Reduced serum albumin as a risk factor for poor prognosis in critically ill patients receiving renal replacement therapy.

BACKGROUND: Albumin is the primary body protein, which can predict the poor prognosis of several critical diseases. However, there are a few scientific studies on the relationship between albumin and the prognosis of dialysis patients. This study aims to explore the impact of hypoalbuminemia on the prognosis of critically ill patients with acute kidney injury (AKI) receiving continuous renal replacement therapy (CRRT). METHODS: This was a secondary study. Clinical, biochemical, and 28-day and 90-day mortality rates for critical patients with AKI who received CRRT between 2009 and 2016 were searched from the database to determine the effect of hypoalbuminemia on poor outcomes by univariate, multivariate, smooth curve fitting, and subgroup analysis. RESULTS: A total of 837 participants were enrolled in this study. Multivariate Cox proportional hazard regression analysis showed that hypoalbuminemia was associated with both 28-day and 90-day mortality risks after full adjustment for confounding variables, with an adjusted hazard ratio (95% confidence interval) of 0.63 (0.50-0.80) and 0.63 (0.51-0.78), respectively for each 1 g/dL increase of albumin. Stratified analysis showed that hypoalbuminemia was not associated with poor prognosis in oliguria. CONCLUSION: Hypoalbuminemia is associated with poor prognosis in critically ill AKI patients with CRRT; therefore, measuring albumin may be helpful for predicting the prognosis. However, in those with oliguria, this conclusion is not valid.

Low albumin level and longer interval to closure increase the early complications after ileostomy closure.

BACKGROUND: Loop ileostomy has an important role in mitigating the serious effects of anastomotic leakage in colorectal surgery. However, the morbidity and mortality associated with ileostomy reversal cannot be overlooked. We investigated the possible risk factors for complications following ileostomy reversal. METHODS: All patients who underwent loop ileostomy closure between 2008 and 2017 at Inje University Busan Paik Hospital were identified. Medical records on patient characteristics, preoperative management, surgical techniques, postoperative management, chemotherapy/radiotherapy, and complications were retrospectively analyzed in a prospectively collected database. RESULTS: A total of 354 patients underwent loop ileostomy closure. The overall complication rate was 23.7%, with Clavien-Dindo grade I as the most common (15.8%), 5.6% in grade II, 2.2% in grade III-V, and three patients died. The two most common complications were wound infection (11.6%) and small bowel obstruction (4.8%). In univariable and multivariable analyses, closure technique or chemotherapy did not affect the outcome, but low serum albumin <3.5 g/dL (OR 7.248, CI 2.416-22.838, p < 0.001) and longer interval to ileostomy closure (OR 1.977, CI 1.167-3.350, p = 0.0113) were independent contributing factors for morbidities of ileostomy closure. CONCLUSIONS: Closure technique or chemotherapy did not affect the complication of ileostomy closure. However, serum albumin <3.5 g/dL and a longer interval to ileostomy closure were identified as risk factors for morbidity of ileostomy closure. These two factors should be corrected and planned before ileostomy closure.

Systematic review and meta-analysis of risk factor for postoperative delirium following spinal surgery.

BACKGROUND: Postoperative delirium is a common psychiatric disorder among patients who undergo spinal surgery. The purpose of current meta-analysis was to assess the potential risk factors related to delirium in spinal surgery. METHODS: We searched the following databases: PubMed, EMBASE, the Cochrane Library, and Web of Science, from inception to July 2020. Two reviewers independently assessed the quality of the included studies using the previously described Newcastle-Ottawa Scale (NOS). We included spinal surgery patients who suffered with delirium or not. Stata 12.0 was used for meta-analysis. RESULTS: Thirteen trial studies that met our inclusion criteria were incorporated into the meta-analysis. Postoperative delirium was associated with an increase of the duration of hospital stay (P = 0.044) and increased perioperative readmission rate (P = 0.013) and economic costs (P = 0.002). This meta-analysis demonstrates that there were twenty-two risk factors: general characteristic: old age, female patients, history of surgery, diabetes mellitus, hypertension; preoperative data: low hematocrit, low hemoglobin, low albumin, low sodium, depression; operative data: operating time, total blood loss; postoperative data: low sodium, low hemoglobin, low hematocrit, low albumin, fever, low potassium, blood sugar, and visual analog scale (VAS). CONCLUSIONS: Delirium not only prolongs the length of hospital stay, but also increases readmission rate and the economic costs. Several risk factors including old age, female patients, history of surgery, diabetes mellitus, low hematocrit, low hemoglobin, low albumin, low sodium, depression; operative data: operating time, total blood loss, low sodium, low hemoglobin, low hematocrit, low albumin, fever, low potassium, blood sugar, and VAS were significant predictors for postoperative delirium after spinal surgery.

