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.

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.

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 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 beneficial effects of intradialytic parenteral nutrition in hemodialysis patients with protein energy wasting: a prospective randomized controlled trial.

In hemodialysis (HD) patients, protein-energy wasting (PEW) is highly prevalent and firstly treated with oral nutritional supplements (ONS). The extent to which intradialytic parenteral nutrition (IDPN) contributes to improve PEW status in HD patients intolerable to ONS remains unclear. Maintenance PEW HD patients being unable to tolerate ONS adverse effects, and having spontaneous energy and protein intake of ≥ 20 kcal/kg/day and ≥ 0.8 g/kg/day, respectively were randomly assigned 1:1 into IDPN and control groups. In IDPN group, most concentrated 3-in-1, fish-oil based parenteral nutrition was infused during HD for 3 months. The control group received intensive dietary counselling once weekly for 3 months. Both groups were then followed for additional 3 months after intervention. A total of 38 patients were randomized (mean age 67.6 years). After 3 months, serum albumin was significantly higher in the IDPN (n = 18) compared with control group (from 3.5 ± 0.3 to 3.8 ± 0.2 vs from 3.6 ± 0.3 to 3.5 ± 0.3 g/dL, respectively, p = 0.01). Spontaneous dietary intake (p = 0.04), body weight (p = 0.01), and malnutrition inflammation score (MIS, p = 0.01) were improved in the IDPN, but not in the control group. Muscle mass, strength, serum prealbumin, interleukin-6, high sensitivity-c reactive protein, and acylated ghrelin were not significantly different but leptin levels increased in the control group after 3 months (p = 0.03). At 6 months, serum albumin in the IDPN group was persistently higher than baseline (p = 0.04). Neither volume overload nor uncontrolled hyperglycemia was found throughout the study. In conclusion, a 3-month IDPN supplementation demonstrated a significant increase in serum albumin, body weight, spontaneous oral intake, and MIS; and appeared to be superior to continuing intensive dietary counselling among HD patients intolerable to ONS. The impacts of IDPN therapy on clinical outcomes may require larger scale with longer period of study.

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.

The role of once-weekly online hemodiafiltration with low protein diet for initiation of renal replacement therapy: A case series.

Incremental hemodialysis (HD) has become an exciting approach according to the recognition of the importance of preserving residual kidney function (RKF). However, not all incident HD patients are suitable for this approach, particularly once-weekly HD. This is the first study which reported the effectiveness of once-weekly online-hemodiafiltration (OL-HDF) plus low protein diet (LPD) in incident HD patients. All stage 5 CKD patients who had chosen HD as their treatment modality at the HD center of King Chulalongkorn Memorial Hospital, Bangkok, Thailand, with RKF ⩾ 3 mL/min calculated by renal clearance of urea and urine output ⩾ 800 mL/day, started the treatment with once-weekly OL-HDF. Dietitians advised patients to consume LPD (0.6-0.8 g/kg/day) on non-dialysis days and a regular protein diet on the dialysis day (1.2 g/kg/day). Eleven incident HD patients were enrolled in the study. The mean RKF and urine volume at baseline were 4.56 ± 2.21 mL/min and 2,019.54 ± 743.73 mL/day, respectively. After 6 and 12 months of follow-up, the mean RKF of the patients who remained in the once-weekly OL-HDF protocol were 3.82 ± 1.68 mL/min and 3.28 ± 0.95 mL/min, respectively. The median duration of once-weekly OL-HDF before transitioning to twice- or thrice-weekly OL-HDF was 7 months (3-24 months). The most common indication for stepping prescription was too low RKF. We reported that dialysis initiation in the university-based center with once-weekly OL-HDF in carefully selected incident HD patients combined with LPD under serial monitoring is practical. Further studies on the clinical benefits of once-weekly OL-HDF are still required.

A Randomized Controlled Trial of Comparative Efficacy between Sodium Bicarbonate and Heparin as A Locking Solution for Tunneled Central Venous Catheters Among Patients Requiring Maintenance Hemodialysis.

