Role of hypoalbuminemia and hypocholesterolemia as copredictors of mortality in acute renal failure.

Role of hypoalbuminemia and hypocholesterolemia as co-predictors of mortality in acute renal failure. BACKGROUND: Hypoalbuminemia (LA) and hypocholesterolemia (LC) have been reported to portend high mortality in both older patients and in patients with end-stage renal disease. Even though low levels have been reported in critically ill patients, they have not been clearly defined as predictors of mortality in acute renal failure (ARF). The impact of LA and LC on mortality in ARF is evaluated in this study. METHODS: We conducted a computer-assisted three-year retrospective review of all cases of de novo ARF seen at an inner city tertiary-care facility. One hundred cases met the criteria for inclusion in the study. We employed both univariate and multivariate logistic regression models to estimate the relative risks (RR) and 95% confidence intervals (CI) of mortality associated with several variables. RESULTS: Predictors associated with a high risk of death identified in this study include LC < or = 150 mg/dl (< or = 3.9 mmol/liter; RR, 7.4; CI, 2.7 to 20.3), LA < or =35 g/liter (RR, 5.0; CI, 1.9 to 13.2), sepsis (RR, 9.4; CI, 3.7 to 23.9), mechanical ventilation (RR, 10.8; CI, 2.8 to 41.0), oliguria (RR 17.0; CI, 6.2 to 46.6), and multisystem organ failure (RR 24.7; CI, 10.3 to 59.1). The overall gross mortality was 39%, but mortality among intensive care unit patients was 82%. Survival was 82% among patients with serum albumin >35 g/liter versus 48% among those with serum albumin < or =35 g/liter (chi2 = 11.9, P = 0.0006). Similarly, survival was higher among patients with cholesterol >150 mg/dl (>3.9 mmol/liter) than those whose levels were < or =150 mg/dl (< or =3.9 mmol/liter; 85 vs. 44%, ch 17.3, P<0.0001). Significant association between LA and LC was observed (R = 0.4, P<0.0001). Age, gender, level of plasma creatinine, and underlying chronic medical conditions were not predictive of mortality. CONCLUSION: Survival in ARF is significantly altered by the levels of albumin and cholesterol. Because both LC and LA can be cytokine mediated, their presence in ARF should be considered ominous.     

Vascular access calcification predicts mortality in hemodialysis patients

Vascular calcification is a recognized risk factor for cardiovascular mortality in patients with end-stage renal disease. The aim of this study was to identify risk factors for vascular access calcification and to determine if patients with this disorder are at increased risk of death. Vascular access calcification was found in 49 of 212 hemodialysis patients as measured by plain X-ray (arteriovenous fistula or synthetic graft) in two dimensions. Male gender, diabetes mellitus, and length of time on dialysis were independent predictors for access calcification determined by logistic regression multivariate analysis. Serum parameters were not independently related to access calcification. Kaplan-Meier analysis showed an increased mortality risk, and Cox regression analysis confirmed that vascular access calcification was an independent mortality predictor. Our study suggests that detection of vascular access calcification is a cost-effective method to identify patients at increased mortality risk.     

Human serum paraoxonase concentration predicts cardiovascular mortality in hemodialysis patients

