Clinical improvement of sepsis by extracorporeal centrifugal leukocyte apheresis in a porcine model.

BACKGROUND: Extracorporeal blood purification therapies targeting removal of the downstream products of the inflammatory cascade in sepsis have failed to improve mortality. As an upstream process of the inflammatory cascade, activated white blood cells should be a potential therapeutic target for sepsis, and the effect of removing such cells by extracorporeal centrifugal leukocytapheresis (LCAP) is worth considering. METHODS: Fourteen peritonitis-induced septic pigs were randomly assigned to receive a sham operation (control group, n = 7) or one session of LCAP at 12 h after sepsis induction (treatment group, n = 7). Samples from peripheral blood at various time-points and from LCAP collection were tested. All pigs were euthanized at 48 h, and lung, kidney, liver and spleen tissues were obtained for histopathological examination. RESULTS: Two pigs died in accidents before the induction of sepsis, and 12 pigs were finally included for the statistical analysis. A significant clinical improvement was present in the treatment group relative to the control group in terms of the mean arterial blood pressure (MAP), oxygen tension (PaO2), lactic acid level, oxygenation index (PaO2/FiO2), and carbon dioxide tension (PaCO2, P < 0.05). Flow cytometry tests showed that a mixture of B cells, dendritic cells, T helper cells, cytotoxic T cells, monocytes and neutrophils were removed from the circulation by LCAP, resulting in sepsis-induced change trends in the control cells; these change trends were all flattened in the treatment group, although nonsignificantly. CONCLUSIONS: LCAP may exert a wide-spectrum and bidirectional immunomodulatory effect on sepsis, accompanied by improvements in hemodynamics and oxygenation status.

Gut dysbiosis-influence on amygdala-based functional activity in patients with end stage renal disease: a preliminary study.

Patients with end-stage renal disease (ESRD) are notably accompanied by cognitive disorder and anxiety or depressive symptom. We aimed to explore the linkages of the amygdala-based MR parameters, cognitive and mood performance, systematic inflammation and gut microbiota in ESRD. This prospective study enrolled 28 ESRD patients (13 males and 15 females, mean age of 43.9 ± 13.8 years) and 19 age- and sex-matched healthy control (HC) (12 males and 7 females, mean age of 44.1 ± 10.0 years). All subjects underwent cognitive assessment, inflammatory factor and stool microbiota analysis, and brain MRI analysis [amygdala-based functional connectivity and voxel-based morphometry (VBM)]. ERSD was separated by different microbiota strains. All factors were compared between ESRD and HC, as well as between ESRD subgroups. Pearson correlation analysis and causal mediation analysis were conducted to further investigate the relationship among the factors derived from the gut microbiota, brain and systemic inflammation. ESRD displayed gut dysbiosis and increased systemic inflammation when compared to HC (all P < 0.05). Meanwhile, ESRD showed smaller VBM in amygdala, decreased functional connectivity in left amygdala - right inferior parietal lobe [P < 0.05, Gaussian Random Field (GRF) corrected] and worse cognitive or mood performance. Moreover, ESRD-B (Prevutella mainly), when compared to ESRD-A (Bacteroides mainly), displayed increased interleukin-6, self-rating anxiety scale and functional connectivity in left amygdala - bilateral anterior cingulate cortex / medial superior frontal cortex (P < 0.05, GRF corrected). Furthermore, the correlation network of ESRD showed that both gut dysbiosis and amygdala-based alteration were correlated with cognitive performance and systemic inflammation. Causal mediation analysis validated that the disrupted distribution of Roseburia indirectly regulated the amygdala-based functional connectivity through tumor necrosis factor-alpha. The gut dysbiosis induced by ESRD was closely related to pro-inflammatory cytokines, amygdala-based phenotype, and mood performance. The lower abundance in Roseburia indirectly modulated amygdala-based functional connectivity pattern by tumor necrosis factor-alpha, which might provide a new way in diagnosis and treatment in patients of ESRD with depressive/anxious mood.

The association of bioimpedance analysis parameters with the outcomes of critically ill patients.

