Low‐Volume Tidal Peritoneal Dialysis Is a Preferable Mode in Patients Initiating Urgent‐Start Automated Peritoneal Dialysis: A Randomized,Open‐Label,Prospective Control Study

The aim of this study is to evaluate the safety of low‐volume tidal peritoneal dialysis (TPD) and intermittent peritoneal dialysis (IPD) in ESRD patients initiating automated peritoneal dialysis (APD) after an acute catheter insertion. Clinical outcomes of patients who received either TPD or IPD using an APD system were compared in a randomized, open‐label, prospective control study in a single‐center setting. From May 2011 to May 2013, 49 patients were enrolled and 27 patients received low‐volume TPD treatment, whereas 22 patients underwent low‐volume IPD right after Tenckhoff catheter insertion. The incidence of complications during the 14‐day APD treatment were observed. After APD treatment, all the patients were transferred to continuous ambulatory peritoneal dialysis and followed up for 2 years. The IPD group demonstrated a significantly higher incidence of catheter‐related complications (omental wrapping 27.3% vs. 0% and suction pain 18.2% vs. 0%) than the TPD group after adjusting for age, gender, baseline diabetes, systolic blood pressure , BMI, and the experience of the operators. However, the short duration of APD treatment with either IPD or TPD mode did not affect the long‐time technical survival. In patients immediately after catheter insertion, low‐volume TPD mode demonstrated a lower incidence of catheter‐related complications compared to IPD. Although our results provided evidence that TPD is a preferable APD mode for this specific population, definitive conclusions about TPD benefit cannot be made, owing to early termination of the trial.     

Risk Factors for Encapsulating Peritoneal Sclerosis in Long‐Term Peritoneal Dialysis: A Retrospective Observational Study

Encapsulating peritoneal sclerosis (EPS) is a serious complication that occurs in patients with long‐term peritoneal dialysis (PD). Investigation of risk factors that contribute to EPS in patients on long‐term PD therapy is needed. In a retrospective, observational study, data were collected for 107 patients treated with PD therapy for more than 5 years. Fifty cases of EPS were compared with 57 cases of non‐EPS. To evaluate the impact of PD‐associated peritonitis in EPS, univariate and multivariate logistic regression models were applied. Episodes of peritonitis, number of peritonitis episodes and the duration of peritonitis were included as explanatory variables in addition to previously reported risk factors. D/P Cr and serum β2MG levels in the EPS and non‐EPS groups were: 0.82 ± 0.10 and 0.67 ± 0.12 (P < 0.01), and 33.8 ± 8.54 and 29.2 ± 8.18 mg/L (P < 0.01), respectively. Episodes of peritonitis, number of peritonitis episodes and the duration of peritonitis was 68% and 42% (P < 0.01), 1.80 ± 2.19 and 0.75 ± 1.07 times (P < 0.01), and 18.1 ± 15.3 and 10.2 ± 4.90 days (P < 0.01), in the EPS and non‐EPS groups, respectively. Furthermore, multivariate logistic regression models demonstrated that both D/P Cr and the duration of peritonitis were independently associated with EPS (P < 0.01 and P < 0.05, respectively). In patients on long‐term PD therapy, D/P Cr and the duration of peritonitis are independently associated with EPS. Earlier treatment to promote an early recovery from PD‐associated peritonitis could be critical in preventing EPS.     

Acute Kidney Injury in Critically Ill Patients: A Prospective Randomized Study of Tidal Peritoneal Dialysis Versus Continuous Renal Replacement Therapy

Few studies have discussed the role of peritoneal dialysis (PD) in managing acute kidney injury (AKI) in critically ill patients. The present study compares the outcome of AKI in intensive care unit (ICU) patients randomized to treatment with tidal PD (TPD) or continuous venovenous hemodiafiltration (CVVHDF). One hundred and twenty‐five ICU patients with AKI were randomly allotted to CVVHDF, (Group A, N = 62) or TPD, (group B, N = 63). Cause and severity of renal injury were assessed at the time of initiating dialysis. The primary outcome was hospital mortality at 28 days, and secondary outcomes were time to recovery of renal function, duration of stay in the ICU, metabolic and fluid control, and improvement of sensorial and hemodynamic parameters. No statistically significant differences were observed between groups in regard to patients’ characteristics. The survival at 28 days was significantly better in the patients treated with TPD when compared to CVVHDF (69.8% vs. 46.8%, P < 0.01). Infectious complications were significantly less (P < 0.01) in the TPD group (9.5%) when compared to the CVVHDF group (17.7%). Recovery of kidney function (60.3% vs. 35.5%), median time to resolution of AKI and the median duration of ICU stay of 9 days (7–11) vs. 19 days (13–20) were all in favor of TPD (P < 0.01). This study suggests that there are better outcomes with TPD compared to CRRT in the treatment of critically ill patients with AKI.     