AIMS: Human serum paraoxonase (PON1) is associated with high-density lipoprotein, and inhibits oxidative modification of low-density lipoprotein. Therefore, PON1 is supposed to contribute to the prevention of atherosclerosis. We and other investigators have shown that the enzymatic activities and concentrations of PON1 were decreased in maintenance hemodialysis (HD) patients. However, the effect of PON1 status on the long-term outcome of HD patients has not been reported. In this study, we examined the association between baseline PON 1 status and cardiovascular mortality in an observation study of an outpatient HD population. PATIENTS AND METHODS: The relation between baseline cardiovascular risk factors and clinical events was investigated, during 6 years of follow-up, in 81 HD patients (50 males and 31 females) whose enzymatic activities, concentrations and genetic polymorphisms of PON1 had been determined in a previous study. RESULTS: During follow-up for 6 years, we recorded 42 deaths, including 24 fatal cardiovascular events. In univariate analyses, baseline PON1 concentration was associated with not only cardiovascular mortality (p < 0.005), but also all-cause mortality (p < 0.001) during the period of follow-up, as were age, preexisting cardiovascular disease (CVD) and hemoglobin concentration. In a multivariate Cox regression analysis, PON1 concentration retained significant associations with cardiovascular mortality (p < 0.05) and all-cause mortality (p < 0.005) even after correction of known risk factors for CVD or mortality in HD patients. Using Kaplan-Meier survival curves, we assessed the association between low and high concentrations of PON1 divided according to the median value (7.52 U/ml). Significantly increased cardiovascular mortality (log rank 6.125, p = 0.01) and all-cause mortality (log rank 7.113, p < 0.01) were detected in the patients with low PON1 concentrations. CONCLUSIONS: These data suggest that low PON 1 concentration may be an independent predictor of cardiovascular mortality in maintenance HD patients.     

Serum alkaline phosphatase predicts mortality among maintenance hemodialysis patients

Several observational studies have demonstrated that serum levels of minerals and parathyroid hormone (PTH) have U- or J-shaped associations with mortality in maintenance hemodialysis patients, but the relationship between serum alkaline phosphatase (AlkPhos) and risk for all-cause or cardiovascular death is unknown. In this study, a 3-yr cohort of 73,960 hemodialysis patients in DaVita outpatient dialysis were studied, and the hazard ratios for all-cause and cardiovascular death were higher across 20-U/L increments of AlkPhos, including within the various strata of intact PTH and serum aspartate aminotransferase. In the fully adjusted model, which accounted for demographics, comorbidity, surrogates of malnutrition and inflammation, minerals, PTH, and aspartate aminotransferase, AlkPhos > or =120 U/L was associated with a hazard ratio for death of 1.25 (95% confidence interval 1.21 to 1.29; P < 0.001). This association remained among diverse subgroups of hemodialysis patients, including those positive for hepatitis C antibody. A rise in AlkPhos by 10 U/L during the first 6 mo was incrementally associated with increased risk for death during the subsequent 2.5 yr. In summary, high levels of serum AlkPhos, especially >120 U/L, are associated with mortality among hemodialysis patients. Prospective controlled trials will be necessary to test whether serum AlkPhos measurements could be used to improve the management of renal osteodystrophy.     

Ankle-brachial blood pressure index predicts all-cause and cardiovascular mortality in hemodialysis patients

A reduction in ankle-brachial BP index (ABPI) is associated with generalized atherosclerotic diseases and predicts cardiovascular mortality and morbidity in several patient populations. However, a large-scale analysis of ABPI is lacking for hemodialysis (HD) patients, and its use in this population is not fully validated. A cohort of 1010 Japanese patients undergoing chronic hemodialysis was studied between November 1999 and May 2002. Mean age at entry was 60.6 +/- 12.5 yr, and duration of follow-up was 22.3 +/- 5.6 mo. Patients were stratified into five groups (< 0.9, > or = 0.9 to < 1.0, > or = 1.0 to < 1.1, > or = 1.1 to < 1.3, and > or = 1.3) by ABPI measured at entry by an oscillometric method. The frequency distribution of ABPI was 16.5% of patients < 0.9, 8.6% of patients > or = 0.9 to < 1.0, 16.9% of patients 1.0 > or = to < 1.1, and 47.0% of patients > or 1.1 to < 1.3, whereas 10.9% of patients had an abnormally high ABPI (> or = 1.3). The relative risk of a history of diabetes mellitus (DM), cardiovascular, and cerebrovascular disease was significantly higher in patients with lower ABPI than those with ABPI > or = 1.1 to <1.3. During the study period, 77 cardiovascular and 41 noncardiovascular fatal events occurred. On the basis of Cox proportional hazards regression analysis, ABPI emerged as a strong independent predictor of all-cause and cardiovascular mortality. After adjustment for confounding variables, the hazard ratio (HR) for ABPI < 0.9 was 4.04 (95% confidence interval, 2.38 to 6.95) for all-cause mortality and 5.90 (2.83 to 12.29) for cardiovascular mortality. Even those with modest reductions in the ABPI (> or = 0.9 to <1.1) appeared to be at increased risk. Patients having abnormally high ABPI (> or = 1.3) also had poor prognosis (HR, 2.33 [1.11 to 4.89] and 3.04 [1.14 to 8.12] for all-cause and cardiovascular mortality, respectively). Thus, the present findings validate ABPI as a powerful and independent predictor for all-cause and cardiovascular mortality among hemodialysis patients.     