BACKGROUND: The association between bioimpedance analysis (BIA) parameters and the outcomes of critically ill patients was explored through a retrospective investigation. METHODS: The study enrolled patients in the intensive care units of our hospital who had a record of BIA measurements as well as disease severity scores assessed by Acute Physiology and Chronic Health Evaluation II (APACHE II), Simplified Acute Physiology Score II (SAPS II) and Sequential Organ Failure Assessment (SOFA). The associations between clinical conditions, outcomes and BIA parameters were analysed. The relationship between individual bioimpedance values and the current frequencies fit well to a natural logarithmic function, providing a regression coefficient S value. Other parameters obtained from the BIA measurements included phase angle (PA), the ratio of bioimpedance at high and low frequencies (IR), extracellular water (ECW), intracellular water (ICW) and total body water (TBW). RESULTS: Among 201 enrolled patients, the 90-day in-hospital mortality was 35.8%. Compared to the survivors at 7-days, for the non-survivors, the IR, S value, ratio of ECW/weight and ratio of ECW/TBW were higher, and the PA was lower (P < 0.05). Compared to the survivors at 90-days, for the non-survivors, the IR, S value and ratio of ECW/weight were higher, and the PA was lower (P < 0.05). Multinomial logistic regression analysis results showed that only SAPS II and S value were independent risk factors for 7-day and 90-day death (P < 0.01). When analysed by ROC, the AUC of the S value for predicting 7-day and 90-day death was non-significantly lower than SAPS II (S vs. SAPS II, 0.729 vs. 0.747 (7-day); 0.701 vs. 0.779 (90-day), P > 0.05). Importantly, both the 7-day and the 90-day mortality in patients with S values ≤-25.5 were 0; for the others, the mortality increased with the rise of S value. For patients with SAPS II ≤33, the mortality varied minimally; and for patients with SAPS II >55, the mortality was 100%. CONCLUSIONS: The S value and SAPS II are independent risk factors for 7-day and 90-day death in critically ill patients; the former may have a greater negative predictive value, while the latter may have a greater positive predictive value.

The gut microbiota-inflammation-brain axis in end-stage renal disease: perspectives from default mode network.

The gut-brain axis in end-stage renal disease (ESRD) is attracting more and more attention. However, the mechanism of gut-brain axis based cognitive disorders in ESRD patients remains unclear. The purpose of this study was to investigate the linkages between the gut microbiota, inflammatory cytokines, brain default mode network (DMN) and cognitive function in ESRD patients. Methods: This prospective study enrolled 28 ESRD patients (13 males and 15 females, mean age of 44 ± 14 years) and 19 healthy controls (HCs) (12 males and 7 females, mean age of 44 ± 10 years). All subjects underwent stool microbiota analysis, blood inflammatory cytokines examination, brain MRI scans and cognitive assessments. Resting state functional MRI (rs-fMRI) data were used to construct DMN and graph theory was applied to characterize network topological properties. Two samples t-test was applied for the comparisons between ESRD and HCs. Correlation analysis and mediation analysis were conducted among factors with significant group differences. Results: ESRD patients displayed gut microbiota alterations, increased systemic inflammation and worse cognitive performance compared to HCs (all p < 0.05). Graph analysis revealed disrupted DMN topological organization, aberrant nodal centralities and functional connectivities (FCs) in ESRD patients relative to HCs (all p < 0.05, FDR corrected). Significant correlations were found between gut microbiota, inflammatory cytokines, DMN network measures and cognitive assessments. Mediation analysis found that gut microbiota alteration impaired DMN connectivity by increasing systemic inflammation. Conclusion: The present study first revealed gut microbiota alterations, systemic inflammation, DMN dissociation and cognitive dysfunction in ESRD patients simultaneously and further illuminated their inner relationship.

Autologous Hematopoietic Stem Cell Transplantation for Refractory Lupus Nephritis.