A Clinical Tool to Predict Low Serum Selenium in Patients with Worsening Heart Failure.

Selenium is an essential micronutrient, and a low selenium concentration (<100 µg/L) is associated with a poorer quality of life and exercise capacity, and an impaired prognosis in patients with worsening heart failure. Measuring selenium concentrations routinely is laborious and costly, and although its clinical utility is yet to be proven, an easy implemented model to predict selenium status is desirable. A stepwise multivariable logistic regression analysis was performed using routinely measured clinical factors. Low selenium was independently predicted by: older age, lower serum albumin, higher N-terminal pro-B-type natriuretic peptide levels, worse kidney function, and the presence of orthopnea and iron deficiency. A 10-points risk-model was developed, and a score of ≥6 points identified >80% of patients with low selenium (sensitivity of 44%, specificity of 80%). Given that selenium and iron overlap in their physiological roles, we evaluated the shared determinants and prognostic associates. Both deficiencies shared similar clinical characteristics, including the model risk factors and, in addition, a low protein intake and high levels of C-reactive protein. Low selenium was associated with a similar or worse prognosis compared to iron deficiency. In conclusion, although it is difficult to exclude low selenium based on clinical characteristics alone, we provide a prediction tool which identifies heart failure patients at higher risk of having a low selenium status.

Vitamin D, calcium and albumin bloodserum levels in Belgian orthopedic patients - is systematic screening justified?

In the setting of fracture care, orthopedic surgeons are primarily focused on treating the fracture itself, but more and more attention is being paid to prevention of such fractures and identifying risk factors associated with worse postoperative prognoses. In our study we collected postoperative vitamin D, calcium and albumin bloodserum levels from 163 patients who were admitted with a femur fracture and from 233 patients who were admitted for an elective hip arthroplasty during the period of 365 days. Results : 84.21% of the fracture population had a vitamin D deficiency (< 20 ng/mL) as well as 77.30% of the elective hip arthroplasty population. There were no significant seasonal differences in the fracture population. 80.27% of the fracture population had an albumin deficiency (< 29 g/L) compared to 38.75% of the reference population. There were no significant statistical differences in vitamin D and albumin bloodserum levels between the under 75 years old age group and the over 75 years old age group. We can make the tentative assumption that systematic screening for all hip fracture patients and all elective hip arthroplasty patients admitted to our orthopedic ward - independent of their age, season or pathology - is justified and we advise other hospitals to implement this as well.

Investigating the Impact of Albumin on the Liver Uptake of Pitavastatin and Warfarin in Nagase Analbuminemic Rats.