Platelet-to-lymphocyte ratio predicts mortality better than neutrophil-to-lymphocyte ratio in hemodialysis patients

Purpose

Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were established showing the poor prognosis in some diseases, such as cardiovascular diseases and malignancies. The risk of mortality in patients with end-stage renal disease (ESRD) was higher than normal population. In this study, we aimed to investigate the relationship between NLR, PLR, and all-cause mortality in prevalent hemodialysis (HD) patients.

Methods

Eighty patients were enrolled in study. NLR and PLR obtained by dividing absolute neutrophil to absolute lymphocyte count and absolute platelet count to absolute lymphocyte count, respectively. The patients were followed prospectively for 24 months. The primary end point was all-cause mortality.

Results

Mean levels of neutrophil, lymphocyte, and platelet were 3904 ± 1543/mm³, 1442 ± 494/mm³, 174 ± 56 × 10³/mm³, respectively. Twenty-one patients died before the follow-up at 24 months. Median NLR and PLR were 2.52 and 130.4, respectively. All-cause mortality was higher in patients with high NLR group compared to the patients with low NLR group (18.8 vs. 7.5 %, p = 0.031) and in patients with higher PLR group compared to patients with lower PLR group (18.8 vs. 7.5 %, p = 0.022). Following adjusted Cox regression analysis, the association of mortality and high NLR was lost (p = 0.54), but the significance of the association of high PLR and mortality increased (p = 0.013).

Conclusion

Although both NLR and PLR were associated with all-cause mortality in prevalent HD patients, only PLR could independently predict all-cause mortality in these populations.

     

Prealbumin, mortality, and cause-specific hospitalization in hemodialysis patients

BACKGROUND: Prealbumin (transthyretin) is a hepatic secretory protein thought to be important in the evaluation of nutritional deficiency and nutrition support. Prior studies have suggested that the serum prealbumin concentration is independently associated with mortality in hemodialysis patients, even with adjustment for serum albumin and other nutritional parameters. METHODS: To determine whether prealbumin was independently associated with mortality and morbidity (cause-specific hospitalization) in hemodialysis patients, we analyzed data on 7815 hemodialysis patients with at least one determination of serum prealbumin during the last three months of 1997. Unadjusted, case mix-adjusted, and multivariable-adjusted relative risks of death were calculated for categories of serum prealbumin using proportional hazards regression. We also determined whether the prealbumin concentration was associated with all-cause, cardiovascular, infection-related, and vascular access-related hospitalization. RESULTS: The relative risk (RR) of death was inversely related to the serum prealbumin concentration. Relative to prealbumin > or =40 mg/dL, the adjusted RRs of death were 2.41, 1.85, 1.49, and 1.23 for prealbumin <15, 15-20, 20-25, and 25-30 mg/dL, respectively. The adjusted RRs of hospitalization due to infection were 2.97, 1.95, 1.81, and 1.61 for prealbumin <15, 15-20, 20-25, and 25-30 mg/dL, respectively. The adjusted RRs of vascular access-related hospitalization were 0.48, 0.52, 0.58, and 0.71 for prealbumin <15, 15-20, 20-25, and 25-30 mg/dL, respectively. While serum albumin was strongly associated with mortality and all-cause hospitalization, it was not associated with hospitalization due to infection, and lower levels were associated with higher rather than lower rates of vascular access-related hospitalization. CONCLUSION: In hemodialysis patients, lower prealbumin concentrations were associated with mortality and hospitalization due to infection, independent of serum albumin and other clinical characteristics. Higher prealbumin concentrations were associated with vascular access-related hospitalization. In light of these findings, more intensive study into the determinants and biological actions of prealbumin (transthyretin) in end-stage renal disease is warranted.     

