非对称性二甲基精氨酸与卒中

非对称性二甲基精氨酸(ADMA)是一氧化氮合酶(NOS)抑制剂.ADMA是通过左旋精氨酸残基甲基化形成的,可抑制血管活性物质NO的生成,导致内皮功能不全和血管性疾病.大量研究表明,ADMA可能是一种卒中危险因素.在高同型半胱氨酸血症、颈动脉狭窄和心血管疾病患者中,ADMA表达显著增高.     

Association of Vascular Access Type with Mortality,Hospitalization, and Transfer to In-Center Hemodialysis in Patients Undergoing Home Hemodialysis

Background and objectives

In individuals undergoing in-center hemodialysis (HD), use of central venous catheters (CVCs) is associated with worse clinical outcomes compared with use of arteriovenous access. However, it is unclear whether a similar difference in risk by vascular access type is present in patients undergoing home HD.

Design, setting, participants, & measurements

Our study examined the associations of vascular access type with all-cause mortality, hospitalization, and transfer to in-center HD in patients who initiated home HD from 2007 to 2011 in 464 facilities in 43 states in the United States. Patients were followed through December 31, 2011. Data were analyzed using competing risks hazards regression, with vascular access type at the start of home HD as the primary exposure in a propensity score–matched cohort (1052 patients; 526 with CVC and 526 with arteriovenous access).

Results

Over a median follow-up of 312 days, 110 patients died, 604 had at least one hospitalization, and 202 transferred to in-center hemodialysis. Compared with arteriovenous access use, CVC use was associated with higher risk for mortality (hazard ratio, 1.73; 95% confidence interval, 1.18 to 2.54) and hospitalization (hazard ratio, 1.19; 95% confidence interval, 1.02 to 1.39). CVC use was not associated with increased risk for transfer to in-center HD. The results of analyses in the entire unmatched cohort (2481 patients), with vascular access type modeled as a baseline exposure at start of home HD or a time-varying exposure, were similar. Analyses among a propensity score–matched cohort of patients undergoing in-center HD also showed similar risks for death and hospitalization with use of CVCs.

Conclusions

In a large cohort of patients on home HD, CVC use was associated with higher risk for mortality and hospitalization. Additional studies are needed to identify interventions which may reduce risk associated with use of CVCs among patients undergoing home HD.     

Associations of Self-Reported Physical Activity Types and Levels with Quality of Life,Depression Symptoms,and Mortality in Hemodialysis Patients: The DOPPS

Background and objectives

Physical activity has been associated with better health status in diverse populations, but the association in patients on maintenance hemodialysis is less established. Patient-reported physical activities and associations with mortality, health-related quality of life, and depression symptoms in patients on maintenance hemodialysis in 12 countries were examined.

Design, setting, participants, & measurements

In total, 5763 patients enrolled in phase 4 of the Dialysis Outcomes and Practice Patterns Study (2009–2011) were classified into five aerobic physical activity categories (never/rarely active to very active) and by muscle strength/flexibility activity using the Rapid Assessment of Physical Activity questionnaire. The Kidney Disease Quality of Life scale was used for health-related quality of life. The Center for Epidemiologic Studies Depression scale was used for depression symptoms. Linear regression was used for associations of physical activity with health-related quality of life and depression symptoms scores. Cox regression was used for association of physical activity with mortality.

Results

The median (interquartile range) of follow-up was 1.6 (0.9–2.5) years; 29% of patients were classified as never/rarely active, 20% of patients were classified as very active, and 20.5% of patients reported strength/flexibility activities. Percentages of very active patients were greater in clinics offering exercise programs. Aerobic activity, but not strength/flexibility activity, was associated positively with health-related quality of life and inversely with depression symptoms and mortality (adjusted hazard ratio of death for very active versus never/rarely active, 0.60; 95% confidence interval, 0.47 to 0.77). Similar associations with aerobic activity were observed in strata of age, sex, time on dialysis, and diabetes status.

Conclusions

The findings are consistent with the health benefits of aerobic physical activity for patients on maintenance hemodialysis. Greater physical activity was observed in facilities providing exercise programs, suggesting a possible opportunity for improving patient outcomes.     

Intravenous Iron Exposure and Mortality in Patients on Hemodialysis

Background and objectives

Clinical trials assessing effects of larger cumulative iron exposure with outcomes are lacking, and observational studies have been limited by assessment of short-term exposure only and/or failure to assess cause-specific mortality. The associations between short- and long-term iron exposure on all-cause and cause-specific mortality were examined.

