Renal CD81 interacts with sodium potassium 2 chloride cotransporter and sodium chloride cotransporter in rats with lipopolysaccharide-induced preeclampsia.

The kidney regulates blood pressure through salt/water reabsorption affected by tubular sodium transporters. Expanding our prior research on placental cluster of differentiation 81 (CD81), this study explores the interaction of renal CD81 with sodium transporters in preeclampsia (PE). Effects of renal CD81 with sodium transporters were determined in lipopolysaccharide (LPS)-induced PE rats and immortalized mouse renal distal convoluted tubule cells. Urinary exosomal CD81, sodium potassium 2 chloride cotransporter (NKCC2), and sodium chloride cotransporter (NCC) were measured in PE patients. LPS-PE rats had hypertension from gestational days (GD) 6 to 18 and proteinuria from GD9 to GD18. Urinary CD81 in both groups tented to rise during pregnancy. Renal CD81, not sodium transporters, was higher in LPS-PE than controls on GD14. On GD18, LPS-PE rats exhibited higher CD81 in kidneys and urine exosomes, higher renal total and phosphorylated renal NKCC2 and NCC with elevated mRNAs, and lower ubiquitinated NCC than controls. CD81 was co-immunoprecipitated with NKCC2 or NCC in kidney homogenates and co-immunostained with NKCC2 or NCC in apical membranes of renal tubules. In plasma membrane fractions, LPS-PE rats had greater amounts of CD81, NKCC2, and NCC than controls with enhanced co-immunoprecipitations of CD81 with NKCC2 or NCC. In renal distal convoluted tubule cells, silencing CD81 with siRNA inhibited NCC and prevented LPS-induced NCC elevation. Further, PE patients had higher CD81 in original urines, urine exosomes and higher NKCC2 and NCC in urine exosomes than controls. Thus, the upregulation of renal CD81 on NKCC2 and NCC may contribute to the sustained hypertension observed in LPS-PE model. Urine CD81 with NKCC2 and NCC may be used as biomarkers for PE.

Targeting ferroptosis attenuates podocytes injury and delays tubulointerstitial fibrosis in focal segmental glomerulosclerosis.

Ferroptosis is a non-apoptotic form of cell death, involved in chronic kidney diseases (CKD) and acute kidney injury (AKI), so far, the role of ferroptosis in focal segmental glomerulosclerosis (FSGS) remains largely unknown. We aimed to investigate the role of ferroptosis in FSGS, in this study, we found the reduced expression of GPX4 in podocytes, as well as tubular epithelial cells (TECs), from patients with FSGS. Treatment with ferrostatin-1 (Fer-1), a potent and selective ferroptosis inhibitor, significantly reduced proteinuria, prevented glomerulosclerosis, attenuated podocyte injury in ADR-induced FSGS murine model. As expected, ADR treatment caused downregulation of GPX4 in human podocytes, treatment with Fer-1 greatly blocked the downregulation of GPX4, restored the GSH level and attenuated cell death. Furthermore, Fer-1 treatment greatly delayed the development of tubulointerstitial fibrosis in ADR-induced FSGS murine model. Taken together, ferroptosis is involved in the pathogenesis of FSGS, targeting ferroptosis is a promising therapeutic option for patients with FSGS.

Efficacy and Safety of Ferric Citrate on Hyperphosphatemia among Chinese Patients with Chronic Kidney Disease Undergoing Hemodialysis: A Phase III Multicenter Randomized Open-Label Active-Drug-Controlled Study.

