Low Serum Albumin Concentration Research Articles

The Influence of Albumin Level in Critically Ill Children to Length of Stay and Mortality in Paediatric Intensive Care Unit.

BACKGROUND:The use of albumin in the critical care setting is a very controversial issue. Low serum albumin concentration in critical illness is associated with a poor outcome.AIM:We aimed to evaluate the influence of albumin level in critically ill children to the length of stay and mortality in the Pediatric Intensive Care Unit (PICU) Haji Adam Malik General Hospital, Medan, Indonesia.METHODS:The study used an observational method with a cross-sectional design. The population of the study was all patients with major postoperative surgery and critically ill that admitted to the PICU at Haji Adam Malik Hospital from the period of June 2008 to September 2008. The albumin level of the subjects was determined on the first day admitted.RESULTS:The group with hypoalbuminemia (< 3 g/dL) was given albumin supplementation according to a protocol in the PICU. The group with hypoalbuminemia have an average length of stay 7.6 days (9.7%) and mortality of 12 subjects (36.4%). The group with normal albumin level have 4.7 days (5.0%) and mortality 13 subjects (37.1%). There was no significant effect of albumin level to mortality.CONCLUSION:Albumin level did not affect the length of stay and mortality in PICU.

Magnesium and liver disease.

Magnesium is a vital cation that takes part in many cellular processes. Magnesium balance can be disturbed in multiple conditions, and differences in magnesium concentration can be responsible for numerous physiological and pathological processes. Magnesium deficiency is commonly associated with liver diseases, and may result from low nutrient uptake, greater urinary secretion, low serum albumin concentration, or hormone inactivation. In turn, low magnesium content in serum and liver tissue can lead to the progression of these diseases, due to a disruption in mitochondrial function, defective protein kinase C (PKC) translocation, inflammatory responses, oxidative stress, or metabolic disorders. Furthermore, magnesium supplementation can improve liver function in certain liver diseases. This paper comprehensively reviews the changes in magnesium concentrations associated with liver cirrhosis, alcoholic liver disease (ALD), liver cancer, and viral hepatitis, and explains how such changes may in turn impact these disease processes.

Influence of allochthonous organic matters on algae removal: Organic removal and floc characteristics

Algae are ubiquitous in surface water and affect the quality of surface water resources significantly by producing toxins as well as taste and odor compounds which adversely affect aquatic ecosystems and human health. This study was conducted to evaluate the effectiveness of three aluminum coagulants on algae removal by coagulation. Laboratory tests demonstrated that the maximum algae removal rates was 98.3% and 96.7% respectively by using PACl and Al13 as coagulants, while the maximum algae removal rate was 88.3% by using Al2(SO4)3 as coagulant at 0.1 mmol/L. According to the results, it also can be noticed that PACl and Al13 had a wide working pH range. In addition, the influence of allochthonous organic matters on algae removal during coagulation was also discussed. The removal rate was increased with a low bovine serum albumin (BSA) concentration owing to improving the adsorption-bridging. A poor coagulation performance was observed with the increasing of BSA dosage since the excess BSA molecules may prevent molecules from approaching and seize the active sites, causing coagulation inhibited. The addition of humic acid (HA) and sodium alginate (NaAlg) had adverse effects on the removal of turbidity and algae, attributed to the preferentially reaction between negative functional groups in HA/NaAlg and coagulant. Thick flocs were formed with the increasing of allochthonous organic matters as the calculation results of fractal dimension (Df). According to high pressure size exclusion chromatography (HPSEC) and three-dimensional fluorescence excitation-emission matrix spectrometry (3D-EEMs), allochthonous organic matter with high molecular weight (MW) can be completely removed, while the organics with low MW regardless of its origin were difficult to remove.

Characterization of Kcnk3-Mutated Rat, a Novel Model of Pulmonary Hypertension.