Design, setting, participants, & measurements

The study included 14,078 United States patients on dialysis initiating dialysis between 2003 and 2008. Intravenous iron dose accumulations over 1-, 3-, and 6-month rolling windows were related to all-cause, cardiovascular, and infection-related mortality in Cox proportional hazards models that used marginal structural modeling to control for time-dependent confounding.

Results

Patients in the 1-month model cohort (n=14,078) were followed a median of 19 months, during which there were 27.6% all-cause deaths, 13.5% cardiovascular deaths, and 3% infection-related deaths. A reduced risk of all-cause mortality with receipt of >150–350 (hazard ratio, 0.78; 95% confidence interval, 0.64 to 0.95) or >350 mg (hazard ratio, 0.79; 95% confidence interval, 0.62 to 0.99) intravenous iron compared with >0–150 mg over 1 month was observed. There was no relation of 1-month intravenous iron dose with cardiovascular or infection-related mortality and no relation of 3- or 6-month cumulative intravenous iron dose with all-cause or cardiovascular mortality. There was a nonstatistically significant increase in infection-related mortality with receipt of >1050 mg intravenous iron in 3 months (hazard ratio, 1.69; 95% confidence interval, 0.87 to 3.28) and >2100 mg in 6 months (hazard ratio, 1.59; 95% confidence interval, 0.73 to 3.46).

Conclusions

Among patients on incident dialysis, receipt of ≤1050 mg intravenous iron in 3 months or 2100 mg in 6 months was not associated with all-cause, cardiovascular, or infection-related mortality. However, nonstatistically significant findings suggested the possibility of infection-related mortality with receipt of >1050 mg in 3 months or >2100 mg in 6 months. Randomized clinical trials are needed to assess the safety of exposure to greater cumulative intravenous iron doses.     

Changes in Serum Asymmetric Dimethylarginine and Endothelial Markers Levels With Varying Periods of Hemodialysis

Asymmetric dimethylarginine (ADMA) as a uremia toxin is accumulated in end‐stage renal disease (ESRD) patients. Elevated ADMA level has been shown to be predictive of cardiovascular diseases (CVDs) and all‐cause mortality in ESRD. Therefore, we investigated the effect of prolonged hemodialysis (HD) treatment on the levels of serum ADMA, arginine, nitric oxide (NO), soluble intercellular adhesion molecule‐1 (sICAM‐1) and soluble vascular cell adhesion molecule‐1 (sVCAM‐1). Seventy‐five patients (M/F = 40/35) with chronic renal failure (CRF) and who were on HD were divided into five groups with differing treatment periods of HD; from 6 to 24 months to 97–120 months. Fifteen apparently healthy subjects acted as controls. The serum levels of ADMA, sICAM‐1 and sVCAM‐1 were increased in all patient groups compared to the control group. No significant difference was observed when the patient groups were compared in terms of HD treatment periods. Nitric oxide levels were lower in the three groups who were treated for periods of 49–72, 73–96, 97–120 months compared to the control group. The L‐arginine to ADMA ratio was decreased in all patient groups compared to controls. Consequently, our investigations have shown that in HD continued for more than 4 years NO levels began to decrease significantly and the levels of serum ADMA, sICAM‐1 and sVCAM‐1 levels increased although this increase was not affected by the period in which hemodialysis treatment was applied.     

Clinical Outcomes after Parathyroidectomy in a Nationwide Cohort of Patients on Hemodialysis

Background and objectives

Patients receiving dialysis undergo parathyroidectomy to improve laboratory parameters in resistant hyperparathyroidism with the assumption that clinical outcomes will also improve. However, no randomized clinical trial data demonstrate the benefits of parathyroidectomy. This study aimed to evaluate clinical outcomes up to 1 year after parathyroidectomy in a nationwide sample of patients receiving hemodialysis.

Design, setting, participants, & measurements

Using data from the US Renal Data System, this study identified prevalent hemodialysis patients aged ≥18 years with Medicare as primary payers who underwent parathyroidectomy from 2007 to 2009. Baseline characteristics and comorbid conditions were assessed in the year preceding parathyroidectomy; clinical events were identified in the year preceding and the year after parathyroidectomy. After parathyroidectomy, patients were censored at death, loss of Medicare coverage, kidney transplant, change in dialysis modality, or 365 days. This study estimated cause-specific event rates for both periods and rate ratios comparing event rates in the postparathyroidectomy versus preparathyroidectomy periods.