INTRODUCTION: Hyperphosphatemia in chronic kidney disease (CKD) patients is positively associated with mortality. Ferric citrate is a potent phosphorus binder that lowers serum phosphorus level and improves iron metabolism. We compared its efficacy and safety with active drugs in Chinese CKD patients with hemodialysis. METHODS: Chinese patients undergoing hemodialysis were randomized into two treatment groups in a 1:1 ratio, receiving either ferric citrate or sevelamer carbonate, respectively, for 12 weeks. Serum phosphorus levels, calcium concentration, and iron metabolism parameters were evaluated every 2 weeks. Frequency and severity of adverse events were recorded. RESULTS: 217 (90.4%) patients completed the study with balanced demographic and baseline characteristics between two groups. Ferric citrate decreased the serum phosphorus level to 0.59 ± 0.54 mmol/L, comparable to 0.56 ± 0.62 mmol/L by sevelamer carbonate. There was no significant difference between two groups (p > 0.05) in the proportion of patients with serum phosphorus levels reaching the target range, the response rate to the study drug, and the changes of corrected serum calcium concentrations, and intact-PTH levels at the end of treatment. The change of iron metabolism indicators in the ferric citrate group was significantly higher than those in the sevelamer carbonate group. There are 47 (40.5%) patients in the ferric citrate group, and 26 (21.3%) patients in the sevelamer carbonate group experienced drug-related treatment emergent adverse events (TEAEs); most were mild and tolerable. Common drug-related TEAEs were gastrointestinal disorders, including diarrhea (12.9 vs. 2.5%), fecal discoloration (14.7 vs. 0%), and constipation (1.7 vs. 7.4%) in ferric citrate and sevelamer carbonate group. CONCLUSION: Ferric citrate capsules have good efficacy and safety in the control of hyperphosphatemia in adult patients with CKD undergoing hemodialysis. Efficacy is not inferior to sevelamer carbonate. The TEAEs were mostly mild and tolerated by the patients.

Relationship Between Intimal Thickness on Ultrasonography and Long-Term Patency of Arteriovenous Fistula Restenosis After Cutting Balloon Versus High Pressure Balloon Angioplasty.

BACKGROUND: To investigate the relationship between intimal thickness on ultrasonography and long-term patency of arteriovenous fistula restenosis after cutting balloon and high pressure balloon angioplasty. METHODS: We retrospectively compared the outcomes between cutting balloon angioplasty and high pressure balloon angioplasty in 149 patients with hemodialysis access restenosis. The relationship of intimal thickness and primary assisted patency of hemodialysis access on ultrasonography was investigated as the primary outcome, using Kaplan-Meier survival analysis and Cox proportional hazards model. The second outcomes included residual diameter, blood flow, and venous pressure of hemodialysis access before and after angiography and balloon diameter and inflation pressure. RESULTS: Primary assisted patency in cutting balloon angioplasty was 90.6%, which was significantly (P = 0.001) more than that of 37.9% in high pressure balloon angioplasty during the 20-month follow-up period. Cox proportional hazards model screened significant factors including procedure type (high pressure or cutting, P = 0.004), inflation pressure (P = 0.013), preoperative intimal thickness (P = 0.009), and difference of intimal thickness (P = 0.029). Finally, procedure type (P = 0.012) and preoperative intimal thickness (P = 0.033) were identified for predicting primary assisted patency by multivariate Cox proportional hazards model. CONCLUSIONS: Compared to high pressure balloon angioplasty for treating patients with hemodialysis access restenosis, cutting balloon angioplasty had a better primary assisted patency. The increase of intimal thickness on ultrasonography after angiography was inversely correlated with primary assisted patency.

Successful management of concurrent COVID-19 and Pneumocystis Jirovecii Pneumonia in kidney transplant recipients: a case series.

