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.

     

On-line Hemodiafiltration in Southeast Asia: A Three-year Prospective Study of a Single Center

Abstract: Growing evidence suggests the superiority of on-line hemodiafiltration (HDF) compared with the conventional hemodialysis technique in many aspects; however, on-line HDF is still not used worldwide, including in Southeast Asia. The purpose of this study is to compare various clinical outcomes between on-line HDF and high-flux hemodialysis (HFHD). This was a single-center three-year prospective observational study that demonstrated the clinical parameters after switching from HFHD to on-line HDF in 22 HDF patients, whose average age was 58.1 ± 13.3 years. The incidence of intradialytic undesired events, including hypotension, decreased and an apparent increase in appetite and an improvement in overall well-being were recorded by most patients after switching to on-line HDF. The data for dry weight, body mass index, and normalized protein nitrogen appearance, which represent nutritional status, showed a significant improvement while still maintaining a satisfactory albumin level. The adequacy in terms of urea reduction ratio significantly increased. The serum predialysis β₂-microglobulin levels were reduced by 25.7% from 31.1 ± 3.1 to 23.1 ± 4.8 mg/L (P < 0.05) at six months and remained constant during the three years of follow-up. The patients' lipid profile was well controlled, and the mean C-reactive protein value was still maintained in the normal range. In conclusion, our three-year experience showed that on-line HDF is a well-tolerated treatment with a lower incidence of intradialytic undesired events. The potential benefits may include the effective removal of higher molecular weight uremic toxins and an improved nutritional status, along with a low inflammatory state.     

Tissue engineering of an implantable bioartificial hemofilter

The first step in the tissue engineering of an implantable bioartificial kidney is the development of an implant that produces ultrafiltrate to replace glomerular function. A fabricated device containing synthetic hollow hemofiltration fibers was placed around the femoral vascular pedicle in rats, which initiated new tissue formation with a mature and durable neocapillary bed. The transudate fluid produced by this newly formed capillary bed accumulated through the hollow fibers into a subcutaneous port to allow evaluation of the fluid. In its first phase, this study evaluated various hollow fibers and tissue induction processes by the measurement of fluid volume, urea nitrogen, and total protein continuously for 6 weeks. New tissues formed within the implants surrounding the fibers, and the vascular density, vessel sizes, and percent cross-sectional vascular area were assessed by means of histomorphometric analysis after 6 weeks. The volume of fluid formation correlated with both vascular density and fiber membrane surface area. The implant fluid-to-serum ratios demonstrated a permselective filtrate. In a second phase, platelet-derived growth factor and vascular endothelial growth factor versus carrier alone were infused directly into the implants for the first 4 weeks in vivo through osmotic pumps and followed up to 9 weeks. Cumulative implant fluid volumes were significantly greater in the growth factor-treated group than in control animals and were associated with greater numbers of small-caliber blood vessels. These results provide the initial proof of concept in developing a tissue-engineered hemofilter prototype on a small scale in a rodent model.     

Regional citrate anticoagulation reduces polymorphonuclear cell degranulation in critically ill patients treated with continuous venovenous hemofiltration

Citrate which chelates ionized calcium can be used as regional anticoagulation in continuous venovenous hemofiltration (CVVH). This is the first study conducted to examine the potentially additive benefit effect of regional citrate anticoagulation (RCA) on polymorphonuclear (PMN) cell degranulation of myeloperoxidase (MPO) and cytokines production in patients with critically acute kidney injury (AKI) undergoing CVVH treatment. This prospective randomized controlled trial was conducted in 20 critically ill patients with AKI who underwent CVVH. The patients were randomized into regional citrate group (n=10) and heparin group (n=10). The pre-dilution CVVH with polyethersulfone dialyzers were utilized in both groups. The levels of pre-filter and post-filter MPO as well as inflammatory and anti-inflammatory cytokines were measured at baseline, 6h, and 24 h after initiating CVVH. In the heparin group, the post-filter serum MPO levels were significantly higher than the pre-filter (median 49.0 vs. 60.5 ng/mL, P<0.05) at 6 h. There were no significant differences between pre- and post-dialyzer MPO levels in the citrate group. Citrate could significantly decrease systemic pre-filter serum MPO levels from baseline at 6 h (median 43.5 vs. 17.3 ng/mL, P<0.01) as well as IL-8 levels (P<0.05) whereas heparin provided only significant TNF-α reduction (P<0.05). The CVVH circuit survival in the citrate group was longer than the heparin group. In conclusion, citrate, utilized as a regional anticoagulant in CVVH, can reduce both membrane bioincompatibility-induced and systemic oxidative stress and inflammation, and can prolong CVVH circuit survival time.     