Results

Of 4435 patients who underwent parathyroidectomy, 2.0% died during the parathyroidectomy hospitalization and the 30 days after discharge. During the 30 days after discharge, 23.8% of patients were rehospitalized; 29.3% of these patients required intensive care. In the year after parathyroidectomy, hospitalizations were higher by 39%, hospital days by 58%, intensive care unit admissions by 69%, and emergency room/observation visits requiring hypocalcemia treatment by 20-fold compared with the preceding year. Cause-specific hospitalizations were higher for acute myocardial infarction (rate ratio, 1.98; 95% confidence interval, 1.60 to 2.46) and dysrhythmia (rate ratio 1.4; 95% confidence interval1.16 to 1.78); fracture rates did not differ (rate ratio 0.82; 95% confidence interval 0.6 to 1.1).

Conclusions

Parathyroidectomy is associated with significant morbidity in the 30 days after hospital discharge and in the year after the procedure. Awareness of clinical events will assist in developing evidence-based risk/benefit determinations for the indication for parathyroidectomy.     

AKI Complications in Critically Ill Patients: Association with Mortality Rates and RRT

Background and objectives

AKI is associated with short- and long-term mortality. However, the exact contribution of AKI complications to the burden of mortality and whether RRT has any beneficial effect on reducing mortality rates in critically ill AKI patients are unknown.

Design, setting, participants, & measurements

This was a retrospective analysis using data from the Multiparameter Intelligent Monitoring in Intensive Care II project. A total of 18,410 adult patients were enrolled from four intensive care units from a university hospital from 2001 to 2008.

Results

Overall, 10,245 patients developed AKI. After adjustments, the odds ratios (ORs) for hospital mortality were 1.73 (95% confidence interval [95% CI], 1.52 to 1.98) for AKI stage 1, 1.88 (95% CI, 1.57 to 2.25) for stage 2, and 2.89 (95% CI, 2.41 to 3.46) for stage 3. Totals of 33%, 59%, and 70% of the excess mortality rates associated with AKI stages 1, 2, and 3, respectively, were attenuated by the inclusion of each AKI-related complication in the model. The main burden of excess hospital mortality associated with AKI was attenuated by metabolic acidosis and cumulative fluid balance. Long-term mortality was not attenuated by any of the associated complications. Next, we used two different approaches to explore the associations between RRT, AKI complications, and hospital mortality: multivariate analysis and propensity score matching. In both approaches, the sensitivity analysis for RRT was associated with a better hospital survival in only the following AKI-related subgroups: hyperkalemia (OR, 0.55; 95% CI, 0.35 to 0.85), metabolic acidosis (OR, 0.70; 95% CI, 0.53 to 0.92), cumulative fluid balance >5% of body weight (OR, 0.60; 95% CI, 0.40 to 0.88), and azotemia (OR, 0.57; 95% CI, 0.40 to 0.81).

Conclusions

A majority of the excess risk of mortality associated with AKI was attenuated by its fluid volume and metabolic complications, particularly in severe AKI. In addition, this study demonstrated that RRT is associated with a better outcome in patients with AKI-related complications.     

非对称性二甲基精氨酸与血管内皮功能

非对称性二甲基精氨酸是内源性一氧化氮合酶抑制剂,研究表明,非对称性二甲基精氨酸与血管内皮功能失调密切相关,血浆中非对称性二甲基精氨酸水平的升高是内皮功能失调的新的危险因子。     

Quality-of-Life and Mortality in Hemodialysis Patients: Roles of Race and Nutritional Status

Summary

Background and objectives

Maintenance hemodialysis (MHD) patients often have protein-energy wasting, poor health-related quality of life (QoL), and high premature death rates, whereas African-American MHD patients have greater survival than non-African-American patients. We hypothesized that poor QoL scores and their nutritional correlates have a bearing on racial survival disparities of MHD patients.

Design, setting, participants, & measurements

We examined associations between baseline self-administered SF36 questionnaire–derived QoL scores with nutritional markers by multivariate linear regression and with survival by Cox models and cubic splines in the 6-year cohort of 705 MHD patients, including 223 African Americans.

Results

Worse SF36 mental and physical health scores were associated with lower serum albumin and creatinine levels but higher total body fat percentage. Spline analyses confirmed mortality predictability of worse QoL, with an almost strictly linear association for mental health score in African Americans, although the race–QoL interaction was not statistically significant. In fully adjusted analyses, the mental health score showed a more robust and linear association with mortality than the physical health score in all MHD patients and both races: death hazard ratios for (95% confidence interval) each 10 unit lower mental health score were 1.12 (1.05–1.19) and 1.10 (1.03–1.18) for all and African American patients, respectively.

