR, 0.39; 95% CI, 0.24-0.65; P = .0003). Cox multivariate models showed nitinol stent (HR, 0.42; 95% CI, 0.25-0.73; P = .002), age (HR, 1.04; 95% CI, 1.01-1.08; P = .031), and incidence of ulcer/gangrene (HR, 2.35; 95% CI, 1.17-4.75; P = .017) were independent predictors of restenosis. CONCLUSION These data suggest that nitinol stent implantation improves primary patency in SFA after PTA compared with the stainless steel stent, even in hemodialysis patients with PAD.

Prognostic values of C-reactive protein levels on clinical outcome after endovascular therapy in hemodialysis patients with peripheral artery disease

PURPOSE Endovascular therapy (EVT) has been widely performed for peripheral artery disease. However, the high restenosis rate after EVT remains a major problem in patients on hemodialysis. Recent studies suggest that C-reactive protein (CRP) reflects vascular wall inflammation and can predict adverse events. We evaluated the possible prognostic values of CRP on outcomes in hemodialysis patients undergoing EVT. METHODS A total of 234 hemodialysis patients undergoing EVT for peripheral artery disease were enrolled and followed-up for up to 5 years. They were divided into tertiles according to serum CRP levels (lowest tertile, < 1.4 mg/L; middle tertile, 1.4-6.0 mg/L; highest tertile, ≥ 6.0 mg/L). We analyzed the incidence of any reintervention or above-ankle amputation of the limb index (RAO) and any-cause death. RESULTS Kaplan-Meier analysis showed that the event-free rate from the composite end point of RAO and any-cause death for 5 years was 60.2% in the lowest tertile, 50.0% in the middle tertile, and 25.1% in the highest tertile (P < .0001). The survival rate from any-cause death for 5 years was 81.5% in the lowest tertile, 65.2% in the middle tertile, and 59.3% in the highest tertile (P = .0078). Even after adjusting for other risk factors at baseline, preprocedural CRP levels were a significant predictive factor for RAO and any-cause death after EVT in a multivariable Cox analysis. CONCLUSIONS Elevated preprocedural serum CRP levels were associated with RAO and any-cause death after EVT in hemodialysis patients with peripheral artery disease.

Primary peritonitis associated with streptococcal toxic shock-like syndrome: report of a case.

Several reports over the past 15 years describe severe group A streptococcal infections causing septic shock, soft-tissue necrosis, and multiple organ failure; a phenomenon known as streptococcal toxic shock-like syndrome (TSLS). However, primary peritonitis associated with TSLS is rare. We report the case of a 40-year-old man admitted with pain in both thighs, hypotension, and severe abdominal pain. His daughter had been diagnosed with streptococcal pharyngitis 3 days earlier. We performed an emergency laparotomy for peritonitis, and culture of the ascites was positive for group A β-hemolytic streptococcus (GAS). Further serotyping of the isolated GAS strain revealed the T-type 22 and the pyrogenic exotoxin gene, spe-C. The criteria for TSLS were clearly met, including the isolation of GAS from ascites, hypotension, liver failure, renal failure, coagulopathy, myositis, and a generalized erythematous macular rash with desquamation.

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.

The Association of Ankle Brachial Index, Protein-Energy Wasting, and Inflammation Status with Cardiovascular Mortality in Patients on Chronic Hemodialysis

