Dialyzer reprocessing: Considerations and pitfalls for effective and safe hemodialysis.

BACKGROUND: Dialyzer reprocessing for dialyzer reuse in the same patient has been developed since the early time in hemodialysis history to save cost and time related to reassembling the new dialyzer during that time. The procedure can reduce the first-use and allergic reactions from using incompatible cellulosic dialyzer membrane by altering some manufacturing chemicals. METHODS: All of established literatures regarding recent dialyzer reprocessing methods and considerations were extensively reviewed and summarized. RESULTS: Dialyzer reprocessing can be performed by multiple protocols but involves common steps including bedside rinsing after use, cleaning, dialyzer testing to prevent excessive drop in dialyzer clearance and membrane integrity, high-level disinfection or sterilization either by chemicals or heat, storage, and preparation for subsequent dialysis session by adequate rinsing to reduce the residual reprocessing chemical to the safe level. Compared with the single-use strategy, evidence is conflicting for the mortality advantages or disadvantages of dialyzer reuse, with some showing increased mortality in patients receiving peracetic acid sterilization. Keys for the effective and safe dialyzer reuse involve strict adherence to specific manufacturer's protocol, adequate dialysis water quality complied with the Association for the Advancement of Medical Instrumentation standard, measurement of the total cell volume to prevent inadequate hemodialysis, and infectious control consideration. In the present era, single-use strategy is increasingly adopted due to the decreased cost for dialyzer manufacturing. Environmental concerns of higher solid waste from dialyzer disposal in single-use dialysis should be compared with the liquid waste from reprocessing chemicals along with plastic waste and cardboard in reuse dialysis. CONCLUSION: Dialyzer reprocessing with adequate regulation is considered as an acceptable option for cost-effective hemodialysis, compared with the single-use strategy.

Determination of the number of times for reuse of hemodialysis dialyzer through macrophage responses against dialyzer-eluted protein, a proposed method.

BACKGROUND: Although the number of times dialyzer-reuse in hemodialysis is currently determined by the total volume of the dialyzer, the determination by macrophage activation using dialyzer-eluted protein might predict systemic inflammation. OBJECTIVE: The pro-inflammatory activities of the proteins from 5- and 15-times reused dialyzers were tested as a proof of concept experiment. METHODS: Accumulated proteins in dialyzers were eluted by the roller pump (the recirculation of 100 mL of buffer in a dialyzer with a roller pump at 15 mL/min for 2 h) or infusion procedures (infusion of 100 mL buffer in a dialyzer for 2 h) using chaotropic or potassium phosphate buffers (KPB) before the activation on macrophages cell lines (THP-1-derived human macrophages or RAW264.7 murine macrophages). RESULTS: The concentrations of dialyzer-eluted protein from both methods were not different and the infusion procedure was further used. The eluted proteins (by both buffers) from 15-times-reused dialyzers reduced cell viability, increased supernatant cytokines (TNF-α and IL-6), and upregulated pro-inflammatory genes (IL-1ß and iNOS) in either THP-1-derived or RAW264.7 macrophages (higher responses in RAW264.7 cells) compared with the new dialyzer. Meanwhile, the 5-times-reused dialyzer protein did not reduce cell viability but enhanced some of these pro-inflammatory macrophage markers. CONCLUSIONS: Due to the simpler preparation of KPB over chaotropic buffer with an easier protocol of RAW264.7 over THP-1-derived macrophages, the responses of RAW264.7 against dialyzer-eluted protein with infusion method using KPB buffer were proposed for determination of the number of times dialyzer reuse in hemodialysis.

TMAO reductase, a biomarker for gut permeability defect induced inflammation, in mouse model of chronic kidney disease and dextran sulfate solution-induced mucositis.

BACKGROUND: The excretion of trimethylamine N-oxide (TMAO) (uremic toxin) into the intestine might be enhanced, due to the limited renal elimination in chronic kidney disease (CKD), possibly induced TMAO reductase (a TMAO-neutralizing enzyme) in gut bacteria. Detection of TMAO reductase in serum could be used as a biomarker of gut permeability defect. OBJECTIVE: To explore the correlation between serum TMAO reductase, gut leakage, and systemic inflammation in CKD. METHODS: Mouse models of gut leakage; including 5/6 nephrectomy-induced chronic kidney disease (CKD), a model without colitis, and 1.5% dextran sulfate solution (DSS), a colitis model, were performed. In parallel, serum samples from patients with chronic hemodialysis (n = 48) and the healthy control (n = 20) were analyzed. RESULTS: Gut-leakage (FITC-dextran, endotoxemia, and reduced intestinal tight junction protein) was detected in both CKD and DSS models. While TMAO reductase and TMAO were elevated in the serum of both mouse models and patients, TMAO reductase correlated with TMAO, gut- leakage, and serum IL-6 only in mice but not in patients. Notably, endotoxemia was used as a surrogate marker of gut leakage in patients. In patients, TMAO reductase and TMAO did not correlate with serum IL-6 and vascular complications using the ankle-brachial index and cardio-ankle vascular index. CONCLUSIONS: Serum TMAO reductase was elevated in CKD mice and patients with CKD. Serum TMAO reductase was correlated with TMAO and gut-leakage only in mice but not in patients. Further studies in patients are needed to determine the benefit of serum TMAO reductase in patients with CKD.