BACKGROUND AND OBJECTIVES: Our study evaluated the efficiency and safety of autologous hematopoietic stem cell transplantation treatment for patients with refractory lupus nephritis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: From July 2011 to January 2015, a total of 22 patients with refractory lupus nephritis were enrolled in this study. Peripheral blood stem cells were mobilized with cyclophosphamide and granulocyte colony stimulating factor and reinfused after treatment with cyclophosphamide and antithymocyte globulin. The primary end point was the rate of remission, and secondary end points included the survival and relapse rates, changes in proteinuria, kidney function, and serology immunologic test. All complications were recorded for safety assessment. RESULTS: Twenty-two patients were enrolled and underwent stem cell mobilization. There were nine men and 13 women, with a median lupus nephritis duration of 46 (33-71) months. The mean number of CD34+ cells was (7.3±3.8)×106/kg. All patients had successful engraftment, and the median times of granulocyte and platelet engraftment were 8 (7-9) and 9 (6-10) days, respectively. The major complications of stem cell transplantation were fever and gastrointestinal tract symptoms. The treatment-related mortality was 5% (one of 22). After a median follow-up of 72 (60-80) months, 18 (82%) patients achieved completed remission, one (5%) patient achieved partial remission, and one patient had no response and received peritoneal dialysis at 12 months after transplantation. The 5-year overall survival and disease-free survival rates were 91% and 53%, respectively. Six patients experienced relapse during the follow-up, and the relapse rate was 27%. CONCLUSIONS: Autologous hematopoietic stem cell transplant could be used as a treatment option for refractory lupus nephritis, because it was relatively safe and associated with good outcomes.

Vascular Access in Patients Treated with Continuous Renal Replacement Therapy: A Report from a Single Center in China.

Our aim was to analyze the practice pattern of vascular access use and complication rates in patients receiving continuous renal replacement therapy from a large Chinese urban medical center. Patients who had received continuous renal replacement therapy (CRRT) from April to October 2014 in our center were included in this study. Demographic data, primary disease, department for hospitalization, blood pressure, heart rate, Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation (APACHE II) score, presence of mechanical ventilation, CRRT modalities, choice of functioning vascular access, site and duration of catheter insertion, presence of recatheterization, cumulative catheter indwelling time, catheter malfunction and catheter-related infections, as well as laboratory test results, were collected. A total of 292 patients were enrolled in our study, including 175 males (59.9%) and 117 females (40.1%), aged 50.8 ± 18.6 years (range, 12 to 94 years). Acute kidney injury, multiple organ dysfunction syndrome, and systemic inflammatory response syndrome were the main indications for treatment with CRRT. Initial vascular access was non-cuffed temporary catheters in 280 patients and was preferentially obtained in the right internal jugular vein (54.3%). There were 32 (11.4%) patients requiring re-catheterization. Catheter malfunction occurred in 7.14% of all patients, and the median time of catheter malfunction was found at the 5th day. By multivariate analysis, it was found that the main risk factors of catheter malfunction were cumulative treatment time of CRRT and the level of hemoglobin. The average time of catheter-related infections was 10.7 days after insertion and the catheter-related infections occurred at a rate of 7.19 per 1000 catheter days. The main risk factors for catheter-related infections were cumulative time of catheterization and the level of serum albumin. In this cohort of critically ill patients, the main risk factors for catheter malfunction were cumulative CRRT time and the level of hemoglobin. In addition, the main risk factors for catheter-related infections were cumulative time of catheterization and the level of serum albumin.

New modes of continuous renal replacement therapy using a refiltering technique to reduce micronutrient loss.

INTRODUCTION: Micronutrient depletion is a major drawback of high-dose continuous renal replacement therapy (CRRT). We tested two novel CRRT modes, double-filtration hemofiltration (DHF) and dialysate-recycling hemodiafiltration (DHDF), aimed at reducing micronutrient loss while maintaining a high clearance rate of midsized solutes comparable to that of high-volume hemofiltration (HVHF). METHODS: Forty patients with renal failure requiring CRRT were randomly assigned to receive predilutional standard-volume hemofiltration (SVHF, effluent rate 35 mL/kg/h), predilutional HVHF (100 mL/kg/h), DHF (35 mL/kg/h), and DHDF (30 mL/kg/h). In the two novel modes of CRRT, part of the high-volume primary effluent fluid produced by a high-flux filter (AV600S) was refiltered by two low-flux filters (15 L) for recycling as replacement fluid in DHF and dialysate in DHDF, while the remainder was discarded as final effluent fluid. Specimens were collected for measurement of trace elements, folic acid, amino acids (AAs), ß2-microglobulin, cystatin C, and creatinine and for calculation of solute clearance. FINDINGS: The clearance of 17 AAs, phosphorus, folic acid, copper, and zinc by DHF and DHDF was much lower than that by HVHF and comparable to that by SVHF. The estimated amount of AA loss by SVHF, HVHF, DHF, and DHDF was 10.3 (7.2-13.4) g/d, 22.1 (17.8-24.0) g/d, 10.6 (8.6-14.0) g/d, and 10.0 (8.6-11.4) g/d, respectively. Clearance of cystatin C and ß2-microglobulin by DHF and DHDF was much greater than that by SVHF and equal to that by HVHF. DISCUSSION: Compared to HVHF, DHF, and DHDF have an equal capacity for removal of large solutes but show substantially reduced micronutrient loss.