BACKGROUND: Sodium bicarbonate (NaHCO3) is one of the promising solutions that has good safety profile and theoretical advantages regarding antimicrobial and antithrombotic properties but there are still limited reports. OBJECTIVE: To compare the efficacy in lowering rate of catheter loss due to catheter-related thrombosis (CRT) or catheter-related blood stream infection (CRBSI) between sodium bicarbonate and heparin lock in prevalent chronic hemodialysis (HD) patients. DESIGN: A multicenter, randomized, open-label study. SETTING: In a developing country, Thailand. PATIENTS: Chronic HD patients with tunneled central venous catheter. MEASUREMENTS: Catheter loss rate, rate of catheter-related blood stream infection, catheter-related thrombosis, and exit site or tunnel infection. METHODS: The prospective multicenter randomized controlled trial was conducted, we randomly assigned 118 patients undergoing HD with tunneled central venous catheter to receive a catheter locking solution of sodium bicarbonate or heparin. The primary outcome was a catheter loss rate due to CRT or CRBSI, while the secondary outcome was a composite outcome of CRT, CRBSI, or exit site/tunnel infection (ESI/TI). RESULTS: The present study was stopped early due to an excess of catheter-related thrombosis in the sodium bicarbonate group. From the first 6 weeks of follow-up, there were no catheter losses due to CRT or CRBSI in both groups. The sodium bicarbonate group had a significantly higher rate of the secondary composite outcomes and this was entirely caused by CRT with the median time to thrombosis of 23.6 days. Every CRT event could be successfully rescued by using a single dose of recombinant tissue plasminogen activator (rt-PA). LIMITATIONS: Short follow-up period. CONCLUSIONS: In prevalent HD patients with tunneled CVCs, use of a sodium bicarbonate locking solution for prevention of CRT is inferior to heparin and is associated with a high rate of catheter-related thrombosis. TRIAL REGISTRATION: The study was registered with the Thai Clinical Trials Registry TCTR 20200610003.

CONTEXTE: Le bicarbonate de sodium (NaHCO3) figure parmi les solutions prometteuses présentant un bon profil de tolérance et des bienfaits théoriques en matière de propriétés antimicrobiennes et antithrombotiques. Les rapports en faisant état demeurent toutefois limités. OBJECTIFS: Comparer l'efficacité du NaHCO3 par rapport à l'héparine en tant que solutions de verrouillage du cathéter dans la réduction du taux d'échec du cathéter en raison d'une thrombose due au cathéter (TDC) ou d'une septicémie due au cathéter (SDC) chez les patients suivant des traitements d'hémodialyse (HD) de façon chronique. TYPE D'ÉTUDE: Essai randomisé ouvert mené dans plusieurs centers. CADRE: Étude réalisée en Thaïlande, un pays en développement. SUJETS: Patients sous HD chronique par cathéter veineux central tunnelisé. MESURES: Le taux d'échec du cathéter, le taux de SDC, le taux de TDC et le taux d'infections au point d'émergence cutané ou de tunnelites. MÉTHODOLOGIE: Cet essai prospectif randomisé et contrôlé est multicentrique et porte sur 118 patients HD avec cathéter veineux central tunnelisé. Les sujets ont été répartis aléatoirement pour recevoir une solution de NaHCO3 ou d'héparine comme solution de verrouillage du cathéter. Le principal critère d'évaluation était l'échec du cathéter en raison d'une TDC ou d'une SDC. Le critère d'évaluation secondaire était un résultat combiné de TDC, de SDC ou d'une infection au point d'émergence/ tunnelite. RÉSULTATS: L'étude a été interrompue prématurément en raison d'un trop grand nombre de thromboses liées au cathéter dans le groupe recevant le NaHCO3. Dans les six premières semaines de suivi, aucun échec dû à une thrombose ou à une septicémie n'avait été observé dans les deux groupes. Le groupe NaHCO3 a montré un taux significativement plus élevé d'événements liés au critère d'évaluation secondaire, et cela était entièrement causé par TDC; le délai médian avant la thrombose était de 23,6 jours. Chaque TDC a pu être restaurée avec succès grâce à une seule dose d'activateur tissulaire du plasminogène (rt-PA). LIMITES: Courte période de suivi. CONCLUSION: Chez les patients prévalents suivant des traitements d'hémodialyse via un cathéter veineux central tunnelisé, l'utilization du NaHCO3 comme solution de verrouillage du cathéter a été associée à un taux élevé de thromboses dues au cathéter et s'est avérée moins efficace que l'héparine pour les prévenir. ENREGISTREMENT DE L'ESSAI: L'essai est enregistré au registre des essais cliniques thaïlandais TCTR 20200610003.

