Association of calciprotein particles with serum phosphorus among patients undergoing conventional and extended-hours haemodialysis.

Background and hypothesis: Extended-hours haemodialysis (HD) is associated with better clinical outcomes than conventional HD. We investigated whether extended-hours HD and conventional HD have varying effects on blood levels of calciprotein particles (CPPs) and phosphorus, which have been identified as major pathogenic molecules for vascular calcification. Methods: Patients who underwent conventional or extended in-centre daytime HD between January and March 2020 were included. Plasma CPP levels, representing only secondary CPPs (CPP-II), were measured in pre-dialysis samples. Linear and non-linear associations between CPPs and serum phosphorus levels were examined across dialysis modalities. Results: A total of 382 participants (185 undergoing extended-hours HD and 197 undergoing conventional HD) were included in the analysis. The median age of participants was 71 years, 65% of the patients were men and the mean phosphorus level was 5.4 mg/dl. Plasma CPP (CPP-II) levels were lower in the extended-hours HD group than in the conventional HD group [40 018 (arbitrary units) AU versus 75 728 AU; P < .01]. Multivariable linear regression analysis showed that extended-hours HD was associated with lower natural logarithmic plasma CPP (CPP-II) levels: -0.64 (95% confidence interval -0.74 to -0.55). A restricted cubic spline function indicated that extended-hours HD was associated with lower plasma CPP (CPP-II) levels across levels of serum phosphorus, with significant differences observed between groups, especially in hyperphosphataemic conditions (P for interaction <.01). Conclusions: The extended-hours HD group had lower CPP levels than the conventional HD group despite no significant differences in serum phosphorus levels, which may contribute to better clinical outcomes in patients on extended-hours HD.

Relationship between peak aortic jet velocity and progression of aortic stenosis in patients undergoing hemodialysis.

BACKGROUND: The natural history of aortic stenosis (AS) progression, especially before severe AS development, is not well documented. We aimed to investigate the time course of peak aortic jet velocity (Vmax) and AS progression risk according to baseline Vmax, particularly whether there is a Vmax threshold. METHODS: In a retrospective multicenter cohort study of patients on hemodialysis with aortic valve calcification, we investigated the time series of Vmax and the relationship between the baseline Vmax and progression to severe AS by analyzing longitudinal echocardiographic data. RESULTS: Among 758 included patients (mean age, 71 years; 65% male), patients with Vmax <1.5, 1.5-1.9, 2.0-2.4, 2.5-2.9, and 3.0-3.9 m/s were 395 (52%), 216 (29%), 85 (11%), 39 (5.1%), and 23 (3.0%), respectively. The Vmax slope was gradual (mean 0.05-0.07 m/s/year) at Vmax <2 m/s, but steeper (mean 0.13-0.21 m/s/year) at Vmax ≥2 m/s. During a median 3.2-year follow-up, 52 (6.9%) patients developed severe AS. While patients with Vmax <2 m/s rarely developed severe AS, the risk of those with Vmax ≥2 m/s increased remarkably with an increasing baseline Vmax; the adjusted incidence rates in patients with Vmax <1.5, 1.5-1.9, 2.0-2.4, 2.5-2.9, and 3.0-3.9 m/s were 0.59, 0.57, 4.25, 13.8, and 56.1 per 100 person-years, respectively; the adjusted hazard ratio per 0.2 m/s increase in the baseline Vmax was 1.49 (95% confidence interval: 1.32-1.68) when Vmax ≥2 m/s. CONCLUSIONS: The risk of progression to severe AS increased with the baseline Vmax primarily at ≥2 m/s; a Vmax threshold of 2 m/s was observed.

Number of calcified aortic valve leaflets: natural history and prognostic value in patients undergoing haemodialysis.

