Effects of Mineralocorticoid Receptor Antagonists for Chronic Kidney Disease: A Systemic Review and Meta-Analysis.

BACKGROUND: Mineralocorticoid receptor blockade could be a potential approach for the inhibition of chronic kidney disease (CKD) progression. The benefits and harms of different mineralocorticoid receptor antagonists (MRAs) in CKD are inconsistent. OBJECTIVES: The aim of the study was to summarize the benefits and harms of MRAs for CKD patients. METHODS: We searched MEDLINE, EMBASE, and the Cochrane databases for trials assessing the effects of MRAs on non-dialysis-dependent CKD populations. Treatment and adverse effects were summarized using meta-analysis. RESULTS: Fifty-three trials with 6 different MRAs involving 22,792 participants were included. Compared with the control group, MRAs reduced urinary albumin-to-creatinine ratio (weighted mean difference [WMD], -90.90 mg/g, 95% CI, -140.17 to -41.64 mg/g), 24-h urinary protein excretion (WMD, -0.20 g, 95% CI, -0.28 to -0.12 g), estimated glomerular filtration rate (eGFR) (WMD, -1.99 mL/min/1.73 m2, 95% CI, -3.28 to -0.70 mL/min/1.73 m2), chronic renal failure events (RR, 0.86, 95% CI, 0.79-0.93), and cardiovascular events (RR, 0.84, 95% CI, 0.77-0.92). MRAs increased the incidence of hyperkalemia (RR, 2.04, 95% CI, 1.73-2.40) and hypotension (RR, 1.80, 95% CI, 1.41-2.31). MRAs reduced the incidence of peripheral edema (RR, 0.65, 95% CI, 0.56-0.75) but not the risk of acute kidney injury (RR, 0.94, 95% CI, 0.79-1.13). Nonsteroidal MRAs (RR, 0.66, 95% CI, 0.57-0.75) but not steroidal MRAs (RR, 0.20, 95% CI, 0.02-1.68) significantly reduced the risk of peripheral edema. Steroidal MRAs (RR, 5.68, 95% CI, 1.26-25.67) but not nonsteroidal MRAs (RR, 0.52, 95% CI, 0.22-1.22) increased the risk of breast disorders. CONCLUSIONS: In the CKD patients, MRAs, particularly in combination with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, reduced albuminuria/proteinuria, eGFR, and the incidence of chronic renal failure, cardiovascular and peripheral edema events, whereas increasing the incidence of hyperkalemia and hypotension, without the augment of acute kidney injury events. Nonsteroidal MRAs were superior in the reduction of more albuminuria with fewer peripheral edema events and without the augment of breast disorder events.

Aspirin intervention before ICU admission reduced the mortality in critically ill patients with acute kidney injury: results from the MIMIC-IV.

Background: Aspirin, with its pleiotropic effects such as anti-inflammatory and anti-platelet aggregation, has been widely used for anti-inflammatory, analgesic, and cardiovascular diseases. However, the association between the use of aspirin before the intensive care unit (ICU) and clinical outcomes in critically ill patients with acute kidney injury (AKI) is unknown. Methods: Patients with AKI in this retrospective observational study were selected from the Marketplace for Medical Information in Intensive Care IV (MIMIC-IV). The association between aspirin intervention and 30-day mortality was assessed using Cox proportional hazards model. Logistic regression models were used to assess the association of aspirin intervention with the risks of intracranial hemorrhage, gastrointestinal bleeding and blood transfusion. The propensity score matching (PSM) method was adopted to balance the baseline variables. Sensitivity analysis was performed to validate the results by multiple interpolations for the missing data. Results: The study included 4237 pre-ICU aspirin users and 9745 non-users. In multivariate models, we found a decreased risk of mortality in those who received aspirin before ICU compared to those who did not (30-day:hazard ratio [HR], 0.70; 95% CI, 0.62-0.79; p < 0.001; 90-day:HR, 0.70; 95% CI, 0.63-0.77, p < 0.001; 180-day:HR, 0.72; 95%CI,0.65-0.79, p < 0.001). This benefit was consistent in the post-PSM analyses, sensitivity analyses, and subgroup analyses. Moreover, aspirin intervention was associated with a reduced risk of intracranial hemorrhage and gastrointestinal bleeding (HR, 0.16; 95% CI, 0.10-0.25; p < 0.001; HR, 0.59; 95% CI, 0.38-0.88, p = 0.012) after being adjusted by relating covariates, whereas with a increased risk of blood transfusion (HR, 1.28; 95% CI, 1.16-1.46; p < 0.001). Conclusion: Patients with AKI treated with aspirin before ICU admission might have reduced 30-day, 90-day and 180-day mortality without increasing the risk of intracranial hemorrhage (ICH) or gastrointestinal bleeding, but may increase the risk of transfusion.