Comparative efficacy between hemodialysis using super high-flux dialyzer with hemoperfusion and high-volume postdilution online hemodiafiltration in removing protein bound and middle molecule uremic toxins: A cross-over randomized controlled trial.

BACKGROUND: Hemodialysis (HD) using super high-flux dialyzer (HD + SHF) comparably removed uremic toxins to high-volume postdilution online hemodiafiltration (olHDF). Integration of hemoperfusion (HP) to HD + SHF (HD + SHF + HP) might provide superior uremic toxin removing capability to high-volume postdilution olHDF. METHOD: The present study was conducted in thrice-a-week HD patients to compare the efficacy in removing indoxyl sulfate (IS), beta-2 microglobulin (ß2 M), and urea between high-volume postdilution ol-HDF and HD + SHF + HP, comprising HD + SHF as the main treatment plus HD + SHF + HP 1/week in the first 4 weeks and 1/2 weeks in the second 4 weeks. RESULTS: Ten prevalent HD patients with blood flow rate (BFR) above 400 ml/min were randomized into two sequences of 8-week treatment periods of HD + SHF + HP and later high-volume postdilution olHDF or vice versa. When compared with high-volume postdilution olHDF (convective volume of 26.02 ± 1.8 L/session), HD + SHF + HP provided comparable values of percentage reduction ratio of IS (52.0 ± 11.7 vs. 56.3 ± 7.5%, p = 0.14) and ß2 M (83.7 ± 4.9 vs. 84.0 ± 4.3%, p = 0.37) and slightly lower urea reduction ratio. Despite greater dialysate albumin loss (p = 0.008), there was no significant change in serum albumin level in HD + SHF + HP group. CONCLUSIONS: HD + SHF + HP could not provide superior efficacy in removing uremic toxins to high-volume postdilution olHDF. The use of low BFR of 200 ml/min during the first 2 h of HD + SHF + HP session, according to the instruction of manufacturer, might impair the efficacy of the HD + SHF part in removing uremic toxins.

Comparative Effectiveness between Expanded Hemodialysis (Hemodialysis Using a Medium Cut-Off Dialyzer) and Mixed-Dilution Online Hemodiafiltration Using a High-Flux Dialyzer in Removing Middle-Molecule Uremic Toxins.

INTRODUCTION: Expanded hemodialysis (HD using a medium cut-off dialyzer [HD + MCO]) provides comparable or better removal of various uremic toxins, particularly large middle-molecule uremic toxins, than post-dilution online hemodiafiltration (olHDF). Uremic toxin-removing effectiveness between HD + MCO and mixed-dilution olHDF, one of the currently most efficient olHDF modalities, has not been assessed. METHOD: This randomized controlled trial was conducted in 14 prevalent thrice-a-week HD patients with blood flow rate above 400 mL/min. The patients were randomized into two sequences of 2-week treatment periods of HD + MCO and later mixed-dilution olHDF or vice versa. The reduction ratio (RR) values of small-molecule as well as middle-molecule uremic toxins and protein-bound uremic toxins were measured at baseline and at the end of the treatment. RESULTS: When compared with mixed-dilution olHDF, HD + MCO provided slightly lower ß2M RR, but the value was still higher than 75%; showed similar κFLC RR, IS RR, and URR; and yielded significantly higher RR values of α1M (p < 0.001) and λFLC (p < 0.001). Despite higher albumin loss in HD + MCO, the serum albumin levels at the end of the study were comparable between both groups. CONCLUSION: Expanded HD (HD + MCO) provided similar effectiveness in removing various uremic toxins and could exhibit greater removal of large middle-molecule uremic toxins, such as α1M and λFLC. Expanded HD can be used as an effective alternative option for mixed-dilution olHDF.