Evaluation of Intradialytic Hypertension Using Bioelectrical Impedance Combined With Echocardiography in Maintenance Hemodialysis Patients.

Although intra-dialytic hypertension (IDH) has been noted in clinical settings for many years, its pathogenesis remains unclear. In this cross-sectional study, we analyzed IDH incidence in our center and the correlation between postdialysis volume state and IDH. One hundred thirty-one maintenance hemodialysis (MHD) patients were enrolled in our study, and bioelectrical impedance (BIA) and echocardiography (ECG) were recorded. In addition, demographic data were collected, and laboratory examinations were conducted. The patients were grouped into four groups according to the change in systolic blood pressure (SBP) between predialysis and postdialysis. The incidence of IDH was 10.7%. The proportion of extracellular water to total body weight (ECW/TW), as evaluated by BIA, was significantly higher in the IDH group than in the other three groups both in pre-and post-dialysis. In particular, postdialysis SBP was highest in the highest tertile interval of ECW/TW. In addition, among the four groups, left ventricular volume (LVV) was highest in the IDH group. Binary logistic analyses revealed that predialysis SBP, postdialysis ECW/TW and LVV were independent risk factors of intradialytic hypertension. When predicting IDH, the AUC of the ROC curve was higher for ECW/TW combined with LVV (0.752, 95% CI 0.613-0.896) than for either LVV or ECW/TW alone. Our study further showed that post-dialysis volume expansion is an important factor for the development of IDH.

Severe Acute Valproic Acid Intoxication Successfully Treated with Liver Support Therapy.

Valproic acid (VPA) is widely used for the treatment of epilepsy. However, its overdose can cause intoxication and could be life-threatening. Due to the lack of specific antidote and poorness of endogenous clearance, extracorporeal treatment for severe intoxication cases is indicated. Here, we report a case of severe intoxication of VPA which was successfully treated with liver support therapy. A previously healthy woman was admitted due to coma and hypotension after intentional ingestion of 20 g of sodium valproate. Her serum concentration of VPA measured on admission was 420.84 mg/L. In addition to standard therapy, she received two sessions of extracorporeal blood purification using a system based on fractionated plasma separation and adsorption mode integrated with continuous veno-venous haemofiltration (FPSA-CVVH), which is usually used for liver support therapy at our hospital. Her serum concentration of VPA decreased dramatically to 40.18 mg/L and her consciousness recovered completely within 24 hr after admission. Therefore, although haemodialysis has been reported to be effective in the treatment for VPA poisoning, FPSA-CVVH may provide an option for patients who require bedside therapy but have an unstable haemodynamic status or other conditions that result in inability to endure haemodialysis.

Asparaginase-associated concurrence of hyperlipidemia, hyperglobulinemia, and thrombocytosis was successfully treated by centrifuge/membrane hybrid double-filtration plasmapheresis.

Asparaginase-associated concurrence of hyperlipidemia, hyperglobulinemia, and thrombocytosis is a rare complication requiring aggressive lipoprotein apheresis, but no one of currently available lipoprotein apheresis methods can simultaneously resolve the 3 abnormalities. Herein, we reported a construction of double-filtration plasmapheresis (DFPP) using a combination of centrifugal/membranous plasma separation techniques to successfully treat a patient with hyperlipidemia, hyperglobulinemia, and thrombocytosis. A male presented with severe hyperlipidemia, hyperglobulinemia, and thrombocytosis during asparaginase treatment for NK/T-cell lymphoblastic lymphoma and was scheduled to receive lipoprotein apheresis. To simultaneously remove lipoproteins, immunoglobulin, and deplete platelets from blood, a centrifuge/membrane hybrid DFPP was constructed as following steps: plasma and part of platelets were separated first from whole blood by centrifugal technique and then divided by a fraction plasma separator into 2 parts: platelets and plasma components with large size, which were discarded; and those containing albumin, which were returned to blood with a supplement of extrinsic albumin solution. DFPP lasted 240 minutes uneventfully, processing 5450-mL plasma. The concentrations of plasma components before DFPP were as follows: triglycerides 38.22 mmol/L, total cholesterols 22.98 mmol/L, immunoglobulin A (IgA) 15.7 g/L, IgG 12.7 g/L, and IgM 14.3 g/L; whereas after treatment were 5.69 mmol/L, 2.38 mmol/L, 2.5 g/L, 7.7 g/L, and 0.4 g/L, respectively. The respective reduction ratio was 85.1%, 89.6%, 83.9%, 39.4%, and 96.9%. Platelet count decreased by 40.4% (from 612 × 10(9)/L to 365 × 10(9)/L). Centrifuge/membrane hybrid DFPP can simultaneously remove lipoproteins, immunoglobulin, and deplete platelets, with a success in treatment of asparaginase treatment-induced hyperlipidemia, hyperglobulinemia, and thrombocytosis, and may be useful for patients requiring DFPP but with particular situations.

