Daisuke Kamoi

Geriatric nutritional risk index accurately predicts cardiovascular mortality in incident hemodialysis patients

BACKGROUND Cardiovascular disease (CVD) is a leading cause of death in end-stage renal disease (ESRD) patients. Protein-energy wasting (PEW) or malnutrition is common in this population, and is associated with increasing risk of mortality. The geriatric nutritional risk index (GNRI) has been developed as a tool to assess the nutritional risk, and is associated with mortality not only in elderly patients but also in ESRD patients. However, whether the GNRI could predict the mortality due to CVD remains unclear in this population. We investigated the prognostic value of GNRI at initiation of hemodialysis (HD) therapy for CVD mortality in a large cohort of ESRD patients. METHODS Serum albumin, body weight, and height for calculating GNRI were measured in 1568 ESRD patients. Thereafter, the patients were divided into quartiles according to GNRI levels [quartile 1 (Q1): < 84.9; Q2: 85.0-91.1; Q3: 91.2-97.2; and Q4: >97.3], and were followed up for up to 10 years. RESULTS GNRI levels independently correlated with serum C-reactive-protein levels (β = -0.126, p < 0.0001). Rates of freedom from CVD mortality for 10 years were 57.9%, 73.3%, 80.8%, and 89.2% in Q1, Q2, Q3, and Q4, respectively (p < 0.0001). The GNRI was an independent predictor of CVD mortality (hazard ratio 3.42, 95% confidence interval 2.05-5.70, p < 0.0001 for Q1 vs. Q4). C-index was also greater in an established CVD risk model with GNRI (0.749) compared to that with albumin (0.730), body mass index (0.732), and alone (0.710). Similar results were observed for all-cause mortality. CONCLUSION GNRI at initiation of HD therapy could predict CVD mortality with incremental value of the predictability compared to serum albumin and body mass index in ESRD patients.

Association of Cardiac Valvular Calcifications and C-Reactive Protein With Cardiovascular Mortality in Incident Hemodialysis Patients: A Japanese Cohort Study

BACKGROUND Cardiac valve calcification is seen frequently in patients undergoing dialysis. Serum C-reactive protein (CRP) level also is reported to predict future cardiovascular events. We investigated the association among valve calcification, CRP level, and mortality in patients with end-stage renal disease who were just beginning hemodialysis (HD) therapy. STUDY DESIGN Observational cohort. SETTING & PARTICIPANTS 1,290 consecutive patients who just started HD therapy were enrolled and were followed up to 10 years. PREDICTOR Patients were divided into 3 groups according to number of calcified valves: those without valve calcification, those with calcification in a single (aortic or mitral) valve, and those with calcification in both valves. They also were divided into tertiles according to CRP level. OUTCOMES Cardiovascular and all-cause mortality. MEASUREMENTS Echocardiography and CRP measurement were performed within 1 month after beginning HD therapy. RESULTS During follow-up (median, 51 months), 335 (25.9%) patients died, including 156 (12.1%) of cardiovascular disease. The adjusted HR for cardiovascular mortality was 2.80 (95% CI, 1.63-4.81) for 2 calcifications versus 0 (P < 0.001). Furthermore, the risk of cardiovascular mortality was 3.66-fold higher in patients with calcifications in both valves (highest tertile of CRP) compared with patients without valve calcification (lowest tertile of CRP; P < 0.001). LIMITATIONS Precise medical treatments or therapeutic interventions were not evaluated. CONCLUSIONS Valve calcification and elevated CRP levels were not only related to additively increased risk of mortality, but also improved the prediction of mortality in patients with end-stage renal disease who had just begun HD therapy.

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.

Effects of oral cilostazol 100 mg BID on long-term patency after percutaneous transluminal angioplasty in patients with femoropopliteal disease undergoing hemodialysis: a retrospective chart review in Japanese patients.