BACKGROUND: Pneumocystis pneumonia (PCP) is a life-threatening pulmonary fungal infection that predominantly affects immunocompromised individuals, including kidney transplant recipients. Recent years have witnessed a rising incidence of PCP in this vulnerable population, leading to graft loss and increased mortality. Immunosuppression, which is essential in transplant recipients, heightens susceptibility to viral and opportunistic infections, magnifying the clinical challenge. Concurrently, the global impact of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been profound. Kidney transplant recipients have faced severe outcomes when infected with SARS-CoV-2, often requiring intensive care. Co-infection with COVID-19 and PCP in this context represents a complex clinical scenario that requires precise management strategies, involving a delicate balance between immunosuppression and immune activation. Although there have been case reports on management of COVID-19 and PCP in kidney transplant recipients, guidance on how to tackle these infections when they occur concurrently remains limited. CASE PRESENTATIONS: We have encountered four kidney transplant recipients with concurrent COVID-19 and PCP infection. These patients received comprehensive treatment that included adjustment of their maintenance immunosuppressive regimen, anti-pneumocystis therapy, treatment for COVID-19 and other infections, and symptomatic and supportive care. After this multifaceted treatment strategy, all of these patients improved significantly and had favorable outcomes. CONCLUSIONS: We have successfully managed four kidney transplant recipients co-infected with COVID-19 and PCP. While PCP is a known complication of immunosuppressive therapy, its incidence in patients with COVID-19 highlights the complexity of dual infections. Our findings suggest that tailored immunosuppressive regimens, coupled with antiviral and antimicrobial therapies, can lead to clinical improvement in such cases. Further research is needed to refine risk assessment and therapeutic strategies, which will ultimately enhance the care of this vulnerable population.

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.

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.

The Mediating Effect of Symptom Burden in the Depression and Quality of Life in Patients with Maintenance Hemodialysis.

Objective: To investigate current status of quality of life and the association between depression and symptom burden in a sample of Chinese maintenance hemodialysis (MHD) patients. Methods: A self-designed patient general information questionnaire, disease-related information questionnaire, dialysis patient symptom burden scale, depression scale, and quality of survival scale were used to investigate 380 maintenance haemodialysis patients in haemodialysis centres. A regression model of the factors affecting the quality of survival was established using structural equation modelling. Results: The regression model data had a high goodness of fit: c2/df = 4.736, RMSEA = 0.099, GFI = 0.918, CFI = 0.972, TLI = 0.962, SRMR = 0.0469. Structural equation model analysis showed that depression had a positive predictive effect on symptom burden, ß = 0.398, P < 0.001; Symptom burden had a negative predictive effect on the quality of life, ß =-0.851, P < 0.001; and Depression had a negative predictive effect on the quality of life, ß =-0.151, P < 0.001. Depression indirectly affects the quality of life through symptom burdens. Conclusion: Depression and symptom burden directly or indirectly affect the quality of life in patients with maintenance hemodialysis. Symptom burden moderates the relationship between depression and quality of life as a mediating variable.

GYY4137, a H2S donor, ameliorates kidney injuries in diabetic mice by modifying renal ROS-associated enzymes.

Diabetic nephropathy (DN) is a common microvascular complication of both type 1 and type 2 diabetes mellitus and often advances to end-stage renal disease. Oxidative stress plays an important role in the pathogenesis and progress of DN. Hydrogen sulfide (H2S) is considered as a promising candidate for the management of DN. But the antioxidant effects of H2S in DN have not been fully studied. In mouse model induced by high-fat diet and streptozotocin, GYY4137, a H2S donor, ameliorated albuminuria at weeks 6 & 8 and decreased serum creatinine at week 8, but not hyperglycemia. Renal nitrotyrosine and urinary 8-isoprostane were reduced along with the suppressed levels of renal laminin and kidney-injury-molecule 1. Renal NADPH oxidase (NOX) 2 was lower but heme oxygenase (HO) 2, paraoxonase (PON) 1, PON2 were higher in DN+GYY than DN group. NOX1, NOX4, HO1, superoxide dismutases 1-3 were similar between groups. Except for a rise at HO2, all the affected enzymes were unchanged in mRNA levels. The affected reactive-oxygen-species (ROS) enzymes were mainly located in the renal sodium-hydrogen-exchanger positive proximal tubules with similar distribution but changed immunofluorence in GYY4137 treated DN mice. Kidney morphological alterations in DN mice under light and electrical-microscopes were also improved by GYY4137. Thus, exogenous H2S administration may improve the renal oxidative damage in DN by reducing ROS production and enhancing ROS cleavage in kidney via the affected enzymes. This study may shed a light on therapeutic applications in diabetic nephropathy with H2S donors in the future.

A low-salt diet with candesartan administration is associated with acute kidney injury in nephritis by increasing nitric oxide.