AIMS: Aortic valve calcification in aortic sclerosis, a precursor of aortic stenosis (AS), is not always present in all three leaflets; how calcification develops in each leaflet is unknown. We aimed to investigate the natural history of calcification development in each aortic valve leaflet and the prognostic value of the number of calcified leaflets. METHODS AND RESULTS: In a retrospective multicentre cohort study of patients undergoing haemodialysis without AS, we observed calcification development in each aortic valve leaflet using echocardiography. We investigated the association between the number of calcified leaflets and AS development and mortality using time-to-event analysis. Among the 1507 patients (mean age, 66 years; 66% male) included in the longitudinal echocardiography analysis, 709 (47%) had aortic sclerosis at baseline: one-leaflet calcified, 370 (52%); two-leaflet calcified, 215 (30%); and three-leaflet calcified, 124 (17%). The median time for one calcified leaflet increase was 3-4 years, and 251 (17%) patients developed AS during a median 3.2-year follow-up. The increased number of calcified aortic valve leaflets was associated with developing AS; compared with that of one-leaflet calcified, the adjusted hazard ratios (aHRs) [95% confidence intervals (CIs)] of two- and three-leaflet calcified were 2.12 (1.49-3.00) and 4.43 (3.01-6.52), respectively; the aHR (95% CI) per one calcified leaflet increase was 2.24 (1.96-2.55). It was also associated with all-cause mortality; the aHR (95% CI) per one calcified leaflet increase was 1.18 (1.08-1.27). CONCLUSION: The number of calcified aortic valve leaflets strongly predicted AS development and even mortality in patients undergoing haemodialysis, suggesting the usefulness of assessing calcification for each valve leaflet separately using echocardiography.

Exercise intolerance and malnutrition associated with all-cause mortality in elderly patients undergoing peritoneal dialysis: a single-center prospective cohort study.

BACKGROUND: Low physical function and malnutrition in elderly patients undergoing peritoneal dialysis (PD) are important issues that may be associated with prognosis. We aimed to determine the association between physical function and nutritional status and survival in elderly patients undergoing PD. METHODS: This single-center, prospective cohort study included 45 stable, ambulatory patients undergoing PD. Physical function was measured using the 6-min walk distance (6MWD) test, 10-m walk speed, handgrip strength, lower extremity muscle strength, and short physical performance battery. Nutritional status was assessed using albumin levels and the Geriatric Nutritional Risk Index (GNRI). Patients were divided into two groups according to adverse events. Receiver operating characteristic curve analysis was used to predict mortality. The relationships between all-cause mortality and physical function and nutritional status were studied using Kaplan-Meier analysis and the log-rank test. RESULTS: The mean patient age was 75.3 ± 6.5 years. The median follow-up time was 32 (interquartile range 18-51) months, during which 11 deaths occurred. Death during follow-up was significantly associated with lower 6MWD (237.4 ± 120.2 vs. 355.2 ± 105.9 m), lower GNRI (77.3 ± 16.3 vs. 89.3 ± 8.1), and lower albumin levels (2.8 ± 0.6 vs. 3.3 ± 0.4 mg/dL) at baseline (p < 0.05). The cut-off values were 338 m, 83.3, and 2.95 g/dL for the 6MWD, GNRI, and albumin levels, respectively. The 6MWD test, GNRI, and albumin levels were significantly associated with all-cause mortality (p < 0.05). Additionally, the group with combined exercise intolerance and malnutrition had a lower survival rate (p < 0.05). CONCLUSION: Lower 6MWD and malnutrition are predictors of mortality in elderly patients undergoing PD.

Effects of cognitive impairment and assisted peritoneal dialysis on exit-site infection in older patients.

BACKGROUND: Elderly peritoneal dialysis (PD) patients required assistance for a variety of PD-related tasks. The usefulness of assisted PD in reducing the peritonitis risk has been reported; however, there is little evidence on the effectiveness of assisted PD in preventing exit-site infections in older patients. METHODS: This was a single-center, prospective cohort study. Thirty-three patients (mean age: 74.8 ± 5.9 years) on PD were evaluated for cognitive impairment (CI) using the Japanese version of the Montreal Cognitive Assessment. They were also evaluated to determine whether they performed the exit-site care procedure alone or with assistance. Patients were categorized into four groups based on the presence or absence of CI and the presence or absence of exit-site care assistance. They were followed up until the occurrence of peritonitis and exit-site infection at the end of the follow-up. RESULTS: Altogether, 8, 8, and 17 patients were assigned to the "without CI and without assistance", "without CI and with assistance", and "with CI and with assistance groups", respectively; no patients were assigned to the "with CI and without assistance group". Six and 16 patients experienced peritonitis and exit-site infection during follow-up, respectively. Kaplan-Meier analysis and log-rank tests revealed that the "without CI and without assistance group" was significantly associated with exit-site infection (log-rank < 0.05). CONCLUSION: Patients who did not receive assistance for exit-site care were at a higher risk of exit-site infections, even in the absence of CI. Caregiver assistance is important for preventing exit-site infections in older patients on PD.