QT dispersion predicts mortality and correlates with both coronary artery calcification and atherosclerosis in hemodialysis patients

Purpose

QT dispersion (QTd) was shown to be an independent predictor of mortality in hemodialysis (HD) patients. It may be hypothesized that coronary artery calcification is related to QTd in HD patients because widespread calcification may also involve the cardiac conducting system in these patients. In this study, we aimed to investigate the relationships of corrected QTd (QTcd) with coronary artery calcification score (CACS), carotid plaque score (CPS) and possible influence of these parameters on survival of HD patients.

Methods

Seventy-two HD patients (33 male, 39 female) were enrolled into the study. Mean age of the patients was 44 ± 12 years. Mean follow-up duration was 77 ± 24 months. CACS was determined by computed tomography. QTcd values were calculated as the difference of maximum and minimum QT intervals. Left ventricular mass index (LVMI) and CPS were measured by echocardiography.

Results

QTcd was significantly correlated with CACS (r = 0.233, p = 0.049), CPS (r = 0.354, p = 0.003) and LVMI (p = 0.011, r = 0.299). CPS was found to be significantly higher in the group with high QTcd (>60 ms) [2 (1–4) versus 0 (0–1), p = 0.02]. CACS was significantly correlated with age (r = 0.44, p < 0.001), LVMI (r = 0.52, p < 0.001) and CPS (r = 0.32, p = 0.003). In Kaplan–Meier analysis, survival of patients with high QTcd was significantly lower than the patients with low QTcd. In Cox regression analysis for predicting mortality, age, serum albumin and QTcd were found to be the independent predictors of mortality.

Conclusions

QTcd independently predicted mortality, and it was significantly associated with coronary artery calcification, left ventricular hypertrophy and atherosclerosis in HD patients.     

Skin autofluorescence, a measure of cumulative metabolic stress and advanced glycation end products, predicts mortality in hemodialysis patients

Tissue advanced glycation end products (AGE) are a measure of cumulative metabolic stress and trigger cytokines driven inflammatory reactions. AGE are thought to contribute to the chronic complications of diabetes and ESRD. Tissue autofluorescence is related to the accumulation of AGE. Therefore, skin autofluorescence (AF) may provide prognostic information on mortality in hemodialysis (HD) patients. Skin AF was measured noninvasively with an AF reader at baseline in 109 HD patients. Overall and cardiovascular mortality was monitored prospectively during a period of 3 yr. The AF reader was validated against AGE contents in skin biopsies from 29 dialysis patients. Forty-two of the 109 (38.5%) HD patients died. Cox regression analysis showed that AF was an independent predictor of overall and cardiovascular mortality (for overall mortality odds ratio [OR] 3.9), as were pre-existing cardiovascular disease (CVD; OR 3.1), C-reactive protein (OR 1.1), and serum albumin (OR 0.3). Multivariate analysis revealed that 65% of the variance in AF could be attributed to the independent effects of age, dialysis and renal failure duration, presence of diabetes, triglycerides levels, and C-reactive protein. AF was also independently linked to the presence of CVD at baseline (OR 8.8; P < 0.001). AF correlated with collagen-linked fluorescence (r = 0.71, P < 0.001), pentosidine (r = 0.75, P < 0.001), and carboxy(m)ethyllysine (both r = 0.45, P < 0.01). Skin AF is a strong and independent predictor of mortality in ESRD. This supports a role for AGE as a contributor to mortality and CVD and warrants interventions specifically aimed at AGE accumulation.     

