NFAT inhibitor 11R-VIVIT ameliorates mouse renal fibrosis after ischemia-reperfusion-induced acute kidney injury.

Acute kidney injury (AKI) with maladaptive tubular repair leads to renal fibrosis and progresses to chronic kidney disease (CKD). At present, there is no curative drug to interrupt AKI-to-CKD progression. The nuclear factor of the activated T cell (NFAT) family was initially identified as a transcription factor expressed in most immune cells and involved in the transcription of cytokine genes and other genes critical for the immune response. NFAT2 is also expressed in renal tubular epithelial cells (RTECs) and podocytes and plays an important regulatory role in the kidney. In this study, we investigated the renoprotective effect of 11R-VIVIT, a peptide inhibitor of NFAT, on renal fibrosis in the AKI-to-CKD transition and the underlying mechanisms. We first examined human renal biopsy tissues and found that the expression of NFAT2 was significantly increased in RTECs in patients with severe renal fibrosis. We then established a mouse model of AKI-to-CKD transition using bilateral ischemia-reperfusion injury (Bi-IRI). The mice were treated with 11R-VIVIT (5 mg/kg, i.p.) on Days 1, 3, 10, 17 and 24 after Bi-IRI. We showed that the expression of NFAT2 was markedly increased in RTECs in the AKI-to-CKD transition. 11R-VIVIT administration significantly inhibited the nuclear translocation of NFAT2 in RTECs, decreased the levels of serum creatinine and blood urea nitrogen, and attenuated renal tubulointerstitial fibrosis but had no toxic side effects on the heart and liver. In addition, we showed that 11R-VIVIT administration alleviated RTEC apoptosis after Bi-IRI. Consistently, preapplication of 11R-VIVIT (100 nM) and transfection with NFAT2-targeted siRNA markedly suppressed TGFß-induced HK-2 cell apoptosis in vitro. In conclusion, 11R-VIVIT administration inhibits IRI-induced NFAT2 activation and prevents AKI-to-CKD progression. Inhibiting NFAT2 may be a promising new therapeutic strategy for preventing renal fibrosis after IR-AKI.

High glucose induces Drp1-mediated mitochondrial fission via the Orai1 calcium channel to participate in diabetic cardiomyocyte hypertrophy.

Mitochondrial dysfunction and impaired Ca2+ handling are involved in the development of diabetic cardiomyopathy (DCM). Dynamic relative protein 1 (Drp1) regulates mitochondrial fission by changing its level of phosphorylation, and the Orai1 (Ca2+ release-activated calcium channel protein 1) calcium channel is important for the increase in Ca2+ entry into cardiomyocytes. We aimed to explore the mechanism of Drp1 and Orai1 in cardiomyocyte hypertrophy caused by high glucose (HG). We found that Zucker diabetic fat rats induced by administration of a high-fat diet develop cardiac hypertrophy and impaired cardiac function, accompanied by the activation of mitochondrial dynamics and calcium handling pathway-related proteins. Moreover, HG induces cardiomyocyte hypertrophy, accompanied by abnormal mitochondrial morphology and function, and increased Orai1-mediated Ca2+ influx. Mechanistically, the Drp1 inhibitor mitochondrial division inhibitor 1 (Mdivi-1) prevents cardiomyocyte hypertrophy induced by HG by reducing phosphorylation of Drp1 at serine 616 (S616) and increasing phosphorylation at S637. Inhibition of Orai1 with single guide RNA (sgOrai1) or an inhibitor (BTP2) not only suppressed Drp1 activity and calmodulin-binding catalytic subunit A (CnA) and phosphorylated-extracellular signal-regulated kinase (p-ERK1/2) expression but also alleviated mitochondrial dysfunction and cardiomyocyte hypertrophy caused by HG. In addition, the CnA inhibitor cyclosporin A and p-ERK1/2 inhibitor U0126 improved HG-induced cardiomyocyte hypertrophy by promoting and inhibiting phosphorylation of Drp1 at S637 and S616, respectively. In summary, we identified Drp1 as a downstream target of Orai1-mediated Ca2+ entry, via activation by p-ERK1/2-mediated phosphorylation at S616 or CnA-mediated dephosphorylation at S637 in DCM. Thus, the Orai1-Drp1 axis is a novel target for treating DCM.