All-cause and cardiovascular mortality in patients undergoing hemodialysis with aortic sclerosis and mild-to-moderate aortic stenosis: A cohort study.

BACKGROUND AND AIMS: Mild-to-moderate aortic stenosis (AS) and aortic sclerosis, a precursor of AS, are associated with mortality in the general population; however, their association in patients undergoing hemodialysis with higher morbidity of AS is unknown. Thus, we investigated the mortality of aortic sclerosis and mild-to-moderate AS in patients undergoing hemodialysis. METHODS: This was a retrospective multicenter cohort study of consecutive patients undergoing hemodialysis at nine dialysis facilities who underwent screening echocardiography between January 2008 and December 2019. We investigated the mortality of patients with aortic sclerosis or mild-to-moderate AS using multivariable Cox proportional hazards regression. RESULTS: Among 1,878 patients undergoing hemodialysis, those with normal aortic valves, aortic sclerosis, mild AS, moderate AS, severe AS, and prosthetic aortic valves were 844 (45%), 793 (42%), 161 (8.6%), 38 (2.0%), 11 (0.6%), and 31 (1.7%), respectively. After excluding patients with severe AS and prosthetic aortic valves, we performed comparative analysis on 1,836 patients (mean age, 67 years; 66% male). In a median follow-up of 3.6 years, crude death rates (per 100 person-years) were 5.2, 10.6, and 13.0 in patients with normal aortic valves, aortic sclerosis, and mild-to-moderate AS, respectively. Compared with normal aortic valves, both aortic sclerosis and mild-to-moderate AS were associated with all-cause and cardiovascular death: adjusted hazard ratios (95% confidence intervals) were 1.36 (1.13-1.65) and 1.36 (1.02-1.80) for all-cause death; and 1.52 (1.06-2.17) and 1.74 (1.04-2.92) for cardiovascular death, respectively. CONCLUSIONS: Aortic sclerosis and mild-to-moderate AS were independent risk factors for all-cause and cardiovascular death in patients undergoing hemodialysis.

Predicting a target exercise heart rate that reflects the anaerobic threshold in nonbeta-blocked hemodialysis patients: The Karvonen and heart rate reserve formulas.

The aim of this study was to evaluate constants of the Karvonen (k) and heart rate reserve (HRR) (α) formulas that correspond to the anaerobic threshold (AT) to conveniently estimate the intensity of exercise therapy in nonbeta-blocked patients undergoing hemodialysis. Twenty-three patients undergoing hemodialysis performed cardiopulmonary exercise testing (CPX) and their HR at AT was measured. The predictor coefficients for a target HR corresponding to AT were calculated for each patient based on CPX. Interclass correlation coefficients (ICC) and Bland-Altman analysis were used to evaluate the reliability of the formulas. Mean values of coefficient k of the Karvonen formula and α of the HRR formula were 0.24 ± 0.11 and 17.4 ± 8, respectively. The target HR calculated with k = 0.24 and α = 17 had significant ICC between HR at AT (0.74 and 0.77, respectively; P < 0.05). Using the Karvonen and HRR formulas to determine a target HR corresponding to AT is a simple and easy method that can be used to develop exercise programs for hemodialysis patients.

A Prospective, Randomized Clinical Trial of Etelcalcetide in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism (the DUET Trial).