The epidemiology and characteristics of acute kidney injury in the Southeast Asia intensive care unit: a prospective multicentre study.

BACKGROUND: Etiologies for acute kidney injury (AKI) vary by geographic region and socioeconomic status. While considerable information is now available on AKI in the Americas, Europe and China, large comprehensive epidemiologic studies of AKI from Southeast Asia (SEA) are still lacking. The aim of this study was to investigate the rates and characteristics of AKI among intensive care unit (ICU) patients in Thailand. METHODS: We conducted the largest prospective observational study of AKI in SEA. The data were serially collected on the first 28 days of ICU admission by registration in electronic web-based format. AKI status was defined by full Kidney Disease: Improving Global Outcome criteria. We used AKI occurrence as the clinical outcome and explored the impact of modifiable and non-modifiable risk factors on the development and progression of AKI. RESULTS: We enrolled 5476 patients from 17 ICU centres across Thailand from February 2013 to July 2015. After excluding patients with end-stage renal disease and those with incomplete data, AKI occurred in 2471 of 4668 patients (52.9%). Overall, the maximum AKI stage was Stage 1 in 7.5%, Stage 2 in 16.5% and Stage 3 in 28.9%. In the multivariable adjusted model, we found that older age, female sex, admission to a regional hospital, medical ICU, high body mass index, primary diagnosis of cardiovascular-related disease and infectious disease, higher Acute Physiology and Chronic Health Evaluation II, non-renal Sequential Organ Failure Assessment scores, underlying anemia and use of vasopressors were all independent risk factors for AKI development. CONCLUSIONS: In Thai ICUs, AKI is very common. Identification of risk factors of AKI development will help in the development of a prognostic scoring model for this population and should help in decision making for timely intervention, ultimately leading to better clinical outcomes.

Clinical and subclinical acute kidney injury in multidrug-resistant septic patients treated with colistimethate sodium: Incidence and clinical outcomes.

AIM: Colistimethate sodium (CMS) has been postulated as the principal cause of high incidence of clinical acute kidney injury (AKI) in multidrug-resistance (MDR) septic patients with normal baseline serum creatinine (sCr) who were treated with CMS. This prospective observational study was conducted to examine the incidence and clinical outcomes of clinical and subclinical AKI in MDR septic patients receiving CMS. METHODS: Forty-two MDR septic patients with normal sCr who required CMS were included. Clinical AKI was diagnosed by increased sCr levels according to the KDIGO2012 criteria while subclinical AKI was identified by elevated levels of urinary neutrophil gelatinase-associated lipocalin (uNGAL > 150 ng/mL) or urinary liver-type fatty-acid-binding protein (uL-FABP > 10.5 ng/mL). RESULTS: Clinical AKI was noted in 47.6% of patients on day 5 and 38.1% on day 7 after initiating CMS. By using uL-FABP, subclinical AKI was observed in 45.2% and 54.8% on day 5 and 7, respectively. At baseline prior to CMS treatment, subclinical AKI was already present in 90%. The baseline uL-FABP was superior to the baseline uNGAL in early prediction of clinical AKI on day 5. The subclinical AKI patients had comparable worse outcomes as clinical AKI patients. CONCLUSION: The incidence of subclinical AKI in MDR septic patients before CMS treatment was extremely high. The baseline uL-FABP provided the best predictive capacity of clinical AKI. The causes of clinical AKI might include the persistence of sepsis process, subclinical AKI and CMS nephrotoxicity. Proper management of subclinical AKI patients before CMS initiation should be concerned to prevent further renal damage and improve patient and renal outcomes.

High sensitivity Troponin-I levels in asymptomatic hemodialysis patients.

Reduction in renal clearance and removal by hemodialysis adversely affect the level and utility of high-sensitivity troponin I (hsTnI) for diagnosis of acute myocardial infarction (AMI) in hemodialysis (HD) patients. Furthermore, HD process itself might cause undesirable myocardial injury and enhance post HD hsTnI levels. This comparative cross-sectional study was conducted to compare the hsTnI levels between 100 asymptomatic HD patients and their 107 matched non-chronic kidney disease (CKD) population. The hsTnI levels in HD group were higher than non-CKD group [median (IQR): 54.3 (20.6-152.7) vs. 18 (6.2-66.1) ng/L, p < .001)]. The hsTnI levels reduced after HD process from 54.3 (20.6-152.7) ng/L in pre-HD to 27.1 (12.3-91.4) ng/L in post-HD (p = .015). Of interest, 25% of HD patients had increment of hsTnI after HD and might represent HD-induced myocardial injury. The significant risk factors were high hemoglobin level and high blood flow rate. In conclusion, the baseline hsTnI levels in asymptomatic HD patients were higher than non-CKD population. The dynamic change of hsTnI over time would be essential for the diagnosis of AMI. Certain numbers of asymptomatic HD patients had HD-induced silent myocardial injury and should be aggressively investigated to prevent further cardiovascular mortality.