Conclusions

MHD patients with higher percentage body fat or lower serum albumin or creatinine concentration perceive a poorer QoL. Poor mental health in all and poor physical health in non-African American patients correlate with mortality. Improving QoL by interventions that can improve the nutritional status without increasing body fat warrants clinical trials.     

Associations of Depressive Symptoms and Pain with Dialysis Adherence,Health Resource Utilization,and Mortality in Patients Receiving Chronic Hemodialysis

Background and objectives

Depressive symptoms and pain are common in patients receiving chronic hemodialysis, yet their effect on dialysis adherence, health resource utilization, and mortality is not fully understood. This study sought to characterize the longitudinal associations of these symptoms with dialysis adherence, emergency department (ED) visits, hospitalizations, and mortality.

Design, setting, participants, & measurements

As part of a trial comparing symptom management strategies in patients receiving chronic hemodialysis, this study prospectively assessed depressive symptoms using the Patient Health Questionnaire 9, and pain using the Short-Form McGill Pain Questionnaire, monthly between 2009 and 2011. This study used negative binomial, Poisson, and proportional hazards regression to analyze the longitudinal associations of depressive symptoms and pain, scaled based on 5-point increments in symptom scores, with missed and abbreviated hemodialysis treatments, ED visits, hospitalizations, and mortality, respectively.

Results

Among 286 patients, moderate-to-severe depressive symptoms were identified on 788 of 4452 (18%) assessments and pain was reported on 3537 of 4459 (79%) assessments. Depressive symptoms were independently associated with missed (incident rate ratio [IRR], 1.21; 95% confidence interval [95% CI], 1.10 to 1.33) and abbreviated (IRR, 1.08; 95% CI, 1.03 to 1.14) hemodialysis treatments, ED visits (IRR, 1.24; 95% CI, 1.12 to 1.37), hospitalizations (IRR, 1.19; 95% CI, 1.10 to 1.30), and mortality (IRR, 1.40; 95% CI, 1.11 to 1.77). Pain was independently associated with abbreviated hemodialysis treatments (IRR, 1.03; 95% CI, 1.01 to 1.06) and hospitalizations (IRR, 1.05; 95% CI, 1.00 to 1.10). Severe pain was independently associated with abbreviated hemodialysis treatments (IRR, 1.16; 95% CI, 1.06 to 1.28), ED visits (IRR, 1.58; 95% CI, 1.28 to 1.94), and hospitalizations (IRR, 1.22; 95% CI, 1.03 to 1.45), but not mortality (hazard ratio, 1.71; 95% CI, 0.81 to 2.96).

Conclusions

Depressive symptoms and pain are independently associated with dialysis nonadherence and health services utilization. Depressive symptoms are also associated with mortality. Interventions to alleviate these symptoms have the potential to reduce costs and improve patient-centered outcomes.     

Comparison of Subdural Hematoma Risk between Hemodialysis and Peritoneal Dialysis Patients with ESRD

Background and objectives

This study compared the risk of subdural hematoma (SDH) and subsequent mortality in hemodialysis (HD) and peritoneal dialysis (PD) patients with ESRD.

Design, setting, participants, & measurements

Claims data were obtained from the National Health Insurance Administration Research Database in Taiwan. This retrospective cohort study comprised 10,136 PD patients and 10,136 HD patients with newly diagnosed ESRD from 1998 to 2010. Patients were matched by propensity score and year of dialysis initiation. Incidence rates and hazard ratios of SDH as well as odds ratios of subsequent 30-day deaths from SDH were evaluated from the date of the first dialysis session to the date when SDH was diagnosed, or the date of renal transplantation, death, withdraw from insurance, or the end of the follow-up period (December 31, 2011).

Results

Median (25th percentile, 75th percentile) follow-up times for SDH events were 3.61 years (1.91, 6.33) and 3.33 years (1.83, 5.66) in the HD and PD cohorts, respectively. The overall SDH incidence rate (95% confidence interval [95% CI]) was 61.4% higher in the HD cohort than in the PD cohort (34.7 [95% CI, 31.4 to 35.4] versus 21.5 [95% CI, 20.2 to 22.9] per 10,000 person-years, with an adjusted hazard ratio of 1.62 [95% CI, 1.17 to 2.33]). Approximately 152 of 253 (60%) of SDH events were associated with trauma. Subsequent 30-day SDH-related mortality was not statistically higher in HD patients than in PD patients (29.1% versus 25.3%; adjusted odds ratio, 1.30; 95% CI, 0.70 to 2.41).