High Correlation Between Clearance of Renal Protein‐Bound Uremic Toxins (Indoxyl Sulfate and p‐Cresyl Sulfate) and Renal Water‐Soluble Toxins in Peritoneal Dialysis Patients

Peritoneal dialysis (PD) is characterized by a slow continuous removal of solutes. Traditionally, dialysis adequacy is quantified by referring to the kinetics of urea nitrogen (UN) and creatinine (Cr) clearance. The efficacy of middle molecular substances and protein‐bound solutes as markers for peritoneal dialysis adequacy is not clear. The aim of this cross‐sectional study was to investigate correlations between the clearance of indoxyl sulfate (IS), p‐cresyl sulfate (PCS), UN, and Cr in the peritoneum and kidneys and to compare the overall clearances of IS and PCS between non‐anuric and anuric groups in PD patients. We recruited a total of 175 patients who had been undergoing continuous ambulatory PD (CAPD) or automated PD (APD) for at least 4 months. We measured total IS and PCS concentrations in serum, dialysate, and urine samples. Free IS and PCS concentrations were measured in all serum samples. IS and PCS clearances via both kidney and peritoneum were measured. The mean concentration of IS in the urine samples was 9.2‐fold higher than that in the dialysate samples, and concentration of PCS in the urine samples was 8.5‐fold higher than that in the dialysate samples. Peritoneal UN and Cr clearances were not correlated with peritoneal PCS clearance (P > 0.05) but were mildly correlated with peritoneal IS clearance. The peritoneal IS and PCS clearances in the different peritoneal equilibration test groups were similar. The renal UN and Cr clearances were strongly correlated with renal PCS and IS clearances (P > 0.89, P < 0.001). In addition, non‐anuric patients showed better elimination of total PCS (10.3 mg/day [range, 1.6–19.8] vs. 5.2 mg/day [range, 0–14]; P < 0.001] and IS (37.9 mg/day [range, 25.6–56.7] vs. 24.8 mg/day [range, 17.1–41.6]; P < 0.001) than anuric patients. This cross‐sectional study showed that peritoneal clearance of water‐soluble solutes is not correlated with that of PCS but is mildly correlated with that of IS. However, the renal clearances of IS and PCS show strong positive correlation with the renal clearances of UN and Cr. This study confirms the important role of residual renal function in the removal of protein‐bound uremic toxins.     

Bioimpedance Spectroscopy‐Based Fluid Status in Combined Dialysis Compared With Hemodialysis and Peritoneal Dialysis: A Cross‐Sectional Study

Combination therapy with peritoneal dialysis and hemodialysis (PD+HD) is widely used in Japan for PD patients with decreased residual renal function. However, fluid status in PD+HD patients has not been well studied. In this cross‐sectional study, we compared fluid status in 41 PD+HD patients with that in 103 HD and 92 PD patients using the bioimpedance spectroscopy. Extracellular water normalized to patient height (NECW, kg/m) was the highest in pre‐HD (8.3 ± 1.6) followed by PD (7.9 ± 2.7), PD+HD (7.5 ± 2.5), and post‐HD patients (6.9 ± 1.5) (P < 0.01). By multiple linear regression analysis, PD+HD was associated with a significantly lower NECW than pre‐HD (β = ?0.8, P = 0.03) and similar to PD (β = ?0.5, P = 0.24) and post‐HD (β = 0.6, P = 0.08) after adjustment for age, sex, diabetic nephropathy, ischemic heart disease, dialysis period, and daily urine volume. There was no correlation between NECW and daily urine volume in all dialysis groups. Average daily fluid removal (a sum of urine volume and ultrafiltration volume by dialysis) was positively correlated with NECW in PD+HD and pre‐HD, but not in PD and post‐HD patients. Our results suggest that fluid status in PD+HD patients with decreased residual renal function is acceptable as compared with that in HD and PD patients.     

