Japanese Dialysis Outcomes Research Articles

Association of Nutritional Risk Index With Infection-Related Hospitalization and Death After Hospitalization in Patients Undergoing Maintenance Hemodialysis

Patients undergoing dialysis frequently experience hospitalization due to cardiovascular disease (CVD) and infection. This population is also at high risk of rehospitalization and subsequent death. In addition to serious outcomes, hospitalization incurs substantial medical cost. Prevention of hospitalization is accordingly an urgent matter. Here, we examined whether nutritional disorder was associated with hospitalization and subsequent death. The study was conducted under a prospective design using data from the Japanese Dialysis Outcomes and Practice Pattern Study. The exposure was the Nutritional Risk Index for Japanese Hemodialysis (NRI-JH), through which patients were divided into low-, medium-, and high-risk groups, with the low-risk group as referent. The primary outcome was CVD-related or infection-related hospitalization. Secondary outcome was all-cause mortality. For exploratory analyses, the associations of baseline or latest NRI-JH just before hospitalization, with death after hospitalizations, were examined. Of 4021 patients, 566 patients had CVD-related hospitalization and 375 had infection-related hospitalization during a median follow-up of 2.6years. NRI-JH at baseline was significantly associated with infection-related hospitalization but not with CVD-related hospitalization, in multivariable Cox models (hazard ratio [HR] 1.46, 95% confidential interval [CI]: 1.09 to 1.97, P=.012 for medium-risk vs. low-risk group) (HR 2.46, 95% CI: 1.81 to 3.35, P<.001 for high-risk vs. low-risk group). NRI-JH was also associated with all-cause mortality. In addition, the baseline and latest high-risk NRI-JH groups were significantly associated with death after both CVD-related and infection-related hospitalizations. A higher nutritional risk as evaluated by NRI-JH was associated with infection-related hospitalization but not with CVD-related hospitalization. However, NRI-JH was significantly associated with death after both CVD-related and infection-related hospitalizations, suggesting that nutritional risk may be separately involved in hospitalization or subsequent death. NRI-JH may be useful in the planning of individual care to improve outcomes.

Association between magnesium, erythropoietin resistance and mortality: the Japanese Dialysis Outcomes and Practice Patterns Study (J-DOPPS).

Limited data are now available to evaluate the relationship between serum magnesium level, anemia and mortality in the dialysis population. Using data from the Japanese Dialysis Outcomes and Practice Patterns Study (J-DOPPS) phases 5 and 6, we analyzed the association between serum magnesium (s-Mg) levels and the erythropoiesis-stimulating agents resistance index (ERI) as the primary outcome. To estimate the longitudinal relationship, a mixed-effect model was used with ERI at each 4-month period as the dependent variable and quintiles of s-Mg at the previous 4-month period as the independent variable. We also examined incidence of infectious events, and the all-cause and cardiovascular disease (CVD)-related deaths as secondary outcomes by Cox regression with quintiles of s-Mg at baseline. Of the 4776 participants in J-DOPPS, 1650 were included in the analysis. The median of s-Mg at baseline was 2.5 mg/dL. A significant linear association of s-Mg with ERI (P for trend <.001) was revealed. Low and high s-Mg levels were not associated with the clinical outcomes of interest, except for the highest quintile of s-Mg being significantly associated with lower incidence of all-cause mortality and CVD-related deaths compared with the middle (reference) quintile. We observed that lower s-Mg levels subsequently induced higher ERI and that mild higher s-Mg levels were possibly associated with good rather than poor outcomes in Japanese hemodialysis patients. Adjustment of s-Mg levels may be proposed as a new strategy at a low cost and risk to reduce the risk of premature mortality.