Double Filtration Plasmapheresis in the Treatment of Antineutrophil Cytoplasmic Autoantibody Associated Vasculitis With Severe Renal Failure: A Preliminary Study of 15 Patients.

Our aim was to investigate the clinical efficacy of double filtration plasmapheresis (DFPP) in the treatment of antineutrophil cytoplasmic autoantibody-(ANCA) associated vasculitis (AAV) with severe renal involvement. Fifteen AAV patients who had severe renal failure (median SCr 5.6(IQR 5.2-9.0) mg/dL) and needed initial renal replacement therapy (RRT) were treated with DFPP and immunosuppressive therapy. Two plasma volumes were processed during each DFPP session. The changes of serum ANCA and renal function were investigated. After the DFPP treatment for three to five sessions, serum MPO-ANCA level decreased from 250.0 ± 86.9 RU/mL to 70.5 ± 64.7RU/mL (P = 0.00), with a median reduction rate of 67.6%. Eleven patients (73.3%) no longer needed from RRT 3 months after DFPP treatment, while another four patients remained on dialysis. During the follow up for median 10 (IQR 6-24) months, SCr level decreased to normal in one patient, one patient progressed into ESRD. The 1 year renal survival rate was 62.9%. Five (33.3%) patients were complicated with pulmonary infection. DFPP combined with immunosuppressive therapy could increase the renal recovery rate through rapidly decreasing serum ANCA levels for AAV patients with severe renal failure, but its clinical efficacy and impact on long-term renal survival require further studies.

Sarcopenia in patients undergoing maintenance hemodialysis: incidence rate, risk factors and its effect on survival risk.

BACKGROUND: Sarcopenia is a degenerative syndrome mainly characterized by the atrophy of skeletal muscle, along with the decrease of muscle strength and function. However, there are currently few studies concerning sarcopenia in patients undergoing maintenance hemodialysis dialysis (MHD). This study was aimed to investigate the incidence of sarcopenia in MHD patients and its influencing factors, as well as its impact on survival risk. METHOD: All 131 MHD patients enrolled in our study were tested with bioelectrical impedance analysis (BIA) and grip strength. Demographic data was collected and anthropometric measurement and laboratory examination were conducted. RESULTS: The total incidence of sarcopenia within the 131 MHD patients was 13.7% and the incidence of sarcopenia in patients over 60 years was 33.3%. The dialysis duration, with or without diabetes, serum phosphorus and pre-albumin levels of sarcopenic patients were significantly different from those of non-sarcopenicones; the modified quantitative subjective global assessment (MQSGA) scores of sarcopenic patients were higher than those without sarcopenia. Multivariate analysis showed that dialysis duration, diabetes and serum phosphorus level were independent risk factors for sarcopenia in MHD patients. Kaplan-Meier survival analysis showed a one-year survival of 88.9% in sarcopenic patients, which was significantly lower than non-sarcopenic patients. CONCLUSION: The incidence of sarcopenia in MHD patients was high and increased gradually with age. Dialysis duration, diabetes, serum phosphorus level and malnutrition predisposed the patients to sarcopenia. One-year follow-up found that the mortality risk of sarcopenic patients was higher than that of non-sarcopenic patients.

Severe Hemolysis in a Patient With Erythrocytosis During Coupled Plasma Filtration Adsorption Therapy Was Prevented by Changing From Membrane-Based Technique to a Centrifuge-Based One.