Monocarboxylate Transporter‐1 Mediates the Protective Effects of Neutral‐pH Bicarbonate/Lactate‐Buffered Peritoneal Dialysis Fluid on Cell Viability and Apoptosis

We investigated the effects of bicarbonate/lactate‐buffered peritoneal dialysis fluid (B/L‐PDF) and lactate‐buffered PDF (L‐PDF) on cell viability and apoptosis, focusing on monocarboxylate transporters (MCTs). MCT‐1 transports lactate into cells. Cell viability and apoptosis of human peritoneal mesothelial cells (HPMCs) were examined by water‐soluble tetrazolium salt‐1 and TUNEL assays, respectively. The relative number of viable HPMCs was significantly decreased by L‐PDF at 48 h (8.8 ± 0.4%) compared with cells cultured in M199, but not by B/L‐PDF (66.7 ± 1.1%). Apoptosis was markedly induced by L‐PDF at 48 h (69.3 ± 16.2%), but not by B/L‐PDF (2.6 ± 0.3%). Knockdown of MCT‐1 by small interfering RNA (siRNA) attenuated the L‐PDF‐induced reduction of viable cells and increased apoptosis compared with control siRNA, but MCT‐4 knockdown had no effect. B/L‐PDF had lesser effects on cell viability and apoptosis of HPMCs compared with L‐PDF. These results suggest that B/L‐PDF biocompatibility occurs by avoiding the induction of apoptosis in HPMCs.     

Hepcidin/Ferritin Ratios Differ Among Non‐Dialyzed Chronic Kidney Disease Patients,and Patients on Hemodialysis and Peritoneal Dialysis

The serum levels of hepcidin generally increase in patients with chronic kidney disease (CKD) due to inflammation or a decline in the glomerular filtration rate. However, the differences in the ferrokinetics among dialysis modalities are unclear. We investigated the relationship between serum levels of hepcidin and ferritin among non‐dialyzed CKD (ND), hemodialysis (HD), and peritoneal dialysis (PD) patients. We recruited 285 CKD patients (117 ND, 80 HD, and 88 PD patients) and measured the serum levels of hepcidin‐25, ferritin, hemoglobin, iron, transferrin saturation (TSAT), albumin, and high sensitivity C‐reactive protein (hs‐CRP). Hepcidin‐25 levels were elevated in all CKD patients and were significantly higher in PD than in ND and HD patients. The hepcidin/ferritin ratio was significantly higher in PD patients independent of TSAT, hemoglobin, hs‐CRP, and serum albumin. Hepcidin/ferritin ratio, associated with both dialysis modality and inflammation, is expected to be a useful indicator of anemia in CKD.     

Reduction of Elevated Cytokine Levels in Acute/Acute‐on‐Chronic Liver Failure Using Super‐Large Pore Albumin Dialysis Treatment: An In Vitro Study

The removal of small water soluble toxins and albumin‐bound toxins in acute liver failure patients (ALF) or acute‐on‐chronic liver failure (AocLF) patients has been established using extracorporeal liver support devices (e.g. Molecular Adsorbents Recirculating System; MARS). However, reduction of elevated cytokines in ALF/AocLF using MARS is still not efficient enough to lower patients' serum cytokine levels. New membranes with larger pores or higher cut‐offs should be considered in extracorporeal liver support devices based on albumin dialysis in order to address these problems, as the introduction of super‐large pore membranes could counterbalance high production rates of cytokines and further improve detoxification in vivo. Using an established in vitro two compartment albumin dialysis model, three novel membranes of different pore sizes were compared with the MARS Flux membrane for cytokine removal and detoxification qualities in vitro. Comparing the membranes, no improvement in the removal of water soluble toxins was found. Albumin‐bound toxins were removed more efficiently using novel large (Emic2) to super‐large pore sized membranes (S20; HCO Gambro). Clearance of cytokines IL‐6 and tumor necrosis factor‐α was drastically improved using super‐large pore membranes. The Emic2 membrane predominantly removed IL‐6. In vitro data suggest that the usage of larger pore sized membranes in albumin dialysis can efficiently reduce elevated cytokine levels and liver failure toxins. Using large to super‐large pore membranes might exert effects on patients' serum cytokine levels. Combined with increased detoxification this could lead to higher survival in ALF/AocLF. Promising membranes for clinical evaluation have been identified.     