A low-salt diet may activate the renin-angiotensin-aldosterone system (RAAS) and is often applied simultaneously with RAAS inhibitors, especially for treatment of proteinuric nephritis. To explore the effect of a low-salt diet combined with angiotensin receptor blockers (ARB) on kidney function, the proteinuric nephritis model was induced by single intravenous injection of doxorubicin, and then the SD rats were administrated with candesartan intraperitoneal injection and fed with different salt diets. Rats with low-salt plus candesartan, not either alone, experienced acute kidney injury (AKI) at day 7 and could not self-restore when extending the experiment time from 7 days to 21 days, unless switching low-salt to normal-salt. Among three nitric oxide synthetases (NOS), endothelial NOS (eNOS) was obviously elevated and PI3K-Akt-eNOS signal pathway was activated. NG-Nitro-L-Arginine Methyl Ester (L-NAME), an eNOS inhibitor, reversed the decreased blood pressure and recovered the kidney dysfunction induced by low-salt with candesartan. The increased TUNEL-positive cells, Bax/Bcl-2 and cleaved-caspase3 protein abundance was ameliorated by L-NAME in vivo. In vitro, sodium nitroprusside, a nitric oxide donor, can also increase Bax/Bcl-2 and cleaved-caspase3 protein level in HK-2 cell. Thus, low-salt diet combined with candesartan in nephritis rats led to AKI, and the mechanism involved the increase of eNOS/NO, which linked to the decrease of blood pressure and the increase of apoptosis. This study provides practical guidance for salt intake in cases of RAS inhibitor usage clinically.

Efficient removal of serum bilirubin by a novel artificial liver support system using albumin convection: a pilot study.

BACKGROUND/AIMS: To compare the efficacy of a new artificial liver support system, fractionated plasma separation and adsorption integrated with hemofiltration, with the old system, plasma adsorption. METHODS: Sixteen patients with acute liver failure each received a first session of treatment using the old system, in which plasma was perfused through an adsorber. They then received a second session using the new system, in which albumin-rich plasma separated using a fraction plasma separator was ultrafiltrated using a hemofilter and perfused through an adsorber before being returned to blood. RESULTS: The new system had a higher clearance of bilirubin and slower decline of clearance over time. There was a lower reduction ratio of bilirubin, bile acid, urea, and creatinine; longer prolongation of coagulation parameters; and greater decline in albumin level using the old system compared with the new one. CONCLUSIONS: Use of the novel system results in more efficient removal of toxins and fewer deterious effects than the old system.

[Effect of interleukin-10 level and human leukocyte antigen-DR expression as prognostic predictors in critically ill patients undergoing continuous renal replacement therapy].

OBJECTIVE: To inquire into interleukin-10 (IL--10) level and monocyte expression of human leukocyte antigen--DR (HLA--DR) are predictors of infection and prognosis in critically ill patients undergoing continuous renal replacement therapy (CRRT). METHODS: A total of 43 critically ill patients undergoing continuous veno-venous hemofiltration (CVVH) were recruited from the intensive care unit (ICU). Anti--coagulated blood was obtained at 1 day before and 4 days after undergoing CVVH, and plasma IL--10 level (enzyme linked immunosorbent assay) and HLA--DR expression (flow cytometry) were determined. Thirty healthy subjects were enrolled as controls. In addition, the correlation between IL--10 and acute physiology and chronic health evaluation II (APACHEII) score was assessed. RESULTS: (1)Altogether, 7 patients died among a total of 43 critically ill patients, the mortality was 16.3%. Eighteen patients had negative cultures during the study (group I), and 19 patients had positive cultures (group II), and in 6 patients positive bacterial culture appeared 72 hours after the beginning of the treatment (group III). (2) The IL--10 level (ng/L) was higher in patients than in healthy subjects [23.46 (46.71) vs. 0.32 (0.45), P < 0.01]. Compared with group I, the levels of IL--10 in group II and III were higher significantly [40.20 (46.44), 41.78 (49.63) vs. 7.33 (21.05), both P < 0.05]. Continuous observation revealed that IL--10 rapidly lowered in group I after treatment [4.50 (7.44) vs. 7.33 (21.05), P < 0.05], while there was no apparent change in patients of other two groups. It was found that IL--10 was significant positive correlation with the APACHEII score (r = 0.71, P < 0.01).(3) HLA--DR was lower in patients than in healthy individuals [21.65% (25.62%) vs. 90.39% (9.80%), P < 0.01]. After CVVH, HLA--DR expression was obviously increased in group I [64.95% (35.03%) vs. 32.45% (45.03%), P < 0.01]. However, there were no significant changes in the other two groups. The patients who died had persistent and extremely low HLA--DR expression. CONCLUSIONS: (1)A significant discriminative power of IL--10 levels in predicting disease severity was found among the patients receiving CRRT, and persistently high IL--10 level predicts poor prognosis. (2) Persistently low monocyte HLA--DR expression may indicate concomitant or impending infection in patients receiving CRRT.