Predictive value of monocyte to HDL-C ratio for coronary artery lesions and intravenous immunoglobulin resistance in Kawasaki disease.

We aimed to investigate the predictive validity of monocyte to high-density lipoprotein cholesterol ratio (MHR) for coronary artery lesions (CALs) and intravenous immunoglobulin (IVIG) resistance in complete Kawasaki disease (KD). MHR values of a total of 207 complete KD patients were calculated and analyzed with regard to their clinical characteristics and outcomes. We compared the differences in clinical data and laboratory parameters between CAL+ group and CAL- group as well as between IVIG-resistant group and IVIG-responsive group. Spearman's correlation analysis was applied to evaluate the correlation between C-reactive protein (CRP) and MHR. Multivariate logistic regression was used to identify risk factors of CALs and IVIG resistance. Receiver operating characteristic (ROC) curve analysis was chosen to determine the optimal cut-off value of MHR and its validity in predicting CALs and IVIG resistance. The MHR level was significantly higher in the CAL+ group, with cut-off value of 1.30 g/L, yielding a sensitivity of 0.753 and specificity of 0.805, as well as in IVIG-resistant group, with cut-off value of 1.03 g/L, yielding a sensitivity of 0.97 and specificity of 0.485. Multivariate logistic regression showed that MHR was an independent risk factor for CALs but not for IVIG resistance. According to the Spearman's correlation analysis, CRP was positively correlated with the MHR. CONCLUSIONS: As a practical, cost-effective inflammatory biomarker, MHR has a significantly predictive value in complete KD children complicated with CALs and IVIG-resistance. Paying more attention to the changes of MHR in KD children may contribute to better understanding of KD development and prognosis in clinical practice. WHAT IS KNOWN: • CALs are the most prevalent serious sequela of KD, and approximately 10%~20% of patients do not respond to IVIG therapy. • MHR could be a convenient biomarker to predict the development and progression of CVDs. It has been reported that the MHR is a new prognostic biomarker in several CVDs. WHAT IS NEW: • MHR has a significantly predictive value in KD children complicated with CALs and IVIG-resistance. • Compared with the molecular and immunological biomarkers that have been reported, MHR has the characteristics of practical, cost-effective, higher sensitivity and specificity, which can be used as a predictive indicator in complete KD patients.

Excess selenium intake is associated with microalbuminuria in female but not in male among adults with obesity: Results from NHANES 2009-2018.

Introduction: Selenium is a critical trace element with antioxidant activities that has been related to the preservation of kidney function. Few studies, however, have looked at the effects of excess selenium on kidneys. The purpose of the present study was performed to investigate the relationship between dietary selenium intake and the prevalence of microalbuminuria in American adults with obesity. Methods: A total of 8,547 participants with obesity in the National Health and Nutrition Examination Survey (NHANES) with the age of 19 years or older were included in the present study. Multivariable regression and subgroup analyses were performed to examine the association between dietary selenium and microalbuminuria in the two genders, separately. A selenium intake above the median was defined as high selenium intake. Results: Dietary selenium intake was significantly higher in men compared to women (139.49 µg/day vs. 101.06 µg/day; P < 0.0001). Among female participants, the prevalence of microalbuminuria was significantly higher in participants with a high selenium intake compared with those without a high selenium intake (13.82 vs. 9.96%; P = 0.008), whereas this difference did not exist in male participants (10.79 vs. 11.97%; P = 0.40). Dietary selenium is not significantly correlated with microalbuminuria (P = 0.68) in the male population, whereas each 1 µg/day of increase in selenium consumption was independently associated with a 6h higher risk of microalbuminuria (OR = 1.006; 95% CI, 1.001-1.011, P = 0.01) in females. Conclusion: According to our research, excessive selenium consumption is positively correlated with microalbuminuria in females with obesity, but not in males with obesity.