Protein-energy wasting (PEW) is highly prevalent in hemodialysis (HD) patients. We investigated the association of abnormal ankle brachial index (ABI), PEW, and chronic inflammation status with clinical prognosis in HD patients. A total of 973 HD patients were enrolled and were followed-up for 8 years. As a marker of the PEW, geriatric nutritional risk index (GNRI) was used. Cut-off levels were 91.2 for GNRI defined from previous studies and 1.9 mg/L for C-reactive protein (CRP) as median value, respectively. Abnormal ABI was seen in 332 (34.1%) patients. Declined GNRI and elevated CRP levels were independently associated with abnormal ABI (odds ratio (OR) 0.97, 95% confidence interval (CI) 0.96–0.99, p = 0.0009 and OR 1.40, 95% CI 1.07–1.83, p = 0.013, respectively). GNRI levels were also independently correlated with CRP levels (β = −0.126, p < 0.0001). During follow-up period, 283 (29.1%) patients died, including 123 (12.6%) due to cardiovascular disease (CVD). Abnormal ABI (adjusted hazard ratio (HR) 1.62, 95% CI 1.13–2.32, p = 0.0096), GNRI < 91.2 (adjusted HR 1.57, 95% CI 1.06–2.33, p = 0.023) and CRP > 1.9 mg/L (adjusted HR 1.89, 95% CI 1.31–2.77, p = 0.0007) independently predicted mortality due to CVD, respectively. In conclusion, abnormal ABI, GNRI, and CRP levels were closely associated with each other, and the combination of these variables increase their predictive values for the risk of mortality due to CVD and all-cause mortality in HD patients.

Treatment with cilostazol improves clinical outcome after endovascular therapy in hemodialysis patients with peripheral artery disease

BACKGROUND Cilostazol has been reported to prevent atherosclerotic events in the general population. However, data have been limited whether there are beneficial effects of cilostazol use on long-term clinical outcomes after endovascular therapy in hemodialysis (HD) patients with peripheral artery disease (PAD). METHODS AND RESULTS This study consisted of 595 HD patients undergoing endovascular therapy for a clinical diagnosis of PAD. They were divided into two groups: patients receiving 100mg cilostazol twice daily in conjunction with standard therapy (n=249 patients, cilostazol group) and those not administered cilostazol (n=346 patients, control group). A propensity score analysis was performed to adjust for baseline differences between the two groups. The propensity score-adjusted 10-year event-free survival rate from major adverse cardiovascular events (MACE) was significantly higher in the cilostazol group than in the control group [58.6% vs. 43.7%, hazard ratio (HR) 0.57; 95% confidence interval (CI) 0.41-0.79; p=0.0010]. Notably, the adjusted stroke-free rate was significantly higher in the cilostazol group than in the control group (81.6% vs. 74.7%; HR=0.48; 95% CI, 0.25-0.92, p=0.028). Even after adjusting for other confounders, treatment with cilostazol was an independent predictor for prevention of MACE and stroke (p=0.0028 and p=0.039, respectively). CONCLUSIONS Cilostazol administration improves long-term clinical outcomes including prevention of MACE and stroke after endovascular therapy in HD patients with PAD.

Clinical Outcomes after Isolated Infrapopliteal Revascularization in Hemodialysis Patients with Critical Limb Ischemia: Endovascular Therapy versus Bypass Surgery

Aim: To investigate the long-term clinical outcome of endovascular therapy (EVT) or bypass surgery in patients on hemodialysis (HD) with critical limb ischemia due to isolated infrapopliteal disease. Methods: We enrolled 254 consecutive HD patients successfully undergoing infrapopliteal revascularization by EVT (126 patients) and bypass surgery (128 patients). They were followed up for five years. Amputation-free survival (AFS) and incidence of any re-intervention were evaluated. A propensity score from all baseline variables was incorporated into Cox analysis. Results: In the EVT group, age was higher (p = 0.039), diabetes and coronary artery disease were more frequent (p = 0.004 and p = 0.0052, respectively), and tissue loss was more rarely observed (p < 0.0001) than in the bypass group. During the follow-up period, 21 major amputations and 64 deaths occurred. The propensity score-adjusted AFS rate at 5 years was comparable between groups (61.0% in EVT group vs. 55.1% in the bypass group, adjusted hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.52–1.42, p = 0.58). The adjusted survival rates were also similar between groups for amputation and all-cause mortality. However, freedom from any reintervention was markedly lower in the EVT than in the bypass group (48.6% vs. 84.6%, adjusted-HR, 3.56, 95% CI 1.95–6.75, p < 0.0001). Conclusions: The rate of AFS was broadly comparable between the two strategies, although compared with bypass surgery, EVT had much higher rates for re-intervention.