Infectious Risk and Variability of Hemoglobin Level in Patients Undergoing Hemodialysis

In the management of anemia in chronic kidney disease, hemoglobin levels often fall below or exceed target ranges. Past retrospective cohort studies of patients undergoing hemodialysis with conventional erythropoiesis stimulating agents (ESAs) found that hemoglobin level fluctuations predicted mortality and cardiovascular adverse events; long-acting agents were thereafter widely available. An updated validation by a prospective cohort study was needed. Using Cox regression models, we evaluated associations between hemoglobin variability and all-cause death, hospitalization, and cardiovascular, thrombotic, or infectious adverse event outcomes in 3063 hemodialysis patients' data from the Japanese Dialysis Outcomes and Practice Patterns Study (J-DOPPS) from 2012 to2018. During a median follow-up time of 2.5 years, all-cause mortality was lowest in the first quartile and tended to be higher in groups with greater hemoglobin variability (hazard ratio [HR]: 95% confidence interval for the fourth quartile of an absolute value of hemoglobin variability: 1.44 [0.99-2.08], P for trend= 0.056). Infectious event incidence in these patients was also lower in the first quartile than for the other quartiles (P for trend< 0.01). The association was more pronounced in patients with lower serum ferritin levels or iron supplementation. Cardiovascular and thrombotic event incidence was not associated with hemoglobin variability. Maintenance hemodialysis patients on ESA treatment with higher hemoglobin variability are at higher risk for all-cause mortality and particularly infectious events.

Association of erythropoietin resistance and fibroblast growth factor 23 in dialysis patients: Results from the Japanese Dialysis Outcomes and Practice Patterns Study.

BackgroundFibroblast growth factor 23 (FGF23) plays an important role in chronic kidney disease (CKD)‐related mineral and bone disorders. High FGF23 levels are associated with increased risk of anaemia in non‐haemodialysis CKD patients. FGF23 also negatively regulates erythropoiesis in mice. We hypothesized that higher FGF23 levels are associated with increased erythropoietin hyporesponsiveness among haemodialysis patients.MethodsThe study included 1044 patients from the Japanese Dialysis Outcomes and Practice Patterns Study (J‐DOPPS) phase 5 (2012‐2015). The outcome was erythropoiesis‐stimulating agent hyporesponsiveness (ESA‐hypo), defined as mean Hgb <10 g/dL and standardized mean ESA dose >6000 u/week over 4 months following FGF23 measurement. The association between ESA‐hypo and FGF23 was estimated using multivariable‐adjusted logistic generalized estimating equation regression models.ResultsPatients with higher levels of FGF23 were younger and had higher levels of serum albumin, creatinine, albumin‐corrected calcium, phosphorus, PTH, 25(OH)‐vitamin D, and had higher percentages of intravenous (IV) iron, IV vitamin D and cinacalcet use. ESA‐hypo was present in 144 patients (13.8%). Compared with the third quintile of FGF23 levels, the odds ratio (95% CI) of ESA‐hypo was 2.14 (0.99, 4.62) and 1.74 (0.74, 4.11) for the first and fifth quintiles, respectively.ConclusionThe lowest and highest levels of FGF23 were associated with higher odds of ESA‐hypo in patients on maintenance haemodialysis, although the associations were not statistically significant. The relationship between FGF23 and anaemia, and particularly the increased risks of ESA‐hypo at low FGF23 levels which might be the result of energy saving, must be confirmed in larger clinical studies.

Changes in Quality of Life in Older Hemodialysis Patients: A Cohort Study on Dialysis Outcomes and Practice Patterns

Background: Despite improvements in dialysis treatment, mortality rates remain high, especially among older hemodialysis patients. Quality of life (QOL) among hemodialysis patients is strongly associated with higher risk of death. This study aimed to describe the health-related QOL and its change in older maintenance hemodialysis patients and to demonstrate characteristics associated with health-related QOL. Methods: Data on 892 maintenance hemodialysis patients aged 60 years or older who were surveyed using the Kidney Disease Quality of Life Short Form at baseline and 2 years after study enrollment in phases 4 (2009–2011) and 5 (2012–2014) of the Japanese Dialysis Outcomes and Practice Patterns Study were analyzed. We categorized participants into 3 age groups (60–69, 70–79, and ≥80 years) and described baseline physical component summary (PCS) and mental component summary (MCS) scores, as well as their distribution of changes after 2 years across each category. Results: Hemodialysis patients aged 70–79 years and ≥80 years had lower PCS scores than those aged 60–69 years (median: 70–79 years = 43.1; interquartile range [IQR], 35.2–49.4; ≥80 years = 38.8; IQR, 31.6–43.8; 60–69 years = 45.4; IQR, 37.5–51.4; p < 0.001). In contrast, MCS scores did not significantly differ by age category (70–79 years = 45.6; IQR, 38.4–53.7; ≥80 years = 45.4; IQR, 36.9–55.1; 60–69 years = 46.8; IQR, 39.5–55.7; p = 0.1). As dialysis vintage lengthened, the PCS score significantly became lower, whereas no association was found with change in the MCS score. The MCS score declined over time in older patients, especially among those aged 80 years and older after 2 years’ follow-up. Conclusions: Physical QOL became worse as dialysis vintage lengthened. In contrast, mental QOL declined over time within a relatively short period among older maintenance hemodialysis patients.