The effect of polymyxin B hemoperfusion on modulation of human leukocyte antigen DR in severe sepsis patients.

BACKGROUND: Recent randomized trials have not found that polymyxin B hemoperfusion (PMX-HP) improves outcomes for patients with sepsis. However, it remains unclear whether the therapy could provide benefit for highly selected patients. Monocyte human leukocyte antigen (mHLA-DR) expression, a critical step in the immune response, is decreased during sepsis and leads to worsening sepsis outcomes. One recent study found that PMX-HP increased mHLA-DR expression while another found that the treatment removed HLA-DR-positive cells. METHODS: We conducted a randomized controlled trial in patients with blood endotoxin activity assay (EAA) level ≥ 0.6. Patients in the PMX-HP group received a 2-h PMX-HP treatment plus standard treatment for 2 consecutive days. Patients in the non-PMX-HP group received only standard treatment. The primary outcome compared the groups on median change in mHLA-DR expression between day 3 and baseline. Secondary outcomes compared the groups on the mean or median change in CD11b expression, neutrophil chemotaxis, presepsin, cardiovascular Sequential Organ Failure Assessment (CVS SOFA) score, vasopressor dose, and EAA level between day 3 and baseline. We further compared the groups on mortality, ICU-free days, ventilator-free days, dialysis dependence status, renal recovery, serum creatinine, vasopressor-free days, and major adverse kidney events (MAKE 28), measured on day 28. RESULTS: Fifty-nine patients were randomized to PMX-HP (n = 29) and non-PMX-HP (n = 30) groups. At baseline, mHLA-DR expression, CD11b, neutrophil chemotaxis, and clinical parameters were comparable between groups. The median change in mHLA-DR expression between day 3 and baseline was higher in PMX-HP patients than in patients receiving standard therapy alone (P = 0.027). The mean change in CD11b between day 3 and baseline was significantly lower in the PMX-HP group than in the non-PMX-HP group (P = 0.002). There were no significant changes from baseline in neutrophil chemotaxis, presepsin, CVS SOFA scores, vasopressor doses, or EAA level between groups. On day 28 after enrollment, mortality, ICU-free days, ventilator-free days, dialysis dependence status, renal recovery, serum creatinine, vasopressor-free days, and MAKE 28 were comparable between groups. CONCLUSION: PMX-HP improved mHLA-DR expression in severe sepsis patients. Future studies should examine the potential benefit of PMX-HP in patients with low mHLA-DR expression. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02413541 . Registered on 3 March 2015.

Early versus standard initiation of renal replacement therapy in furosemide stress test non-responsive acute kidney injury patients (the FST trial).

BACKGROUND: The timing of initiation of renal replacement therapy (RRT) in severe acute kidney injury (AKI) remains controversial, with early initiation resulting in unnecessary therapy for some patients while expectant therapy may delay RRT for other patients. The furosemide stress test (FST) has been shown to predict the need for RRT and therefore could be used to exclude low-risk patients from enrollment in trials of RRT timing. We conducted this multicenter pilot study to determine whether FST could be used to screen patients at high risk for RRT and to determine the feasibility of incorporating FST into a trial of early initiation of RRT. METHODS: FST was performed using intravenous furosemide (1 mg/kg in furosemide-naive patients or 1.5 mg/kg in previous furosemide users). FST-nonresponsive patients (urine output less than 200 mL in 2 h) were then randomized to early (initiation within 6 h) or standard (initiation by urgent indication) RRT. RESULTS: FST was completed in all patients (100%). Only 6/44 (13.6%) FST-responsive patients ultimately received RRT while 47/60 (78.3%) nonresponders randomized to standard RRT either received RRT or died (P <  0.001). Among 118 FST-nonresponsive patients, 98.3% in the early RRT arm and 75% in the standard RRT arm received RRT. The adherence to the protocol was 94.8% and 100% in the early and standard RRT group, respectively. We observed no differences in 28-day mortality (62.1 versus 58.3%, P = 0.68), 7-day fluid balance, or RRT dependence at day 28. However, hypophosphatemia occurred more frequently in the early RRT arm (P = 0.002). CONCLUSION: The furosemide stress test appears to be feasible and effective in identifying patients for randomization to different RRT initiation times. Our findings should guide implementation of large-scale randomized controlled trials for the timing of RRT initiation. TRIAL REGISTRATION: clinicaltrials.gov, NCT02730117 . Registered 6 April 2016.