INTRODUCTION: The clinical trial on the Development of a treatment strategy for chronic kidney disease‒mineral and bone disorder by a mUltilateral mechanism of ETelcalcetide hydrochloride, or the DUET trial, was designed to determine the efficacy of etelcalcetide, an intravenous calcimimetic, for control of secondary hyperparathyroidism (SHPT). METHODS: Eligible SHPT maintenance hemodialysis patients (n = 124) were randomized (1:1:1) for inclusion in the DUET trial, a 12-week, multicenter, open-label, parallel-group study (jRCTs041180108), and assigned to either an etelcalcetide + active vitamin D group (group E+D), an etelcalcetide + oral calcium preparation group (group E+Ca), or a control group (group C). The primary endpoint was number of patients with a 50% reduction from baseline of intact parathyroid hormone (iPTH) levels, and iPTH levels ≤ 240 pg/mL at 12 weeks after start of the trial. RESULTS: The proportion of patients reaching the primary endpoint (95% confidence interval [CI]) was 90.0% (76.3%-97.2%) in group E+D, 56.8% (39.5%-72.9%) in group E+Ca, and 19.5% (8.8%-34.9%) in group C. Etelcalcetide treatment led to a significant increase in the number of patients achieving the endpoint (odds ratio, 13.4; 95% CI, 5.10-35.3) on logistic regression analysis, with iPTH, corrected serum calcium, and phosphate at baseline as covariates. Significantly more patients achieved the endpoint in group E+D compared with group E+Ca (odds ratio, 6.35; 95% CI, 1.79-22.48). There were fewer hypocalcemic visits in group E+D compared with group E+Ca (P = 0.018), yet the former group was prone to hyperphosphatemia. CONCLUSION: Etelcalcetide showed good control of iPTH for maintenance hemodialysis patients with SHPT. Active vitamin D was useful in correcting hypocalcemia, but the oral calcium preparation was superior for suppression of hyperphosphatemia.

Additional prognostic value of toe-brachial index beyond ankle-brachial index in hemodialysis patients.

BACKGROUND: Ankle-brachial index (ABI), the first-line diagnostic test for peripheral artery disease, can be falsely elevated when ankle arteries are incompressible, showing a J-shaped association with mortality. In this situation, toe-brachial index (TBI) is the recommended test. However, whether TBI provides additional prognostic information beyond ABI in patients on hemodialysis is unknown. METHODS: In this retrospective cohort study of 247 Japanese prevalent hemodialysis patients (mean age 66.8 [SD 11.6] years), we evaluated mortality (116 deaths over a median follow-up of 5.2 years) related to quartiles of ABI and TBI, as well as three categories of low ABI (≤0.9), normal/high ABI (> 0.9) + low TBI (≤0.6), and normal/high ABI + normal TBI (> 0.6) using multivariable Cox models. RESULTS: ABI showed a J-shaped association with mortality (adjusted hazard ratio 2.72 [95% CI, 1.52-4.88] in the lowest quartile and 1.59 [95% CI, 0.87-2.90] in the highest quartile vs. the second highest). Lower TBI showed a potentially dose-response association with mortality (e.g., adjusted hazard ratios 2.63 [95% CI, 1.36-5.12] and 2.89 [95% CI, 1.49-5.61] in the lowest two quartiles vs. the highest). When three categories by both ABI and TBI were analyzed, those with low ABI (≤0.9) experienced the highest risk followed by normal/high ABI (> 0.9) + low TBI (≤0.6). Among patients with normal/high ABI (> 0.9), the increased mortality risk in individuals with low TBI (≤0.6) compared to those with normal TBI (> 0.6) were significant (adjusted hazard ratio 1.84 [95% CI, 1.12-3.02]). CONCLUSIONS: Lower TBI was independently associated with mortality in patients on hemodialysis and has the potential to classify mortality risk in patients with normal/high ABI. Our results support the importance of evaluating TBI in addition to ABI in this clinical population.

After peritoneal dialysis discontinuation: When will we remove peritoneal dialysis catheter?

Most of the peritoneal dialysis patients stop their peritoneal dialysis therapy and transfer to hemodialysis or kidney transplantation. In Japan, most end-stage kidney disease patients select hemodialysis after peritoneal dialysis discontinuation. Peritoneal dialysis catheter will be removed after stopping peritoneal dialysis. If peritoneal dialysis patients suffer from refractory peritonitis or severe tunnel infection, we remove the peritoneal dialysis catheter immediately. However, the causes of peritoneal dialysis discontinuation are ultrafiltration failure or peritoneal membrane dysfunction, and we have to consider the timing of peritoneal dialysis catheter removal. Encapsulating peritoneal sclerosis is the most important adverse event of peritoneal dialysis. And encapsulating peritoneal sclerosis often develops after stopping peritoneal dialysis. Risk factors associated with encapsulating peritoneal sclerosis are high peritoneal equilibration test values, longer peritoneal dialysis period, frequent peritonitis, and so on. There is no evidence to prevent encapsulating peritoneal sclerosis completely. Therefore, we can preserve the peritoneal dialysis catheter and assess the changes of peritoneal function after peritoneal dialysis discontinuation, if patient is suspected to have high risk of encapsulating peritoneal sclerosis.