Coupled plasma filtration adsorption (CPFA) usually adopts membrane to separate plasma from blood. Here, we reported a case with erythrocytosis experienced severe hemolysis and membrane rupture during CPFA, which was avoided by changing from membrane-based technique to a centrifuge-based one. A 66-year-old man was to receive CPFA for severe hyperbilirubinemia (total bilirubin 922 µmol/L, direct bilirubin 638 µmol/L) caused by obstruction of biliary tract. He had erythrocytosis (hemoglobin 230 g/L, hematocrit 0.634) for years because of untreated tetralogy of Fallot. Severe hemolysis and membrane rupture occurred immediately after blood entering into the plasma separator even at a low flow rate (50 mL/min) and persisted after changing a new separator. Finally, centrifugal plasma separation technique was used for CPFA in this patient, and no hemolysis occurred. After 3 sessions of CPFA, total bilirubin level decreased to 199 µmol/L with an average decline by 35% per session. Thereafter, the patient received endoscopic biliary stent implantation, and total bilirubin level returned to nearly normal. Therefore, centrifugal-based plasma separation can also be used in CPFA and may be superior to a membrane-based one in patients with hyperviscosity.

Randomized Controlled Trial to Evaluate Regional Citrate Anticoagulation Plus Low-Dose of Dalteparin in Continuous Veno-Venous Hemofiltration.

BACKGROUND/AIMS: To evaluate the efficacy and safety of regional citrate anticoagulation (RCA) plus low-dose dalteparin in patients receiving continuous veno-venous hemofiltration (CVVH). METHODS: Patients requiring pre-dilution CVVH at 4 l/h were randomly assigned to group A (RCA only), group B (normal-dose dalteparin anticoagulation only) or group C (RCA plus low-dose dalteparin). The primary endpoint was filter runtime and the secondary endpoints were premature clotting of the filter and anticoagulation-related side effects. RESULTS: Fifty-three patients completed the study. The mean filter runtime was significantly longer in group C (40.4 ± 30.9 h) than those in group A (21.2 ± 13.5 h, p = 0.006) and group B (25.1 ± 24.0 h, p = 0.040). The rate of premature clotting, new onset of bleeding, hypocalcemia and metabolic acidosis did not differ significantly in three groups. CONCLUSIONS: RCA plus low-dose dalteparin prolonged filter runtime compared with RCA only or normal-dose dalteparin only without increasing the incidence of anticoagulation-related complications.

Fluid overload at start of continuous renal replacement therapy is associated with poorer clinical condition and outcome: a prospective observational study on the combined use of bioimpedance vector analysis and serum N-terminal pro-B-type natriuretic peptide measurement.

INTRODUCTION: It is unclear whether the fluid status, as determined by bioimpedance vector analysis (BIVA) combined with serum N-terminal pro-B-type natriuretic peptides (NT-pro-BNP) measurement, is associated with treatment outcome among patients receiving continuous renal replacement therapy (CRRT). Our objective was to answer this question. METHODS: Patients who were in the intensive care units of a university teaching hospital and who required CRRT were screened for enrollment. For the enrolled patients, BIVA and serum NT-pro BNP measurement were performed just before the start of CRRT and 3 days afterward. According to the BIVA and NT-pro BNP measurement results, the patients were divided into four groups according to fluid status type: type 1, both normal; type 2, normal BIVA results and abnormal NT-pro BNP levels; type 3, abnormal BIVA results and normal NT-pro BNP levels; and type 4, both abnormal. The associations between fluid status and outcome were analyzed. RESULTS: Eighty-nine patients were enrolled, 58 were males, and the mean age was 49.0 ± 17.2 years. The mean score of Acute Physiology and Chronic Health Evaluation II (APACHE II) was 18.8 ± 8.6. The fluid status before CRRT start was as follows: type 1, 21.3% (19 out of 89); type 2, 16.9% (15 out of 89); type 3, 11.2% (10 out of 89); and type 4, 50.6% (45 out of 89). There were significant differences between fluid status types before starting CRRT on baseline values for APACHE II scores, serum creatinine, hemoglobin, platelet count, urine volume, and incidences of oliguria and acute kidney injury (P <0.05). There were significant differences between patients with different fluid status before CRRT start on hospital mortality--type 1, 26.3% (5 out of 19); type 2, 33.3% (5 out of 15); type 3, 40% (4 out of 10); and type 4, 64.4% (29 out of 45) (P = 0.019)--as well as renal function recovery rates: type 1, 57.1% (4 out of 7); type 2, 67.7% (6 out of 9); type 3, 50% (3 out of 6); and type 4, 23.7% (9 out of 38) (P = 0.051). CONCLUSIONS: Fluid status abnormalities were common among patients receiving CRRT. Different types of fluid status distinguished by BIVA combined with serum NT-pro BNP measurements corresponded to different clinical conditions and treatment outcomes, which implies a value of this method for evaluation of fluid status among patients receiving CRRT.