Pulmonary arterial hypertension is a severe lethal cardiopulmonary disease. Loss of function mutations in KCNK3 (potassium channel subfamily K member 3) gene, which encodes an outward rectifier K+ channel, have been identified in pulmonary arterial hypertension patients. We have demonstrated that KCNK3 dysfunction is common to heritable and nonheritable pulmonary arterial hypertension and to experimental pulmonary hypertension (PH). Finally, KCNK3 is not functional in mouse pulmonary vasculature. Using CRISPR/Cas9 technology, we generated a 94 bp out of frame deletion in exon 1 of Kcnk3 gene and characterized these rats at the electrophysiological, echocardiographic, hemodynamic, morphological, cellular, and molecular levels to decipher the cellular mechanisms associated with loss of KCNK3. Using patch-clamp technique, we validated our transgenic strategy by demonstrating the absence of KCNK3 current in freshly isolated pulmonary arterial smooth muscle cells from Kcnk3-mutated rats. At 4 months of age, echocardiographic parameters revealed shortening of the pulmonary artery acceleration time associated with elevation of the right ventricular systolic pressure. Kcnk3-mutated rats developed more severe PH than wild-type rats after monocrotaline exposure or chronic hypoxia exposure. Kcnk3-mutation induced a lung distal neomuscularization and perivascular extracellular matrix activation. Lungs of Kcnk3-mutated rats were characterized by overactivation of ERK1/2 (extracellular signal-regulated kinase1-/2), AKT (protein kinase B), SRC, and overexpression of HIF1-α (hypoxia-inducible factor-1 α), survivin, and VWF (Von Willebrand factor). Linked with plasma membrane depolarization, reduced endothelial-NOS expression and desensitization of endothelial-derived hyperpolarizing factor, Kcnk3-mutated rats presented predisposition to vasoconstriction of pulmonary arteries and a severe loss of sildenafil-induced pulmonary arteries relaxation. Moreover, we showed strong alteration of right ventricular cardiomyocyte excitability. Finally, Kcnk3-mutated rats developed age-dependent PH associated with low serum-albumin concentration. We established the first Kcnk3-mutated rat model of PH. Our results confirm that KCNK3 loss of function is a key event in pulmonary arterial hypertension pathogenesis. This model presents new opportunities for understanding the initiating mechanisms of PH and testing biologically relevant therapeutic molecules in the context of PH.

Population pharmacokinetics of total and unbound concentrations of intravenous posaconazole in adult critically ill patients

BackgroundThe population pharmacokinetics of total and unbound posaconazole following intravenous administration has not yet been described for the critically ill patient population. The aim of this work was, therefore, to describe the total and unbound population pharmacokinetics of intravenous posaconazole in critically ill patients and identify optimal dosing regimens.MethodsThis was a prospective observational population pharmacokinetic study in critically ill adult patients with presumed/confirmed invasive fungal infection. A single dose of 300 mg posaconazole was administered intravenously as an add-on to standard antifungal therapy, and serial plasma samples were collected over 48 h. Total and unbound posaconazole concentrations, measured by chromatographic method, were used to develop a population pharmacokinetic model and perform dosing simulations in R using Pmetrics.ResultsFrom eight patients, 93 pairs of total and unbound concentrations were measured. A two-compartment linear model with capacity-limited plasma protein binding best described the concentration-time data. Albumin and body mass index (BMI) were included as covariates in the final model. Mean (SD) parameter estimates for the volume of the central compartment (V) and the elimination rate constant were 72 (43) L and 42.1 (23.7) h−1, respectively. Dosing simulations showed that high BMI was associated with a reduced probability of achieving target total and unbound posaconazole concentrations. Low serum albumin concentration was associated with a reduced probability of attaining target total but not unbound posaconazole concentrations.ConclusionsAn important clinical message of this study is that critically ill patients with increased BMI may require larger than approved loading doses of intravenous posaconazole when considering currently recommended dosing targets. Variability in plasma albumin concentration appears unlikely to affect dosing requirements when the assessment is based on unbound concentrations. Where available, therapeutic drug monitoring of unbound concentrations may be useful.

Closed Fracture Diagnosed by Bedside Ultrasonography During Hemodialysis: A Report of Seven Cases and Relevant Clinical Characteristics.