How to carry out monthly blood flow surveillance of fistula in large-scale hemodialysis units: A cross-sectional study.

BACKGROUND: The important effect of regular blood flow surveillance on arteriovenous fistula maintenance is emphasized. The ultrasonic dilution technique for blood flow surveillance can be performed during hemodialysis, but there are some limitations. Blood flow is traditionally measured by duplex Doppler ultrasound during the nondialysis period. However, the surveillance workload for arteriovenous fistula has increased with the rapid increase in the hemodialysis population size. Efficient methods for blood flow surveillance during hemodialysis are needed. METHODS: Eighty-four hemodialysis patients with a forearm radiocephalic arteriovenous fistula were enrolled in this cross-sectional study. Each received blood flow measurements using ultrasonic dilution technique and duplex Doppler ultrasound during hemodialysis. Duplex Doppler ultrasound measurements included the blood flow of the brachial artery and radial artery. The correlations between these variables were analyzed. RESULTS: The correlation coefficients (r) between flow measured by ultrasonic dilution technique and brachial artery flow measured by duplex Doppler ultrasound, between flow measured by ultrasonic dilution technique and radial artery flow measured by duplex Doppler ultrasound, and between brachial artery flow and radial artery flow measured by duplex Doppler ultrasound were 0.724, 0.784, and 0.749, respectively (all p < 0.001). CONCLUSION: Blood flow measured by ultrasonic dilution technique was positively correlated with blood flow measured by duplex Doppler ultrasound during hemodialysis, suggesting that duplex Doppler ultrasound can be used to monitor the trends in the blood flow of the brachial artery and radial artery for timely intervention to improve patency during hemodialysis.

It is time to implement prepump arterial pressure monitoring during hemodialysis: A retrospective multicenter study.

INTRODUCTION: Prepump arterial pressure (Pa) indicates the ease or difficulty with which the blood pump can draw blood from vascular access (inflow) during hemodialysis. The absolute prepump arterial pressure to blood pump speed (Qb) ratio (|Pa/Qb|) may reflect the dysfunction of other vascular accesses. There is no consensus on the impact of |Pa/Qb| on arteriovenous fistula dysfunction. This study aimed to demonstrate the impact of |Pa/Qb| on arteriovenous fistula dysfunction. METHODS: In this retrospective analysis, 490 hemodialysis patients with arteriovenous fistula from three hospitals were enrolled. Data were extracted from the I-Diapro database and hospital case systems. The absolute values for |Pa/Qb| and other data collected in the first month of enrollment were used to predict arteriovenous fistula dysfunction and determine the |Pa/Qb| cutoff value. Based on this value, patients were grouped, and 1-year arteriovenous fistula function was analyzed. Patients were followed until arteriovenous fistula dysfunction, until access type replacement, or for 12 months. RESULTS: The area under the receiver operating characteristic curve for fistula dysfunction over 1 year was 0.65, with an optimal |Pa/Qb| value, sensitivity, and specificity of 0.499, 60.7%, and 72.6%, respectively. |Pa/Qb| > 0.499 was associated with earlier intervention (317.37 ± 7.68 vs 345.96 ± 3.64 days), lower survival (p < 0.001), and a 3.26-fold greater risk of arteriovenous fistula dysfunction (p < 0.001) than |Pa/Qb| ⩽ 0.499. CONCLUSIONS: |Pa/Qb| was an independent risk factor for arteriovenous fistula dysfunction. Nurses should emphasize |Pa/Qb| monitoring and properly set blood pump speed according to this ratio to protect arteriovenous fistula function. |Pa/Qb| > 0.499 might be a predictive measure of arteriovenous fistula dysfunction.