The role of intraoperative parameters on predicting laparoscopic abdominal surgery associated acute kidney injury.

BACKGROUND: Laparoscopic abdominal surgery has been widely used to reduce the length of hospital stay and complications from open abdominal surgery. During the operation, the creation of pneumoperitoneum is used for better visualization of the operating field. However, the effect of pneumoperitoneum on kidney function is unknown. We aimed to identify risk factors and predictors associated with AKI development following laparoscopic abdominal surgery. METHODS: A single-center prospective cohort study of laparoscopic abdominal surgery patients between June 2012 and December 2013. Acute kidney injury (AKI) was identified by Kidney Disease Improving Global Outcome (KDIGO) criteria. Urinary neutrophil gelatinase associated lipocalin (uNGAL) was measured on the first 3 days after surgery as a surrogate marker of AKI. RESULTS: Of the 64 patients, 23 (35%) developed postoperative AKI. The mean age, initial blood pressure, and initial glomerular filtration rate were not different between AKI and non-AKI groups. Inflation time and exposure index were significantly higher in the AKI group compared to non-AKI group (192.0 vs 151.1 min, p = 0.045, and 2325.9 vs 1866.1 mmHg-minutes, p = 0.035). Operation time, mean intra-abdominal pressure, duration of intraoperative hypotension, amount of blood loss and intravenous fluid were not different between groups. In multivariable analysis adjusted for age, diabetes, baseline estimated glomerular filtration rate, and type of operation (urological surgery), exposure index was significantly associated with postoperative AKI, with odds ratio (95% CI) 1.47 (1.05-2.04), p = 0.024. By combining the intraoperative parameters with clinical model the area under the receiver operating characteristic curve was 0.71 (95% CI 0.58-0.84). CONCLUSIONS: AKI was a common condition in laparoscopic abdominal surgery. Exposure index has been proposed as a novel predictor of laparoscopic abdominal surgery associated AKI.

A double-blind, randomized, placebo-controlled trial of combined calcitriol and ergocalciferol versus ergocalciferol alone in chronic kidney disease with proteinuria.

BACKGROUND: KDOQI guideline suggests that nutritional vitamin D should be supplemented in chronic kidney disease (CKD) patients who have vitamin D insufficiency/deficiency. However, there are scarce data regarding the additional benefit of active vitamin D supplement in CKD patients who were receiving nutritional vitamin D supplement. This study was conducted to explore the effect of adding active vitamin D to nutritional vitamin D supplement on proteinuria and kidney function in CKD with vitamin D insufficiency/deficiency. METHODS: This double-blind, randomized placebo-controlled trial was performed to answer the above question. Sixty-eight patients with CKD stage 3-4, urine protein to creatinine ratio (UPCR) > 1 g/g, and serum 25OH-D level < 30 ng/mL were enrolled. Patients were randomly assigned to receive 12-week treatment with oral ergocalciferol plus placebo (n = 36) or oral ergocalciferol plus calcitriol (n = 32). RESULTS: The mean baseline values of UPCR of both groups were comparable (3.6 ± 3.8 g/g in combined group and 3.5 ± 3.0 g/g in ergocalciferol group). Following 12-week treatment, there were significant reductions in UPCR from baseline in both groups (2.3 ± 2.1 g/g in combined group and 2.4 ± 2.0 g/g in ergocalciferol group). The percentage reductions in UPCR of both groups were not significantly different. The mean eGFR and blood pressure did not differ between baseline and 12-week follow-up and between both groups. No severe hypercalcemia or serious side effects were noted in both groups. CONCLUSIONS: The proteinuria lowering effect of ergocalciferol in CKD patients with vitamin D deficiency was demonstrated. Additional calcitriol supplement did not have more effects on proteinuria. TRIAL REGISTRATION: (Thai Clinical Trials Registry (TCTR) 20140929002 ). Date of registration: September 27, 2014.

High-dose ascorbate with low-dose amphotericin B attenuates severity of disease in a model of the reappearance of candidemia during sepsis in the mouse.