Patients undergoing dialysis have a high incidence of fracture, and early diagnosis is important. We report seven cases of closed rib or upper-limb fractures diagnosed by bedside ultrasonography during maintenance hemodialysis sessions and describe relevant clinical characteristics. We identified seven patients who were injured by falls in their homes. No injuries occurred on the day of dialysis. Five of the 7 patients did not visit the emergency room. All patients complained of persistent unexplained pain during a regular hemodialysis session. Ultrasonography (US) was performed during dialysis sessions, without any reports of pain. Before US evaluation, the sensitivity of radiography for diagnosis of fracture was 25%, while the sensitivity of US was 100%. Compared with other patients in our clinic, these patients were significantly older and had lower serum albumin concentrations and lower hemodialysis efficiency as determined by Kt/V. They also had a higher incidence of diabetes and a greater need for vasopressors during dialysis. These findings were consistent with the results of previous studies of the characteristics of fractures in dialysis patients. However, blood levels of creatinine, corrected calcium, phosphate, intact parathyroid hormone, and hemoglobin, as well as bone density and blood pressure, after the previous dialysis session were not different. To our knowledge, this is the first report of closed fracture of superficial bone diagnosed by bedside ultrasonography during a hemodialysis session. Ultrasonography is especially useful for diagnosis in these cases because it is noninvasive and highly accurate. Doctors should determine the differential diagnosis for closed fracture in patients undergoing dialysis, especially in those who are older, have diabetes, and are malnourished, and in those with recent contusions and persistent pain.

Predictive risk factors for exudative retinal detachment after vitrectomy for proliferative diabetic retinopathy.

This retrospective study investigated the risk factors of exudative retinal detachment (ERD) occurring after vitrectomy performed to treat proliferative diabetic retinopathy (PDR).All patients were treated with vitrectomy for PDR. Patients with history(s) of the following were excluded: ocular surgery (except phacoemulsification combined with intraocular lens implantation or retinal laser photocoagulation); ocular trauma; systemic diseases; ocular diseases; uveitis; scleritis; tumor; congenital ocular disorders; or others.Included were 205 eyes of 169 patients, of whom 18 (8.78%) developed ERD with varying degrees of exudative choroidal detachment after 1 to 3 days. Binary logistic regression showed the following association with the development of ERD: lower serum albumin concentration (P = .001); without intravitreal anti-vascular endothelial growth factor (anti-VEGF) drug injection before vitrectomy (P = .044); and history of phacoemulsification combined with intraocular lens implantation (P = .046). No association was found with gender; age; systolic pressure; diastolic pressure; panretinal photocoagulation; intraocular pressure on the 1st postoperative day; intraocular pressure on the 2nd postoperative day; serum albumin concentration; or blood urea nitrogen.Risk factors for ERD after vitrectomy for PDR include low serum albumin concentration, without history of intravitreal anti-VEGF drug injection before surgery, and a history of phacoemulsification combined with intraocular lens implantation.

Serum Albumin and Future Risk of Hip, Humeral, and Wrist Fractures in Caucasian Men: New Findings from a Prospective Cohort Study

Objective: Low serum albumin concentration is associated with poor health outcomes, but its relationship with the risk of fractures has not been reliably quantified. We aimed to assess the prospective association of serum albumin with the risk of fractures in a general population. Subjects and Methods: Baseline serum albumin concentrations were measured in 2,245 men aged 42–61 years in the Kuopio Is­chemic Heart Disease study. Hazard ratios (HRs) (95% confidence intervals) were calculated for incident fractures. Results: A total of 121 fractures (hip, humeral, or wrist) were recorded during a median follow-up of 25.6 years. The risk of fractures increased linearly below a serum albumin concentration of ∼48 g/L. The age-adjusted HR (95% CI) for fractures per 1 standard deviation lower serum albumin was 1.24 (1.05–1.48). On further adjustment for several conventional and emerging risk factors, the HR was attenuated to 1.21 (1.01–1.45). Comparing the bottom versus top quartile of serum albumin levels, the corresponding adjusted HRs were 2.48 (1.37–4.48) and 2.26 (1.23–4.14). The association of serum albumin with fracture risk did not differ substantially according to age, body mass index, blood pressure, physical activity, alcohol consumption, socioeconomic status, inflammation, prevalent diseases, and smoking. Serum albumin at a threshold of 41.5 g/L demonstrated an area under the curve of 0.5850. Conclusion: In middle-aged Caucasian men, low serum albumin is associated with an increased risk of future fractures. The potential relevance of serum albumin concentrations in fracture prevention and prediction deserves further evaluation.