Novel mutation in the SALL1 gene in a four-generation Chinese family with uraemia: A case report.

BACKGROUND: Approximately 10% of adults and nearly all children who receive renal replacement therapy have inherited risk factors or are related to genetic factors. In the past, due to the limitations of detection technology and the nonspecific manifestations of uraemia, the etiological diagnosis is unclear. In addition to common monogenic diseases and complex disorders, advanced testing techniques have led to the recognition of more hereditary renal diseases. Here, we report a four-generation Chinese family in which four individuals had a novel SALL1 mutation and presented with uraemia or abnormal urine tests. CASE SUMMARY: A 32-year-old man presented with end-stage renal disease with a 4-year history of dialysis. His father and paternal aunt both had a history of unexplained renal failure with haemodialysis, and his 10-year-old daughter presented with proteinuria. The patient had multiple congenital abnormalities, including bilateral overlapping toes, unilateral dysplastic external ears, and sensorineural hearing loss. His family members also presented with similar defects. Genetic testing revealed that the proband carried a novel heterozygous shift mutation in SALL1_exon 2 (c.3437delG), and Sanger sequencing confirmed the same mutation in all affected family members. CONCLUSION: We report a novel SALL1 exon 2 (c.3437delG) mutation and clinical syndrome with kidney disease, bilateral overlapping toes, unilateral dysplastic external ears, and sensorineural hearing loss in a four-generation Chinese family.

A geniposide-phospholipid complex ameliorates posthyperuricemia chronic kidney disease induced by inflammatory reactions and oxidative stress.

Hyperuricemia is a common metabolic disease and is one of the factors that could induce chronic kidney disease (CKD). Geniposide (GEN) is a typical natural iridoid glucoside compound with a series of biological activities, but the poor bioavailability of GEN limits its clinical application. In this context, the pharmacological activity of the geniposide-phospholipid complex (GEN-PLC) in ameliorating posthyperuricemia CKD was evaluated by in vitro and in vivo experiments in this study. In vitro cell experiments showed that GEN-PLC treatment markedly decreased inflammatory cytokine levels and reactive oxygen species levels compared with those of GEN in uric acid-treated HKC cells. In vivo research results confirmed that a high concentration of uric acid could cause CKD by increasing inflammatory cytokines and reactive oxygen species in hyperuricemic mice. At the same time, GEN-PLC could regulate the PI3K/AKT/NF-κB and Keap1/Nrf2/HO-1 signaling pathways to effectively inhibit the inflammatory response and oxidative stress, thereby ameliorating posthyperuricemia CKD, and the therapeutic effect was better than that of GEN. In addition, the preparation technology of GEN-PLC was optimized, and the physiochemical analysis explained the intermolecular interactions of the two components. Based on the research results, GEN-PLC could enhance the bioavailability of GEN and become a promising candidate for clinical drug development.

Synthesis and bioactivity evaluation of novel nuciferine derivatives with antihyperuricemia and nephroprotective effects.

Hyperuricemia is a common metabolic disease with a series of complications. Nuciferine, a typical aporphine alkaloid natural compound extracted from the leaves of Nelumbo nucifera Gaertn., was confirmed to have an antihyperuricemia effect. In the present study, 30 novel nuciferine derivatives were designed and synthesized. The effects of all derivatives on the regulation of URAT1 were studied in a uric acid-induced HK-2 cell model with benzbromarone as a positive control. The results indicated that Compound 1j showed the optimal URAT1 inhibitory activity through repressing PI3K/Akt pathway in HK-2 cells and the inhibitory effect was similar to that of benzbromarone. In addition, in vivo experiments demonstrated that Compound 1j could reduce uric acid levels and ameliorate kidney damage in hyperuricemic mice. On the one hand, Compound 1j could inhibit the expression of URAT1 and GLUT9 to increase the uric acid excretion index. On the other hand, Compound 1j could regulate the TLR4/IκBα/NF-κB signaling pathway to reduce the levels of inflammatory cytokines, thereby alleviating kidney damage. Meanwhile, a molecular docking assay revealed the potential molecular binding power (-9.79 kcal/mol) between Compound 1j and URAT1, which was more tightly bound than the lead compound nuciferine (-7.44 kcal/mol). Based on these results, Compound 1j may be a future drug for the development of new potential antihyperuricemia and nephroprotective drug candidates.