Can the fistula arm be used to lift heavy items? Six-pound dumbbells versus handgrip exercise in a 6-month follow-up secondary analysis of a randomized controlled trial.

INTRODUCTION: Patients with arteriovenous fistulas are advised to avoid carrying heavy objects draped over the fistula arm. Awareness gradually leads to overprotection and a reduction in the use of the fistula arm. However, restricting motion in the fistula arm leads to decreased quality of life and diminished muscle strength. The current safety recommendations regarding lifting heavy items with the fistula arm are primarily based on experience. Few studies have provided evidence clarifying the scope of safe activity and the influence of load bearing on the continued patency of arteriovenous fistulas. METHODS: This prospective observation was based on a long-term follow-up study in which 86 hemodialysis recipients with arteriovenous fistulas were randomized into either a dumbbell group or a handgrip group. The dumbbell group exercised with 6-lb dumbbells, while the handgrip group squeezed rubber balls. Postintervention primary patency and adverse events at the 6-month follow-up were analyzed. RESULTS: No significant difference in postintervention primary patency was observed between the dumbbell group and the handgrip group at 6 months (97.4% vs 95.0%). There were two participants with high-flow fistulas in the dumbbell group and three in the handgrip group, with no significant difference between the two groups (5.3% vs 7.5%). In both groups, there were no other adverse events reported regarding cardiac failure, aneurysm, puncture site hematoma, or hemorrhage. CONCLUSION: Hemodialysis patients can safely use their fistula arm to lift objects weighing less than 6 lb, which encourages increased motion and helps preserve the functionality of the fistula arm.

[Effects of C-reactive protein on the expression of transforming growth factor ß1 and receptors on human renal tubular epithelial cells].

OBJECTIVE: To explore the effect of C-reactive protein (CRP) on the expression of Fcγ receptors in human renal tubular epithelial cells and determine the role of Fcγ receptors in CRP-induced expression of transforming growth factor ß1 (TGFß1). METHODS: Human renal tubular epithelial cells (HK-2) were cultured and stimulated with recombinant human CRP. The mRNA expression of Fcγ receptors, including FcγRI (CD64), FcγRIIa (CD32a) and FcγRIII (CD16), was detected by real-time polymerase chain reaction (PCR). On the basis of real-time PCR results, CD32a was selected for further analysis: the CD32a expression in HK-2 cells incubated with 10 mg/L CRP for 24 h was determined by flow cytometry and Western blotting. HK-2 cells were preincubated with or without anti-CD32a IgG, followed by the addition of recombinant human CRP. Subsequently the biological effects of CRP were tested. TGFß1, type I collagen (ColI) and type IV collagen (ColIV) released into media were detected by enzyme-linked immunosorbent assay. And TGFß1 mRNA expression was measured by real-time PCR. RESULTS: On real-time PCR, CRP was found to significantly up-regulate the CD32a mRNA expression in HK-2 cells in a dose-dependent manner (P < 0.01). The peak up-regulation was observed at a dose of 10 mg/L. In contrast, mRNAs of CD16 and CD64 were not detected in HK-2 cells. Flow cytometry showed that CD32a expressed on HK-2 cells incubated with 10 mg/L recombinant human CRP for 24 h accounted for 23.35% ± 7.43%, significantly higher than that on non-CRP-treated cells (1.66% ± 0.28%, P < 0.01). Western blotting showed that CRP up-regulated CD32a expression in a dose-dependent manner. And 10 mg/L CRP induced the peak effect. Antibodies to CD32a inhibited the stimulatory effect of CRP on the generation of TGFß1, ColI and ColIV (all P < 0.05) and down-regulated the expression of TGFß1 mRNA (P < 0.01). CONCLUSION: The stimulation of CRP can significantly increase CD32a expression in renal tubular epithelial cells and up-regulate the expression of transforming growth factor TGFß1 through CD32a receptor.

[Cardiovascular risk profile in systemic lupus erythematosus: a cross-sectional study of 879 patients].