Clearance of myoglobin by high cutoff continuous veno-venous hemodialysis in a patient with rhabdomyolysis: a case report.

Continuous veno-venous hemodialysis using high cutoff filters (HCO-CVVHD) is a promising technique, which may be effective to decrease the extremely high level of circulating myoglobin in patients with rhabdomyolysis (RM). Here, we report a patient with RM caused by heat stroke who was successfully treated by HCO-CVVHD. A male patient received HCO-CVVHD with 4 L/h dialysate for 5 days and then pre-dilution continuous veno-venous hemofiltration (CVVH) at a dose of 4 L/h until recovery of renal function. The clearance of myoglobin and albumin at 5 minutes, and at 4, 12, and 24 hours were calculated. The serum myoglobin level decreased from a peak of 25,400 ng/mL on admission to 133 ng/mL at discharge. During HCO-CVVHD, the mean clearances of serum myoglobin at four timepoints were 61.3 (range, 61.0-61.6), 52.3 (38.9-65.8), 47.3 (46.8-47.9), and 43.7 (39.5-48.0) mL/min, respectively, and the mean clearances of albumin were 12.4 (range, 11.8-13.1), 3.1 (2.5-3.8), 1.2 (1.0-1.4), and 0.8 (0.6-1.0) mL/min, respectively. During CVVH, the clearance rates of myoglobin at 5 minutes and 24 hours were 17.0 and 3.8 mL/min, respectively, with a negligible clearance of albumin. HCO-CVVHD can effectively decrease serum myoglobin in patients with RM because of much higher clearance of myoglobin than CVVH. However, attention should be paid to albumin loss during HCO-CVVHD.

Comparison of double filtration plasmapheresis with immunoadsorption therapy in patients with anti-glomerular basement membrane nephritis.

BACKGROUND: Double filtration plasmapheresis (DFPP) and (IA) are both used to clear antibody. However, the clinical efficacy and safety of DFPP in patients with anti-glomerular basement membrane (anti-GBM) disease are unclear. METHODS: The 28 enrolled patients diagnosed serologically and pathologically with anti-GBM disease from 2003 to 2013 included 16 treated with DFPP and 12 with IA, with all patients administered immunosuppressive agents. DFPP consisted of an EC50W filter for plasma separation and an EC20W filter for plasma fractionation. A double volume of plasma was processed, and each patient received a 30-40 g human albumin supplement during each session. IA consisted of 10 cycles per session, with 8-10 sessions performed daily or every other day and each session regenerating 30-60 L of plasma. Serum anti-GBM antibodies and IgG were measured, and urinary and blood tests were performed, before and after each procedure. Renal function and outcome were determined. RESULTS: The 28 patients consisted of 13 males and 15 females, of median age 44.5 years (range, 22.5-57 years). Six patients had pulmonary hemorrhage and 18 had serum creatinine concentrations >500 umol/L. The average serum creatinine concentration at early onset of disease was 525 umol/L while the peak concentration was 813 umol/L. All patients showed progressive increases in serum creatinine and required CRRT during the course of disease. Pathological examination showed an average 73.9% of crescents (range, 54.6-95.4%).The clinical and pathological features of the DPPP and IA groups were similar. Efficacy of clearing anti-GBM antibody was similar in the two groups (59.0 vs. 71.2%, P = 1.00), although fewer patients in the DFPP group experienced reduced IgG (62.7 vs. 83.5%, p = 0.002). One patient each had a pulmonary hemorrhage and a subcutaneous hemorrhage during treatment, but there were no other serious complications. At the end of follow-up, patient survival and renal survival were similar in the DFPP and IA groups. CONCLUSION: DPPP plus immunosuppressive therapy efficiently and safely removed anti-GBM antibodies. The fewer plasma-associated side effects and reduced loss of IgG suggest that DFPP may be a better treatment choice for anti-GBM disease, especially in patients with insufficient plasma.