The Effect of Acidosis on Albumin Level in Patients Treated With Regular Hemodialysis (Single Center Study)

BACKGROUND: Hypoalbuminemia is the most powerful predictor of mortality in end-stage renal disease on hemodialysis. Metabolic acidosis induces net negative nitrogen and total body protein balance. Some patients undergoing maintenance dialysis have low plasma bicarbonate levels due to inadequate dialysis. We aimed to evaluate the role of metabolic acidosis on serum albumin concentration in patients with end stage renal disease on hemodialysis, and to determine differences of serum bicarbonate level before and after hemodialysis in actual situation. &#x0D; &#x0D; METHODS: This cross sectional comparative study was conducted in the Iraqi Center for Hemodialysis/ Baghdad Teaching Hospital from June to December 2015. It included 100 subjects with end stage renal disease on hemodialysis. They were divided equally into cases with low albumin and comparison group with normal albumin level. Serum bicarbonate and the Kt/V were measured for all subjects before, after, and before next hemodialysis session to show the adequacy of dialysis.&#x0D; &#x0D; RESULTS: There was a significant association between low bicarbonate and low albumin level in hemodialysis patient and between numbers and duration of dialysis session with albumin. Low Kt/V was significantly associated with hypoalbuminemia. There was no statistically significant association between age and gender with hypoalbuminemia.&#x0D; &#x0D; CONCLUSION: This study shows that patients with metabolic acidosis had a lower serum albumin concentration and there was a significant correlation between numbers, duration and adequacy of hemodialysis sessions and albumin level. We recommend to increase the numbers of dialysis centers in Iraq and adjust the bicarbonate doses in dialysate according to patient&amp;rsquo;s bicarbonate levels.

Relationship of muscle cramps to quality of life and sleep disturbance in patients with chronic liver diseases: A nationwide study.

Although muscle cramps frequently occur in patients with cirrhosis, the importance of muscle cramps remains unclear. The aims of this study were to investigate the relationship of muscle cramps with quality of life (QOL) and sleep disturbance. In addition, this multi-institutional collaborative study in Japan investigated factors associated with muscle cramps in patients with cirrhosis. A total of 1788 patients with chronic liver diseases including both non-cirrhosis and cirrhosis completed a questionnaire survey investigating: (i) frequency of muscle cramps, (ii) relationship of muscle cramps to poor QOL and sleep disturbance, (iii) characteristics of patients who require therapeutic intervention and (iv) characteristics of patients prone to experiencing muscle cramps. This study revealed that 51.8% of patients with cirrhosis have experienced muscle cramps. People who experienced muscle cramps were more likely to have reduced QOL and sleep disturbance if muscle cramps had (i) high frequency (occurring daily to a few times per week, P<.01); (ii) long duration (between a few minutes and a few hours, P<.01) and (iii) intense severity (visual analogue scale ≥4, P<.01). Age, female sex, positive results for hepatitis C virus, low serum albumin concentration, and cirrhosis were independent factors related to the severity of muscle cramps. Muscle cramps occurred with great frequency and were associated with various factors such as age, sex, hepatitis C virus and liver function. Many patients experience poor QOL (26.3%) due to muscle cramps, and therapeutic interventions are therefore needed.

Association of low serum albumin concentration with reduced overall survival for patients with metastatic head and neck cancer receiving anti-programmed death receptor-1 therapy.

6057Background: Immunotherapy efficacy is modulated by immune competence which lacks well established clinical measures. Nutritional status influences immune competence and has been associated with...

Serum albumin concentration as an independent prognostic indicator in patients with pulmonary arterial hypertension.