Selective Inhibition of Histone Deacetylase Class IIa With MC1568 Ameliorates Podocyte Injury.

Histone deacetylases (HDACs) inhibitors are promising therapeutic agents against proteinuric kidney diseases, here, we investigated the effect of MC1568, a selective inhibitor of HDAC class IIa, on the development and progression of nephrotic syndrome in a murine model induced by Adriamycin (ADR). In kidney tissues of FSGS patients, all four members of HDAC IIa were significantly upregulated in podocytes. In ADR-treated cultured human podocyte, expression of HDAC IIa were induced, meanwhile inhibition of HDAC IIa with MC1568 restored cytoskeleton structure and suppressed expression of desmin and α-SMA. In mice, administration of MC1568 at 14 days after ADR ameliorated proteinuria and podocyte injury, also decreased expression of Fibronectin and α-SMA. Mechanistically, MC1568 inhibited ADR induced ß-catenin activation in vitro and in vivo. Together, these finding demonstrate that HDAC IIa inhibition ameliorates podocyte injury and proteinuria, which provide a possibility that MC1568 may be used in nephrotic syndrome.

Assessment of Urinary Exosomal NHE3 as a Biomarker of Acute Kidney Injury.

The diagnosis of acute kidney injury (AKI) traditionally depends on the serum creatinine (Scr) and urine output, which lack sufficient sensitivity and specificity. Using urinary exosomes as a biomarker has unique advantages. To assess whether urinary exosomal Na+/H+ exchanger isoform 3 (NHE3) protein could serve as a biomarker of AKI, we constructed four AKI rat models: cisplatin (7.5 mg/kg) injected intraperitoneally (IP), furosemide (20 mg/kg, IP) with a low-NaCl (0.03%) diet, a low-NaCl (0.03%) diet with candesartan (1 mg/kg, IP) and bilateral ischemia and reperfusion (I/R) injury for 40 min. Additionally, we assessed six sepsis-associated AKI patients and six healthy volunteers. Urinary exosomes were extracted by ultracentrifugation, and the NHE3 protein abundance was tested by immunoblotting for all the AKI rats and human subjects. The isolated cup-shaped particles with an average diameter of 70 nm and enrichment in CD63 were identified as exosomes. NHE3 abundance was six times higher in exosomes than in the whole urine. In cisplatin-induced AKI rats, urinary exosomal NHE3 was increased on day 2, one day earlier than the increases in Scr and blood urea nitrogen (BUN). In additional rats, urinary exosomal NHE3 decreased along with the decline in Scr after EPO pretreatment. In volume-depletion AKI induced by furosemide injection with a low-NaCl diet, the urinary exosomal NHE3 expression was higher than that in the control. Under a low-NaCl diet with candesartan-related AKI, the urinary exosomal NHE3 was elevated on day 5, earlier than Scr. In I/R-injury AKI, the urinary exosomal NHE3 was also raised compared with that in the control. In humans, the urinary exosomal NHE3 level was also elevated in sepsis-associated AKI patients in comparison with that in the healthy volunteers. The urinary exosomal NHE3 was increased in multiple AKI; it may be used as a diagnostic biomarker of AKI.

Improvement of immune dysfunction in patients with severe acute pancreatitis by high-volume hemofiltration: a preliminary report.