DALI Low‐Density Lipoprotein Apheresis in Homozygous and Heterozygous Familial Hypercholesterolemic Patients Using Low‐Dose Citrate Anticoagulation

Abstract: The purpose of this study was to clarify the efficacy and safety of direct adsorption of lipoprotein low‐density lipoprotein apheresis (DALI LDL apheresis) in patients with severe homozygous and heterozygous familial hypercholesterolemia who showed minor adverse effects during treatment with the usual DALI configuration (AC 1:20) through the use of a new system with low‐dose citrate anticoagulation (AC 1:40) developed in order to minimize citrate‐related adverse effects. Serum total cholesterol and LDL‐cholesterol (LDL‐C) showed a decrease of 57% to 61%, and 62 % to 67%, respectively, in the 2 patients. Serum lipoprotein (a) (Lp[a]) was higher in the homozygous patient (Patient 1: MD) and within the normal range in the heterozygous patient (Patient 2: ES). In the former, Lp(a) was reduced by 52%. Serum high‐density lipoprotein cholesterol (HDL‐C) showed a statistically insignificant acute reduction: 15% to 19%. The observed reduction is mainly related to the well‐known effect of hemodilution. The cardiovascular risk (total cholesterol/HDL‐C) was reduced in both patients (46% to 54%) as expected. Serum triglycerides were reduced by 33% to 49%. The mean blood volume processed per session was 7,600 ml. Fifteen treatments for each patient have successfully been completed without the appearance of any clinically significant subjective and objective symptoms related to treatment with the new system.     

Pre‐Dialysis Neutrophil‐Lymphocyte Ratio,a Novel and Strong Short‐Term Predictor of All‐Cause Mortality in Patients With Diabetic Nephropathy: Results From a Single‐Center Study

Neutrophil‐lymphocyte ratio (NLR) is an inflammatory marker affecting the prognosis of end‐stage renal disease (ESRD) patients. This study aimed to evaluate NLR levels predicting all‐cause mortality in ESRD patients with diabetic nephropathy (DN), which have not been evaluated. We recruited 151 isolated DN patients who started hemodialysis between January 2009 and December 2014 at the Japanese Red Cross Ishinomaki Hospital. The primary outcomes were 1‐ and 3‐year survival rates. The association between NLR and survival rate was evaluated using the Kaplan–Meier method and Cox proportional hazard regression analysis. Patients with an NLR ≥ 3.5 had a significantly higher mortality rate than did those with an NLR < 3.5 (log rank P = 0.02). The area under the curve (AUC) of 1‐year survival for NLR was significantly larger than that for other commonly used nutritional and inflammatory variables. NLR was a more accurate predictor than other well‐known markers.     

Association Between Dialysis Modalities and Risk of Coronary Artery Disease: A Population‐Based Cohort Study in Taiwan

The hemodynamic effects of hemodialysis (HD) and peritoneal dialysis (PD) on end‐stage renal disease (ESRD) patients differ. The influence of dialysis modalities on the cardiovascular system has not been well investigated. We aimed to evaluate the association between dialysis modalities and risk of coronary artery disease (CAD) by using the claim data of Taiwan's Longitudinal Health Insurance Database. This study followed up a cohort of 1624 new onset ESRD patients (≥18 years old), who had started renal replacement therapy during 2000 to 2010; and was followed until 2012. After adjusting for potential confounders, patients who underwent HD had significantly higher risks of incidence of CAD, in comparison with patients who underwent PD (adjusted hazard ratio = 1.47; 95% confidence interval = 1.01–2.11). An increased risk of incident CAD was distinguished in patients receiving HD, compared with those on PD. Further studies are warranted to explore the underlying mechanism and improve dialysis outcomes.     

New‐Onset Diabetes Mellitus in Peritoneal Dialysis and Hemodialysis Patients: Frequency,Risk Factors,and Prognosis—A Review

New‐onset diabetes mellitus (NODM) is observed in both hemodialysis (HD) and peritoneal dialysis (PD) patients. The prevalence of NODM in dialysis patients is slightly higher compared to subjects of the general population. Based on currently published data there is no convincing evidence that the risk of NODM is different between HD and PD patients. Data on the effect of glucose load on risk of NODM in dialysis patients remain controversial. PD modality (automated or continuous ambulatory PD) has no significant influence on NODM incidence. Chronic inflammation is associated with NODM in dialysis patients. Reported differences in NODM between PD and HD patients are possibly also influenced by differences in demographic factors between these patient groups. Mortality in NODM patients is lower than mortality in patients with preexisting DM. This may be partly explained by the younger age and lower number of comorbidities in patients with NODM.     