The impact of CASR A990G polymorphism in response to cinacalcet treatment in hemodialysis patients with secondary hyperparathyroidism.

The objective of this study was to determine the impact of calcium sensing receptor (CASR) A990G genetic polymorphism on parathyroid hormone (PTH) lowering response to cinacalcet treatment when controlling for significant influencing clinical factors. This retrospective study was conducted on 135 Thai hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT). CASR A990G genotypes were determined. The patients were identified as either G carriers (heterozygous or homozygous CASR 990G allele carriers) or noncarriers (homozygous CASR 990A carriers). Tested covariates were baseline PTH level (bPTH), baseline serum phosphate (bPhos), baseline serum calcium (bCa), baseline calcitriol equivalent dose (bCtriol), baseline ergocalciferol dose (bErgo), and age. The ANCOVA showed that intact PTH levels after 12 weeks of cinacalcet treatment (PTHw12) was significantly lower among G carriers compared with noncarriers after controlling for bPTH, bPhos, bCtriol, and bErgo (F(1, 127) = 15.472, p < 0.001), with the adjusted mean difference of 253.7 pg/mL. The logistic regression analysis revealed that the odds of a G carrier achieving 30% PTH reduction after 12-week cinacalcet treatment were 3.968 times greater than the odds for a noncarrier after adjusting for bPhos, bCtriol, and age. In conclusion, the CASR A990G polymorphism significantly influences cinacalcet response in HD patients with SHPT.

Effects of intradialytic cycling exercise on daily physical activity, physical fitness, body composition, and clinical parameters in high-volume online hemodiafiltration patients: a pilot randomized-controlled trial.

PURPOSE: The mortality of dialysis patients treated with high-volume online hemodiafiltration (OL-HDF) is better than hemodialysis, but is still higher than healthy population. Low daily physical activity increases cardiovascular mortality. Addition of intradialytic exercise (IDX) program might improve physical activity and health status in OL-HDF patients. This pilot open-labeled randomized-controlled trial was conducted to evaluate the effects of IDX on physical activity and other clinical parameters in OL-HDF patients. METHODS: Twelve OL-HDF patients were randomized into control (n = 6) or IDX (n = 6) groups. The subjects in IDX group were trained to exercise using a cycle ergometer for 60 min during each OL-HDF session. Physical activity measured as daily step count using a wrist-worn triaxial accelerometer, physical fitness, or cardiorespiratory fitness assessed by VO2max and other physical performance tests, lean body mass determined by the Dual-energy X-ray absorptiometry (DXA), quality of life (QOL), and various parameters were compared between baseline and 6 months. RESULTS: The baseline physical activity status was comparable. Following 6-month IDX, the physical activity was significantly improved in IDX group [+ 1048.79 (+ 741.50, + 2792.54) vs. - 362.06 (- 1626.82, - 167.47) steps/day, p = 0.01], while physical fitness and QOL were unchanged. The lean body mass parameters were preserved in the IDX group while seemed to decrease in the control group. Serum albumin was significantly increased in the IDX group (p = 0.01). The hemoglobin changes were significantly better (p = 0.01) and the erythropoietin resistance index was significantly lower in the IDX group (p = 0.03). Phosphate reduction was significantly greater in the IDX group (p = 0.04). CONCLUSIONS: IDX could improve physical activity and other metabolic parameters in OL-HDF patients and these might contribute to further improvement in clinical and survival outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Registration: NCT03353844.