Serum albumin is a strong prognostic indicator for many disease processes, yet limited data exist regarding its prognostic relationship in pulmonary arterial hypertension (PAH). Our study aims to assess the relationship of hypoalbuminemia with disease severity and mortality in this population. Serum albumin concentrations are a predictor of outcomes in PAH. A retrospective review of all patients with World Health Organization group 1 PAH evaluated between March 2001 and August 2008 was performed. Patients were stratified into groups based on serum albumin concentration ≤3.3 g/dL (hypoalbuminemia) vs >3.3 g/dL. Clinical, hemodynamic, and survival comparisons were compared between groups using Student t test and χ2 test, followed by univariate analysis and multivariate logistic regression. A total of 163/273 (59.7%) patients had a documented serum albumin concentration. Hypoalbuminemia was present in 41 (25.2%) patients and serum albumin ≤3.3 g/dL represented the lowest quartile of serum albumin. Patients with hypoalbuminemia had higher rates of renal dysfunction (26.8% vs 9.8%, P =0.0069) and hepatic dysfunction (29.3% vs 6.6%, P <0.001), and lower hemoglobin levels (11.6 vs 13.4 g/dL, P < 0.001). Hemodynamic and functional capacity assessments were comparable between groups. Independent predictors of mortality included low albumin levels (hazard ratio [HR]: 0.485, P = 0.008), high right atrial systolic area (HR: 1.062, P = 0.003), low Fick-derived cardiac index (HR: 1.465, P = 0.016), and high New York Heart Association functional class (HR: 1.767, P = 0.042). Patients with hypoalbuminemia demonstrated a significantly lower survival rate at latest follow-up (P = 0.01). Lower serum albumin concentrations in patients with PAH are associated with higher mortality and can serve as a marker of disease severity in this patient population.

Clinical Response and Complications are not Associated with Drug Levels in Patients with Severe Ulcerative Colitis on IV Cyclosporine Induction Therapy.

IV ciclosporin therapy is effective in steroid-refractory ulcerative colitis. The optimal drug level to achieve response and minimize complications during induction therapy is not known. The primary aim was to evaluate if serum ciclosporin drug levels are associated with increased risk of colectomy within 90 days of hospitalization. Secondary aims were to determine if ciclosporin levels are associated with avoidance of colectomy at 7 and 30 days, if ciclosporin levels are associated with drug-related and postoperative complications, and if patient-specific factors are associated with response to ciclosporin. We conducted a retrospective analysis of 81 hospitalized patients with steroid-refractory ulcerative colitis treated with ciclosporin. Risk factors for colectomy within 7, 30, and 90 days, medication-specific and postoperative complications were compared by first, mean, and peak ciclosporin level during IV induction therapy. There were 47 patients (58%) who underwent surgery. There were no differences between initial, mean, and peak ciclosporin levels among responders and nonresponders and treatment-related or postoperative complications. Responders within 90 days had lower C-reactive-protein levels (20mg/L vs. 38mg/L, P = 0.01), lower serum albumin concentrations (3.4g/dL vs. 3.7g/dL, P = 0.03), and higher rates of kidney injury (50% vs 17%, P = 0.002). Initial, mean, and peak serum levels of ciclosporin did not correlate with response or toxicity. However, C-reactive-protein levels levels and kidney injury may be helpful in predicting clinical response to ciclosporin.

“When is Glutamine Supplementation Beneficial?”

The role of glutamine in metabolic processes has been quite extensively researched and described, though no consensus exists as to its role in treatment. It is considered significant mainly for ICU patients; though no clear criteria for including glutamine in treatment have been defined. It is known that glutamine should be administered as a complement to nutritional treatment, and not independently. The purpose of the paper was to identify practical criteria for determining the clinical benefits of glutamine supplementation. The study was performed in the years 2007-2015 at the 1st Department of General and Transplantation Surgery and Nutritional Therapy of the Lublin Medical University in Lublin, Poland. It included patients scheduled for surgery due to a gastrointestinal cancer. The final study group included 105 patients, 48 female and 57 male. We found that low blood concentration of glutamine was correlated with a higher incidence of postoperative complications. ROC analysis allowed for identification of glutamine concentration below which there is a very high risk of complications. The threshold glutamine value identified was 205.15 nmol/ml. Low total lymphocyte count and serum albumin concentration can help identify patients in whom glutamine supplementation can decrease postoperative complication incidence, especially in the case of malnourished patients. Glutamine supplementation before a scheduled surgical procedure may benefit patients with a preoperative glutamine concentration below 205.15 nmol/ml. Glutamine supplementation can benefit malnourished patients.