N-terminal pro brain natriuretic peptide predicts mortality in patients with end-stage renal disease in hemodialysis

Concentrations of N-terminal pro brain natriuretic peptide (NT-proBNP) increase in patients with heart failure and other cardiovascular (CV) diseases and are strong prognostic markers. In patients with end-stage renal disease (ESRD) in hemodialysis (HD), levels of NT-proBNP are almost always raised. In ESRD patients undergoing HD, we aimed at (i) identifying the factors that affect levels of NT-proBNP, (ii) determining the effect of HD on NT-proBNP, and (iii) determining the prognostic impact of NT-proBNP. A total of 109 patients underwent physical examination, electrocardiogram, and echocardiography. Serum NT-proBNP was measured before and after HD (Elecsys 2010). NT-proBNP levels were markedly elevated (pre-HD 4079 pg/ml, post-HD 2759 pg/ml, P<0.001). There was a strong inverse correlation between NT-proBNP and left ventricular ejection fraction (LVEF) (P=0.043), 24-h urine production (P=0.006), and K(t)/V (efficacy of dialysis) (P=0.016) and a positive correlation with left ventricular hypertrophy (LVH) (P=0.014). Patients with higher concentrations, both pre- and post-HD had an increased mortality rate compared to those with lower concentrations (P=0.007, P=0.002). We found age (P=0.009) and NT-proBNP (pre-HD P=0.007, post-HD P=0.001) predictive of death. Our findings demonstrate that CV disease in terms of LVH and reduced LVEF in addition to 24-h urine production and K(t)/V determine NT-proBNP levels. Post-HD levels of NT-proBNP were lower than pre-HD levels; both predictive of mortality.     

Hyperhomocysteinemia predicts cardiovascular outcomes in hemodialysis patients

BACKGROUND: We prospectively tested the prediction power of homocysteinemia for all-cause and cardiovascular outcomes in a cohort of 175 hemodialysis patients followed for 29 +/- 12 months. METHODS: Survival analysis was performed by the Cox's proportional hazard model and data were expressed as hazard ratio and 95% confidence interval (CI). RESULTS: During the follow-up period 51 patients died, 31 of them (61%) of cardiovascular causes and 16 patients developed non-fatal atherothrombotic complications. Plasma total homocysteine was an independent predictor of cardiovascular mortality (P=0.01). Combined analysis of fatal and non-fatal atherothrombotic events showed that homocysteine was a strong and independent predictor of these outcomes because the risk of these events was 8.2 times higher (95% CI 1.9 to 32.2) in patients in the third homocysteine tertile than in those in the first tertile (P=0.005). CONCLUSIONS: There is a clear association between hyperhomocysteinemia and incident cardiovascular mortality and atherothrombotic events in hemodialysis patients. Intervention studies are needed to determine whether the accumulation of this substance has a causal role in the pathogenesis of cardiovascular damage in patients undergoing hemodialysis.     

Interleukin-8 predicts 60-day mortality in premature infants with necrotizing enterocolitis

Objective

The purpose of this study was to evaluate the predictiveness of circulating interleukin (IL)-8 for 60-day mortality in premature infants with necrotizing enterocolitis (NEC).

Background

NEC affects up to 5% of premature infants and remains a leading cause of mortality among neonates.

Methods

A total of 113 infants with surgically (n = 50) or medically (n = 63) treated NEC were retrospectively analyzed. Laboratory parameters including serum IL-8 were assessed at the diagnosis of NEC and during the preoperative workup.

Results

The 60-day mortality was 19% (22/113), 10% (6/63) in medical and 33% (16/50) in surgical NEC. IL-8 levels significantly correlated with 60-day mortality (odds ratio: 1.38; CI 1.14–1.67; p = 0.001). Median IL-8 levels at diagnosis were significantly higher in neonates who were later treated surgically (median = 2625 pg/ml; range: 27–7500) compared with those treated medically (median = 156 pg/ml; range: 5–7500; p < 0.001). The AUC to discriminate between medical and surgical NEC was 0.82 (CI, 0.74–0.90), and an exploratory IL-8 cutoff point could be established at 1783 pg/ml (sensitivity of 90.5%; specificity of 59.2%).

Conclusions

Our findings that serum IL-8 (i) correlates directly with 60-day mortality and (ii) differs significantly between medically and surgically treated infants may change the process of therapeutic decision making in NEC.     