OBJECTIVE: To investigate the prevalence of cardiovascular diseases (CVD) in patients with systemic lupus erythematosus (SLE) and estimate the associated risk factors for CVD. METHODS: This cross-sectional study was conducted in 879 SLE patients treated in our hospital between March, 2006 and March, 2011. The demographic data and the clinical data including SLE duration, therapeutic regimen, renal pathological data, estimated glomerular filtration rate (eGFR), SLE Disease Activity Index (SLEDAI), and associated biochemical parameters were analyzed. Cardiovascular ultrasound was used for detecting and analyzing the cardiovascular structural and functional abnormalities. RESULTS: Eighty-five cases of CVD were found in the 879 SLE cases (9.7%). After age stratification, CVD was identified in 5.8%, 9.0%, 14.0% and 20.0% in SLE patients aged ≤19, 20-39, 40-59 and ≥60 years, respectively, showing a tendency to increase with age (P=0.002). The prevalence of CVD differed significantly between patients with and those without lupus nephritis (P=0.001). Among the 85 patients with CVD, 23.5% (20/85) had left ventricular hypertrophy, 49.5% (42/85) had congestive heart failure, 20.0% (17/85) had stroke, 3.5% (3/85) had angina pectoris, and 3.5% (3/85) had peripheral CVD. Compared to those without CVD, patients with CVD had a longer SLE duration (P=0.002), a longer time of steroids treatment (P=0.026), a higher blood pressure (P=0.0006), a lower eGFR (P=0.001), and a lower concentration of HDL (P=0.007). Logistic regression analysis showed that SBP, eGFR, HDL, SLE duration, SLEDAI index, serum C3 and hs-CRP were the risk factors for CVD in SLE patients (P=0.033). CONCLUSION: SLE is associated with a high risk of CVD which increases with age, and SLE patients with lupus nephritis have an even higher risk for CVD. SBP, eGFR, HDL, SLE duration, SLEDAI index, serum C3 and hs-CRP are the risk factors for CVD in SLE patients.

[The sensitivity and accuracy of RIFLE and AKIN criteria for acute kidney injury diagnosis in intensive care unit patients].

OBJECTIVE: To evaluate the sensitivity/accuracy of 2 different acute kidney injury (AKI) diagnosis/classification criteria, the RIFLE (risk, injury, failure, loss of kidney function, end-stage kidney disease) and the acute kidney injury network (AKIN), for patients in intensive care unit (ICU). METHODS: Clinical data were collected from all adult patients admitted to the Department of Intensive Medicine in Guangdong General Hospital between October 2009 and July 2010, and AKI cases were identified/classified using RIFLE and AKIN criteria separately, for statistical evaluation of their diagnostic sensitivity, and accuracy in hospital mortality prediction. RESULTS: In all 524 patients evaluated, AKI were identified by RIFLE criteria in 95 of them, while by AKIN, 135. The AKI incidence by RIFLE (18.1%), and AKIN (25.8%) were significantly different (P < 0.05). Meanwhile, AKI incidence was found independent from the mortality, either by RIFLE or AKIN (both P < 0.001). In all patients, the area under the receiver operator characteristic curve (ROC curve), the index for hospital mortality prediction, was 0.7293 for RIFLE [with 95% confidence interval (95%CI) ranging from 0.6005 to 0.8581, P < 0.001], and for AKIN, 0.7777 (95%CI: 0.6664 - 0.8890, P < 0.001). No significant difference was found between the total hospital mortality by the two criteria (37.9% vs. 34.1%, P > 0.05). CONCLUSION: Although AKIN criteria has higher sensitivity in AKI diagnosis, it is not different from the RIFLE criteria in predicting hospital mortality in critically ill patients.

[Evaluation of continuous venous-venous hemofiltration combined with coupled plasma filtration adsorption for treatment of systemic inflammation response syndrome with acute renal failure].