Amphotericin B (Ampho B) isa fungicidal drug that causes cell wall injury. Pharmacological ascorbate induces the extracellular prooxidants, which might enter the Ampho B-induced cell wall porosity and act synergistically.W e tested low-dose Ampho B with a short course of pharmacological ascorbate using a mouse model of sepsis preconditioned with an injection of Candida albicans 6 h prior to cecal ligation and puncture (CLP). In this model, candidemia reappeared as early as 6 h after CLP with a predictably high mortality rate. This characteristic mimics sepsis in the phase of immunosuppression inpatients. Using the model, at 12- and 18-h post-CLP, we administered isotonic (pH neutralized) pharmacological ascorbate intravenously with low-dose Ampho B or sodium deoxycholate, vehicle-controlled, administered IP. The survival rate of low-dose Ampho B plus ascorbate was 53%, compared with < 11% for low-dose Ampho B or high-dose Ampho B alone. In addition, a beneficial effect was demonstrated in terms of kidney damage,liver injury, spleen histopathology, and serum markers at 24 h after CLP. Kidney injury was less severe in low-dose Ampho B plus ascorbate combination therapy due to less severe sepsis. Moreover, ascorbate enhanced the effectiveness of phagocytosis against C. albicans in human phagocytic cells. Taken together, the data indicate that the new mouse model simulates sepsis-induced immunosuppression and that the combination of pharmacological ascorbate with an antifungal drug is a potentially effective treatment that may reduce nephrotoxicity, and perhaps also increase fungicidal activity in patients with systemic candidiasis caused by Candida albicans.

Urine neutrophil gelatinase-associated lipocalin: a diagnostic and prognostic marker for acute kidney injury (AKI) in hospitalized cirrhotic patients with AKI-prone conditions.

BACKGROUND: Acute kidney injury (AKI) is known to increase mortality in hospitalized cirrhotic patients; therefore early identification is utmost significance. There are only a few studies evaluating the cut-off level of urine neutrophil gelatinase-associated lipocalin (uNGAL) for diagnosing AKI and its prognostic value in cirrhotic patients. We aimed to determine the accuracy of uNGAL as a biomarker for early identification of AKI and to determine the cut-off level of uNGAL for diagnosing AKI in hospitalized cirrhotic patients; and (2) to explore the association of 30-day liver-related mortality with uNGAL level. METHODS AND MATERIAL: We prospectively enrolled cirrhotic patients admitted at the King Chulalongkorn Memorial Hospital during May 1, 2011 to Dec 31, 2013. UNGAL levels were measured within 24 h after admission. Clinical and laboratory data were obtained. Patients were followed up to 30 days. RESULTS: Of 137 cirrhotic hospitalized patients, 121 cirrhotic patients (88.3 %) with AKI-prone conditions were included with mean age of 57.3 ± 14.7 years. Thirty-five patients (29 %) developed AKI within 72 h of admission. The causes of AKI were prerenal azotemia (68.6 %), acute tubular necrosis (25.7 %), hepatorenal syndrome (5.7 %), respectively. The mean uNGAL level was significantly higher in the patients who developed AKI compared with those who did not (290.6 ± 356.3 vs. 54.4 ± 73.7 ng/mL; P = 0.0001). The AUC of uNGAL for diagnosing AKI was 0.83 (95 % [CI]: 0.76-0.91) with the optimal cut-off level of 56 ng/mL, providing 77.1 % sensitivity and 73.3 % specificity. Fourteen percent of subjects died during the 30-day follow-up period. The mean uNGAL levels were significantly higher in the mortality group. The AUC of uNGAL in predicting mortality was 0.75 (95 % [CI]: 0.66-0.85), with a best cut-off level of 72 ng/mL providing 70.6 % sensitivity and 69.2 % specificity. However, in multivariate logistic regression analysis, uNGAL is not an independent factor for 30-day liver-related mortality prediction. CONCLUSIONS: uNGAL is a valid marker for the early detection of AKI in hospitalized cirrhotic patients with AKI-prone conditions; however, its level could not independently predict 30-day liver-related mortality.

A Randomized Controlled Study of Efficacy and Safety of Accelerated Versus Standard Hepatitis B Vaccination in Patients With Advanced CKD.