Interdialytic Weight Gain Effects on Hemoglobin Concentration and Cardiovascular Events

IntroductionAlthough predialysis hemoglobin concentration is affected by interdialytic weight gain (IDWG), the interaction between these parameters is not well understood.MethodsUsing data from the Japanese Dialysis Outcomes and Practice Pattern Study phases 1–5, we analyzed patients who underwent maintenance hemodialysis. The exposure variable was hemoglobin concentration, and the effect modifier was IDWG at baseline. These 2 categorical variables were then combined and analyzed. The primary outcome was major adverse cardiovascular events (MACEs). Hazard ratios were estimated using a Cox model for the association between exposure and MACEs after adjusting for potential confounders. We examined additive interactions between hemoglobin concentration and IDWG by calculating the relative excess risk due to interaction, which is defined as a departure from the additivity of effects.ResultsA total of 8234 patients were enrolled. During a median follow-up of 2.1 years, 1062 (12.9%) patients developed MACEs. In IDWG categories of <6%, adjusted hazard ratios for MACEs tended to be lower as hemoglobin concentration increased. In IDWG categories of ≥6%, point estimation of MACEs with hemoglobin concentration of ≥11.0 g/dl–<12.0 g/dl was higher than that with hemoglobin concentration of ≥10.0 g/dl–<11.0 g/dl. The relative excess risk due to interaction was 0.22 (95% confidence interval 0.02–0.42) between IDWG category of ≥6% and hemoglobin categories of ≥11.0 g/dl–<12.0 g/dl, indicating a synergistic interaction.ConclusionsThe association between hemoglobin concentration and MACEs differed across IDWG. Consideration should be given to the upper limit of hemoglobin concentration in patients with high IDWG.

The Normalized Protein Catabolic Rate and Mortality Risk of Patients on Hemodialysis by Frailty Status: The Japanese Dialysis Outcomes and Practice Pattern Study

The appropriate protein intake for patients on hemodialysis complicated with frailty remains highly controversial. We conducted a prospective cohort study using data from Japanese Dialysis Outcomes and Practice Pattern Study. The patients were separated by their baseline of normalized protein catabolic rate (nPCR) into 3 categories: low (nPCR<1.0), medium (1.0≤nPCR <1.2), and high (nPCR ≥1.2). The frailty score was calculated based on the 12-item Short Form, and frailty was defined in cases with a total score of ≥2 points. The all-cause mortality was compared between groups using a Cox proportional hazard model. A total of 2,404 patients were included in the longitudinal analysis, 1,096 (45.6%) of whom had frailty. Patients in the low-nPCR group showed a higher prevalence of frailty than those in the other groups. In the Cox proportional hazard model, no significant differences in the all-cause mortality were noted between the low-nPCR and medium-nPCR groups or the high-nPCR and medium-nPCR groups. Furthermore, no significant differences were noted among any groups when subjects were limited to patients with frailty. Patients with a low nPCR have a higher prevalence of frailty and incidence of mortality than those with a medium nPCR. Patients with a high nPCR did not show a lower survival rate than those with a medium nPCR in this study. To clarify the appropriate protein intake for patients on hemodialysis with frailty, an intervention study or large-scale, long-term cohort study will be needed.