Albumin has been suggested to enhance the hepatic uptake of organic anion-transporting polypeptide (Oatp) substrates in various in vitro as well as liver perfusion models. However, it is not known whether the interplay between albumin and Oatp substrates is an experimental artifact or if this interaction occurs in vivo. The objective of this work was to investigate the hepatic uptake of warfarin and pitavastatin, which are both extensively bound to albumin but only pitavastatin being an Oatp substrate. Experiments were conducted in Nagase analbuminemic rats (NAR) which exhibit reduced albumin levels compared with F344 (wild type, WT). The fraction unbound (f u) was 140- and 10-fold greater in NAR plasma for warfarin and pitavastatin, respectively, whereas no meaningful differences were observed with tissue binding. In vitro, pitavastatin uptake into hepatocytes reconstituted in WT plasma was 17- and 3-fold greater than when reconstituted in buffer or NAR plasma, respectively. In vivo, the free tissue-to-free plasma ratios (K p,u,u) from brain and liver in intact WT and NAR were not significantly different for warfarin. Contrarily, liver K p,u,u of pitavastatin was 6-fold higher in WT animals, which corresponded to a 2.3-fold reduction in free plasma and 2.6-fold increase in free liver exposure. These results suggest that the enhanced hepatic uptake by albumin is not necessarily an experimental artifact but is also a relevant phenomenon in vivo. This work raises the possibility that other plasma proteins may also effect the function of additional drug transporters, and that modulating plasma protein binding may exhibit meaningful clinical relevance in the disposition of drugs. SIGNIFICANCE STATEMENT: The interplay between albumin and Oatp substrates has been reported in hepatocytes and in liver perfusion studies, but the in vivo relevance of this interaction has yet to be elucidated. Using NAR and its corresponding WT animal, this study demonstrates that albumin may indeed enhance the hepatic uptake of pitavastatin in intact animals. In vivo demonstration of this interplay not only provides further justification for continued investigation into this particular mechanism but also raises the possibility that other plasma proteins may affect additional drug transporters and that modulating plasma protein binding may exhibit meaningful clinical relevance in the disposition of drugs.

Identification of ApoA4 as a sphingosine 1-phosphate chaperone in ApoM- and albumin-deficient mice.

HDL-bound ApoM and albumin are protein chaperones for the circulating bioactive lipid, sphingosine 1-phosphate (S1P); in this role, they support essential extracellular S1P signaling functions in the vascular and immune systems. We previously showed that ApoM- and albumin-bound S1P exhibit differences in receptor activation and biological functions. Whether the physiological functions of S1P require chaperones is not clear. We examined ApoM-deficient, albumin-deficient, and double-KO (DKO) mice for circulatory S1P and its biological functions. In albumin-deficient mice, ApoM was upregulated, thus enabling S1P functions in embryonic development and postnatal adult life. The Apom:Alb DKO mice reproduced, were viable, and exhibited largely normal vascular and immune functions, which suggested sufficient extracellular S1P signaling. However, Apom:Alb DKO mice had reduced levels (∼25%) of plasma S1P, suggesting that novel S1P chaperones exist to mediate S1P functions. In this study, we report the identification of ApoA4 as a novel S1P binding protein. Recombinant ApoA4 bound to S1P, activated multiple S1P receptors, and promoted vascular endothelial barrier function, all reflective of its function as a S1P chaperone in the absence of ApoM and albumin. We suggest that multiple S1P chaperones evolved to support complex and essential extracellular signaling functions of this lysolipid mediator in a redundant manner.

Prolonged respiratory failure due to pulmonary embolism in a young woman: a case report.

BACKGROUND: The pathophysiology of pulmonary edema is generally considered to result from elevated pulmonary capillary hydrostatic pressure due to increased left atrial pressure in consequence of a failing left ventricle. CASE PRESENTATION: We present a case of pulmonary edema secondary to severe hypalbuminemia under excessive respiratory drive in a 29-year-old Caucasian woman in respiratory distress with detected bilateral central pulmonary embolism. CONCLUSION: In conjunction with severe hypalbuminemia, even the negative intrathoracic pressure swings of respiratory distress may cause pulmonary edema. Detrimental consequences of non-invasive ventilation due to uncontrolled tidal volume and pressure swings need to be considered when treating patients in hypoxemic respiratory failure with low serum albumin.

Sarcopenia and Low Serum Albumin Level Synergistically Increase the Risk of Incident Disability in Older Adults.