Super high-flux hemodialysis provides comparable effectiveness with high-volume postdilution online hemodiafiltration in removing protein-bound and middle-molecule uremic toxins: A prospective cross-over randomized controlled trial.

Although high-volume postdilution online hemodiafiltration (ol-HDF) is superior to high-flux HD in removing all kinds of uremic toxins and improving survival, this treatment is not available in most HD centers. The present study was conducted to compare the effectiveness in removals of protein-bound (indoxyl sulfate [IS]), middle-molecule [beta-2 microglobulin (B2M) and alpha-1 microglobulin (A1MG)], and small-molecule uremic toxins between super high-flux HD (SHF-HD), HD with a novel SHF dialyzer and high-volume postdilution ol-HDF in a noninferiority fashion. Fifteen prevalent HD patients were randomly allocated into two sequences of 12-week treatment periods of SHF-HD treatment and later high-volume postdilution ol-HDF period or vice versa. Each treatment period was divided by a wash-out phase of 4-week high-flux HD. Twelve of 15 patients could complete the study. When compared with high-volume postdilution ol-HDF (convective volume of 24.4 ± 3.52 L), SHF-HD provided comparable reduction ratio values of IS, B2M, and A1MG with mean difference of 5.87 (95% confidence interval [CI] -1.63, 13.37), 1.98 (95% CI,-0.21, 4.18), and 22.96 (95% CI, -1.91, 47.83), respectively. The spKt/Vurea was not different. The predialysis levels of all uremic toxins at baseline and after 12-week treatment did not differ between both groups. Although albumin loss in dialysate in SHF-HD was greater than high-volume postdilution ol-HDF, the serum albumin levels after 12-week SHF-HD treatment were significantly higher than baseline. In conclusion, SHF-HD provides noninferior effectiveness to high-volume postdilution ol-HDF in removing various uremic toxins with significantly increased serum albumin levels despite higher albumin loss. SHF-HD might be an effectively alternative treatment when high-volume postdilution ol-HDF is not available.

Effect of Maintenance Intravenous Iron Treatment on Erythropoietin Dose in Chronic Hemodialysis Patients: A Multicenter Randomized Controlled Trial.

BACKGROUND: There is no consensus on intravenous (IV) iron supplement dose, schedule, and serum ferritin target in functional iron deficiency anemia to maintain optimum target levels of iron stores by several guidelines. OBJECTIVE: To examine the effect of IV iron supplementation to different targets of serum ferritin on erythropoietin dose and inflammatory markers in chronic hemodialysis (HD) patients with functional iron deficiency anemia. DESIGN: A multicenter, randomized, open-label study. SETTING: In a developing country, Thailand. PATIENTS: Chronic HD patients with functional iron deficiency anemia. MEASUREMENTS: Erythropoietin resistance index, high-sensitivity C-reactive protein, and fibroblast growth factor 23. METHODS: Two hundred adult chronic HD patients with transferrin saturation less than 30% and serum ferritin of 200 to 400 ng/mL were randomized 1:1 to maintain serum ferritin 200 to 400 ng/mL (low-serum ferritin group, N = 100) or 600 to 700 ng/mL (high-serum ferritin group, N = 100). During a 6-week titration period, participants randomized to the high-serum ferritin group initially received 600 mg IV iron (100 mg every week), while the participants in the low-serum ferritin group did not receive IV iron. During the 6-month follow-up period, the dose of IV iron was adjusted by protocol. RESULTS: The mean dose of IV iron was 108.3 ± 28.2 mg/month in the low-serum ferritin group and 192.3 ± 36.2 mg/month in the high-serum ferritin group. The mean serum ferritin was 367.0 ± 224.9 ng/mL in the low ferritin group and 619.6 ± 265.2 ng/mL in the high ferritin group. The erythropoietin resistance index was significantly decreased in the high-serum ferritin group compared to the low-serum ferritin group after receiving IV iron in the 6-week titration period (mean difference: -113.43 ± 189.14 vs 41.08 ± 207.38 unit/week/g/dL; P < .001) and 3-month follow-up period (mean differences: -88.88 ± 234.43 vs -10.48 ± 217.75 unit/week/g/dL; P = .02). LIMITATIONS: Short follow-up period. CONCLUSION: Maintaining a serum ferritin level of 600 to 700 ng/mL by IV iron administration of approximately 200 mg per month as a maintenance protocol can decrease erythropoietin dose requirements in chronic HD patients with functional iron deficiency anemia. TRIALS REGISTRATION: The study was registered with the Thai Clinical Trials Registry TCTR20180903003.