Iron,coronary artery calcification,and mortality in patients undergoing hemodialysis

ObjectiveA high coronary artery calcification score (CACS) may be associated with high mortality in patients undergoing hemodialysis (HD). Recently, effects of iron on vascular smooth muscle cell calcification have been described. We aimed to investigate the relationships between iron, CACS, and mortality in HD patients.MethodsWe studied 173 consecutive patients who were undergoing maintenance HD. Laboratory data and Agatston’s CACS were obtained at baseline for two groups of patients: those with CACS ≥400 (n = 109) and those with CACS <400 (n = 64). Logistic regression analyses for CACS ≥400 and Cox proportional hazard analyses for mortality were conducted.ResultsThe median (interquartile range) age and duration of dialysis of the participants were 67 (60–75) years and 73 (37–138) months, respectively. Serum iron (Fe) and transferrin saturation (TSAT) levels were significantly lower in participants with CACS ≥400 than in those with CACS <400, although the serum ferritin concentration did not differ between the groups. TSAT ≥21% was significantly associated with CACS ≥400 (odds ratio 0.46, p<0.05). TSAT ≥17%, Fe ≥63 µg/dL, and ferritin ≥200 ng/mL appear to protect against 5-year all-cause mortality in HD patients, independent of conventional risk factors of all-cause mortality (p < 0.05).ConclusionWe have identified associations between iron, CACS, and mortality in HD patients. Lower TSAT was found to be an independent predictor of CACS ≥400, and iron deficiency (low TSAT, iron, or ferritin) was a significant predictor of 5-year all-cause mortality in HD patients.     

Interleukin-6 modulates hepatic and muscle protein synthesis during hemodialysis

Increased demand for amino acids to sustain acute-phase protein synthesis could be the stimulus for the increased muscle protein catabolism during hemodialysis (HD). This could be attenuated by intradialytic amino-acid infusion. To test this, we measured the fractional synthesis rates of albumin, fibrinogen, and muscle protein in eight patients with end-stage renal disease at baseline before dialysis and during HD without or with amino-acid infusion. The percentage change in the fractional synthesis rates of albumin, fibrinogen, and muscle protein from baseline was significantly higher during HD with amino-acid infusion than without amino-acid infusion. Leg muscle proteolysis was significantly increased during unsupplemented HD compared with baseline, but this was not decreased by amino-acid infusion. Arteriovenous balance studies across the leg showed a net efflux of interleukin-6 (IL-6) from the muscle into the vein during HD. The fractional synthesis rate of albumin, fibrinogen, and muscle protein correlated with each other and with the IL-6 efflux from the leg. Leg muscle protein catabolism was positively related to IL-6 release from the leg and not associated with amino-acid availability. Our results show that intradialytic cytokine activation and not amino-acid depletion is the major protein catabolic signal during HD.     

Mitochondrial DNA injury and mortality in hemodialysis patients

The role of mitochondrial injury in the pathogenesis of complications of uremia is incompletely defined, although diminished bioenergetic capacity and the accumulation of mitochondrial DNA (mtDNA) mutations have been reported. This study was undertaken to evaluate the prevalence of mtDNA injury in 180 patients who had ESRD and were enrolled into the baseline phase of the HEMO study and to relate these markers to all-cause mortality. The mitochondrial injury markers studied in peripheral blood mononuclear cells were the mtDNA copy number per cell, measured by quantitative PCR, and the presence of the mtDNA(4977) mutation. After frequency-matching healthy control subjects for age, mtDNA copy number was lower among older dialysis patients compared with older healthy subjects (P = 0.01). A one-log increase in mtDNA copy number was independently associated with a decreased hazard for mortality (adjusted hazard ratio 0.64; 95% confidence interval 0.46 to 0.89). The mtDNA(4977) deletion was present in 48 (31%) patients and was independently associated with a decreased hazard for mortality (adjusted hazard ratio 0.33; 95% confidence interval 0.19 to 0.56). In summary, the mtDNA(4977) seems to predict survival in ESRD, but a reduced mitochondrial copy number seems to predict a poor outcome. Although further exploration of these associations is needed, evaluation of mitochondrial DNA copy number and somatic mtDNA mutations may provide simple genomic biomarkers to predict clinical outcomes among patients with ESRD.