OBJECTIVE: The aim of this study was to investigate the effect of high-volume hemofiltration (HVHF) on ameliorating immune dysfunction in patients with severe acute pancreatitis (SAP). METHODS: Twelve patients diagnosed with SAP admitted to the intensive care unit of general surgery, Jinling Hospital, from January 2004 to December 2006 were included in this study. They were assigned to the standard medical therapy group (SMT group, n=4) or HVHF group (n=8) immediately after enrollment, in a 1:2 ratio. The SMT group were given standard treatment for SAP, while the HVHF group were given standard as well as 72-hour HVHF treatment initiated within 2 hours after enrollment. Patients in the 2 groups were comparable for the baseline clinical parameters. All patients were monitored over a 72-hour observation period for continuous clinical status, blood cell counts including monocytes, CD4+ and CD8+ T cells, and HLA-DR expression on monocytes. Blood samples were collected from those patients at 0, 6, 12, 24, 48, and 72 hour after enrollment for measurement of plasma Th1-type cytokines (interleukin-1 [IL-1], IL-2, interferon-gamma [IFN-gamma], and tumor necrosis factor-alpha [TNF-alpha]) and Th2-type cytokines (IL-4, IL-5, IL-6, IL-IO, and IL-13) using ELISA. RESULTS: Within 72 hours, all measured cytokines except IL-4 were maintained at high levels, accompanied with a low level of peripheral monocytes, CD4+ and CD8+ T cell counts, and HLA-DR expression. Seventy-two hours later, plasma cytokines IFN-gamma, IL-1, IL-2, IL-5, IL-10, and IL-13 (p<0.05), but not TNF-alpha and IL-6, in patients in the HVHF group were significantly reduced, while there was no change for these parameters in the SMT group. Plasma levels of IFN-gamma, TNF-alpha, IL-1, IL-2, IL-5, and IL-13 in the HVHF group were significantly lower than those in the SMT group. Peripheral CD4+ and CD8+ T cells, monocyte count, and HLA-DR expression were increased significantly (p<0.05) only in the HVHF group, not in the SMT group. HLA-DR expression in the HVHF group was significant higher than that in the SMT group (p<0.05). CONCLUSIONS: HVHF significantly reduced plasma inflammatory cytokine concentrations including those of IFN-gamma, TNF-alpha, IL-1, IL-2, IL-5, and IL-13, while it increased monocyte HLA-DR expression in patients with SAP. The association of plasma cytokine reduction and cellular immune function recovery and clinical outcome needs further investigation.

Crush syndrome after the Wenchuan earthquake: new experience with regional citrate anticoagulation continuous veno-venous hemofiltration.

PURPOSE: Acute renal failure (ARF) related to crush syndrome is usually treated with hemodialysis. Continuous veno-venous hemofiltration (CVVH) has seldom been adopted in this situation due to the main drawback of continuous anticoagulation. The purpose of this study was to evaluate the effectiveness and safety of regional citrate anticoagulation (RCA)-CVVH in two crush syndrome patients following the Wenchaun earthquake. METHODS: Two victims from the Wenchuan earthquake in Southwest China were admitted to our hospital on May 23, 2008, 11 days after their injury. The total entrapment time under the rubble was 5.5 and 22.5 hrs respectively. They remained oliguric on admission, in spite of vigorous treatment in the local hospital including aggressive fluid infusion, fasciotomy and intermittent hemodialysis. On admission, their serum myoglobin levels were 765 and 829 ng/mL, respectively. Further debridement and drainage were performed. RCA-CVVH was conducted; the citrate containing substitution fluid was infused in a pre-dilution manner at a rate of 4 l/h; calcium was infused through a separate access to the venous inlet of the double lumen catheter. The infusion rate was adjusted according to the serum ionized calcium and whole blood activated clotting time (WBACT). A low dose of low molecular weight heparin (LMWH) was infused at the rate of 150 approximately 300 U/h simultaneously for anticoagulation after anemia had been corrected and their wounds were stable. RCA-CVVH was substituted by conventional CVVH and LMWH anticoagulation when case 2 complicated with hypoxia. RESULTS: RCA-CVVH was well tolerated, hemodynamic status was stable, and no complications related with RCA-CVVH were noted. The body temperature and WBC decreased to normal range, while anemia and hypoalbuminia were corrected. The levels of serum myoglobin and creatine phosphokinase were also decreased to normal range. Their urine volume increased after 20 and 22 days of oliguria and the tubular function of the patients recovered well. Although the second case encountered acute cholecystitis and acute lung injury in the hospital, both the patients recuperated and neither of them underwent amputation. CONCLUSIONS: The present two crush patients have been successfully treated, but due to the limits of the small sample, it is difficult to generalize whether RCA-CVVH is safe enough for crush syndrome with a high risk of bleeding diathesis. Additional investigation with a larger number of patients is required. Fluid equilibrium, nutritional support, prevention of bleeding and infection are fundamental in this situation.

