Dehua Gong

Removal of neutrophil gelatinase-associated lipocalin by extracorporeal therapies

Neutrophil gelatinase‐associated lipocalin (NGAL) protein is an early biomarker for acute kidney injury (AKI). It is unknown if extracorporeal therapies (EC) have an effect on circulating NGAL levels. This study was designed to describe the kinetics of NGAL molecule in different EC techniques and to evaluate NGAL clearance in different operational conditions. A mock hemofiltration (HF) and hemoperfusion (HP) setup was used. NGAL was added to the blood reservoir and then measured at 30‐minute intervals from arterial, venous, and ultrafiltrate (UF) lines. Removal kinetics and NGAL sieving coefficient were calculated. In our experiments, baseline NGAL concentration averaged 452 μg/L. There was a consistent downward trend throughout the experiment. NGAL concentration in the UF was between 80 and 90 μg/L, though it showed a slight increase in the second hour. The sieving coefficient of NGAL ranged from 0.2 to 0.4 during HF and it appeared to increase with time, suggesting an initial effect of membrane adsorption. HP proved clearly that there was adsorption of NGAL by the membrane and the point of saturation occured at approximately 60 minutes from the start of circulation. Our evaluation demonstrates that NGAL can be adsorbed and ultrafiltrated with polysulfone membranes. This should be taken into consideration when using NGAL as an AKI biomarker in patients undergoing EC circulation.

More Selective Removal of Myeloperoxidase-Anti-Neutrophil Cytoplasmic Antibody From the Circulation of Patients With Vasculitides Using a Novel Double-Filtration Plasmapheresis Therapy

Our aim was to investigate the removal of myeloperoxidase‐anti‐neutrophil cytoplasmic antibody (MPO‐ANCA) from the circulation of patients with vasculitides by double‐filtration plasmapheresis (DFPP) using various primary separator and secondary separator combinations. Nineteen patients diagnosed with vasculitides positive for serum MPO‐ANCA were enrolled and received 56 sessions of DFPP. One patient received three sessions of DFPP using MPS07 (the primary filter)/EC50W (the secondary filter), nine patients received 27 sessions of DFPP using MPS07/EC20W, and the other nine patients received 26 sessions of DFPP using EC50W/EC20W. The sieving coefficients (SC) of albumin, immunoglobulin (Ig)A, IgG and IgM were measured, as well as the reduction ratio in plasma protein concentrations and MPO‐ANCA titer after a single session of DFPP. The MPS07 filter was well permeable for all the above‐mentioned plasma proteins; the EC50W and EC20W filters were permeable for albumin and IgG, less for IgA and IgM. During DFPP using MPS07/EC50W, the reduction ratio of IgG was much lower than IgM and IgA (30.5 ± 9.0% vs. 89.7 ± 5.4% and 61.7 ± 14.8%). During DFPP using MPS07/EC20W, the decline in IgM, IgA, and IgG was 94.2 ± 3.1%, 96.2 ± 2.3%, and 64.7 ± 21.0%, respectively. During DFPP using EC50W/EC20W, the decline in IgM, IgA, and IgG was 2.8 ± 12.9%, 90.9 ± 4.4%, and 43.5 ± 13.8%, respectively. The percentage reduction in MPO‐ANCA titer after a single session of DFPP using EC50W/EC20W was 34.6 ± 14.3%. DFPP using EC50W/EC20W filters may be more selective for the removal of pathogens such as IgG, with subsequently effective reduction of serum ANCA titer.

Endotoxemia after high cutoff hemodialysis for treatment of patient with multiple myeloma can be prevented by using ultrapure dialysate: A case report

To report endotoxemia presented in a case with multiple myeloma (MM) treated by high cutoff hemodialysis (HCO‐HD) being prevented by using ultrapure dialysate. A female inpatient with MM received six times HCO‐HD (HCO 2100 dialyzer) within 3 weeks after initiation of a chemotherapy based on vincristine + epirubicin + dexamethasone protocol. Conventional dialysate was used in the first three times and then changed to ultrapure dialysate due to elevation of body temperature after HCO‐HD. Free light chains (FLC) and endotoxin levels in blood and dialysate were monitored. After six times HCO‐HD, her serum FLC λ decreased from 4689 mg/L to 492.7 mg/L, with a trend of decline of serum creatinine. The clearance, reduction ratio, and removal amount of FLC λ was 38.4 mL/min, 71.0–85.2%, and 9.06–18.02 g, respectively, in the setting of dialysate flow rate 500 mL/min, while in the setting of dialysate flow rate 200 mL/min, the removal efficacy of FLC λ was lower than the former. A rise of body temperature up to 38.5°C after treatment and endotoxemia (endotoxin levels 0.122 EU/mL) was found when using conventional dialysate (endotoxin levels 0.112–0.145 EU/mL), but not seen after changing to ultrapure dialysate. Combined with appropriate chemotherapy, HCO‐HD can effectively remove and reduce blood FLC. Attention should be paid to the endotoxemia and the rise of temperature after treatment when conventional dialysate is used, which can be prevented by using ultrapure dialysate.

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.

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.

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 ≤50×109/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.

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.

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.

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.

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.