Cardiac Venous Left Ventricular Lead Removal and Reimplantation Following Device Infection: A Large Single‐Center Experience

LV Lead Extraction and Reimplantation. Background: Early series of biventricular device removal have contained mostly younger cardiac venous (CV) left ventricular leads and few have reported on rates of successful reimplantation. Methods and Results: We performed a retrospective analysis of all patients referred to the Cleveland Clinic between February 2, 2001 and July 27, 2011 for removal of a biventricular device with a CV pacing lead for an infectious indication. A total of 173 patients were included. The median age of the CV leads was 22.3 months (interquartile range: 5.2–46.3 months). The complete procedural success rate for all leads was 97.7%, with the remaining 2.3% clinical successes. A total of 76.9% of CV leads were removed using simple traction alone with the remaining leads requiring the use of a laser‐powered sheath. A total of 3.5% of leads required intervention (manual dissection or laser‐powered dissection) within the coronary sinus (CS). Major complications occurred in 1.2% of patients. Minor complications occurred in 7.5% of patients, the majority of which were hematomas requiring drainage (6.9%). CV lead reimplantation was attempted in 107 patients of which 88 (82.8%) were successful. Conclusion: CV lead removal in patients with an infected biventricular device is associated with an extremely high procedural success rate and a low incidence of major complications. The use of a laser‐powered sheath is necessary in roughly one‐quarter of cases with a very small percentage requiring intervention within the CS. Reimplantation of CV leads is achievable in roughly 83% of patients, a figure lower than nationally quoted estimates for de novo implantations. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1213–1216, November 2012)     

A phase 1 clinical trial evaluating marizomib,pomalidomide and low‐dose dexamethasone in relapsed and refractory multiple myeloma (NPI‐0052‐107): final study results

Marizomib (MRZ) is an irreversible, pan‐subunit proteasome inhibitor (PI) in clinical development for relapsed/refractory multiple myeloma (RRMM) and glioma. This study analysed MRZ, pomalidomide (POM) and low‐dose dexamethasone (Lo‐DEX) [PMD] in RRMM to evaluate safety and determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D). Intravenous MRZ (0·3–0·5 mg/m²) was administered over 2 h on days 1, 4, 8, 11; POM (3–4 mg) on days 1–21; and Lo‐DEX (5 or 10 mg) on days 1, 2, 4, 5, 8, 9, 11, 12, 15, 16, 22 and 23 of every 28‐day cycle. Thirty‐eight patients were enrolled that had received a median of 4 (range 1–10) prior lines of therapy; all patients received prior lenalidomide and bortezomib. No dose‐limiting toxicities (DLTs) were observed and 0·5 mg/m² MRZ was determined to be the RP2D. The most common treatment‐related ≥Grade 3 adverse events were: neutropenia (11/38 patients: 29%), pneumonia (4/38 patients 11%), anaemia (4/38 patients; 11%) and thrombocytopenia (4/38 patients; 11%). The overall response rate and clinical benefit rate was 53% (19/36) and 64% (23/36), respectively. In conclusion, PMD was well tolerated and demonstrated promising activity in heavily pre‐treated, high‐risk RRMM patients.     

Short‐term low‐dose secondary prophylaxis for severe/moderate haemophilia A children is beneficial to reduce bleed and improve daily activity,but there are obstacle in its execution: a multi‐centre pilot study in China

We recently showed in a single centre trial that low‐dose secondary prophylaxis in severe/moderate haemophilia patients with arthropathy is feasible and beneficial. However, this regimen has not been validated in a multicentre setting and what obstacles are there to prophylaxis remain unclear. (i) Benefit study: to confirm the benefits of similar prophylaxis protocol in severe/moderate haemophilia A (HA) in a multicentre setting in China. (ii) Follow‐up obstacle study: to investigate obstacles in compliance to prophylaxis treatment. (i) Benefit study: severe/moderate HA children with arthropathy from 15 centres were enrolled to undergo an 8‐week on‐demand treatment, followed by 6 to 12‐week low‐dose secondary prophylaxis. Outcomes compared in the two periods include joint and severe bleeding, daily activities and factor consumption. (ii) Obstacle study: questionnaires to investigators to collect data on patient and centre factors contributing to inability to comply with prophylaxis. We enrolled 191 patients from 15 centres. Sixty‐six (34.6%) from three centres completed the prophylaxis protocol, and they had significantly decreased bleeding (78.8% haemarthrosis and 68.9% severe bleedings) and improved daily activities with no increase in factor consumption over that in the on‐demand therapy period. The remaining 125 patients from 12 centres were not compliant to the prophylaxis protocol; questionnaire data indicated that the major obstacles were inability of patients/parents to accept (41.7%) or to adhere (33.3%) to the prophylaxis protocol, mostly because of failure to understand the benefits and to accept the frequent injections. Non‐availability of a centre comprehensive care team was another important determinant. Short‐term low‐dose secondary prophylactic therapy is beneficial without increasing factors consumption for severe/moderate HA with arthropathy in a multi‐centre setting in China. Obstacles to overcome must include improvement in comprehensive care and in education to patient/parents and healthcare personnel.