Time-dependent associations between iron and mortality in hemodialysis patients

The independent association between the indices of iron stores or administered intravenous iron, both of which vary over time, and survival in patients who are on maintenance hemodialysis (MHD) is not clear. It was hypothesized that the observed associations between moderately high levels of three iron markers (serum ferritin, iron, and iron saturation ratio) or administered intravenous iron and all-cause and cardiovascular death is due to the time-varying confounding effect of malnutrition-inflammation-cachexia syndrome (MICS). Time-dependent Cox regression models were examined using prospectively collected data of the 2-yr (July 2001 to June 2003) historical cohort of 58,058 MHD patients from virtually all DaVita dialysis clinics in the United States. After time-dependent and multivariate adjustment for case mix, administered intravenous iron and erythropoietin doses, and available surrogates of MICS, serum ferritin levels between 200 and 1200 ng/ml (reference 100 to 199 ng/ml), serum iron levels between 60 and 120 microg/ml (reference 50 to 59 microg/ml), and iron saturation ratio between 30 and 50% (reference 45 to 50%) were associated with the lowest all-cause and cardiovascular death risks. Compared with those who did not receive intravenous iron, administered intravenous iron up to 400 mg/mo was associated with improved survival, whereas doses >400 mg/mo tended to be associated with higher death rates. The association between serum ferritin levels >800 ng/ml and mortality in MHD patients seems to be due mostly to the confounding effects of MICS. For ascertaining whether the observed associations between moderate doses of administered intravenous iron and improved survival are causal or due to selection bias by indication, clinical trials are warranted.     

Clinical characteristics and mortality in hepatitis C-positive haemodialysis patients: a population based study.

BACKGROUND: The association between hepatitis C virus (HCV) infection and clinical and laboratory measures in maintenance haemodialysis (MHD) patients are poorly understood. METHODS: We analyzed data from over 37,000 MHD patients who underwent MHD for at least 3 months in DaVita dialysis clinics across USA in July 2001. RESULTS: The presence of HCV infection was determined using enzyme immunoassay (EIA), which was performed in 2778 MHD patients and was positive in 363 (13%) individuals. In a multivariate logistic regression model that adjusts for case-mix and available surrogates of malnutrition-inflammation complex syndrome (MICS), the following were independent predictors of HCV infection: younger age, male gender, Black race, Hispanic ethnicity, higher haemoglobin, lower serum albumin, higher total iron binding capacity, higher creatinine, and higher serum glutamic oxaloacetic transaminase (SGOT). Among receiver operating characteristics of commonly measured laboratory values in this population, the SGOT had the highest area. An SGOT > or =25 u/l had an adjusted odds ratio of 4.96 (95% confidence interval: 3.75-6.57) for HCV antibody positivity (sensitivity 50%, specificity 87%). HCV EIA positivity among MHD patients younger than 65 years was associated with 40-80% higher hazard ratio of all-cause and cardiovascular death during the 2 year follow-up (July 2001 to June 2003) after adjustment for case-mix and measures of MICS. CONCLUSION: HCV infection, as diagnosed by EIA, has distinct racial, age and laboratory predilections in MHD patients. HCV positivity among MHD patients younger than 65 years is associated with significantly higher cardiovascular mortality. More diligent HCV detection and treatment may improve cardiovascular survival in MHD patients.     

Association between serum lipids and survival in hemodialysis patients and impact of race

Despite the enormous cardiovascular disease epidemic among maintenance hemodialysis (MHD) patients, total hypercholesterolemia seems paradoxically to be associated with better survival. It was hypothesized that similar paradoxic associations also exist for serum LDL, HDL, and triglycerides. A 3-yr (July 2001 through June 2004) cohort of 15,859 MHD patients was studied in the United States from DaVita dialysis clinics where lipid profile was measured in at least 50% of all outpatients during a given calendar quarter. Cox proportional hazard models were adjusted for case mix and surrogates of malnutrition-inflammation complex. Both total and LDL hypercholesterolemia showed a paradoxic association with better survival. Hypertriglyceridemia (>200 mg/dl) also showed a similar trend, but serum HDL cholesterol did not have any clear association with survival. The association between a low serum LDL <70 mg/dl, which was prevalent among almost 50% of all MHD patients, and a higher all-cause death risk was robust to multivariate adjustment. In the subgroup analyses, these paradoxic associations persisted among most subgroups, although they tended to be stronger among hypoalbuminemic (<3.8 mg/dl) patients and those with a lower dietary protein intake (<1 g/kg per d). However, in black patients, a high serum LDL (>100 mg/ml) was associated with adjusted cardiovascular death hazard ratio of 1.94 (95% confidence interval 1.12 to 2.38; P = 0.02). Despite inverse associations between hyperlipidemia and survival, black MHD patients with high LDL show almost two-fold increase in cardiovascular death risk. Although these associations may not be causal, they call into question whether specific subgroups of dialysis patients are better targets for cholesterol-lowering therapy.     