Introduction: Hepatitis B virus (HBV) vaccination is crucial for seronegative patients with advanced chronic kidney disease (CKD) for protection during dialysis while preparing for transplantation. A standard regimen for HBV vaccination requires 24 weeks to be completed. An accelerated HBV vaccination regimen completed within 8 weeks has shown early effective seroconversion in healthcare workers. However, data for patients with advanced CKD are limited. Methods: A randomized controlled trial was conducted in patients with advanced CKD (estimated glomerular filtration rate [GFR] <30 ml/min per 1.73 m2) and patients on dialysis. The patients were randomly assigned to either a standard HBV vaccination regimen (Engerix B; 40 µg at 0, 4, 8, and 24 weeks) or an accelerated regimen (40 µg at 0, 1, 4, and 8 weeks). The hepatitis B surface antibodies (anti-HBs) were measured at 12, 28, and 52 weeks. Seroconversion were defined as anti-HBs ≥10 IU/l. Results: At 12 weeks, among the intention-to-treat (ITT) population of 133 participants (65 in the accelerated and 68 in the standard groups), the accelerated group demonstrated significantly higher rates of seroconversion (83.08% vs. 63.24%, P = 0.01). In the per-protocol (PP) analysis of 125 patients (62 in the standard and 63 in the accelerated groups), the accelerated group exhibited higher seroconversion rate compared with the standard group (85.71% vs. 69.35%, P = 0.03). At 28 and 52 weeks, the seroconversion rates were similar between the 2 groups. Conclusion: In patients with advanced CKD, the accelerated HBV vaccination regimen demonstrated a significantly higher seroconversion rate at 12 weeks of vaccination. This finding suggests that the accelerated regimen is an effective option to achieve rapid seroconversion before initiating hemodialysis or before undergoing kidney transplantation.

A miniaturized immunoassay platform to measure neutrophil gelatinase-associated lipocalin (NGAL) for diagnosis of acute kidney injury.

In this study, we describe the development and evaluation of a slide-based immunoassay platform for the detection of neutrophil gelatinase associated-lipocalin (NGAL) in plasma and urine samples. The capture NGAL antibody was immobilized onto a microscope slide before an analysis of NGAL based on a sandwich immunoassay was further carried out. This assay system exhibited linearity between 50 to 1000 ng/ml of NGAL. The coefficients of variability (CVs) indicated good reproducibility and repeatability of the system. The levels of plasma NGAL measured by the slide-based system were highly correlated with those of ELISA, while this system over-predicted urine NGAL.

The validation of estimated glomerular filtration rate (eGFR) equation for renal transplant recipients.

BACKGROUND: The re-expressed Modification of Diet in the Renal Disease (MDRD) equation and the Chronic Kidney Disease Epidemiology (CKD-EPI) equation were developed to estimate glomerular filtration rate in non-transplant chronic kidney disease (CKD) patients. The Nankivell equation was created to estimate GFR in transplant recipients. However, none of these formulas have been validated in Asian renal transplant patients. Several recently published studies have highlighted the need to adapt estimated glomerular filtration rate (eGFR) equations to the race of their patients. Although the eGFR equation for Thai CKD has been derived, it has not been validated for transplant recipients. Our study aimed validating the Nankivell equation, re-expressed MDRD equation, CKD-EPI, re-expressed MDRD equation with Thai racial factor correction, as well as the Thai eGFR equation in Thai renal transplant recipients. METHODS: A total of 97 adult Thai renal transplant recipients were studied. The 99mTc-DTPA plasma clearance was used as a reference GFR. The serum creatinine was determined by IDMS reference enzymatic methods (CrEnz). RESULTS: The mean reference GFR and CrEnz were 67.86 ± 20.72 ml/min/1.73 m2 and 1.23 ± 0.59 mg/dl. The bias estimated by Bland-Altman analysis can be expressed as -12.11 ± 15.87 ml/ min/1.73 m2 for the Nankivell equation, 2.72 ± 13.90 ml/min/1.73 m2 for the re-expressed IDMS-traceable MDRD equation, -2.59 ± 14.16 ml/min/1.73 m2 for the CKD-EPI equation, -7.05 ± 17.34 ml/min/1.73 m2 for the Thai re-expressed MDRD with Thai racial factor, and -8.62 ± 16.00 ml/min/1.73 m2 for the Thai eGFR equation. The CKD-EPI equation provided the best accuracy and precision in terms of Pearson correlation coefficient, mean difference, error, and accuracy within 10%, 20%, and 30%. CONCLUSIONS: The equations derived mainly from Caucasian and/or non-transplant status can be applied to Thai transplantation recipients with some bias. The CKD-EPI had the least bias compared with other eGFR equations.

Enhanced external counterpulsation, focusing on its effect on kidney function, and utilization in patients with kidney diseases: a systematic review.