Low Predialysis Plasma Calculated Osmolality Is Associated with Higher All-Cause Mortality: The Japanese Dialysis Outcomes and Practice Patterns Study (J-DOPPS)

Introduction: Patients undergoing hemodialysis (HD) have higher predialysis plasma osmolality. Several studies have suggested lower osmolality to be associated with worse outcomes in patients not undergoing HD. However, no studies have examined the association between osmolality and mortality among patients undergoing HD. Objective: We aimed to examine the association between predialysis plasma calculated osmolality and all-cause mortality. Methods: This was a prospective cohort study of 1,240 patients undergoing HD participating in the Japanese Dialysis Outcomes and Practice Patterns Study phase 5 (2012–2015). The exposure was predialysis plasma osmolality, calculated as 2 × (serum sodium concentration [mmol/L]) + (serum urea nitrogen [mg/dL])/2.8 + (serum glucose [mg/dL])/18. The primary outcome was all-cause mortality. The secondary outcome was the change in systolic blood pressure (SBP) during HD. We used a marginal structural model with stabilized weights to estimate the association between calculated osmolality and all-cause mortality in the presence of time-varying confounders affected by prior exposure. Results: Mean baseline plasma calculated osmolality was 306.8 ± 8.6 mOsm/kg. Low predialysis calculated osmolality was associated with higher mortality (adjusted hazard ratio 1.52, 95% confidence interval [CI]: 1.30–1.78 by each 10 mOsm/L lower osmolality). The association was consistent across clinically relevant subgroups. Predialysis osmolality was significantly associated with intradialytic SBP change (mean difference 0.96 [95% CI: 0.05–1.88] mm Hg per each 10 mOsm/L lower osmolality). Conclusions: Low predialysis calculated osmolality was an independent risk factor of all-cause mortality.

Length of hospital stay is associated with a decline in activities of daily living in hemodialysis patients: a prospective cohort study

BackgroundThe impact of length of hospital stay on activities of daily living (ADLs) has not specifically been investigated among dialysis patients. Therefore, we attempt to verify the association between the length of hospital stay and the decline in ADLs among hemodialysis patients.MethodsThis prospective cohort study used data from the Japanese Dialysis Outcomes and Practice Patterns Study (J-DOPPS). We included 2442 hemodialysis patients aged ≥40 years from the J-DOPPS phase V (2012–2015) and subsequently excluded those who had already lost basic activities of daily living (BADLs) as demonstrated by dependency in at least three of the five BADLs at baseline and for whom changes in ADLs had been evaluated for less than 90 days. The main exposure was the cumulative length of hospital stay during the follow-up period. The primary outcomes were a decline in at least one of the five BADLs and eight instrumental activities of daily living (IADLs). We compared risk ratios (RRs) for 30-day increments for hospital stays with 10-year increments for age and having diabetes.ResultsA total of 849 patients were included in the statistical analysis. The cumulative length of hospital stay was significantly associated with a risk of decline in ADLs (adjusted RRs [95% confidence intervals] per 30-day increments: 1.42 [1.15 to 1.75] for BADLs, 1.38 [1.13 to 1.68] for IADLs). The adjusted RRs [95% CI] for 10-year increments in age were 1.20 [0.96 to 1.50] and 1.21 [1.00 to 1.47]. The adjusted RRs [95% CI] for having diabetes were 1.36 [0.97 to 1.91] for BADLs and 1.38 [1.04 to 1.84] for IADLs.ConclusionThe impact of a 30-day increment in the cumulative length of hospital stay on the decline in ADLs was comparable to that of a 10-year increase in age and having diabetes.

The effect of transportation modality to dialysis facilities on health-related quality of life among hemodialysis patients: results from the Japanese Dialysis Outcomes and Practice Pattern Study.

BackgroundFor hemodialysis (HD) patients, travel to the dialysis facility is an issue that can affect their quality of life (QOL), both physically and mentally. However, evidence on this association of transportation modality with health-related QOL (HRQOL) is scarce.Methods We conducted a cohort study among maintenance HD patients participating in the Japanese Dialysis Outcomes and Practice Pattern Study Phase 5. The study included patients who were functionally independent and able to walk. The primary exposure was the means of transportation to the dialysis facility, categorized into three groups, namely transportation by other drivers (Group 1), transportation via self-driving (Group 2) and transportation by bicycle or walking with or without public transportation (Group 3). The primary outcomes were physical and mental health composite scores (PCS and MCS) in the 12-item Short Form at 1 year after study initiation.ResultsAmong 1225 eligible patients (Group 1, 34.4%; Group 2, 45.0%; Group 3, 20.7%), 835 were analyzed for the primary outcomes. Linear regression analyses revealed that patients in Groups 2 and 3 had significantly higher PCS and MCS at 1 year than those in Group 1 {adjusted mean differences of PCS 1.42 [95% confidence interval (CI) 0.17–2.68] and 1.94 [95% CI 0.65–3.23], respectively, and adjusted mean differences of MCS 2.53 [95% CI 0.92–4.14] and 2.20 [95% CI 0.45–3.95], respectively}.ConclusionsTransportation modality was a significant prognostic factor for both PCS and MCS after 1 year in maintenance HD patients.