The Nutritional and Inflammatory Evaluation in Dialysis patients (NIED) study: overview of the NIED study and the role of dietitians.

The absolute majority of maintenance hemodialysis (MHD) patients die within 5 years of commencing dialysis treatment, mostly because of cardiovascular (CV) disease. The strongest and most common correlates of death in MHD patients are not conventional CV risk factors, but markers of protein-energy malnutrition and inflammation, together also known as malnutrition-inflammation complex syndrome (MICS). Paradoxically, classic risk factors such as obesity and hypercholesterolemia are associated with better survival in MHD patients. It has been hypothesized that this so-called reverse epidemiology is caused by the overwhelming prevalence and dominating effect of MICS in MHD patients. Hence, the key to improving survival and quality of life in MHD patients may be a better understanding of MICS and its interactions with CV disease and outcome. The Nutritional and Inflammatory Evaluation in Dialysis Patients (NIED) study is a longitudinal multicenter cohort study that aims to examine these hypotheses. At any given semiannual round, approximately 360 MHD patients from 8 DaVita dialysis facilities in the Los Angeles area are examined; 900 MHD patients will be cumulatively studied by the end of this 5-year prospective study (October 2001 to September 2006). Repeated measures of markers of nutritional status and inflammation are performed by 10 to 12 dialysis unit dietitians while patients attend their routine HD treatment in their dialysis facilities. All-cause and CV mortality, hospitalization, and quality of life are studied as outcome measures. The collaborating dietitians are the main evaluators and play crucial roles in all aspects of the study. This article reviews the design and infrastructure of the NIED study and reports preliminary findings of the first 12 to 30 months of the study.     

血清铁调素-25与维持性血液透析患者生存预后的关系研究

目的铁调素在铁代谢中起重要调节作用,抑制肠道铁吸收、肝细胞和巨噬细胞铁释放,但其临床应用价值尚不清楚。本研究旨在研究铁调素-25与维持性血液透析(MHD)患者生存预后的关系。 方法本研究为前瞻性观察性队列研究,选取2016年1月至2020年12月在徐州市中心医院血液净化中心的160例MHD患者,根据患者基线血清铁调素-25水平分为低水平组(<30.9 ng/ml)和高水平组(≥30.9 ng/ml),随访5年。采用Kaplan-Meier生存曲线、多因素Cox比例风险模型及基于限制性立方样条的Cox比例风险回归模型分析铁调素-25与死亡风险的关系。 结果与低水平组相比,高水平组患者的基线血清铁、铁蛋白、转铁蛋白饱和度(TSAT)、超敏C反应蛋白(hs-CRP)水平较高,透析前的血肌酐、白蛋白和前白蛋白水平较低。高水平组患者生存预后较差,透析龄较短(P＝0.0011),随访期死亡率较高(P＝0.0023)。血清铁调素-25增加10 ng/mL时,MHD患者全因死亡风险比为1.206(95%CI: 1.100~1.323, P<0.001)。MHD患者的全因死亡风险比在血清铁调素-25<30.9 ng/mL时相对稳定,在血清铁调素-25水平超过30.9 ng/mL之后,随着铁调素水平增加而显著升高。 结论血清铁调素-25水平可作为MHD患者全因死亡事件的独立预测因子,监测血清铁调素-25水平有助于预测MHD患者的生存预后。     