Background: Enhanced external counterpulsation (EECP) is provided by a noninvasive device positively affecting cardiovascular function via mechanisms called diastolic augmentation and systolic unloading. The renal aspects of EECP therapy have not been extensively investigated. Objectives: To assess the effect of EECP on renal function and to determine the application in patients with kidney disease. Methods: MEDLINE, EMBASE, SCOPUS, and Cochrane CENTRAL databases were searched for all studies involving EECP treatments. The title and abstract of all searched literatures were screened, and those focusing on renal outcome or conducting in kidney disease patients were selected. Results: Eight studies were included in the qualitative analysis. EECP increases stroke volume, mean arterial pressure, renal artery blood flow, renal plasma flow, glomerular filtration rate (GFR), plasma atrial natriuretic peptide, urine volume, and urinary sodium chloride excretion, but reduces the plasma concentration of renin and endothelin-1 in healthy subjects. A single session of EECP after radioactive contrast exposure could provide increased contrast clearance, and this reduces contrast-induced kidney injury in patients, irrespective of previous kidney function. Thirty-five-hour sessions of EECP treatment were illustrated to increase long-term estimated GFR in patients with chronic angina and heart failure. In cirrhotic patients, EECP fails to improve GFR and renal vascular resistance. EECP device could maintain blood pressure, decrease angina symptoms, and increase cardiac perfusion in hemodialysis patients. Conclusion: EECP treatment potentially increases renal perfusion and prevents kidney injury in several conditions. EECP possibly provides beneficial effects on hemodynamics and cardiac function in hemodialysis patients.

Efficacy comparison between simple mixed-dilution and simple mid-dilution on-line hemodiafiltration techniques: a crossover study.

Mid-dilution and mixed-dilution on-line hemodiafiltration (OL-HDF) techniques are innovated to overcome the limitations of two standard techniques including predilution and postdilution. Unfortunately, the head-to-head comparisons between these two novel techniques in the same study are still limited. Moreover, the original mid-dilution and mixed-dilution OL-HDF need special dialyzers and special machines. In the present study, simple mid-dilution and simple mixed-dilution OL-HDF were settled with the aim for clinical use in general hemodialysis (HD) centers. The efficacies of uremic toxins removal between both modalities were measured and compared. This prospective randomized crossover study was conducted on 12 stable HD patients undergoing simple mixed-dilution and simple mid-dilution OL-HDF techniques. HD prescriptions were similar in both techniques. The dialysis efficacies were determined by calculating small- (urea, creatinine, and phosphate) and middle-molecule (beta-2 microglobulin [ß2M]) removal. Moreover, potential complications such as high transmembrane pressure (TMP) and protein loss were also observed. Simple mixed-dilution OL-HDF provided significantly greater clearances of urea, creatinine, and ß2M when compared with the simple mid-dilution OL-HDF techniques. Phosphate clearances in both techniques were comparable. In addition, TMP and dialysate albumin loss were not different. There were no intradialytic complications in both techniques. Simple mixed-dilution OL-HDF could provide greater efficacy for small- and middle-molecule clearances and acceptable potential risks, while phosphate removal is comparable.

Long-term efficacy of pre- and post-dilution online hemodiafiltration with dialyzer reuse.

OBJECTIVE: Growing evidence has demonstrated the potential survival benefit of online hemodiafiltration (HDF) over conventional hemodialysis (HD). Previous studies regarding online HDF utilized single-use dialyzer The present study was conducted to compare the long-term clinical parameters between pre- and post-dilution online HDF with the reuse dialyzer MATERIAL AND METHOD: This 2-year historical cohort study was conducted in 20 chronic hemodialysis patients who had undergone thrice-a-week pre-dilution online HDF for at least one year. The patients were switched to post-dilution online HDF for another year. Reuse dialyzers were utilized in both methods. RESULTS: No pyrogenic reactions had been detected throughout the 2-year study period. The C-reactive protein (CRP) and nutritional parameters were in good normal ranges. The normalization of protein equivalent of nitrogen appearance (nPNA) was significantly higher during the post-dilution period (1.25 +/- 0.22 vs. 1.11 +/- 0.14 g/kg/d, p < 0.01). Regarding adequacy of hemodialysis, the post-dilution online HDF showed significantly better Kt/V than the pre-dilution mode (2.46 +/- 0.35 vs. 2.35 +/- 0.35, p < 0.05) whereas the predialysis beta2-microglobulin levels were not different (23.43 +/- 5.35 vs. 23.73 +/- 5.55 mg/L, NS). The numbers of reuse were comparable (17.3 +/- 2.6 vs. 16.4 +/- 2.7, NS). CONCLUSION: Utilizing reuse dialyzer in online HDF could provide efficacy, safety, cost saving, and environmental benefit. The post-dilution technique yielded the better adequacy and nutritional status without causing the limitation in the reuse number and would be the standard mode-of-choice for online HDEF