Recent analysis of status and outcomes of peritoneal dialysis in the Tokai area of Japan: the second report of the Tokai peritoneal dialysis registry.

BACKGROUND: Early withdrawal within 3 years after starting peritoneal dialysis (PD) and PD-related peritonitis have been major obstacles preventing increases in the population of PD patients. To address these problems, we implemented education programs for medical staff. This study analyzed the recent status and outcomes of PD therapy, focusing on findings such as the incidence and prognosis of peritonitis as of 5 years after our last study. METHODS: We investigated background, laboratory data and status of PD therapy, reasons for withdrawal from PD and incidental statements on peritonitis from 2010 to 2012 (R2), and compared findings with those from our last study of 2005-2007 (R1). RESULTS: Early PD therapy withdrawal in R2 clearly improved to 44.7 %, compared with 50.9 % in R1. Peritonitis incidence improved slightly from once per 42.8 months/patient in R1 to once per 47.3 months/patient in R2. Notably, PD-related peritonitis as a cause of mortality improved markedly in R2, but outcomes of PD-related peritonitis did not change significantly between R1 and R2. In contrast, social problems increased as a reason for withdrawal from PD therapy. CONCLUSION: Our efforts at education might have been useful for improving early withdrawal from PD and deaths attributable to PD-related peritonitis. However, since improvements to incidence of PD-related peritonitis were limited by education, further improvement in PD-related peritonitis incidence requires development of new sterilized connecting systems during PD-bag exchanges to decrease PD-related peritonitis opportunities. Construction of medical support systems to address social problems is required to maintain long-term PD therapy.

Standard procedures of endovascular treatment for vascular access stenosis in our facility - clinical usefulness of ultrasonography.

In Japan, the number of patients receiving dialysis is 314,180 at the end of 2013 and 97% are treated with hemodialysis. And the mean age of patients and the percentage of diabetes have been increasing. For this reason, preparations of a new vascular access (VA) and its long-term maintenance have become difficult. In the guidelines by the Japanese Society for Dialysis Therapy (JSDT), endovascular treatment (ET) is positioned as the first line for VA stenosis. The procedure of ET itself is very simple. The revision of Japanese health insurance set an expensive technical fee for ET in 2012. It also added a restriction by which the claims for both technical and material fees would be denied, if the treatment was performed within 3 months after a previous treatment. This makes determination of best treatment timing more important. The functional evaluation using ultrasonography (US) is a useful monitoring index for determination of the ET timing for patients with stenosis. We investigated the cumulative relative frequency of flow volume (FV) and resistant index (RI) of brachial artery in arteriovenous graft (AVG) and arteriovenous fistula (AVF) cases with access failures. As a result, the cut-off values of FV and RI in AVG were 480 mL/min and 0.57, and in AVF were 354 mL/min and 0.61, respectively. Therefore we determine the treatment timing based on these results. Since 2012, active monitoring using US could have decreased the number of treatment patients by 100 per year. This meant that objective evaluation by US enabled treatments at a more suitable time to promote the proper use of medical expenses for EV treatment.

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.

Long-term effects of spironolactone in peritoneal dialysis patients.