Synthesis and biological evaluation of geniposide derivatives as inhibitors of hyperuricemia, inflammatory and fibrosis.

Hyperuricemia is a metabolic disease caused by abnormal purine metabolism in the body. Long-term high levels of uric acid in the body will lead to gout and kidney disease. Xanthine oxidase (XOD) is a key enzyme in the pathogenesis of hyperuricemia. In this context, a series of geniposide derivatives were designed, synthesized and evaluated as xanthine oxidase inhibitors. Most of these compounds exhibited potent XOD inhibitory activities in vitro, and representatives 6a, 6c, 6g and 6j were found to be the most potent inhibitors against the enzyme with IC50 values of 2.15 ± 1.03, 1.37± 0.26, 4.14± 0.79 and 1.86± 0.13 µM, which were 33.03-158.37 fold more active than geniposide, respectively. Compounds 6a, 6c, 6g and 6j were evaluated in hyperuricemia mice, and the results demonstrated that compound 6c showed the strongest anti-hyperuricemia and renal protective activity in vivo. Subsequently, the molecular mechanism of compound 6c was studied in this investigation. In vitro cell experiments showed that compound 6c inhibited the inflammation of HK-2 cells under high uric acid conditions by inhibiting the expressions of TGF-ß, TNF-α and IL-1ß, and reduced the cell fibrosis by decreasing the expressions of α-SMA and Collagen I. The results of the mice experiments indicated that compound 6c efficiently decreased the level of serum uric acid (SUA) in hyperuricemia mice by inhibiting the XOD activity. Moreover, compound 6c effectively reduced the urate accumulation in the kidney and simultaneously decreased inflammation by regulating the expression of the TLR4/IκBα/NF-κB signaling pathway. In addition, consistent with cell experiments, compound 6c also reduced renal fibrosis in hyperuricemia mice, which may be due to compound 6c inhibiting the expression of inflammatory factor TGF-ß. Furthermore, a molecular docking study was performed to gain insight into the binding mode of compound 6c with XOD. These results suggest that compound 6c has the potential to be developed into a novel medicine to reduce blood uric acid and treat renal diseases caused by hyperuricemia.

Family history of esophageal cancer modifies the association of serum lipids and malignant esophageal lesions: a nested case-control study from the "Endoscopic Screening for Esophageal Cancer in China" trial.

BACKGROUND: The association of lipids and cancer has varied greatly among different cancer types, lipid components and study populations. This study is aimed to investigate the association of serum lipids and the risk of malignant lesions in esophageal squamous epithelium. METHODS: In the "Endoscopic Screening for Esophageal Cancer in China" (ESECC) trial, serum samples were collected and tested for total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol at the time of subject enrollment. Cases were defined as malignant esophageal lesions identified by baseline endoscopic examination or by follow-up to May 31, 2018. Controls were randomly selected using incidence density sampling in the same cohort. Conditional logistic models were applied to identify the association of serum lipids and the risk of malignant esophageal lesions. Effect modification was evaluated by testing interaction terms of the factor under assessment and these serum lipid indicators. RESULTS: No consistent association between serum lipid levels and esophageal malignant lesions were found in a pooled analysis of 211 cases and 2101 controls. For individuals with a family history of esophageal cancer (EC), high TC, and LDL-C were associated with a significantly increased risk of having malignant lesions (odds ratio [OR]High vs. Low TC = 2.22, 95% confidence interval [CI]: 1.14-4.35; ORHigh vs. Low LDL-C = 1.93, 95% CI: 1.01-3.65). However, a negative association was observed in participants without an EC family history (ORHigh vs. Low TC = 0.69, 95% CI: 0.48-0.98, Pinteraction = 0.002; ORHigh vs. Low LDL-C = 0.50, 95% CI: 0.34-0.76, Pinteraction < 0.001). CONCLUSIONS: In this study, we found that the association of serum lipids and malignant esophageal lesions might be modified by EC family history. The stratified analysis would be crucial for population-based studies investigating the association of serum lipids and cancer. The mechanism by which a family history of EC modifies this association warrants further investigation.

Antimicrobial susceptibility and microbiological and epidemiological characteristics of hypermucoviscous Klebsiella pneumoniae strains in a tertiary hospital in Hangzhou, China.