Intra-Dialytic Hemoglobin Changes and Cardiovascular Events: A Cohort Study on Dialysis Outcomes and Practice Patterns in Japan

Background: Ultrafiltration during hemodialysis (HD) causes hemoconcentration. Little is known about the relationships between intra-dialytic changes in hemoglobin concentration and cardiovascular events. Thus, this study aimed to elucidate the relationships between intra-dialytic changes in hemoglobin concentration and cardiovascular events among HD patients. Methods: This prospective cohort study was based on the Japanese Dialysis Outcomes and Practice Pattern Study phases 4 and 5. The predictor was the ratio of post-dialysis hemoglobin concentration to pre-dialysis hemoglobin concentration (post-Hb/pre-Hb) at baseline. The primary outcome was major adverse cardiovascular events (MACEs). Hazard ratios (HRs) were estimated using a Cox model for the association between post-Hb/pre-Hb and MACEs, adjusting for potential confounders. Results: A total of 865 patients were enrolled. During a median follow-up of 2.6 years, 145 (16.8%) patients developed MACEs. Patients were divided into 4 categories according to baseline post-Hb/pre-Hb (<1.0, ≥1.0 to <1.1, ≥1.1 to <1.2, and ≥1.2). The multivariable-adjusted HRs for MACEs were 1.69 (95% CI 1.36–2.10), 1.29 (95% CI 1.10–1.51), and 1.31 (95% CI 1.02–1.68) in patients with post-Hb/pre-Hb ratios of <1.0, ≥1.0 to <1.1, and ≥1.2, respectively, compared with the reference post-Hb/pre-Hb ratio of ≥1.1 to <1.2. Cubic spline analyses revealed a U-shaped association between post-Hb/pre-Hb and MACEs. Conclusion: High and low intra-dialytic changes in hemoglobin concentration are associated with a high risk of MACEs in patients undergoing HD.

Haemoglobin concentration and survival of haemodialysis patients before and after experiencing cardiovascular disease: a cohort study from Japanese dialysis outcomes and practice pattern study (J-DOPPS)

ObjectivesDifferences in the association of haemoglobin concentration with mortality or adverse cardiovascular events in haemodialysis patients before and after experiencing cardiovascular disease are unclear. We aimed to assess the influence...

Vitality Measured as Self-reported Energy Level and Clinical Outcomes in Hemodialysis Patients: The Japanese Dialysis Outcomes and Practice Pattern Study (J-DOPPS)

The infrequent assessment of vitality in clinical practice may be partially due to an inadequate understanding of vitality and the lack of a concise method of assessing it. This study aimed to examine the association of a simple 1-item "vitality" question measuring self-reported energy level with clinical outcomes. Prospective cohort study. 3,667 hemodialysis patientsparticipating in the Japanese Dialysis Outcomes and Practice Pattern Study (J-DOPPS), phases 3 to 4 (2005-2011). Responses to a single question from the 12-item Medical Outcomes Study Short Form survey, version 2.0: "How much time during the past 4 weeks did you have a lot of energy?," recorded using a 5-level Likert scale. All-cause mortality and a composite of cardiovascular hospitalizations and all-cause mortality. A pooled ordered logit model was fit to examine correlates of self-reported energy level. Cox and mixed-effects negative binomial regression models were fit for mortality and the composite outcome. Lower self-reported energy level was associated with tachycardia and use of benzodiazepines, hypnotics, and antidepressants. In contrast, higher energy was associated with higher single-pool Kt/V, serum albumin concentration, and body mass index. Compared to the lowest energy level, the second-highest and middle levels were associated with lower all-cause mortality (adjusted HRs [aHRs] of 0.66 [95% CI, 0.47-0.93] and 0.75 [95% CI, 0.59-0.96], respectively). Each 1-level higher self-reported energy was associated with lower mortality (aHR, 0.86; 95% CI, 0.78-0.96). Associations between self-reported energy level and multiple cardiovascular hospitalizations and mortality were similar to those between self-reported energy and mortality. No psychometric assessments were done for the Short Form survey. The response to a single "vitality" question addressing self-reported energy level is associated with adverse clinical outcomes and correlated with potentially modifiable factors.