Rise in serum albumin and creatinine in the first half year on hemodialysis

Rise in serum albumin and creatinine in the first half year on hemodialysis. BACKGROUND: Serum albumin and creatinine have been reported to rise in new hemodialysis patients; however, these trends have not been quantitated in a stable cohort, and their determinants and prognostic value are unknown. METHODS: This study examined the changes in monthly values of serum albumin and creatinine over the first half year of hemodialysis in 115 patients who survived to the start of the sixth month. After verifying that the trends were approximately linear, we calculated the rates of rise (slope) of six predialysis values of serum albumin (months 1 through 6) and of creatinine (months 2 through 7) and examined their associations with age, diabetes, race, baseline 24-hour urine protein and creatinine excretion, and survival during the latter half of the first year. RESULTS: Serum albumin rose by 13% over months 1 through 6 [0.08 +/- 0.12 (SD) g/dl/month, P < 10-9 vs. zero slope]. Patients who survived the entire year had higher mean values for both serum albumin (month 1, P < 0.003; months 3 through 6, P < 10-3) and rate of rise of albumin (0.09 +/- 0.11 g/dl/month vs. 0.01 +/- 0.13 g/dl/month, P < 0.005) than patients who died during months 6 through 12, but the slope was not an independent predictor of survival after adjusting for serum albumin concentration. Baseline proteinuria correlated inversely with serum albumin measured at the first and second months (P < 0.005) and directly with the albumin slope (r = 0.49, P < 10-5). Serum creatinine rose by 12% between months 2 through 7 (0.12 +/- 0.47 mg/dl/month, P < 0.02). Survivors had a significantly higher mean baseline creatinine excretion (P < 0. 03) and serum creatinine (month 2, P < 0.03; months 3 through 7, P < 0.01) but only a marginally higher rate of rise of serum creatinine (0.16 +/- 0.47 mg/dl/month vs. -0.07 +/- 0.48 mg/dl/month, P < 0.06) than patients who died during the second half of the year. Baseline urinary creatinine excretion correlated directly with serum creatinine at month 2 (P < 0.01) and more strongly at months 3 through 7 (P < 10-3), as well as correlating with the creatinine slope (r = 0.26, P < 0.03). CONCLUSIONS: Serum albumin and creatinine rose by 12 to 13% during the first half year of hemodialysis in a stable cohort. The slope of serum albumin versus time predicted survival, but it was not as predictive as the absolute albumin concentration. The pattern of correlations of baseline urinary protein and creatinine excretion with the respective monthly serum values of albumin and creatinine and their slopes is consistent with the hypothesis that as residual renal function declines, progressive retention of protein and creatinine contributes to the respective rises in serum albumin and creatinine.     

Comparing outcome predictability of markers of malnutrition-inflammation complex syndrome in haemodialysis patients.

BACKGROUND: Markers of malnutrition-inflammation complex syndrome (MICS) are reported to predict mortality and hospitalization in maintenance haemodialysis (MHD) patients. However, it is not clear which one is a more sensitive and stronger predictor of outcome. METHODS: We examined the utility of 10 markers of MICS as predictors of prospective mortality and hospitalization, which included malnutrition-inflammation score (MIS), a fully quantitative score adopted from subjective global assessment, and serum levels of C-reactive protein (CRP), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), albumin, pre-albumin, total iron binding capacity, creatinine, total cholesterol and normalized protein nitrogen appearance. A cohort of 378 MHD patients, who were randomly selected from eight DaVita dialysis facilities in the South Bay Los Angeles area, was studied. RESULTS: Patients, aged 54.5+/-14.7 years, included 53% men, 47% Hispanics, 30% African-Americans and 55% diabetics, who had undergone MHD for 37+/-34 months. Over a 12-month follow-up, 39 patients died and 208 were hospitalized at least once. Multivariate Cox and Poisson models that included 11 covariates [gender, age, race, ethnicity, diabetes, dialysis vintage, Charlson co-morbidity index (CCI), insurance status, Kt/V, body mass index and history of cardiovascular disease] were explored for the highest quartiles of inflammatory markers or the lowest quartiles of nutritional markers. The magnitude of relative risk of death and hospitalization was greatest for MIS, CRP and IL-6. In extended multivariate models that included all 10 MICS markers and 11 additional covariates simultaneously, CRP, MIS and CCI were the only consistent predictors of mortality and hospitalization, and their outcome predictabilities were superior to serum albumin. CONCLUSIONS: The MIS appears to be a useful, short-term tool to risk-stratify MHD patients and may circumvent the need for measuring inflammatory markers such as CRP or IL-6.     

Pulmonary hypertension as an independent predictor of cardiovascular mortality and events in hemodialysis patients

Background

Hemodialysis patients are at an increased risk of cardiovascular (CV) morbidity and mortality. Pulmonary hypertension (PH) has been recently reported as a new entity and unrecognized threat in maintenance hemodialysis (MHD) patients, whether PH predicts CV mortality and events in this population remains unknown. The aim of the present study was to determine the value of PH in predicting CV mortality and events in a prospective cohort of MHD patients.

Methods

We studied 278 MHD patients (98 with and 180 without PH) in Guangdong General Hospital Blood Purification Center, Guangzhou, China. All patients had been followed up for 2 years, and in survival analysis, we considered time to death or first cardiovascular event. The endpoints were all-cause mortality, CV mortality and CV events. PH was defined as systolic pulmonary artery pressure (SPAP) ≥ 35 mmHg as determined by Doppler echocardiographic evaluation.