Serum albumin concentration and risk of end-stage renal disease: the REGARDS study.

Serum albumin concentration is a commonly available biomarker with prognostic value in many disease states. It is uncertain whether serum albumin concentrations are associated with incident end-stage renal disease (ESRD) independently of urine albumin-to-creatinine ratio (ACR). A longitudinal evaluation was performed of a population-based community-living cohort from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study. Participants were ≥45 years of age at study entry and had serum albumin, creatinine, cystatin C and spot urine ACR measured at the baseline visit (n = 19633). Estimated glomerular filtration rate (eGFR) was from the Chronic Kidney Disease Epidemiology Collaboration combined creatinine-cystatin C equation. Baseline serum albumin concentration was the predictor variable, and hazard ratios (HRs) for incident ESRD (from US Renal Data System linkage) were calculated in sequentially adjusted models. Age at study entry was 63.9 ± 9.7 years, 62% of the participants were female and 40% were black. Mean eGFR at baseline was 83.3 ± 20.8 mL/min/1.73 m2. Over a median 8-year follow-up, 1.2% (n = 236) developed ESRD. In models adjusted for baseline eGFR, ACR and other ESRD risk factors, the HR for incident ESRD was 1.16 [95% confidence interval (CI) 1.01-1.33] for each standard deviation (0.33 g/dL) lower serum albumin concentration. The HR comparing the lowest (<4 g/dL) and highest quartiles (≥4.4 g/dL) of serum albumin was 1.61 (95% CI 0.98-2.63). Results were qualitatively similar among participants with eGFR <60 and ≥60 mL/min/1.73 m2, and those with and without diabetes. In community-dwelling US adults, lower serum albumin concentration is associated with higher risk of incident ESRD independently of baseline urine ACR, eGFR and other ESRD risk factors.

Pharmacokinetics of Cabotegravir in Subjects with Moderate Hepatic Impairment

BackgroundCabotegravir (CAB) is an integrase inhibitor in phase 3 clinical trials for the treatment and prevention of HIV. CAB undergoes hepatic metabolism primarily via UGT1A1; thus hepatic impairment has the potential to affect CAB exposure.MethodsThis was a multi-center, single-dose, open-label, parallel group study to evaluate the effect of moderate hepatic impairment on the pharmacokinetics (PK) and safety of CAB. Adults with moderate hepatic impairment as determined by Child-Pugh classification score of 7–9 (n = 8) and matched healthy control subjects (n = 8) were enrolled. Control subjects were matched for gender, age (±10 years), and body mass index (BMI) (±25%). Subjects received oral CAB 30 mg as a single dose in the fasted state followed by serial PK sampling for 168 hours. CAB unbound concentrations at 2 and 24 hours after dosing were determined by equilibrium dialysis. Non-compartmental PK analysis was performed; geometric least squares (GLS) mean ratios (hepatic impaired group/control group) and 90% confidence intervals (CI) were generated.ResultsSixteen subjects completed study; 12 (75%) male, mean age 59 years (range: 51–67), mean BMI 29 kg/m2 (range: 21–37), and total Child Pugh score in range of 7–9. CAB PK parameters were similar between subjects with moderate hepatic impairment and matched healthy subjects. The GLS mean ratios (90% CI) for AUC(0-∞), Cmax, C24, CL/F, and t1/2 were 0.73 (0.50, 1.06), 0.69 (0.51, 0.93), 0.73 (0.53, 1.02), 1.38 (0.95, 2.01), and 0.82 (0.65, 1.04), respectively. Although highly protein bound, the unbound fraction of CAB was increased in subjects with moderate hepatic impairment relative to healthy subjects with GLS mean ratio (90%CI) of 2.14 (1.57, 2.90) at 2 hours post dose and 1.90 (1.14, 3.18) at 24 hours post dose; this was associated with lower serum albumin concentrations and was not considered clinically significant. All adverse events (AE) were reported as mild (Grade 1) to moderate (Grade 2) in severity and no serious AEs were reported.ConclusionPlasma exposures of CAB in subjects with moderate hepatic impairment were similar to those in healthy subjects. No dose adjustment of CAB is required for subjects with mild to moderate hepatic impairment.Disclosures J. S. Shaik, GlaxoSmithKline: Employee and Shareholder, Salary; S. Ford, PAREXEL International: Employee, Salary; Y. Lou, PAREXEL International: Employee, Salary; Z. Zhang, PAREXEL International: Employee, Salary; K. Bakshi, GlaxoSmithKline: Employee and Shareholder, Salary; A. Tenorio, ViiV Healthcare: Employee and Shareholder, Salary; C. Trezza, ViiV Healthcare: Employee and Shareholder, Salary; W. Spreen, ViiV Healthcare: Employee and Shareholder, Salary; P. Patel, ViiV Healthcare: Employee and Shareholder, Salary