OBJECTIVES: This study aimed to investigate the additive effects of sarcopenia and low serum albumin level on the risk of incident disability in older adults. DESIGN: Prospective cohort study. SETTING: A Japanese community. PARTICIPANTS: Community-dwelling older adults aged ≥65 years, without disability at baseline (N = 4452). MEASURES: Sarcopenia was defined as the presence of both poor muscle function (low physical performance or muscle strength) and low muscle mass. Low serum albumin level was defined as ≤4.0 g/dL. Other potential confounding factors (demographics, medical history, depressive symptoms, and cognitive function) were also assessed. Incident disability was monitored based on Long-Term Care Insurance certification during follow-up. RESULTS: The median follow-up duration was 30 (interquartile range, 28-32) months. Participants were classified into mutually exclusive groups based on sarcopenia status and serum albumin levels: nonsarcopenia/normal serum albumin (n = 3719), low serum albumin alone (n = 552), sarcopenia alone (n = 132), and sarcopenia/low serum albumin (n = 49). A Cox hazards regression showed that the low serum albumin alone [hazard ratios (HR) = 1.71, 95% confidence interval (CI) = 1.26-2.33], sarcopenia alone (HR = 2.74, 95% CI = 1.58-4.77), and sarcopenia/low serum albumin groups (HR = 3.73, 95% CI = 1.87-7.44) had higher risk of disability than the nonsarcopenia/normal serum albumin group after adjusting for the covariates. CONCLUSIONS/IMPLICATIONS: Sarcopenia and low serum albumin level synergistically increase the risk of incident disability in older adults. Sarcopenia in older adults at risk of malnutrition should be detected early, and appropriate interventions should be implemented.

Early decrease in postoperative serum albumin predicts severe complications in patients with colorectal cancer after curative laparoscopic surgery.

BACKGROUND: Postoperative severe complications are always associated with prolonged hospital stays, increased economic burdens, and poor prognoses in patients with colorectal cancer (CRC). This present study aimed to investigate potential risk factors including serum albumin (Alb) for severe complications in CRC patients. METHODS: Eligible patients with primary CRC undergoing elective laparoscopic colectomy from July 2015 to July 2017 were included. Postoperative severe complications were defined as grade III and IV according to the Clavien-Dindo classification. ∆Alb was defined as (preoperative Alb - nadir Alb within POD2)/preoperative Alb × 100%. The baseline characteristics, intraoperative data, and laboratory data were obtained from the database for the analysis. Univariate and multivariate logistic regression analyses were utilized for the assessment of the association between risk factors and postoperative severe complications. The predictive value of ∆Alb for postoperative severe complications was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 193 patients were finally included in the analysis data set, of which 38 (19.7%) patients had postoperative severe complications. In the final multivariate logistic regression analysis, ∆Alb was the only independent factor associated with postoperative severe complications (OR 1.66, 95%CI 1.18-2.33, p = 0.003). The area under the curve (AUC) of ∆Alb was 0.916, with the sensitivity and specificity of 0.842 and 0.858 (p < 0.001). CONCLUSIONS: The ∆Alb was an independent risk factor for severe complications in CRC patients after curative laparoscopic surgery.

Predictors of 90-day mortality in patients with severe alcoholic hepatitis: Experience with 183 patients at a tertiary care center from India.

BACKGROUND: Severe alcoholic hepatitis (AH) is not an uncommon indication for hospital admission in India. However, there is limited data from India on predictors of mortality in patients of severe AH. We analyzed the data on patients with severe AH admitted to our institute and compared various parameters and severity scores in predicting 90-day mortality. METHODS: In this prospective study, we analyzed patients with severe AH (defined as discriminant function ≥ 32) admitted from January 2015 to February 2017 to our institute. All patients were administered standard treatment according to various guidelines, and their 90-day mortality was determined. Various hematologic, biochemical factors, and severity scores were compared between survivors and patients who died. RESULTS: A total of 183 patients (98% males, median age 41 years [range 20-70 years]) were included in our study. The median model for end-stage liver disease (MELD) was 26 (15-40). Ascites were present in 83% and hepatic encephalopathy in 38%. Only 21 (12%) could be offered steroid therapy, due to contraindications in the remaining. By 90 days, only 103 (56%) patients survived while 80 (44%) died. All patients died due to progressive liver failure and its complications. On multivariate analysis, presence of ascites, hepatic encephalopathy, high bilirubin, low albumin, high creatinine, high INR, and low potassium independently predicted 90-day mortality. All the scores performed significantly in predicting 90-day mortality with no statistically significant difference between them. MELD score had a maximum area under the curve 0.76 for 90-day mortality. A combination of Child class and presence of acute kidney injury (creatinine ≥ 1.35) was good in predicting 90-day mortality. CONCLUSION: Our patients had severe AH characterized by a median MELD score of 26 and had a 90-day mortality of 44%. Most patients were not eligible to receive corticosteroids. Presence of Child C status and high serum creatinine value (≥ 1.35 mg/dL) accurately predicted mortality. Newer treatment options need to be explored for these patients.