Dialysate Calcium Concentration below 3.0 mEq/L Is Not Associated with Improved Outcomes in the Japanese Dialysis Outcomes and Practice Patterns Study

Background: Abnormal chronic kidney disease-mineral and bone disorder (CKD-MBD) markers have been associated with adverse outcomes in hemodialysis (HD) patients. Dialysate calcium concentration (D-Ca) likely influences serum calcium and phosphorus levels. Optimal D-Ca level remains unclear. We hypothesized that higher D-Ca is associated with cardiovascular events and mortality among Japanese HD patients. Methods: Enrollment data of chronic HD patients in the prospective observational study JDOPPS, phases 1–5 (1999–2015), provided exposures and covariates. All-cause mortality, non-arrhythmic cardiovascular events (NonAR-CVE), or their composites were analyzed by D-Ca, and divided into 2.5, 2.75, and 3.0 mEq/L. To minimize confounding by indication, analyses were restricted to facilities in which at least 90% of patients received the same D-Ca prescription. Association of D-Ca level with outcomes was evaluated in Cox models stratified by phase and accounting for facility clustering. Covariates describing patient demographics, comorbidities, laboratory values, CKD-MBD therapy, and facility attributes provided adjustment. Results: Of 9,201 patients included, 25.0% had D-Ca of 2.5 mEq/L; 6.8% D-Ca 2.75; and 68.2% D-Ca 3.0. Median follow-up time was 2.03 years. D-Ca was not associated with all-cause mortality, with hazards ratios for 2.5 vs. 3.0 mEq/L of 0.90 and 95% CI (0.73–1.11), nor with other outcomes. One effect modification occurred, protective for lower D-Ca on NonAR-CVE in the absence of cardiovascular comorbidities (p = 0.032), although corresponding D-Ca effects were not significant after multiple comparisons adjustment (p = 0.261 [D-Ca 2.5] and 0.125 [D-Ca 2.75]). Conclusion: Lowering D-Ca level below 3.0 mEq/L seems not to have a meaningful effect on patient outcomes.

Increased Mortality Rate after Hospitalization Among Chronic Hemodialysis Patients: A Prospective Cohort Study

Background/Aims: Hemodialysis patients are at high risk of hospitalization and their condition may worsen with repeated hospitalization. The aim of this study was to evaluate the impact of the cumulative number of hospitalizations on post-discharge mortality. Methods: This study was a prospective cohort study. We examined 3,359 adult patients on hemodialysis for at least 90 days who participated in the Japanese Dialysis Outcomes and Practice Patterns Study phases 3 and 4 (2005–2012). The patients hospitalized within 3 months before enrollment were excluded. The main exposure was the time-varying cumulative number of hospitalizations during the follow-up period. Hazard ratios (HRs) for all-cause mortality rate after discharge were estimated by time-dependent Cox regressions after adjusting for potential confounders. Results: The median follow-up time was 2.7 years, and 873 (26%) patients experienced at least 1 hospitalization during follow-up. The hospitalization rate was 0.23 per person-year and the mortality rate was 0.036 per person-year. The HR and 95% CI for post-discharge mortality increased as the cumulative number of hospitalizations increased: once, 1.41 (0.99–2.00); and twice or more, 2.27 (1.59–3.23). The cause-specific hospitalization categories, “infectious disease” and “cancer,” affected post-discharge mortality HRs in a similar manner: 2.41(1.32–4.41) and 2.70 (1.23–5.93), respectively. Conclusion: A higher cumulative number of hospitalizations is associated with increased post-discharge mortality in chronic hemodialysis patients. The cause-specific hospitalizations category of “infectious disease” showed an impact on mortality similar to that of hospitalization for “cancer.” Therefore, physicians should pay more attention to reducing preventable hospitalizations.