Association of serum albumin levels with kidney function decline and incident chronic kidney disease in elders.

Previous studies in HIV-infected individuals have demonstrated serum albumin to be strongly associated with kidney function decline, independent of urine albumin and inflammatory markers. Lower serum albumin concentrations may be an under-appreciated risk factor for kidney function decline in elders. We performed a cohort analysis in the Health Aging and Body Composition Study, a cohort of well-functioning, bi-racial, community-dwelling elders between the age of 70 and 79 years. We examined the associations of serum albumin concentration with longitudinal kidney function decline by estimated glomerular filtration rate (eGFR). Outcomes included linear eGFR decline, rapid kidney function decline defined as >30% decrease in eGFR, defined as a final eGFR <60 mL/min/1.73 m2 in those with an eGFR >60 mL/min/1.73 m2 at baseline. Cystatin C-based eGFR was calculated at baseline, Year 3 and Year 10. Mean age was 74 years, and mean eGFR was 73 mL/min/1.73 m2 at baseline. The mean rate of eGFR change was 1.81 mL/min/1.73 m2 per year. After multivariate adjustment, lower serum albumin concentrations were strongly and independently associated with kidney function decline (-0.11 mL/min/1.73 m2 per year for each standard deviation decrease serum albumin; -0.01 to - 0.20) with no attenuation after adjustment for urine albumin and inflammatory markers (-0.12, -0.03 to - 0.22). When divided into quartiles, serum albumin levels ≤3.80 g/dL were associated with increased odds of rapid kidney function decline (odds ratio 1.59; 1.12-2.26) and increased risk of incident chronic kidney disease (incident rate ratio 1.29; 1.03-1.62) relative to levels >4.21g/dL. Urine albumin to creatinine ratio (ACR) was also significantly and independently associated with kidney function decline (-0.08 mL/min/1.73 m2 per year for urine ACR >30 mg/g; -0.82 to - 0.13). Lower serum albumin levels are strongly and independently associated with kidney function decline in elders, independent of clinical risk factors, urine albumin and measured inflammatory markers.

Prognostic Significance of Preoperative Controlling Nutritional Status (CONUT) Score in Patients Undergoing Hepatic Resection for Hepatocellular Carcinoma.

The Controlling Nutritional Status (CONUT) score is an objective tool widely used to assess nutritional status in patients with inflammatory disease, chronic heart failure, and chronic liver disease. The relationship between CONUT score and prognosis in patients who have undergone hepatic resection, however, has not been evaluated. Data were retrospectively collected for 357 consecutive patients with hepatocellular carcinoma (HCC) who had undergone hepatic resection with curative intent between January 2004 and December 2015. The patients were assigned to two groups, those with preoperative CONUT scores ≤3 (low CONUT score) and >3 (high CONUT score), and their clinicopathological characteristics, surgical outcomes, and long-term survival were compared. Of the 357 patients, 69 (19.3%) had high (>3) and 288 (80.7%) had low (≤3) preoperative CONUT scores. High CONUT score was significantly associated with HCV infection, low serum albumin and cholesterol concentrations, low lymphocyte count, shorter prothrombin time, Child-Pugh B and liver damage B scores, and blood transfusion. Multivariate analysis identified six factors prognostic of poor overall survival (older age, liver damage B score, high CONUT score, poor tumor differentiation, the presence of intrahepatic metastases, and blood transfusion) and five factors prognostic of reduced recurrence-free survival (older age, higher ICGR15, larger tumor size, presence of intrahepatic metastasis, and blood transfusion). In patients with HCC, preoperative CONUT scores are predictive of poorer overall survival, even after adjustments for other known predictors.