BACKGROUND Percutaneous transluminal angioplasty (PTA) for femoropopliteal lesions in peripheral artery disease has been performed in patients undergoing hemodialysis as well as in the general population. Cilostazol, a selective inhibitor of phosphodiesterase 3, has been reported to reduce target lesion revascularization after PTA for femoropopliteal lesions in the general population. OBJECTIVE This study investigated the effects of cilostazol use on long-term patency after PTA in patients with femoropopliteal disease undergoing hemodialysis. METHODS In this retrospective study, data from patients undergoing hemodialysis who underwent successful PTA for femoropopliteal disease, defined as a final luminal diameter stenosis <30% without angiographically visual arterial dissection and no in-hospital complications, were included. One study group received long-term treatment with oral cilostazol 100 mg BID after PTA; the control group did not. The duration of follow-up was <or=6 years. The primary outcome of interest was cumulative patency, as measured by the event-free rate 6 years after PTA, with event defined as restenosis of >50% of the vessel diameter in femoropopliteal lesions. Data on baseline characteristics, patency, and covariates (diabetes, hypertension, hyperlipidemia, smoking, coronary artery disease, critical limb ischemia, TransAtlantic Inter-Society Consensus classification, and stenting) were obtained from electronic medical records and telephone interviews with patients. To minimize the effects of selection bias for cilostazol administration, a propensity-matched analysis using Cox univariate and multivariate models including the previously mentioned covariates was conducted. The propensity scores of the 2 groups were matched 1:1 (AUC = 0.69 [receiving operating characteristics analysis]). Data were obtained from electronic medical records and telephone interviews with patients by trained personnel who were blinded to treatment assignment. RESULTS A total of 358 consecutive lesions of 174 patients undergoing hemodialysis were included (103 men, 71 women; mean [SD] age, 66 [11] years; cilostazol group, 61 patients, 121 lesions; control group, 113 patients, 237 lesions). The mean duration of follow-up was 37 (27) months. The 6-year event-free rate of restenosis of >50% of the vessel diameter was significantly higher in the cilostazol group than in the control group (72/121 [59.5%] vs 120/237 [50.6%]; P = 0.005 [logrank test]; hazard ratio [HR] = 0.63; 95% CI, 0.45-0.88; P = 0.008 [Cox univariate analysis]). Also, event-free rates of target lesion revascularization and limb amputation were significantly higher in the cilostazol group than in the control group (40/61 [65.6%] vs 57/113 [50.4%]; P = 0.013 [log-rank test] and 54/61 [88.5%] vs 90/113 [79.6%]; P = 0.047 [logrank test], respectively). On propensity score matching (105 lesions), the baseline characteristics were comparable between the 2 groups. The 6-year eventfree rate of restenosis was significantly higher in the cilostazol group than in the control group (66/105 [62.9%] vs 52/105 [49.5%]; HR = 0.58; 95% CI, 0.38-0.88; P = 0.012 [Cox univariate analysis]). On propensity-matched (Cox multivariate) analysis, cilostazol (HR = 0.51; 95% CI, 0.27-0.84; P = 0.008), age (HR = 1.01; 95% CI, 1.01-1.04; P = 0.031), and critical limb ischemia (HR = 2.21; 95% CI, 1.39-3.53; P = 0.001) were independent predictors of restenosis. None of the patients in the cilostazol group discontinued cilostazol treatment during the follow-up period. Four patients (6.6%) experienced mild headache. CONCLUSION This study found that in these patients with femoropopliteal lesions in peripheral artery disease who were undergoing hemodialysis, those treated with cilostazol 100 mg BID after PTA had a higher mean rate of cumulative patency after PTA than those in the control group.

Propensity Score Analysis of Clinical Outcome After Bypass Surgery vs. Endovascular Therapy for Infrainguinal Artery Disease in Patients With Critical Limb Ischemia

Purpose To compare endovascular therapy (EVT) outcomes to those of bypass surgery (BSG) for infrainguinal artery disease in patients with critical limb ischemia (CLI). Methods A retrospective review was conducted of 1053 CLI patients (1053 first treated limbs) who underwent BSG (n=230) or EVT (n=823) for de novo infrainguinal lesions between January 2004 and December 2009 at 14 Japanese centers. Propensity score analysis was used for risk adjustment in multivariate analysis and for one-to-one matching (n=200 in each group). Amputation-free survival, overall survival, limb salvage, and freedom from major adverse limb events (any repeat revascularization or major amputation) were calculated. Results Mean follow-up was 30±16 months. In the overall series, there was no significant difference at 3 years between the EVT and BSG groups in amputation-free survival (60.5% vs. 62.1%, p=0.84), limb salvage (88.7% vs. 85.4%, p=0.24), or overall survival (65.8% vs. 69.2%, p=0.40). However, freedom from adverse limb events was significantly lower in the EVT group (56.6% vs. 69.2%, p=0.02) at 3 years. In the matched pairs analysis, there was no significant difference in any outcome between BSG and EVT at 3 years: amputation-free survival 66.3% vs. 62.0 (p=0.44), limb salvage 88.8% vs. 84.8% (p=0.44), survival 73.8% vs. 68.8% (p=0.61), and freedom from adverse limb events 61.3% vs. 69.1% (p=0.27). Conclusion Our cohort suggested that the frequency of serious adverse events after EVT was comparable to that after BSG in CLI patients who underwent their first infrainguinal revascularization.