Results

Of the 278 MHD patients, 53 (19.1 %) died as a result of all causes, 28 (10.1 %) died from CV events (52.8 % of causes of death), and 87 (31.3 %) had new-onset CV events. The survival curve showed that all-cause and CV mortality and new-onset CV events were higher in PH group than the non-PH group. In a multivariate Cox proportional hazard model, the adjusted HR for all-cause mortality, CV mortality and CV events was 1.85 [95 % confidence interval (CI) 1.03–3.34], 2.36 (95 % CI 1.05–5.31) and 2.27 (95 % CI 1.44–3.58), respectively.

Conclusions

Our study showed that PH was an independent predictor of all-cause mortality and CV mortality and events in MHD patients. We suggest to evaluate SPAP in MHD patients in order to stratify risk of death and CV events.     

Early posttransplant serum osteoprotegerin levels predict long-term (8-year) patient survival and cardiovascular death in renal transplant patients

The primary objectives of this analysis were to examine the effects of early posttransplantation (10 wk) serum levels of osteoprotegerin (OPG), mannose-binding lectin (MBL), and MBL-associated serine proteases (MASP; MASP-2 and MASP-3) on long-term (8-yr) patient survival, graft survival, and cardiovascular (CV) death. During a period of 16 mo (1995 to 1996), a total of 173 consecutive renal transplant recipients without diabetes before transplantation were included in a prospective study that was designed to address the impact of metabolic CV risk factors on survival and CV end points. Baseline sera from 172 patients were available for analysis. Follow-up data until January 1, 2004, were obtained from a national renal registry. Patients with high (fourth quartile) serum levels of OPG had significantly higher all-cause mortality (hazard ratio [HR] 6.3; 95% confidence interval [CI] 3.3 to 11.8; P<0.001) and CV death (HR 10.8; 95% CI 3.8 to 30.4; P<0.001) than patients with lower OPG concentrations. After multiple Cox regression analysis, high serum levels of OPG remained an independent predictor of all-cause mortality (HR 6.0; 95% CI 3.1 to 11.6, P<0.001) and CV death (HR 8.2; 95% CI 2.5 to 26.4; P<0.001). Multiple linear regression analysis revealed that age, creatinine clearance, and high-sensitivity C-reactive protein all were independently associated with OPG (R2=0.42). No significant association between OPG and death-censored graft loss was revealed. Serum levels of MBL, MASP-2, and MASP-3 were not significantly associated with patient survival, CV death, or graft loss. Early measured posttransplantation serum OPG is a highly significant independent predictor of death from any cause or CV death in white renal transplant recipients.     

Survival predictability of time-varying indicators of bone disease in maintenance hemodialysis patients

Although renal osteodystrophy and vitamin D analogs may be related to survival in maintenance hemodialysis (MHD) patients, most studies have examined associations between baseline values and survival without accounting for variations in clinical and laboratory measures over time. We examined associations between survival and quarterly laboratory values and administered paricalcitol in a 2-year (July 2001-June 2003) cohort of 58,058 MHD patients from all DaVita dialysis clinics in USA using both time-dependent Cox models with repeated measures and fixed-covariate Cox models with only baseline values. Whereas hypercalcemia and hyperphosphatemia were robust predictors of higher death risk in all models, the association between serum calcium and mortality was different in time-varying models. Changes in baseline calcium and phosphorus values beyond the Kidney Disease Outcome Quality Initiative recommended targets were associated with increased mortality. Associations between high serum parathyroid hormone and increased death risk were masked by case-mix characteristics of MHD patients. Time-varying serum alkaline phosphatase had an incremental association with mortality. Administration of any dose of paricalcitol was associated with improved survival in time-varying models. Controlling for nutritional markers may introduce overadjustment bias owing to their strong collinearity with osteodystrophy surrogates. Whereas both time-dependent and fixed-covariate Cox models result in similar associations between osteodystrophy indicators and survival, subtle but potentially clinically relevant differences between the two models exist, probably because fixed models do not account for variations of osteodystrophy indices and changes in medication dose over time.     