[Treatment experience of severe acute pancreatitis on 1033 cases.].

OBJECTIVE: To summary the treatment experience of severe acute pancreatitis (SAP). METHODS: From January 1997 to March 2009, a total of 1033 patients suffered SAP were admitted with a mean APACHE II score 12.0 +/- 4.3. There were 622 males and 411 females, aged from 13 to 98 years old. All patients were cared by the multidisciplinary team with intensivist, endoscopists, gastroenterologists, radiologist, nephrologist and surgeons.Patients treated in SICU in the early phase of the disease. In these 1033 patients, 365 cases received mechanical ventilation, 218 with tracheotomy, 159 cases received high-volume continuous venovenous hemofiltration (CVVH), 179 received nasobiliary drainage, 513 were treated with early enteral nutrition. CT-guided percutaneous catheter drainge for peripancreatic fluid collection was pefromed for 477 times and 438 patients received surgical debridement for infected pancreatic necrosis. RESULTS: In all these 1033 cases, 975 patients (94.4%) survived, and 38 patients died (3.7%). The mortality of patients who received surgical debridement for infected pancreatic necrosis was 7.1% (31/438). CONCLUSION: The muti-discipline management of severe acute pancreatitis can remarkably improve the prognosis of patients.

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.

Amelioration of hemodynamics and oxygen metabolism by continuous venovenous hemofiltration in experimental porcine pancreatitis.

AIM: To investigate the potential role of continuous venovenous hemofiltration (CVVH) in hemodynamics and oxygen metabolism in pigs with severe acute pancreatitis (SAP). METHODS: SAP model was produced by intraductal injection of sodium taurocholate (4%, 1 mL/kg body weight (BW)) and trypsin (2 U/kg BW). Animals were allocated either to untreated controls as group 1 or to one of two treatment groups as group 2 receiving a low-volume CVVH (20 mL/(kg.h)), and group 3 receiving a high-volume CVVH (100 (mL/kg.h)). Swan-Ganz catheter was inserted during the operation. Heart rate, arterial blood pressure, cardiac output, mean pulmonary arterial pressure, pulmonary arterial wedge pressure, central venous pressure, systemic vascular resistance, oxygen delivery, oxygen consumption, oxygen extraction ratio, as well as survival of pigs were evaluated in the study. RESULTS: Survival time was significantly prolonged by low-volume and high-volume CVVHs, which was more pronounced in the latter. High-volume CVVH was significantly superior compared with less intensive treatment modalities (low-volume CVVH) in systemic inflammatory reaction protection. The major hemodynamic finding was that pancreatitis-induced hypotension was significantly attenuated by intensive CVVH (87.4+/-12.5 kPa vs 116.3+/-7.8 kPa, P<0.01). The development of hyperdynamic circulatory failure was simultaneously attenuated, as reflected by a limited increase in cardiac output, an attenuated decrease in systemic vascular resistance and an elevation in oxygen extraction ratio. CONCLUSION: CVVH blunts the pancreatitis-induced cardiovascular response and increases tissue oxygen extraction. The high-volume CVVH is distinctly superior in preventing sepsis-related hemodynamic impairment.

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.