OBJECTIVES: Hypermucoviscous Klebsiella pneumoniae (HMKP) has been increasingly observed among clinical isolates. This study sought to examine the microbiological and epidemiological characteristics of HMKP strains in a tertiary hospital in Hangzhou, China. METHODS: HMKP isolates were collected and were identified via matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF/MS). A string test was performed for the hypermucoviscous phenotype. Susceptibility to various antimicrobial agents was determined. Multilocus sequence typing (MLST), capsular serotypes and virulence-associated genes of HMKP isolates were assessed. RESULTS: A total of 42 HMKP strains with a positive string test were collected, of which 32 (76.2%) were carbapenem-susceptible HMKP (CS-HMKP) and 10 (23.8%) were carbapenem-resistant HMKP (CR-HMKP). CS-HMKP strains were more susceptible to antimicrobial agents than CR-HMKP strains. Capsular serotypes K1 (38.1%; 16/42) and K2 (11.9%; 5/42) were the main capsular serotypes of all HMKP isolates. K57 was first reported in CR-HMKP strains. ST163 was the main sequence type (37.5%; 12/32) among CS-HMKP strains, whilst ST11 was unique to CR-HMKP strains. The regulator of the mucoid phenotype A gene (rmpA) and other virulence factors (allS, kfu, iutA, entB, iroN, fimH and wabG) were present in >80% of HMKP strains. Patients with CR-HMKP strains had a higher mortality rate than those with CS-HMKP strains. CONCLUSION: Capsular serotypes K1 and K2 were the main capsular serotypes of the isolated HMKP strains. The emergence of CR-HMKP should be a concern as it was associated with an increased mortality rate, especially for ST11 CR-HMKP strains, demonstrating the global epidemic of carbapenem resistance.

Oxidative stress modulates the expression of toll­like receptor 3 during respiratory syncytial virus infection in human lung epithelial A549 cells.

Toll­like receptor 3 (TLR3) can react with double stranded RNA and is involved in the inflammatory response to respiratory syncytial virus (RSV) infection. Also, oxidative stress has been reported to be involved in RSV infection. However, the correlation between oxidative stress and TLR3 activation during RSV infection is unclear. Therefore, the present study investigated the association between TLR3 expression and oxidative stress modulation during RSV infection in A549 cells. For comparison, seven treatment groups were established, including RSV­treated cells, N­acetyl­L­cysteine (NAC)+RSV­treated cells, oxidant hydrogen peroxide (H2O2)+RSV­treated cells, normal cell control, inactivated RSV control, NAC control and H2O2 control. The mRNA expression changes of TLR3, interferon regulatory factor­3 (IRF3), nuclear factor­κB (NF­κB) and superoxide dismutase 1 (SOD1) were measured using semi­quantitative reverse transcription­polymerase chain reaction, and the protein changes of TLR3 and phospho­NF­κB p65 were determined using western blot in A549 cells from the different treatment groups. The present study also evaluated the differences in hydroxyl free radical (·OH), nitric oxide (NO) and total SOD activity in the different treatment groups. The results demonstrated that RSV infection of A549 cells increased the levels of ·OH and NO, while decreasing the activity of total SOD. Pretreatment of A549 cells with H2O2 prior to RSV infection upregulated the mRNA and protein expression of TLR3 and NF­κB, and downregulated the mRNA expression of IRF3 and SOD1, as well as the total SOD activity. When the infected cells were pretreated with NAC, the mRNA and protein expression of these genes were reversed. These variations in the TLR3­mediated signaling pathway molecules suggested that oxidative stress may be a key regulator for TLR3 activation during RSV infection. RSV­induced oxidative stress may potentially activate TLR3 and enhance TLR3­mediated inflammation. These results may provide better understanding of the RSV­induced inflammatory and immune pathways, and may also contribute to the drug development and prevention of human RSV diseases.

Liver support therapy with molecular adsorbents recirculating system in liver failure: a summary of 252 cases from 14 centers in China.