Effects of serum magnesium level on mortality in maintenance hemodialysis patients

Objective To investigate the effects of serum magnesium level on all-cause mortality and cardiovascular and cerebrovascular diseases mortality in maintenance hemodialysis (MHD) patients. Methods Clinical data of MHD patients in Shaoxing People's Hospital from June 1, 2016 to June 30, 2018 were collected retrospectively. The patients were divided into low magnesium group (serum magnesium≤0.96 mmol/L), medium magnesium group (serum magnesium 0.97-1.07 mmol/L) and high magnesium group (serum magnesium≥1.08 mmol/L) according to the tertile of mean serum magnesium level. The differences of clinical data and laboratory results were compared among the three groups. Kaplan-Meier method was used to draw the survival curves, and log-rank test was used to compare the survival rate differences. Multivariate Cox regression was used to analyze the relationship between serum magnesium and all-cause mortality and cardiovascular and cerebrovascular diseases mortality in MHD patients. Results A total of 332 patients [194 males (58.4%)] were included in this study, with a median age of 63(51, 72) years and a median follow-up time of 36(20, 45) months. Kaplan-Meier survival analysis showed that the all-cause survival rate and cardiovascular and cerebrovascular diseases survival rate in the low magnesium group were lower than those in the medium magnesium group and the high magnesium group (Log-rank χ2=36.286, P＜0.001; Log-rank χ2=20.145, P＜0.001; respectively). After adjusting for multiple confounding factors, the results of multivariate Cox regression analysis suggested that low serum magnesium was an independent risk factor for all-cause death and cardiovascular and cerebrovascular diseases death in MHD patients. The risk of all-cause death and cardiovascular and cerebrovascular diseases death in the low magnesium group were significantly higher than those in the high magnesium group (HR=2.925, 95%CI 1.352-6.330, P=0.006; HR=3.821, 95% CI 1.394-10.473, P=0.009; respectively). Conclusions Hypomagnesemia may be an independent risk factor for all-cause death and cardiovascular and cerebrovascular diseases death in MHD patients. Low serum magnesium level increases the risk of all-cause death and cardiovascular and cerebrovascular diseases in MHD patients.     

Association of serum magnesium level with all-cause mortality in maintenance hemodialysis patients

Objective To investigate the association of serum magnesium (Mg) level with all-cause mortality in maintenance hemodialysis patients. Methods A multicenter retrospective cohort study was conducted in seven hemodialysis centers of Guizhou province. The adult outpatients who underwent hemodialysis for more than 3 months were included from June 2015 to June 2016. Demographics, baseline clinical and laboratory test results were collected. All patients were followed up until June 30, 2018. Patients were divided into 4 groups according to their baseline serum Mg levels (interquartile range). Kaplan-Meier method was used to compare the survival rates of the four group. Cox regression model was used to analyze the association of Mg with all-cause mortality. Logistic regression was used to analyze the influencing factors of low Mg level. Results A total of 868 hemodialysis dialysis patients with baseline Mg data were enrolled in this study, with age of (55.47±16.17) years old, among whom 59.4% were male. There were 11 (1.3%) patients with hypomagnesemia (Mg＜0.7 mmol/L), 432(49.8%) patients with hypermagnesemia (Mg＞1.05 mmol/L), and 16(1.8%) patients with Mg＞2.0 mmol/L. Median Mg was 1.05 mmol/L and interquartile range was 0.95-1.24 mmol/L. The comparison between Mg quartile groups showed that the difference in age, hemoglobin, serum albumin, serum calcium, parathyroid hormone (PTH), serum creatinine, uric acid and urea nitrogen was statistically significant (all P＜0.05). After a median follow-up of 24 months, 207 patients died. Kaplan-Meier curves showed higher all-cause mortality in patients with Mg≤0.95 mmol/L (Q1 group) (Log-rank test χ2=15.11, P=0.002). However, after adjusting for age, comorbidities and biochemical indicators(especially albumin), there was no statistically significant difference in the hazard ratio for all-cause death among the four groups. Multiple logistic regression analysis results showed that low serum albumin (OR=0.946, 95%CI 0.913-0.979, P=0.002) and low serum uric acid (OR=0.994, 95%CI 0.992-0.997, P＜0.001) were the risk factors for baseline Mg≤0.95 mmol/L. Conclusions Hypomagnesemia is rare in MHD patients, while hypermagnesemia is more common. Baseline serum Mg≤0.95 mmol/L in MHD patients is correlated with increased risk of all-cause death, but it may be not an independent risk factor. Baseline serum Mg≤0.95 mmol/L that occurred is associated with low levels of albumin and serum uric acid.     

The association of lipid levels with mortality in patients on chronic peritoneal dialysis.