OBJECTIVE: To evaluate the clinical efficacy of continuous venous-venous hemofiltration (CVVH) combined with coupled plasma filtration adsorption (CPFA) in the management of systemic inflammation response syndrome (SIRS) complicated by acute renal failure (ARF). METHODS: Thirty patients with SIRS complicated by ARF (including 25 with severe acute pancreatitis, 2 with colonic perforation with infection, and 3 with acute infective endocarditis) were randomly divided into CVVH plus CPFA group (n=14) and CVVH alone group (n=16). The APACHE II score, mean arterial pressure, PaO2/FiO2, TNF-alpha and IL-10 were detected prior to or after the intervention. The feasibility and tolerance of CVVH plus CPFA and the therapy-related adverse reactions were evaluated. RESULTS: The two groups showed no significant differences in the baseline clinical characteristics (P>0.05). The mean arterial pressure and PaO2/FiO2 increased significantly after treatment as compared with the control (P<0.05), with TNF-alpha being reduced and IL-10 elevated. In CVVH plus CPFA group, APACHEII score improved significantly after 10 days (P<0.05). No therapy-related adverse reactions were noted, suggesting good tolerance of CVVH plus CPFA. CONCLUSION: CVVH combined with CPFA is an effective and safe method for improving the clinical outcome of patients with SIRS and ARF.

[Low serum fetuin A is a risk factor of coronary artery calcification in patients starting hemodialysis].

OBJECTIVE: To examine the relationship between reduction of serum fetuin A and coronary artery calcification (CAC) in patients starting hemodialysis. METHODS: Twenty-nine patients on chronic hemodialysis (duration of hemodialysis less than 6 months) were enrolled in this study. Serum fetuin A and such potential CAC-related risk factors as C-reactive protein (CRP), Ca, P, iPTH, body mass index (BMI) were examined. CAC was detected by multislice spiral CT scan (MSCT) and quantified by the modified Agaston's scoring system. All the 29 patients were followed up for 18 months to appraise the cardiovascular events defined as cardiac failure, angina pectoris or myocardial infarction. RESULTS: Eleven patients (78.57%) were found to have CAC as detected by MSCT in low serum fetuin A (below the average serum concentration of 0.71 g/L) group, a rate significantly higher than that in high serum fetuin A group (7 patients, 46.67%, P<0.05). Serum fetuin A in these 29 patients was related with CAC score (Pearson correlation coefficient of -0.734, P=0.001) and stepwise regression analysis indicated that serum fetuin A (standardized beta=-0.568, P=0.003) and age (standardized beta=0.416, P=0.019) were independently correlated to CAC. Such factors as CRP, Ca, P, iPTH, Chol, TG, HDL-C, LDL-C, BMI and blood pressure were excluded from the regression equation. Reduction of serum fetuin A was associated with cardiovascular events (Spearman's rho -0.758, P<0.01). No significant difference was found between low and high serum fetuin A groups by Kaplan-Meier survival analysis (P=0.065). CONCLUSION: Reduced serum fetuin A may be a potential risk factor of coronary artery calcification, and can contribute to cardiovascular events in patients starting hemodialysis.

Combination of urinary kidney injury molecule-1 and interleukin-18 as early biomarker for the diagnosis and progressive assessment of acute kidney injury following cardiopulmonary bypass surgery: a prospective nested case-control study.

The aim of this nested case-control study was to assess the combined use of urinary kidney injury molecule (KIM)-1 and interleukin (IL)-18 for acute kidney injury (AKI) after cardiopulmonary bypass surgery (CPB). From a cohort of 122 subjects who underwent CPB, serial urinary KIM-1 and IL-18 concentrations were determined in 30 AKI and 92 non-AKI patients. An increased level of urinary KIM-1 was associated with the occurrence of AKI, whereas an increased level of IL-18 was related to progressive AKI. The combination of these two biomarkers facilitates the early diagnosis and assessment of the likely progression of AKI after CPB.

Podocyte injury is suppressed by 1,25-dihydroxyvitamin D via modulation of transforming growth factor-beta 1/bone morphogenetic protein-7 signalling in puromycin aminonucleoside nephropathy rats.