Conclusions

HD patients have a higher risk of developing SDH than PD patients. Both patient groups have a high risk of mortality. Routine education on fall prevention is needed for dialysis patients.     

Asymmetric Dimethylarginine and Mortality in Stages 3 to 4 Chronic Kidney Disease

Background and objectives: Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, reduces bioavailability of nitric oxide and induces endothelial dysfunction. This dimethylated amino acid accumulates in chronic kidney disease and may be involved in the pathophysiology of cardiovascular disease (CVD) in this population.Design, settings, participants, & methods: The Modification of Diet in Renal Disease Study was a randomized, controlled trial conducted between 1989 and 1993. We measured ADMA in frozen samples collected at baseline (n = 820) and obtained survival status, up to December 31, 2000, from the National Death Index. We examined the relationship of ADMA with prevalent CVD and performed multivariable Cox models to examine the relationship of ADMA with all-cause and CVD mortality.Results: Mean (SD) age was 52 (12) yr, GFR was 32 ± 12 ml/min per 1.73 m², and ADMA was 0.70 ± 0.25 μmol/L. A 1-SD increase in ADMA was associated with a 31% increased odds of prevalent CVD in an adjusted logistic regression model. During the 10-yr follow-up period, 202 (25%) participants died of any cause, 122 (15%) from CVD, and 545 (66%) reached kidney failure. In multivariable Cox models, a 1-SD increase in ADMA was associated with a 9% increased risk for all-cause and 19% increased risk for CVD mortality.Conclusions: In this cohort of patients with predominantly nondiabetic, stages 3 to 4 chronic kidney disease, there was a strong association of ADMA with prevalent CVD and a modest association with all-cause and CVD mortality.Endothelium-derived nitric oxide, an important mediator of vascular tone and BP regulation, is produced via a reaction catalyzed by nitric oxide synthase (1). Asymmetric dimethylarginine (ADMA), a byproduct of the breakdown of arginine methylated proteins, is an endogenous inhibitor of this reaction (2). Increased ADMA levels lead to nitric oxide depletion, impaired endothelium-dependent vasodilation, reduced free radical scavenging, and plaque rupture with thrombus formation (3–5). Plasma concentrations of ADMA are elevated in cardiovascular high-risk states such as hypertension (6,7), obesity (8), and diabetes (9) and seem to be related to endothelial dysfunction in patients with these conditions. High ADMA levels were an index of carotid intima-media thickness and were associated with future acute coronary events in general population studies (10,11).Levels of ADMA are elevated in chronic kidney disease (CKD) (12,13). This 202-Da amino acid is eliminated unchanged in the urine but is also taken up and degraded in the kidney by the enzyme dimethylarginine dimethylaminohydrolase (DDAH); ADMA accumulation in kidney failure is due to both decreased elimination and reduced DDAH activity (14). High ADMA was an independent risk factor for cardiovascular disease (CVD) and all-cause mortality in a cohort of patients who were on hemodialysis (13,15) and was associated with faster rates of kidney disease progression in patients in the earlier stages of CKD (16); however, data are limited on the relationship between ADMA levels and CVD in patients with CKD before reaching kidney failure (17,18). We therefore examined the relationship of ADMA with prevalent CVD and with all-cause and CVD mortality during long-term follow-up of a cohort of patients with stages 3 to 4 CKD.     

维持性血液透析患者的血压与透析充分性及相关因素分析

目的观察维持性血液透析(MHD)患者血压与透析充分性及其它相关因素间的关系。方法 56例MHD连续12次记录透析前后血压、体重、超滤量(FV),分别计算收缩压(SBP)、舒张压(DBP)和平均动脉压(MAP)的均值,第0、1、2、3个月透析前后测定血液生化值、甲状旁腺激素(PTH)、血红蛋白(Hb)、红细胞压积(Hct),计算尿素清除指数(Kt/V)、尿素下降率(URR)。结果透析充分组(Kt/V≥1.2、URR≥0.65)MHD患者血压明显低于透析不充分组(Kt/V<1.2、URR<0.65)差异有统计学意义(P<0.05);Hct≥0.22组与Hct<0.22组比较MAP差异有统计学意义(P<0.05);Logistic回归分析显示透析间期体重增加量、体重增加率、透析不充分及血清PTH水平与透析前收缩压密切相关(OR=1.98~3.50,P<0.05)。结论充分透析、减少容量负荷是控制MHD患者高血压的关键,透析不充分、透析间期体重增长过多、高血清甲状旁腺激素水平与透析前收缩压升高有密切关系。