ESRD treated with dialysis is associated with increased left ventricular hypertrophy, which, in turn, is related to high mortality. Mineralocorticoid receptor antagonists improve survival in patients with chronic heart failure; however, the effects in patients undergoing dialysis remain uncertain. We conducted a multicenter, open-label, prospective, randomized trial with 158 patients receiving angiotensin-converting enzyme inhibitor or angiotensin type 1 receptor antagonist and undergoing peritoneal dialysis with and without (control group) spironolactone for 2 years. As a primary endpoint, rate of change in left ventricular mass index assessed by echocardiography improved significantly at 6 (P=0.03), 18 (P=0.004), and 24 (P=0.01) months in patients taking spironolactone compared with the control group. Rate of change in left ventricular ejection fraction improved significantly at 24 weeks with spironolactone compared with nontreatment (P=0.02). The benefits of spironolactone were clear in patients with reduced residual renal function. As secondary endpoints, renal Kt/V and dialysate-to-plasma creatinine ratio did not differ significantly between groups during the observation period. No serious adverse effects, such as hyperkalemia, occurred. In this trial, spironolactone prevented cardiac hypertrophy and decreases in left ventricular ejection fraction in patients undergoing peritoneal dialysis, without significant adverse effects. Further studies, including those to determine relative effectiveness in women and men and to evaluate additional secondary endpoints, should confirm these data in a larger cohort.

Efficacy and safety of SBR759, a novel calcium-free, iron (III)-based phosphate binder, versus placebo in chronic kidney disease stage V Japanese patients on maintenance renal replacement therapy.

BACKGROUND: SBR759, an iron (III)-based oral phosphate binder, was developed for the treatment of hyperphosphataemia in chronic kidney disease stage V patients receiving maintenance renal replacement therapy (RRT). Serum phosphate-lowering efficacy and dose response of SBR759 (3-, 6-, 9- and 12-g/day doses) were compared with placebo. METHODS: Japanese patients with hyperphosphataemia (P ≥ 5.5 mg/dL [≥ 1.78 mmol/L]) receiving maintenance RRT (N = 63) were randomised to receive either SBR759 (3-, 6-, 9-, 12-g/day dose) or placebo (12-g/day dose) for 4 weeks. The primary endpoint was change from baseline in 72-h post-dialysis serum phosphate levels at week 4 for different doses of SBR759 versus placebo. Secondary endpoints were change from baseline in serum phosphate levels and dose-dependent efficacy of SBR759 during the 4-week treatment period. RESULTS: SBR759 showed significant reduction in serum phosphate levels compared with placebo at week 4, demonstrating a significant linear dose response (P < 0.001). Incidence of adverse events was comparable between the SBR759 treatment groups (7/13 and 5/12 in the 3- and 12-g/day groups, respectively, and 8/13 in the 6- and 9-g/day groups) and was 6/12 in the placebo group. Discoloured faeces and diarrhoea were the most frequently reported adverse events. Two serious adverse events were reported--one in the SBR759 3-g/day group (1/13, skin ulcer) and one in the SBR759 12-g/day group (1/12, arthralgia). CONCLUSIONS: SBR759 showed significant phosphate-lowering efficacy and dose-dependent response compared with placebo in patients with chronic kidney disease receiving RRT.

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 (ß = -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.

Combined values of serum albumin, C-reactive protein and body mass index at dialysis initiation accurately predicts long-term mortality.

BACKGROUND: Protein-energy wasting and chronic inflammation are prevalent in patients with end-stage renal disease (ESRD). We investigated the combination of serum albumin, C-reactive protein (CRP) and body mass index (BMI) at initiation of hemodialysis therapy as a predictor of all-cause and cardiovascular disease (CVD) mortality in Japanese ESRD patients. METHODS: A total of 1,228 consecutive Japanese ESRD patients on hemodialysis therapy were enrolled and followed for up to 10 years. Patients were divided into quartiles according to levels of albumin, CRP and BMI. Furthermore, to clarify the joint role of these factors, albumin <3.5 g/dl, CRP >4.0 mg/l and BMI <19.6 were defined as risk factors using receiver operating characteristic analysis; thereafter, patients were divided into groups according to the positive number of these factors. RESULTS: Adjusted hazard ratios (HRs) for lower serum albumin, elevated CRP and lower BMI for 10-year all-cause mortality were 1.97, 3.13 and 2.61, respectively. Regarding the combination of these variables, adjusted HRs for mortality were 2.31, 4.28 and 8.07, respectively, in patients having any one factor, any two factors and all three factors. The C-index for an established risk model with these three positive markers was the most accurate for predicting mortality (0.768), as compared to other models with one or two markers. Similar results were seen for CVD mortality. CONCLUSIONS: Serum albumin, CRP and BMI at the start of hemodialysis therapy were able to individually stratify the risk of long-term mortality in ESRD patients. Furthermore, a combination of these variables could more accurately predict mortality.