BACKGROUND: The role of traditional risk factors, including plasma lipids, in the pathogenesis of cardiovascular (CV) disease in chronic dialysis patients is unclear. Previous studies have suggested that lower serum total cholesterol (TC) is associated with higher mortality in patients on chronic haemodialysis (HD). Whether this relationship is specific to the HD population or is common to the uraemic state is unclear. The present study evaluated the association of serum TC and triglycerides with clinical outcomes in chronic peritoneal dialysis (PD) patients. METHODS: Data of 1053 PD patients from the United States Renal Data System (USRDS) prospective Dialysis Morbidity and Mortality Study Wave 2 were examined. Cox regression was used to evaluate the relationship between lipid levels and mortality. RESULTS: Patients with TC levels < or =125 mg/dl (3.24 mmol/l) had a statistically significant increased risk of an all-cause mortality, including those taking or not taking lipid-modifying medications, compared with the reference of 176-225 mg/dl (4.54-5.83 mmol/l). In stratified analysis, this association was demonstrated in patients with serum albumin >3.0 g/dl (30 g/l), but not with albumin < or =3.0 g/dl. Compared with patients with triglyceride levels of 201-300 mg/dl (2.27-3.39 mmol/l), a statistically significant reduction of all-cause, but not CV, mortality was observed in patients with triglyceride levels of 101-200 mg/dl (1.14-2.26 mmol/l), as well as in the subgroup with serum albumin levels <3.0 g/dl (30 g/l) and triglycerides of < or =100 mg/dl (1.13 mmol/l) and 101-200 mg/dl (1.14-2.26 mmol/l). CONCLUSIONS: While confounding factors and causal pathways have not been clearly identified, aggressive lowering of plasma cholesterol in PD patients is not supported by this study, however, treatment of hypertriglyceridaemia may be warranted with triglyceride levels >200 mg/dl (2.26 mmol/l).     

Quality of Life and Outcomes in African Americans with CKD

Low health-related quality of life (HRQOL) has been associated with increased risk for hospitalization and death in ESRD. However, the relationship of HRQOL with outcomes in predialysis CKD is not well understood. We evaluated the association between HRQOL and renal and cardiovascular (CV) outcomes in 1091 African Americans with hypertensive CKD enrolled in the African American Study of Kidney Disease and Hypertension (AASK) trial and cohort studies. Outcomes included CKD progression (doubling of serum creatinine/ESRD), CV events/CV death, and a composite of CKD progression or death from any cause (CKD progression/death). We assessed HRQOL, including mental health composite (MHC) and physical health composite (PHC), using the Short Form-36 survey. Cox regression analyses were used to assess the relationship between outcomes and five-point decrements in MHC and PHC scores using measurements at baseline, at the most recent annual visit (time-varying), or averaged from baseline to the most recent visit (cumulative). During approximately 10 years of follow-up, lower mean PHC score was associated with increased risk of CV events/CV death and CKD progression/death across all analytic approaches, but only time-varying and cumulative decrements were associated with CKD progression. Similarly, lower mean MHC score was associated with increased risk of CV events/CV death regardless of analytic approach, while only time-varying and cumulative decrements in mean MHC score was associated with CKD progression and CKD progression or death. In conclusion, lower HRQOL is associated with a range of adverse outcomes in African Americans with hypertensive CKD.     

Impact of serum albumin and body-mass index on survival in hemodialysis patients

A low body mass index (BMI) and serum albumin are associated with increased risk of mortality in patients with chronic kidney disease (CKD). The purpose of this study was to evaluate BMI and serum albumin as predictors of all-cause and cardiovascular (CV) mortality in hemodialysed (HD) patients. We describe the results of a five-year retrospective observational study with 187 HD patients (54.9 ± 15.6 years old, 54% men, and 46% suffering from diabetes) from RenalCor Clinic in Rio de Janeiro, Brazil. The influence of serum albumin levels and BMI (determined every three months) over all-cause mortality was examined using a Cox model, while the influence of the same factors over CV mortality among all-cause mortality was modeled through a logistic regression. During the five years, 26.7% of the patients died, 62% of which due to CV disease (CVD). Analysis by the Cox model showed that low serum albumin and low BMI were significant predictors of mortality. Patients with higher BMI had a lower hazard of death for all-cause mortality (hazard ratio [HR] = 0.92; P = 0.035) and a 1 g/l increase in serum albumin was associated with significantly lower hazard of death (hazard ratio = 0.9679; P < 0.001). The highest BMI value (>30 kg/m²) was significantly associated with an increase of odds of CV mortality (odds ratio = 1.22, P = 0.03). We confirm here in a Brazilian cohort of hemodialysis patients that both low BMI (<19 kg/m²) and hypoalbuminemia are strong predictors of death.     