Bioartificial kidney in the treatment of acute renal failure associated with sepsis

Acute renal failure (ARF) associated with sepsis has a high rate of mortality. It is not merely a surrogate marker for severity of disease but also an independent predictor of mortality and a separate pathogenic entity, even when nearly physiological doses of fluid and small-molecule clearance are maintained with currently available renal replacement therapies (RRT). The techniques to remove cytokines, including high-volume haemofiltration, haemodialysis using high-cut-off haemofilters, and absorptive techniques, lead to some improvement in outcome but are still insufficient to reverse the complicated biological dysregulation resulting from ARF associated with sepsis. The novel and exciting technique of cell therapy, which is based on the principle of using functional cells to replace a greater range of renal functions, may add significant benefit to current RRT in dealing with this disease process. Because renal tubule cells appear to play critical roles in immunoregulation, renal tubule cell therapy during ARF associated with sepsis should alter the detrimental multiple-organ consequences of sepsis. The development of a bioartificial kidney consisting of a conventional haemofiltration cartridge in series with a renal tubule assist device containing renal proximal tubule cells represents a new therapeutic approach to this clinical disorder. The results to date of large animal studies and recent Phase I/II and Phase II clinical trials show that such a device replaces multiple kidney functions and modifies the sepsis condition to improve survival in ARF.     

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.     

Efficacy of separated system continuous venovenous hemofiltration in critical acute kidney injury

Integrated system continuous venovenous hemofiltration (CVVH), the most popularly utilized mode for continuous renal replacement therapy (CRRT), needs a sophisticated and expensive machine that is available only in limited critical care units. Separated system CVVH, which can be simply set up, might be an effectively alternative to CRRT. A one-year prospective observational study regarding the efficacy of separated system CVVH was conducted with 192 critically ill patients with acute kidney injury. All patients underwent separated system CVVH with the pre-dilution mode and a mean CVVH dose of 34.9±2.7mL/kg/h. The APACHEII score was 23.2±8.4 and the Sequential Organ Failure Assessment score was 12.0±4.3. No complications, including air-embolism or circuit clotting, were observed and the survival rate was 32.3%. Separated system CVVH is simple, safe, and efficient and could provide cheaper treatments than the integrated system. It could thus be an effective, alternative treatment for critical acute kidney injury patients when the integrated mode is unavailable.     

Reliability of Blood Pressure Parameters for Dry Weight Estimation in Hemodialysis Patients

Chronic volume overload resulting from interdialytic weight gain and inadequate fluid removal plays a significant role in poorly controlled high blood pressure. Although bioimpedance has been introduced as an accurate method for assessing hydration status, the instrument is not available in general hemodialysis (HEMO) centers. This study was conducted to explore the correlation between hydration status measured by bioimpedance and blood pressure parameters in chronic HEMO patients. Multifrequency bioimpedance analysis was used to determine pre‐ and post‐dialysis hydration status in 32 stable HEMO patients. Extracellular water/total body water (ECW/TBW) determined by sum of segments from bioimpedance analysis was used as an index of hydration status. The mean age was 57.9 ± 16.4 years. The mean dry weight and body mass index were 57.7 ± 14.5 kg and 22.3 ± 4.7 kg/m², respectively. Pre‐dialysis ECW/TBW was significantly correlated with only pulse pressure (r = 0.5, P = 0.003) whereas post‐dialysis ECW/TBW had significant correlations with pulse pressure, systolic blood pressure, and diastolic blood pressure (r = 0.6, P = 0.001, r = 0.4, P = 0.04, r = ?0.4, and P = 0.02, respectively). After dialysis, the mean values of ECW/TBW, systolic blood pressure, mean arterial pressure, and pulse pressure were significantly decreased. ECW/TBW was used to classify the patients into normohydration (≤0.4) and overhydration (>0.4) groups. Systolic blood pressure, mean arterial pressure, and pulse pressure significantly reduced after dialysis in the normohydration group but did not significantly change in the overhydration group. Pre‐dialysis pulse pressure, post‐dialysis pulse pressure, and post‐dialysis systolic blood pressure in the overhydration group were significantly higher than normohydration group. Due to the simplicity and cost, blood pressure parameters, especially pulse pressure, might be a simple reference for clinicians to determine hydration status in HEMO patients.