CONTEXTE: Il n'existe aucun consensus sur la dose et la posologie du supplément de fer administré par voie intraveineuse (IV) dans le traitement de l'anémie ferriprive fonctionnelle, ni sur la cible de ferritine sérique permettant de maintenir les réserves ferriques optimales définies par les différentes recommandations. OBJECTIF: Examiner l'effet d'un supplément de fer IV, à différentes cibles de ferritine sérique, sur la dose d'érythropoïétine et les marqueurs inflammatoires de patients sous hémodialyse chronique atteints d'une anémie ferriprive fonctionnelle. TYPE D'ÉTUDE: Essai multicentrique ouvert à répartition aléatoire. CADRE: L'étude s'est tenue en Thaïlande, un pays en développement. SUJETS: Des patients sous hémodialyse chronique atteints d'anémie ferriprive fonctionnelle. MESURES: L'indice de résistance à l'érythropoïétine, la protéine C réactive très sensible et le facteur de croissance des fibroblastes 23. MÉTHODOLOGIE: Deux cents adultes sous HD chronique présentant une saturation en transferrine inférieure à 30 % et un taux de ferritine sérique entre 200 et 400 ng/mL ont été répartis en deux groupes (ratio 1:1). On visait le maintien d'un taux de ferritine sérique entre 200 et 400 ng/mL dans le premier groupe (faible taux de ferritine sérique; n=100) et entre 600 et 700 ng/mL dans le deuxième groupe (taux élevé de ferritine sérique; n=100). Au cours d'une période d'ajustement de six semaines, les sujets du groupe à taux élevé de ferritine sérique ont initialement reçu une dose de 600 mg de fer par IV (100 mg par semaine) alors que les sujets de l'autre groupe n'en ont pas reçu. La dose de fer IV a été ajustée selon le protocole au cours des six mois de suivi. RÉSULTATS: La dose moyenne de fer administrée par IV était de 108,3 ±28,2 mg/mois pour les sujets du groupe à faible taux de ferritine sérique et de 192,3 ±36,2 mg/mois pour les sujets du groupe à taux élevé de ferritine sérique. En ce qui concerne les taux de ferritine sérique, ceux-ci s'établissaient respectivement à 367,0 ±224,9 ng/mL et à 619,6 ±265,2 ng/mL. Les sujets du groupe à taux élevé de ferritine sérique présentaient un indice de résistance à l'érythropoïétine significativement réduit par rapport à ceux du groupe à faible taux après avoir reçu un supplément de fer IV durant la période d'ajustement de six semaines (différence moyenne: -113,43 ±189,14 contre 41,08 ±207,38 unités/semaine/g/dL; p<0,001) et après trois mois de suivi (différence moyenne: -88,88 ±234,43 contre -10,48 ±217,75 unités/semaine/g/dL; p=0,02). LIMITES: Courte période de suivi. CONCLUSION: Le maintien d'un taux de ferritine sérique entre 600 et 700 ng/mL par l'administration IV d'une supplémentation en fer, à raison d'environ 200 mg par mois (protocole de maintien), peut contribuer à réduire la posologie d'érythropoïétine chez les patients hémodialysés et atteints d'anémie ferriprive fonctionnelle. ENREGISTREMENT DE L'ESSAI: L'essai a été enregistré selon le registre des essais cliniques thaïlandais TCTR20180903003.

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 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.

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.