Urotensin II is an inverse predictor of death and fatal cardiovascular events in chronic kidney disease

Urotensin II (UTN), a cyclic vasoactive peptide expressed in multiple organs, had higher plasma levels that was previously shown to predict longer survival in dialysis patients. We sought to determine if this association exists in earlier stages of chronic kidney disease (CKD) by studying a cohort of 122 incident clinically stable pre-dialysis patients. Linear models were used to determine associations of UTN with baseline characteristics such as renal function and traditional and nontraditional cardiovascular risk factors. We used Cox regression analysis to model time-to-death as a function of UTN and the same variables for adjustment including a time-varying covariate that indicated progression to end-stage renal disease. No correlation was found between baseline glomerular filtration rate and plasma UTN. In adjusted analysis, UTN correlated directly with serum albumin and, inversely, with history of previous coronary events. During a mean follow-up of 41 months, 43 patients died - 29 from cardiovascular events. After adjusting for potential confounding factors, increased UTN predicted lower risk of death from all-cause and cardiovascular causes. In patients with moderate-to-severe CKD, plasma UTN was found to be an inverse predictor of overall and cardiovascular mortality.     

Hypocholesterolemia is a significant predictor of death in a cohort of chronic hemodialysis patients

BACKGROUND: Although hypocholesterolemia is common in chronic hemodialysis patients, its effect on survival has not been studied in a large patients population. METHODS: A cohort of chronic hemodialysis patients (N = 1167) was prospectively followed from January 1991 to January 2001. The survival impact of this cohort, who were divided according to different baseline levels of serum cholesterol, were calculated with the multivariate Cox proportional hazard analysis after adjusting for baseline clinical and laboratory variables. RESULTS: During the study period, 567 (48.6%) patients died. The mean (SD) baseline level of serum cholesterol was 171.0 (40.8) mg/dL and ranged from 76 to 378 mg/dL. The five-year survival rate was highest (0.812) in the subgroup that had a serum cholesterol range of 200 to 219 mg/dL and was lowest (0.608) in the subgroup with serum cholesterol values of <140 mg/dL. The five-year survival rate was 0.735 in the subgroup with serum cholesterol of > or =220 mg/dL. Serum cholesterol was a significant predictor of death with an adjusted hazards ratio (95% confidence interval) was 0.939 (0.891 to 0.989). In a subgroup of patients with serum albumin values > or =4.5 g/dL (N = 128), the adjusted hazards ratio was even greater at 1.370 (1.105 to 1.692). Other than sex, body mass index and serum albumin were significant determinants of baseline levels of serum cholesterol. CONCLUSIONS: Hypocholesterolemia was an independent predictor of death in patients on chronic hemodialysis. This impact of hypercholesterolemia on survival was only evident in a subgroup of patients whose serum albumin was more than 4.5 g/dL.     

Relative contributions of inflammation and inadequate protein intake to hypoalbuminemia in patients on maintenance hemodialysis

Purpose

Serum albumin is one of the strongest mortality predictors in maintenance hemodialysis (MHD) patients. Yet, the degree to which serum albumin represents dietary protein intake or an inflammatory state, among others, is not clear. We hypothesize that these inadequate protein intake and inflammation contribute somewhat equally to hypoalbuminemia.

Methods

In a cross-sectional analysis, we examined correlates of low serum albumin, <3.8 g/dL, in 812 MHD patients in whom interleukin-6 (IL-6) and normalized protein nitrogen appearance (nPNA), also known as normalized protein catabolic rate (nPCR), were also measured. Logistic regression estimated odds ratios were employed, and spline models were plotted to examine the likelihood of relatively low serum albumin <3.8 g/dL.

Results

Mean age (±SD) of patients was 54 ± 15 years; 53 % of patients were men, 50 % Hispanic, 31 % African–American, and 55 % diabetic. The mean dialysis vintage was 31 ± 34 months (median: 19, inter-quartile range: 7–44 months). The baseline serum albumin, averaged over a 3-month period (mean ± SD), was 3.88 ± 0.38 g/mL. The unadjusted correlation coefficients of l IL-6 and nPNA with serum albumin were ?0.36 and +0.20, respectively (p < 0.001 for each comparison). The likelihood for an albumin <3.8 gr/dL increased linearly with decreasing nPNA and rising serum IL-6. This trend was steeper with increasing serum IL-6 up to a concentration of 30 ng/mL.

Conclusions

Both low protein intakes and a high state of inflammation are associated with low serum albumin in MHD patients.     

An anti-inflammatory and antioxidant nutritional supplement for hypoalbuminemic hemodialysis patients: a pilot/feasibility study.