Sirolimus- vs. paclitaxel-eluting stent to coronary intervention in dialysis patients

BACKGROUND Patients on maintenance hemodialysis (HD) are at high risk for restenosis after percutaneous coronary intervention (PCI) even if treated with a sirolimus-eluting stent (SES). The aim of this study was to compare the effects of SES and paclitaxel-eluting stent (PES) in preventing restenosis in HD patients with coronary artery disease. METHODS A total of 100 consecutive patients on HD who underwent PCI were enrolled into the study. They were randomly assigned to receive either SES or PES. We compared follow-up angiographic outcomes between the SES and PES groups at 8-month follow-up. RESULTS The angiographical restenosis rate, defined as % diameter stenosis>50% at 8-month follow-up, was 19.7% in the SES group and 20.0% in the PES group (p=0.97). Late loss was also similar between the two groups (0.49±0.70 mm vs. 0.48±0.91 mm, P=0.94). There were no significant differences in the rates of all-cause death, non-fatal myocardial infarction, or TLR due to stent restenosis-induced ischemia between the two groups (2.0% vs. 4.0%, p=0.56, 2.0% vs. 4.0%, p=0.56, and 16.0% vs. 12.0%, p=0.57, respectively). CONCLUSIONS There was no significant difference in angiographical outcome at 8-month follow-up between HD patients treated with SES and PES. Even if treated with DES including SES and PES, patients on HD are at high risk of restenosis after PCI.

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.

Comparison of Clinical Outcomes after Surgical and Endovascular Revascularization in Hemodialysis Patients with Critical Limb Ischemia

Aim: The treatment strategy for hemodialysis (HD) patients with critical limb ischemia (CLI) has been clinically debatable. Here we compared clinical outcomes after bypass surgery (BSX) and after endovascular therapy (EVT) using propensity score matching. Methods: A retrospective multicenter database of 246 (68 BSX and 178 EVT) consecutive HD patients with CLI (79% with tissue loss) who underwent infrainguinal revascularization from 2007 to 2009 was used to compare clinical outcomes, including overall survival (OS), major amputation (MA), major adverse limb event (MALE: repeat EVT, surgical reconstruction, or MA), and MALE-free survival after BSX vs. EVT using propensity score matching. Results: The median (interquartile range) follow-up duration after revascularization was 21 (8–33) months. The analysis of the 63 propensity score-matched pairs revealed no significant difference in OS (53% vs. 52%, P = 0.96), MA (25% vs. 14%, P = 0.71), MALE (42% vs. 58%, P = 0.63), and MALE-free survival (33% vs. 11%, P = 0.37) at 3 year after BSX vs. EVT. Conclusions: In HD patients with CLI who underwent infrainguinal revascularization, OS, MA, MALE, and MALE-free survival rates were not significantly different after EVT vs. BSX. The less invasive EVT should be considered as the first-choice therapeutic strategy for HD patients with CLI.

Multimarker Approach to Risk Stratification for Long-Term Mortality in Patients on Chronic Hemodialysis

BACKGROUND We prospectively investigated the prognostic value of the combined use of cardiac troponin T (TnT), B-type natriuretic peptide (BNP), and high-sensitivity C-reactive protein (CRP) for long-term mortality in hemodialysis (HD) patients. METHODS AND RESULTS: Baseline measurements of TnT, BNP, and CRP were performed in 516 patients on chronic HD. Patients were followed up for 10 years. Using the Cox multivariate model with these 3 biomarkers as variables categorized into tertiles for mortality, a simplified score was obtained by underscoring individual biomarkers based on the adjusted hazard ratio (HR). The multimarker score was defined as the sum of these points. TnT, BNP, and CRP levels were individually independent predictors for mortality (P<0.05). Among low-risk (multimarker score <4), intermediate-risk (multimarker score 4-7), and high-risk (multimarker score ≥7) groups, 10-year survival rates were 83.3%, 54.3%, and 27.2% (P<0.0001), respectively. After adjusting for other confounders, the multimarker score had strong predictive power for mortality (HR: 4.26; P<0.0001 for high-risk vs. low-risk group). Furthermore, adding the multimarker score to a baseline model with established risk factors improved the C-index (P<0.01), net reclassification improvement (P<0.0001), and integrated discrimination improvement (P<0.0001) greater than that of any single biomarker or baseline model alone. CONCLUSIONS The multimarker approach (ie, simultaneous assessment of TnT, BNP, and CRP, which individually independently predict prognosis) may improve the prediction of long-term mortality in HD patients.

Efficacy and Safety of Endovascular Therapy for Aortoiliac TASC D Lesions

Background: Although there is increasing evidence of the effectiveness of endovascular therapy for complex aortoiliac (AI) occlusive disease, it is not universally applied to TASC D lesions. Methods: A total of 2096 patients, 2601 limbs with AI occlusive disease, were enrolled. The lesions were categorized as TASC D (395) or TASC A-C (2206), and we compared baseline data, procedure, and follow-up result between the 2 groups. Results: The success rate of the procedure was significantly lower in the TASC D group (91.6% vs 99.3%, P < .01), and more procedure complications occurred in the TASC D group (11.1% vs 5.2%, P < .01). The results of a 5-year follow-up revealed no significant difference in primary patency (77.9% vs 77.1%, P = .17) and major adverse cardiovascular and limb events (MACLE; 30.5% vs 33.4%, P = .42) between the 2 groups. A multivariate analysis revealed complications and critical limb ischemia are independent predictors of MACLE in the TASC D group. Conclusion: The success rate of the procedure was lower in the TASC D group. Complications were more frequent in the TASC D group, and they were related to MACLE.