Albumin handling in different hemodialysis modalities.

Hypoalbuminemia is a major risk factor for morbidity and mortality in dialysis patients. With increasing interest in highly permeable membranes and convective therapies to improve removal of middle molecules, transmembrane albumin loss increases accordingly. Currently, the acceptable upper limit of albumin loss for extracorporeal renal replacement therapies is unknown. In theory, any additional albumin loss should be minimized because it may contribute to hypoalbuminemia and adversely affect the patient's prognosis. However, hypoalbuminemia-associated mortality may be a consequence of inflammation and malnutrition, rather than low albumin levels per se. The purpose of this review is to give an overview of albumin handling with different extracorporeal renal replacement strategies. We conclude that the acceptable upper limit of dialysis-related albumin loss remains unknown. Whether enhanced middle molecule removal outweighs the potential adverse effects of increased albumin loss with novel highly permeable membranes and convective therapies is yet to be determined.

Pregnancy in a patient with congenital analbuminaemia.

Congenital analbuminaemia is a rare autosomal recessive disorder that is characterised by a severe reduction or total absence of serum albumin. This condition has implications for therapeutics as a large proportion of commonly used drugs are plasma protein bound where albumin is the primary component of plasma protein. This is the first case report of pregnancy in a patient with congenital analbuminaemia in the medical literature. In the absence of drug dosage guidelines for patients with congenital analbuminaemia, a list of drugs which may be required for this patient during pregnancy, delivery and/or emergency situations were compiled by a multidisciplinary team. Our patient suffered from polyhydramnios during her pregnancy which was successfully managed with albumin transfusions and had a normal vaginal delivery with no complications in the intrapartum or postpartum period. The management and unique challenges of pregnancy in a patient with congenital analbuminaemia are discussed.

A nucleotide deletion and frame-shift cause analbuminemia in a Turkish family.

Congenital analbuminemia is an autosomal recessive disorder, in which albumin, the major blood protein, is present only in a minute amount. The condition is a rare allelic heterogeneous defect, only about seventy cases have been reported worldwide. To date, more than twenty different mutations within the albumin gene have been found to cause the trait. In our continuing study of the molecular genetics of congenital analbuminemia, we report here the clinical and biochemical findings and the mutation analysis of the gene in two Turkish infants. For the molecular analysis, we used our strategy, based on the screening of the gene by single-strand conformation polymorphism, heteroduplex analysis and direct DNA sequencing. The results showed that both patients are homozygous for the deletion of a cytosine residue in exon 5, in a stretch of four cytosines starting from nucleotide position 524 and ending at position 527 (NM_000477.5(ALB):c.527delC). The subsequent frame-shift inserts a stop codon in position 215, markedly reducing the size of the predicted protein product. The parents are both heterozygous for the same mutation, for which we propose the name Erzurum from the city of origin of the family. In conclusion, our results show that in this family congenital analbuminemia is caused by a novel frame-shift/deletion defect, confirm the inheritance of the trait, and contribute to advance our understanding of the molecular basis underlying this condition.

Evolución del cobre sérico en pacientes sometidos a gastrostomía endoscópica para nutrición enteral a largo plazo.

Introducción y objetivos: el cobre (Cu) es un oligoelemento muy estudiado, pero poco se sabe de su evolución en los pacientes alimentados por gastrostomía endoscópica (GEP). Pretendemos evaluar la evolución del Cu sérico desde la gastrostomía hasta 12 semanas después de la intervención en estos pacientes alimentados con preparaciones domésticas.  Métodos: realizamos un estudio observacional prospectivo para evaluar el Cu sérico, la albúmina, la transferrina y el índice de masa corporal (IMC) en el momento de la GEP, tras 4 semanas y 12 semanas después de la intervención. Los datos incluyen edad, género, NRS 2002 y enfermedad subyacente: cánceres de cabeza y cuello (CCC) y disfagia neurológica (DN). Después de la intervención, estos pacientes fueron alimentados conpreparaciones domésticas. Resultados: 146 enfermos (89 hombres), entre 21-95 años: CCC-56, DN-90. Valores de Cu entre 42-160 µg/dl (normal: 70-140 µg/dl); normales 89% (n = 130); bajos 11% (n = 16), albúmina baja: 53% (n = 77), transferrina baja: 65% (n = 94), IMC bajo: 53% (n = 78). Después de 4 semanas: valores normales de Cu en 93% y bajos en 7%, albúmina baja en 34%, transferrina baja en 52%. Tras 12 semanas: valores normales de Cu en 95% y bajos en 5%, albúmina baja en 25%, transferrina baja en 32%. No encontramos diferencias significativas en el Cusérico cuando se compara edad, género, enfermedad subyacente, IMC, albúmina y transferrina. Conclusiones: la mayoría de los enfermos presentan Cu sérico normal en el momento de la gastrostomía. Para los enfermos con Cu sérico bajo antes del procedimiento, la alimentación con preparaciones domésticas parece suficiente para su normalización progresiva.