BACKGROUND: A low serum albumin concentration < 3.8 g/dL, a marker of malnutrition-inflammation complex syndrome, is observed in approximately half of all maintenance hemodialysis (MHD) patients in the United States and is strongly associated with increased mortality. OBJECTIVES: We hypothesized that a novel oral nutritional intervention with anti-inflammatory and antioxidant properties taken during routine dialysis sessions is well tolerated and corrects hypoalbuminemia in MHD patients. DESIGN: Controlled clinical study. SETTING: An outpatient dialysis facility affiliated with a tertiary care community medical center with six equally distributed hemodialysis shifts and 163 MHD patients. PATIENTS: Among all MHD outpatients of three selected HD shifts (n = 81 patients), 21 subjects had a serum albumin level < 3.8 g/dL. One patient who was hospitalized before the intervention was excluded. The other three dialysis shifts, with 82 MHD outpatients including 20 hypoalbuminemic subjects, were observed as concurrent controls. INTERVENTION: The nutritional intervention included one can of Oxepa and one can of Nepro to be taken together orally during each routine hemodialysis session for 4 weeks. Each can contains 237 mL fluid. Oxepa provides 355 calories and 14.8 g protein per can, includes maltodextrin, medium-chain triglycerides, borage oil, and refined and deodorized fish oil, and is designed for critically ill patients with inflammation and oxidative stress. Each can of Oxepa includes 1,020 mg gamma-linolenic acid, 3,100 mg caprylic acid, 1,080 mg eicosapentaenoic acid, 75 mg taurine, 2,840 IU vitamin A activity, 75 IU vitamin E, and 200 mg vitamin C. Nepro provides 475 calories and 16.7 g protein per can; includes high-oleic safflower oil, corn syrup solids, and fructo-oligosaccharides; and is tailored for the nutritional needs of MHD patients. Oxepa and Nepro also contain L-carnitine, 43 mg and 62 mg, respectively. MAIN OUTCOME MEASURES: Serum albumin pretrial and posttrial. RESULTS: Studied outpatients (12 men and 8 women) were aged 60.4 +/- 13.0 (SD) years. Three patients had started MHD treatment between 1.5 and 3 months before the intervention. Nine patients were diabetic. Preintervention serum albumin, 3.44 +/- 0.34 g/dL (mean +/- SD) increased to 3.68 +/- 0.34 g/dL (P = .001) 4 weeks after the start of the intervention. In 16 patients, serum albumin level increased by 0.2 to 1.3 g/dL, whereas in 4 patients the serum albumin level decreased by 0.2 to 0.6 g/dL. Three patients reported diarrhea, and one diabetic patient had increased serum glucose values. No other side effects were noted. In 20 control outpatients not receiving nutritional intervention, serum albumin did not change from 3.46 +/- 0.20 to 3.47 +/- 10.44 g/dL (P = .47). CONCLUSIONS: In hypoalbuminemic MHD patients, a short-term in-center nutritional intervention with one can of Nepro and one can of Oxepa during HD is practical, convenient, well-tolerated, and associated with a significant increase in serum albumin level. Well-designed randomized placebo-controlled clinical trials are needed to verify the safety and effectiveness of this nutritional intervention and its impact on clinical outcome in hypoalbuminemic MHD patients.     

C-reactive protein and albumin as predictors of all-cause and cardiovascular mortality in chronic kidney disease

BACKGROUND: High C-reactive protein (CRP) and hypoalbuminemia are associated with increased risk of mortality in patients with kidney failure. There are limited data evaluating the relationships between CRP, albumin, and outcomes in chronic kidney disease (CKD) stages 3 and 4. METHODS: The Modification of Diet in Renal Disease (MDRD) Study was a randomized controlled trial conducted between 1989 and 1993. CRP was measured in frozen samples taken at baseline. Survival status and cause of death, up to December 31, 2000, were obtained from the National Death Index. Multivariable Cox models were used to examine the relationship of CRP [stratified into high CRP > or =3.0 mg/L (N= 414) versus low CRP<3.0 mg/L (N= 283)], and serum albumin, with all-cause and cardiovascular mortality. RESULTS: Median follow-up time was 125 months, all-cause mortality was 20% (N= 138) and cardiovascular mortality was 10% (N= 71). In multivariable analyses adjusting for demographic, cardiovascular and kidney disease factors, both high CRP (HR, 95% CI = 1.56, 1.07-2.29) and serum albumin (HR = 0.94 per 0.1 g/dL increase, 95% CI = 0.89-0.99) were independent predictors of all-cause mortality. High CRP (HR 1.94, 95% CI 1.13-3.31), but not serum albumin (HR 0.94, 95% CI 0.87-1.02), was an independent predictor of cardiovascular mortality. CONCLUSION: Both high CRP and low albumin, measured in CKD stages 3 and 4, are independent risk factors for all-cause mortality. High CRP, but not serum albumin, is a risk factor for cardiovascular mortality. These results suggest that high CRP and hypoalbuminemia provide prognostic information independent of each other in CKD.