BACKGROUND: A liver support therapy, named molecular adsorbents recirculating system (MARS), has been used for more than 700 liver failure patients in China. We made here a summary to evaluate the effects of MARS treatment in different applications with emphasis on hepatitis B virus (HBV) based liver failure. METHODS: This report analyzed data of 252 patients (mean age (44.9+/- 12.7) years) in three groups: acute severe hepatitis (ASH), subacute severe hepatitis (SSH) and chronic severe hepatitis (CSH). The largest group was CSH (156 patients, 61.9%), and 188 patients (74.6%, 188/252) were infected with HBV. RESULTS: MARS treatments were associated with significant reduction of albumin bound toxins and water-soluble toxins. Most of the patients showed a positive response with a significant improvement of multiple organ function substantiated by a significant increase in prothrombin time activity (PTA) and median arterial pressure (MAP). There was a decrease in hepatic encephalopathy (HE) grade and Child-Turcotte-Pugh (CTP) scale. Thirty-nine of 188 HBV patients (20.7%) dropped out of the commendatory consecutive therapy ending with lower survival of 43.6% while the rest of the 149 patients had a survival rate of 62.4%. Survival within the ASH and SSH groups were 81.2% and 75.0%, respectively. In the CSH group, end stage patients were predominant (65/151, 43%), whereas the early and middle stage patients had a better prognosis: early stage survival, including orthotopic liver transplantation (OLT) survival of 91.7%, middle stage survival of 75%, end stage survival of 33.8%. CONCLUSIONS: MARS continues to be the most favorable extracorporeal treatment for liver support therapy in China for a wide range of conditions, including the majority of hepatitis B related liver failure conditions. The appropriate application of MARS for the right indications and stage of hepatic failure, as well as the fulfillment of prescribed treatments, will lead to the optimal therapeutic result.

[Study on maternal-fetal status of Pb, As, Cd, Mn and Zn elements and the influence factors].

OBJECTIVE: Trace and toxic elements have great influences on the fetus growth during the pregnancy. The status of Pb, As, Cd, Mn and Zn in maternal and umbilical cord blood and influence factors were analyzed. METHODS: From September 2006 to April 2007, 130 pairs of maternal blood and cord blood in total were collected at the time of spontaneous delivery or cesarean section. At the same time, the development of newborn was measured immediately. The concentrations of elements were determined by inductively coupled plasma mass spectrometry, the relationship of these elements between maternal and cord blood were also analyzed. RESULTS: The median (microg/L) concentration of blood Pb, As, Cd, Mn and Zn in maternal blood were 64.32, 3.81, 0.84, 54.26 and 6312.50. And the median (microg/L) of those elements in cord blood were 35.72, 2.84, 0.32, 78.99 and 2250. The levels of Cd (r=0.341, P=0.000) and As (r=0.552, P=0.000) in maternal blood were positively correlated with the elements in the cord blood. From the questionnaire we conclude that the occupational hazardous factors and room decorated were the risk factors for the blood As and Zn levels. After multilinear regression analysis we also found mother weight, occupational hazardous factors and mother systolic pressure might affect the levels of blood Mn, Zn, As and Cd. CONCLUSIONS: The levels of these elements were affected by environmental and maternal factors. In this study, although the levels of all heavy metals in pregnant women were below those considered hazardous, however, they were still higher than those in the developed countries. The effects of heavy metals of maternal exposure on developing fetuses should deserve attention further.

Preoperative risk factor analysis in orthotopic liver transplantation with pretransplant artificial liver support therapy.

AIM: To assess the value of pre-transplant artificial liver support in reducing the pre-operative risk factors relating to early mortality after orthotopic liver transplantation (OLT). METHODS: Fifty adult patients with various stages and various etiologies undergoing OLT procedures were treated with molecular adsorbent recycling system (MARS) as preoperative liver support therapy. The study included two parts, the first one is to evaluate the medical effectiveness of single MARS treatment with some clinical and laboratory parameters, which were supposed to be the therapeutical pre-transplant risk factors, the second part is to study the patients undergoing OLT using the regression analysis on preoperative risk factors relating to early mortality (30 d) after OLT. RESULTS: In the 50 patients, the statistically significant improvement in the biochemical parameters was observed (pre-treatment and post-treatment). Eight patients avoided the scheduled Ltx due to significant relief of clinical condition or recovery of failing liver function, 8 patients died, 34 patients were successfully bridged to Ltx, the immediate outcome of this 34 patients within 30 d observation was: 28 kept alive and 6 patients died. CONCLUSION: Pre-operative SOFA, level of creatinine, INR, TNF-alpha, IL-10 are the main preoperative risk factors that cause early death after operation, MARS treatment before transplantation can relieve these factors significantly.