Risk factors for wound complications and 30-day mortality after major lower limb amputations in patients with peripheral arterial disease.

Purpose Risk factors for wound complications or 30-day mortality after major amputation in patients with peripheral arterial disease remain unclear. We investigated the outcomes of major amputation in patients with peripheral arterial disease. Methods Patients who underwent major amputation from 2008 to 2015 were retrospectively analyzed. The main outcome measures were risk factors for wound complications and 30-day mortality after major lower limb amputations. Major amputation was defined as above-knee amputation or below-knee amputation. Wound complications were defined as surgical site infection or wound dehiscence. Results In total, 106 consecutive patients underwent major amputation. The average age was 77.3 ± 11.2 years, 67.9% of patients had diabetes mellitus and 35.8% were undergoing hemodialysis. Patients who underwent primary amputation constituted 61.9% of the cohort, and the proportions of above-knee amputation and below-knee amputation were 66.9% and 33.1%, respectively. The wound complication rate was 13.3% overall, 10.3% in above-knee amputation, and 19.5% in below-knee amputation. Multivariate analysis showed that the risk factors for wound complications were female sex (hazard ratio, 4.66; 95% confidence interval, 1.40-17.3; P = 0.01) and below-knee amputation (hazard ratio, 4.36; 95% confidence interval, 1.20-17.6; P = 0.03). The 30-day mortality rate was 7.6%, pneumonia comprised the most frequent cause of 30-day mortality, followed by sepsis and cardiac death. Multivariate analysis showed that a low serum albumin concentration (hazard ratio, 3.87; 95% confidence interval, 1.12-16.3; P = 0.03) was a risk factor for 30-day mortality. Conclusions Female sex and below-knee amputation were risk factors for wound complications. A low serum albumin concentration was a risk factor for 30-day mortality after major amputation in Japanese patients with peripheral arterial disease.

Variability in Trough Total and Unbound Teicoplanin Concentrations and Achievement of Therapeutic Drug Monitoring Targets in Adult Patients with Hematological Malignancy.

The objective of this study was to explore the following aspects of teicoplanin use in patients with hematological malignancy: early attainment of target trough concentrations with current high-dose teicoplanin regimens, variability in unbound teicoplanin fractions, factors associated with observed total and unbound trough concentrations, efficacy and toxicity, and renal function estimation. This was a single-center, prospective study. Samples for determination of trough concentrations were taken on days 3, 4, 7, and 10. Total and unbound teicoplanin concentrations were determined using validated high-performance liquid chromatography methods. Regression analyses were used to identify the factors associated with the trough concentration. Thirty teicoplanin-treated adults with hematological malignancy were recruited. Despite the use of dosages higher than the conventional dosages, the proportions of patients with a trough concentration of ≥20 mg/liter at 48 h and at 72 h were 16.7% and 37.9%, respectively. Renal function was significantly negatively associated with total trough concentrations at 48 h and 72 h (P < 0.05). For an average hematological malignancy patient (creatinine clearance = 70 ml/min), sequential loading doses of at least 12 mg/kg of body weight may be needed to achieve early adequate exposure. In the absence of measured creatinine clearance, estimates obtained using the Cockcroft-Gault (total body weight) equation could prove to be an acceptable surrogate. The unbound fractions of teicoplanin were highly variable (3.4 to 18.8%). Higher unbound fractions were observed in patients with low serum albumin concentrations. Teicoplanin was well tolerated. Teicoplanin loading doses higher than those in current use appear to be necessary. Increased dosing is needed in patients with increased renal function. The high variability in protein binding supports the contention for therapeutic drug monitoring of unbound teicoplanin concentrations. (This study has been registered with EudraCT under registration no. 2013-004535-72.).