Body Mass Index Change and Hospitalization Risk in Elderly Hemodialysis Patients: Results from Japanese Dialysis Outcomes and Practice Patterns Study

Background: Short-term weight gains and losses are associated with a lower and higher mortality risk, respectively, in patients undergoing hemodialysis (HD). However, little is known about their association with the risk of subsequent hospitalization. Methods: In a prospective cohort of 1,804 HD patients aged ≥65 years enrolled in the Japanese Dialysis Outcomes and Practice Patterns Study phases 3 (2005–2008) and 4 (2009–2011), we examined the associations between changes in body mass index (BMI) over a 4-month baseline period (<–3%, –3 to <–1%, –1 to <1% [reference], 1 to <3%, and ≥3%) and subsequent risk of all-cause, cardiovascular, and noncardiovascular hospitalization using Cox models with adjustment for potential confounders. Results: During a median follow-up of 1.2 years, we noted 1,028 incident hospitalizations for any cause, including 275 and 753 hospitalizations for cardiovascular and noncardiovascular causes, respectively. An L-shaped association was observed between BMI change and all-cause hospitalization. The multivariable-adjusted hazard ratios (HRs; 95% CI) of all-cause hospitalization associated with BMI changes of <–3%, –3 to <–1%, 1 to <3%, and ≥3% (vs. –1 to <1%) were 1.29 (1.01–1.65), 1.22 (0.98–1.51), 1.04 (0.83–1.29), and 1.10 (0.83–1.45), respectively. Qualitatively similar associations were present for cardiovascular-related hospitalization (corresponding HRs [95% CI]: 1.58 [1.06–2.37], 1.09 [0.75–1.58], 0.99 [0.72–1.36], and 0.91 [0.51–1.64], respectively) but not for noncardiovascular-related hospitalization (corresponding HRs [95% CI]: 1.19 [0.90–1.57], 1.26 [0.99–1.59], 1.06 [0.84–1.35], and 1.18 [0.86–1.63], respectively). Conclusions: Decreases in BMI over a relatively short-term period were independently associated with higher risk of subsequent hospitalization, particularly cardiovascular-related hospitalization, among elderly HD patients.

Revisiting Interdialytic Weight Gain and Mortality Association With Serum Albumin Interactions: The Japanese Dialysis Outcomes and Practice Pattern Study

The dialysis practice guideline in Japan sets a limit on the allowed interdialytic weight gain (IDWG) <6%. However, the effects of relative gain of fluid volume to body weight may differ in presence of morbid conditions. Here, we examined whether or not the associations between IDWG and mortality differ by serum albumin (sAlb), a nutritional and illness marker. The study type used was prospective cohort study. Patients who participated in the Japan Dialysis Outcomes and Practice Pattern Study (phase 1-4 [1999-2011]) and received thrice-weekly hemodialysis. IDWG was the exposure of interest and was collected every 4 months, divided into 7 categories as follows: <2%, 2% to 3%, 3% to 4% (reference), 4% to 5%, 5% to 6%, 6% to 7%, and >7%. sAlb was treated as both an effect modifier and confounder and dichotomized into ≥3.8g/dL and <3.8g/dL segments, according to the protein-energy wasting criteria proposed by the International Society of Renal Nutrition and Metabolism. The outcome in this study was all-cause mortality. A total of 8,661 patients were analyzed. Time-varying Cox regression analyses revealed that, when sAlb was ≥3.8g/dL, an IDWG >7% was associated with greater risk of mortality (adjusted hazard ratio [AHR] 2.74; 95% confidence interval [CI], 1.49-5.05). When sAlb was <3.8g/dL, however, IDWGs <2% (AHR 1.89; 95% CI, 1.50-2.39) and 4% to 5% (AHR 0.75; 95% CI, 0.58-0.96) were associated with mortality (P for interaction=.001). Cubic spline analyses showed that the mortality increased when IDWG exceeded 6% for patients with sAlb ≥3.8g/dL; in contrast, for patients with sAlb <3.8g/dL, the mortality increased when IDWG was <3% and decreased when IDWG was between 4% and 6%. The main limitation was possible residual confounding. The direction and magnitude of the associations between IDWG and mortality were modified by sAlb. Dialysis experts should take these results into account when revising the clinical practice guidelines.