1. Accumulating evidence suggests that vitamin D and its analogues are renoprotective. However, the precise mechanisms and the molecular targets by which active vitamin D exerts its beneficial effects remain obscure. The objective of the present study was to evaluate the effect of active vitamin D on rats with puromycin aminonucleoside (PAN) nephropathy, a model that is characterized by predominant podocyte injury. 2. The PAN nephropathy rats were created by a single intravenous injection of 100 mg/kg PAN. Changes in renal pathology and podocyte numbers were observed. Real-time polymerase chain reaction (PCR) was performed to examine mRNA expression of nephrin, transforming growth factor (TGF)-beta1 and bone morphogenetic protein (BMP)-7. Protein expression of nephrin, TGF-beta1, BMP-7 and p-Smad2/3 and p-Smad1/5/8 was examined by immunofluorescence, immunohistochemistry and western blotting, respectively. Rats were treated with 1,25(OH)(2)D(3) by gastric gavage at a dose of 2.5 microg/kg per day, starting 2 days before PAN injection and continuing throughout the experiment. 3. A single injection of PAN induced massive proteinuria and elevated serum creatinine on Day 7, both of which were significantly suppressed by 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)). Immunofluorescence and real-time PCR of the podocyte-associated protein nephrin revealed reduced and discontinuous staining and this change was reversed by 1,25(OH)(2)D(3). In PAN nephropathy rats, TGF-beta1 and p-Smad2/3 expression was upregulated, whereas that of BMP-7 and p-Smad1/5/8 was downregulated. Treatment with 1,25(OH)(2)D(3) significantly restored BMP-7/Smad signalling while suppressing TGF-beta1/Smad signalling. 4. In conclusion, 1,25(OH)(2)D(3) can ameliorate podocyte damage and proteinuria induced by PAN. The beneficial effects of 1,25(OH)(2)D(3) on podocytes may be attributable, in part, to direct modulation of TGF-beta1/BMP-7 signalling.

[Prospective study of cystatin C for diagnosis of acute kidney injury after cardiac surgery].

OBJECTIVE: To prospectively study the value of cystatin C in diagnosis of acute kidney injury (AKI) in patients after cardiac surgery. METHODS: A total of 132 patients undergoing cardiopulmonary bypass were enrolled in this prospectively study. From each patient, blood samples were collected everyday before and after operation to detect the serum creatinine (Scr) and cystatin C levels by enzymatic method and particle-enhanced turbidimetric immunoassay (PETIA), respectively, and the glomerular filtration rate (eGFR) was estimated using MDRD equation. AKI diagnosis was made according to the RIFLE criteria of the Acute Dialysis Quality Initiative (ADQI) (R: Scr increased by > or =50%; I: Scr increased by > or =100%; F: Scr increased by > or =200%; L: Loss of kidney function; E: End-stage renal disease). Another AKI diagnostic criterion was also adopted according to the levels of cystatin C increment, namely an increase by > or =50%, > or =100%, and > or =200%. RESULTS: Twenty-nine patients (21.9%) developed AKI of varied severities, including 10 meeting the R-criteria, 12 the I-criteria, 7 the F-criteria, with the other 103 patients without AKI serving as the control group. Cystatin C of the 29 AKI patients was drastically increased in comparison with that of the control group (P<0.001). Significant linear correlation was found between cystatin C and Scr (r=0.732, P<0.001) and between [cystatin C]-1 and estimated GFR (R=0.803, P<0.001). By the two diagnostic criteria based on cystatin C and Scr levels, respectively, the median diagnostic time of AKI was 2 days (range 1-4 days) and 3 days (range 2-5 days) for R criteria (10 patients, P=0.014), 3.5 days (range 1-6 days) and 5 days (range 2-8 days) for I criteria (12 patients, P=0.008), and 5 days (range 3-7 days) and 6.5 days (range 4-9 days) for F criteria (7 patients, P=0.02), respectively. ROC analysis confirmed excellent accuracy of cystatin C in AKI diagnosis (AUC=0.992). With the cut-off value of cystatin C increment by > or =50%, the diagnostic sensitivity and specificity of AKI was 92% and 95%, respectively. CONCLUSION: Cystatin C can serve as a good indicator for AKI diagnosis to allow earlier detection of AKI than Scr-based diagnosis in patients after cardiac surgery.