Decreased platelet count in patients receiving continuous veno-venous hemofiltration: a single-center retrospective study.

BACKGROUND: A decreased platelet count may occur and portend a worse outcome in patients receiving continuous renal replacement therapy (CRRT). We aim to investigate the incidence of decreased platelet count and related risk factors in patients receiving CRRT. METHODS: In this retrospective study, we screened all patients receiving continuous veno-venous hemofiltration (CVVH) at Jinling Hospital between November 2008 and October 2012. The patients were included who received uninterrupted CVVH for more than 72 h and had records of blood test for 4 consecutive days after ruling out pre-existing conditions that may affect the platelet count. Platelet counts before and during CVVH, illness severity, CVVH settings, and outcomes were analyzed. RESULTS: The study included 125 patients. During the 3-day CVVH, 44.8% and 16% patients had a mild decline (20-49.9%) and severe decline (≥ 50%) in the platelet count,respectively; 37.6% and 16.0% patients had mild thrombocytopenia (platelet count 50.1-100 × 109/L) and severe thrombocytopenia (platelet count ≤ 50 × 10(9)/L), respectively. Patients with a severe decline in the platelet count had a significantly lower survival rate than patients without a severe decline in the platelet count (35.0% versus 59.0%, P=0.012), while patients with severe thrombocytopenia had a survival rate similar to those without severe thrombocytopenia (45.0% versus 57.1%, P=0.308). Female gender, older age, and longer course of the disease were independent risk factors for a severe decline in the platelet count. CONCLUSIONS: A decline in the platelet count and thrombocytopenia are quite common in patients receiving CVVH. The severity of the decline in the platelet count rather than the absolute count during CVVH may be associated with hospital mortality. Knowing the risk factors for a severe decline in the platelet count may allow physicians to prevent such an outcome.

Induction therapy with bortezomib and dexamethasone followed by autologous stem cell transplantation versus autologous stem cell transplantation alone in the treatment of renal AL amyloidosis: a randomized controlled trial.

BACKGROUND: Although the use of bortezomib alone and in combination with steroids has shown efficacy in AL amyloidosis, its role in combination with high-dose melphalan and autologous stem cell transplantation (HDM/SCT) is unknown. In this study, we evaluated bortezomib in combination with dexamethasone (BD) for induction chemotherapy prior to HDM/SCT. METHODS: This was a single-center, prospective, randomized controlled trial comparing induction therapy consisting of two BD cycles followed by HDM/SCT (BD + HDM/SCT) with HDM/SCT alone in the treatment of patients with newly diagnosed AL amyloidosis. The hematological and organ responses of the patients were assessed every three months post HDM/SCT. RESULTS: Fifty-six patients newly diagnosed with renal (100%), cardiac (57.1%), liver (7.1%), or nervous system (8.9%) AL amyloidosis were enrolled in this study; 28 patients were assigned to each arm. Two patients died within 100 days of HDM/SCT (3.6% treatment-related mortality). The overall hematologic response rates in the BD + HDM/SCT arm and HDM/SCT arm at three, six and twelve months were 78.5% versus 50%, 82.1% versus 53.5% and 85.7% versus 53.5%, respectively. In the BD + HDM/SCT arm, 15 (53.5%) patients achieved a hematologic response after BD and before HDM/SCT. An intention-to-treat analysis revealed a higher rate of complete remission in the BD + HDM/SCT arm at both 12 and 24 months (67.9% and 70%, respectively) than with the HDM/SCT-only therapy (35.7% and 35%, respectively, P = 0.03). After a median follow-up of 28 months, the survival rates at 24 months post-treatment start were 95.0% in the BD + HDM/SCT group and 69.4% in the HDM/SCT alone group (P = 0.03). CONCLUSIONS: Our preliminary data suggest that the outcome of treating AL amyloidosis with BD induction and HDM/SCT was superior to the outcome of the HDM/SCT treatment alone. TRIAL REGISTRATION: This trial has been registered at clinicaltrials.gov with the number NCT01998503.