Unique hemoglobin A1c level distribution and its relationship with mortality in diabetic hemodialysis patients

Diabetic hemodialysis patients with hemoglobin A1c (HbA1c) levels below 6.5% and over 8.0% face a higher mortality risk. To determine the optimal glycemic control in Japanese patients, we examined the association between HbA1c and mortality in 2,300 Japanese diabetic patients on maintenance hemodialysis with HbA1c levels determined at enrollment in the Japanese Dialysis Outcomes and Practice Patterns Study (JDOPPS) phases 2-5, using Cox regression analysis with adjustment for baseline age, sex, dialysis vintage, 12 general comorbidities, hemoglobin, albumin and creatinine levels, and insulin use; stratification by JDOPPS phase; and facility clustering taken into account. Overall, 54% of patients had HbA1c levels under 6.0, including 14% with HbA1c levels under 5.0. Insulin or oral diabetes medications were used less frequently in patients with higher HbA1c levels. The dependence of mortality on HbA1c level was U shaped. When the group with the lowest mortality (HbA1c 6.0-7.0) was used as a reference, the hazard ratios for HbA1c categories under 5.0, 5.0-6.0, 7.0 to under 8.0, and 8.0 and greater were, respectively, 1.56 (95% confidence interval, 1.05-2.33), 1.26 (0.92-1.71), 1.23 (0.79-1.89), and 2.10 (1.32-3.33) in the adjusted model. The HbA1c level was not associated with self-reported hypoglycemic episodes in JDOPPS phase 5. The HbA1c levels in diabetic hemodialysis patients differ considerably between Japan and those reported from Western countries. Thus, our findings highlight the importance of domestic guidelines for glycemic control by race and country.

Cardiovascular and Stroke Risk in Japanese Hemodialysis Patients With Atrial Fibrillation.

Atrial fibrillation is one of the most common arrhythmias in hemodialysis patients. We evaluated its clinical outcomes among hemodialysis patients with atrial fibrillation in Japan. Using data derived from the Japanese Dialysis Outcomes and Practice Patterns Study, we analyzed backgrounds and outcomes among hemodialysis patients with and without atrial fibrillation in Japan. Among 7002 hemodialysis patients, the prevalence of atrial fibrillation was 5.7% and the incidence was 0.2 per 100 patient-years. Atrial fibrillation was independently associated with all-cause mortality (hazard ratio, 1.32; 95% confidence interval, 1.02-1.71) and cardiovascular events (hazard ratio, 1.39; 95% confidence interval, 1.15-1.68), but not with stroke events (hazard ratio, 0.77; 95% confidence interval, 0.55-1.06) after adjustment for other variables. We conclude that patients with atrial fibrillation experienced higher mortality and more cardiovascular events than did patients without atrial fibrillation, although the risk of stroke was lower than expected.

Pruritus in hemodialysis patients: Results from the Japanese Dialysis Outcomes and Practice Patterns Study (JDOPPS).

Pruritus affects many patients undergoing hemodialysis (HD). In this study, pruritus and its relationship to morbidity, quality of life (QoL), sleep quality, and patient laboratory measures were analyzed in a large sample of Japanese patients undergoing HD. Severity of patient-reported pruritus symptoms experienced during a 4-week period was collected from 6480 Japanese patients undergoing HD in three phases of the Dialysis Outcomes and Practice Patterns Study (DOPPS; 1996-2008; 60-65 study facilities/phase). Adjusted linear and logistic regressions were used to identify associations of pruritus with treatment parameters and QoL outcomes. Adjusted Cox regressions examined the influence of pruritus severity on mortality. Moderate to extreme pruritus was experienced by 44% of prevalent patients undergoing HD in the Japanese Dialysis Outcomes and Practice Patterns Study. Many patient characteristics were significantly associated with pruritus, but this did not explain the large differences in pruritus among facilities (20-70%). Pruritus was slightly less common in patients starting HD than in patients on dialysis >1 year. Patients with moderate to extreme pruritus were more likely to feel drained (adjusted odds ratio = 2.2-5.8, P < 0.0001), have poor sleep quality (adjusted odds ratio = 1.9-3.7, P < 0.0001), and have QoL mental and physical composite scores 2.3-6.7 points lower (P < 0.0001) than patients with no/mild pruritus. Pruritus in patients undergoing HD was associated with a 23% higher mortality risk (P = 0.09). The many poor outcomes associated with pruritus underscore the need for better therapeutic agents to provide relief for the 40-50% of prevalent patients undergoing HD substantially affected by pruritus. Pruritus in new patients with end-stage renal disease likely results from uremia or pre-existing conditions (not HD per se), indicating the need to understand development of pruritus before end-stage renal disease.