Low serum albumin and advanced age predict early mortality in Asian patients with extreme elevations of serum aminotransferase.

OBJECTIVE: Extreme elevations of serum aminotransferases (EESAT), defined as alanine transaminase (ALT) or aspartate transaminase (AST) level of above 3000 U/L, reflect severe liver injury and poor outcomes of the patients. This study aimed to evaluate the prevalence, etiology and clinical outcomes of EESAT in Asian patients and to identify the predictors of early mortality. METHODS: Medical records of patients with EESAT over a 1-year period were retrospectively analyzed for disease prevalence, etiology and clinical outcome. The primary outcome was 28-day mortality (defined as death occurring within 28 days of the onset of EESAT). A logistic regression was performed to identify independent predictors of mortality. RESULTS: A total of 101 patients with a mean age of 57.4 ± 18.0 years met the criteria for EESAT, resulted in a prevalence of 1.4 per 1000 admissions. Altogether 63.4% of the patients were men. The etiologies of EESAT were hypoxic hepatitis (74.2%), viral hepatitis (20.8%), rhabdomyolysis (3.0%), drug-induced hepatitis (1.0%) and choledocholithiasis (1%). The 28-day mortality of EESAT was 53.5%. EESAT due to hypoxic hepatitis was associated with high mortality (70.7%) whereas the mortality risk was low in EESAT from viral hepatitis (9.5%). Serum albumin <28 g/L (HR 5.78, 95% CI 1.41-23.62) and age >55 years (HR 4.81, 95% CI 1.29-17.90) were independent predictors of mortality. CONCLUSIONS: The main etiology of EESAT is hypoxic hepatitis, which carries a high mortality. EESAT due to viral hepatitis is common in Asians and has a good outcome. Low serum albumin and elder age are independent predictors of early mortality in EESAT patients.

Congenital analbuminemia caused by a novel aberrant splicing in the albumin gene.

INTRODUCTION: Congenital analbuminemia is a rare autosomal recessive disorder manifested by the presence of a very low amount of circulating serum albumin. It is an allelic heterogeneous defect, caused by variety of mutations within the albumin gene in homozygous or compound heterozygous state. Herein we report the clinical and molecular characterization of a new case of congenital analbuminemia diagnosed in a female newborn of consanguineous (first degree cousins) parents from Ankara, Turkey, who presented with a low albumin concentration (< 8 g/L) and severe clinical symptoms. MATERIALS AND METHODS: The albumin gene of the index case was screened by single-strand conformation polymorphism, heteroduplex analysis, and direct DNA sequencing. The effect of the splicing mutation was evaluated by examining the cDNA obtained by reverse transcriptase - polymerase chain reaction (RT-PCR) from the albumin mRNA extracted from proband's leukocytes. RESULTS: DNA sequencing revealed that the proband is homozygous, and both parents are heterozygous, for a novel G>A transition at position c.1652+1, the first base of intron 12, which inactivates the strongly conserved GT dinucleotide at the 5' splice site consensus sequence of this intron. The splicing defect results in the complete skipping of the preceding exon (exon 12) and in a frame-shift within exon 13 with a premature stop codon after the translation of three mutant amino acid residues. CONCLUSIONS: Our results confirm the clinical diagnosis of congenital analbuminemia in the proband and the inheritance of the trait and contribute to shed light on the molecular genetics of analbuminemia.