[Risk factors of hypertension in IgA nephropathy].

OBJECTIVE: To explore the risk factors of hypertension in patients with IgA nephropathy in South China. METHODS: The clinical and renal pathological data of 280 primary IgA nephropathy patients diagnosed by biopsy were analyzed to extinguish the risk factors of hypertension. RESULTS: A total of 96 patients were suffered with hypertension (34.3%). A single-variable analysis showed that the age (>or= 40 years), body weight (>or= 60 kg), absence of macrohematuria, duration of disease (>or= 60 months), blood urea nitrogen >or= 8 mmol/L, serum creatinine (>or= 133 micromol/L), hyperuricaemia, degree of 24 h-proteinuria (>or= 1.5 g), segmental glomerular lesions (>or= 25%), globe glomerular sclerosis (>or= 10%), tubular atrophy (>or= 25%), interstitial fibrosis (>or= 25%), interstitial inflammation (>or= 25%) and arteriole hypertrophy (>or= 10%) were all risk factors related to hypertension; multivariate logistic regression analysis showed that serum creatinine, age, arteriole hypertrophy, body weight and 24 h-proteinuria were the independent risk factors. CONCLUSION: Many factors were related the hypertension in patients with IgA nephropathy, while serum creatinine, age, arteriole hypertrophy, body weight and 24 h-proteinuria were the independent risk factors of hypertension.

[Efficacy and safety of coupled plasma filtration adsorption combined with continuous veno-venous hemofiltration for multiple organ dysfunction syndrome patients with acute liver failure].

OBJECTIVE: To evaluate efficacy and safety of coupled plasma filtration adsorption (CPFA) combined with continuous veno-venous hemofiltration (CVVH) for the treatment of multiple organ dysfunction syndrome (MODS) patients with acute liver failure (ALF), and to evaluate the effect of CPFA plus CVVF on inflammatory mediators in these patients. METHODS: A total of 38 cases of 11 MODS patients with ALF (male 6, female 5) were treated with CPFA plus CVVH, and the following clinical indicators including changes in mean arterial pressure (MAP), oxygen index (PaO(2)/FiO(2)), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), IL-6, IL-8, biochemical parameters of liver and kidney function, parameters of systemic inflammatory response syndrome (SIRS) score, and acute physiology and chronic health evaluation II (APACHE II) score were determined before and after the treatment. The degree of improvement in clinical symptoms, feasibility, tolerance toward CPFA plus CVVH, therapy-related adverse reactions and security were simultaneously evaluated. RESULTS: MAP increased by 12 mmHg (1 mmHg=0.133 kPa), and PaO(2)/FiO(2) increased by 40 mmHg after the application of CPFA plus CVVH (both P<0.05), along with significant decrease in TNF-alpha, IL-1 beta, IL-6, IL-8 and markedly lowered levels of serum total bilirubin (IBIL), direct bilirubin (DBIL), blood urea nitrogen (BUN), serum creatinine (SCr) and blood ammonia (all P<0.05). Besides, clinical symptoms, including urinary volume, mental disturbance, jaundice, debility, nausea, vomiting, fever, abdominal distention, anepithymia, and SIRS, APACHE II scores were improved significantly after the CPFA plus CVVH (all P<0.05). No therapy-related adverse reactions, including severe haemorrhage, shock, hypersensitivity, were noted, and patients tolerated well toward CPFA plus CVVH. The total survival rate of patients was 45.5% (5/11 cases) at the end of the treatment. CONCLUSION: Our data indicate that CPFA combined with CVVH is an effective and safe method to improve the prognosis of MODS patients with ALF, the mechanism of which may be related to its effective removal of inflammatory cytokines.