[Preoperation risk factor analysis in orthotopic liver transplantation with pre-transplant artificial liver support therapy].

OBJECTIVES: Orthotopic liver transplantation (OLT) is an accepted therapy for selected patients with advanced liver diseases. However, the early mortality rate after OLT remains relatively high due to the poor selection of candidates with various serious conditions. The aim of this study is to assess the value of pretransplantation artificial liver support treatment in reducing the pre-operation risk factors relating to early mortality after OLT. METHODS: 50 adult patients in various stages of different etiologies who underwent OLT procedures had been treated with molecular adsorbent recycling system (MARS) preoperatively. The study was designed in two parts: the first one was to evaluate the effectiveness of a single MARS therapy by using some clinical and laboratory parameters which were supposed to be therapeutical pretransplantation risk factors. The second part was to study the patients undergoing OLT by using the regression analysis on preoperation risk factors relating to early (within 30 d after OLT) mortality rate. RESULTS: Among the 50 patients, a statistically significant improvement of the biochemical parameters was observed (pretreatment vs posttreatment). 8 patients cancelled their scheduled LTXs due to significant improvements in their clinical conditions or recovery of their failing liver functions. 8 patients died and 34 patients successfully underwent LTX. The immediate outcome (within 30 postoperative days) of these 34 patients was that 28 were kept alive and 6 died. CONCLUSIONS: Preoperation sequential organ failure assessment (SOFA), level of creatinine, INR, TNFalpha, and IL-10 are the main preoperative risk factors relating to early death after an operation. MARS treatment before a transplant operation can relieve these factors significantly, hence improve survival rate of liver transplantation or even make the transplantation unnecessary.

[Therapeutic application of molecular adsorbent recirculation system in the treatment of multiple organ dysfunction syndrome patients].

OBJECTIVE: To assess the effectiveness of molecular adsorbent recirculation system (MARS) to remove nitric oxide(NO) and cytokines in multiple organ dysfunction syndrome(MODS) in patients with severe liver failure. METHODS: Single MARS treatment were performed for 198 times with duration ranging from 6 to 24 hours on 61 MODS patients (42M/19F). The efficacy was evaluated by sequential organ failure assessment, biochemical parameters and the levels of pro-inflammatory cytokines. RESULTS: The MARS therapy resulted in a significant removal of NO and certain cytokines such as tumor necrosis factor-alpha(TNF-alpha), interleukin-2(IL-2), IL-6, IL-8, and lipopolysaccharide-binding protein(LBP), together with marked reduction of other non-water soluble albumin bound toxins and water soluble toxins. These were associated with an improvement of the patients' clinical conditions, including deranged hemodynamics, respiratory function, cardiovascular and renal functions, hepatic encephalopathy, thus resulting in a marked decrease of sequential organ failure assessment(SOFA) score and improved outcome. Twenty-five patients were able to be discharged from the hospital, and successful liver transplantation could be performed in 6 patients. The overall survival rate of 61 patients was 41.0%. CONCLUSION: MARS could be used for the treatment of MODS patients associated with elevated levels of NO and cytokines with satisfactory results.

Artificial liver support molecular adsorbents recirculating system therapy as a bridge to re-transplantation in two cases of long anhepatic duration.

BACKGROUND: Molecular adsorbents recirculating system (MARS) liver support therapy is the development of albumin dialysis. This study was to assess the successful application of MARS artificial liver support therapy as a bridge to re-transplantation in two cases of long anhepatic duration. METHODS: MARS therapy was given after failure plasma-exchange (PE) treatment, which resulted in circulatory derangement and acute renal dysfunction in a 36-year-old male patient. Finally his uncontrolled anhepatic condition led to a successful re-transplantation. In another 48-year-old man who was diagnosed as having primary nonfunction (PNF) during the liver transplantation, 10-hour MARS treatment contributed to smooth bridging of his anhepatic phase. RESULTS: The two anhepatic patients were bridged for 26 and 17 hours respectively to re-transplantation with MARS therapy. CONCLUSION: Our experience proves that MARS artificial liver can be an effective support for long time bridging PNF until re-transplantation is available.