Dietary nitrate supplementation increases nitrate and nitrite concentrations in human skin interstitial fluid.

Acute dietary nitrate (NO3-) supplementation can increase [NO3-], but not nitrite ([NO2-]), in human skeletal muscle, though its effect on [NO3-] and [NO2-] in skin remains unknown. In an independent group design, 11 young adults ingested 140 mL of NO3--rich beetroot juice (BR; 9.6 mmol NO3-), and 6 young adults ingested 140 mL of a NO3--depleted placebo (PL). Skin dialysate, acquired through intradermal microdialysis, and venous blood samples were collected at baseline and every hour post-ingestion up to 4 h to assess dialysate and plasma [NO3-] and [NO2-]. The relative recovery rate of NO3- and NO2- through the microdialysis probe (73.1% and 62.8%), determined in a separate experiment, was used to estimate skin interstitial [NO3-] and [NO2-]. Baseline [NO3-] was lower, whereas baseline [NO2-] was higher in the skin interstitial fluid relative to plasma (both P < 0.001). Acute BR ingestion increased [NO3-] and [NO2-] in the skin interstitial fluid and plasma (all P < 0.001), with the magnitude being smaller in the skin interstitial fluid (e.g., 183 ± 54 vs. 491 ± 62 µM for Δ[NO3-] from baseline and 155 ± 190 vs. 217 ± 204 nM for Δ[NO2-] from baseline at 3 h post BR ingestion, both P ≤ 0.037). However, due to the aforementioned baseline differences, skin interstitial fluid [NO2-] post BR ingestion was higher, whereas [NO3-] was lower relative to plasma (all P < 0.001). These findings extend our understanding of NO3- and NO2- distribution at rest and indicate that acute BR supplementation increases [NO3-] and [NO2-] in human skin interstitial fluid.

Optimized calcium supplementation approach in post-dilution CVVHDF using regional citrate anticoagulation.

BACKGROUND: Regional citrate anticoagulation has been recommended as first choice for anticoagulation of continuous renal replacement therapy. Precise calcium supplementation is important for the safety of regional citrate anticoagulation. In this study we aimed to provide an optimized calcium supplementation approach for regional citrate anticoagulation in post-dilution continuous venous-venous hemodiafiltration. METHODS: Twenty-seven patients receiving post-dilution continuous venous-venous hemodiafiltration anticoagulated by citrate were included in this study. The ionized calcium levels were monitored and maintained in the targeted range. After linear regression analysis of the clearance of non-protein bound calcium and calculating the ratio of the non-protein bound calcium concentration to total calcium concentration, we concluded the mathematical model for calcium supplementation. RESULTS: Positive correlations were found between the clearance of non-protein bound calcium and both dialysate flow rates (r = 0.647, p < 0.001) and ultrafiltration plus substitution fluid flow rates (r = 0.525, p = 0.005). The ratio of the non-protein bound calcium concentration to total calcium concentration values at the pre-filter point after infusion of citrate were constant about 0.83. Based on the clearance and the calcium ratio, the amount of extracorporeal calcium removal can be estimated with a simplified equation. CONCLUSIONS: We provided an optimized calcium supplementation approach for post-dilution continuous venous-venous hemodiafiltration anticoagulated by citrate which may help to estimate the amount of extracorporeal circuit removal of calcium with regard to different dosages of regional citrate anticoagulation.

Clinical research on individualized hemodialysis preventing unconventional hypotension in diabetic nephropathy patient.

OBJECTIVE: This study aims to evaluate the effectiveness of individualized hemodialysis for unconventional hypotension in diabetic nephropathy patients. METHODS: A total of 60 patients were selected and randomly divided into study group and control group. The control group used the standard dialysis model, while the study group used the individualized hemodialysis scheme, in which the dialysis was performed using an individualized dialysis machine temperature control, pattern of natrium, and pattern of step ultrafiltration in combination with dialysate-containing glucose. RESULTS: The total occurrence rate of hypotension, dry weight standard-reaching rate, and blood quality during and after dialysis in the study group were superior to those in the control group (P < 0.05). Furthermore, the symptom scores in the study group (dizziness score, chest distress score, sweating score, muscle spasm score, gastrointestinal symptom score, and temporary mind change score) were lower than those in the control group (P < 0.05). The serum sodium, potassium, and chloride concentration in these two groups after dialysis was not statistically different (P > 0.05). CONCLUSION: The combined application of low temperature, pattern of natrium, pattern of step ultrafiltration, and dialysate-containing glucose individualization is safe and effective for preventing and controlling the occurrence of intradialytic hypotension (IDH), improve symptoms, and improve the dry weight standard-reaching rate.

Zero balance ultrafiltration using dialysate during nationwide bicarbonate shortage: a retrospective analysis.

BACKGROUND: Zero balance ultrafiltration (Z-BUF) utilizing injectable 8.4% sodium bicarbonate is utilized to treat hyperkalemia and metabolic acidosis associated with cardiopulmonary bypass (CPB). The nationwide shortage of injectable 8.4% sodium bicarbonate in 2017 created a predicament for the care of cardiac surgery patients. Given the uncertainty of availability of sodium bicarbonate solutions, our center pro-actively sought a solution to the sodium bicarbonate shortage by performing Z-BUF with dialysate (Z-BUF-D) replacement fluid for patients undergoing cardiopulmonary bypass. METHODS: Single-center, retrospective observational evaluation of the first 46 patients at an academic medical center who underwent Z-BUF using dialysate over a period of 150 days with comparison of these findings to a historical group of 39 patients who underwent Z-BUF with sodium chloride (Z-BUF-S) over the preceding 150 days. The primary outcome was the change in whole blood potassium levels pre- and post-Z-BUF-D. Secondary outcomes included changes in pre- and post-Z-BUF-D serum bicarbonate levels and the amount of serum bicarbonate used in each Z-BUF cohort (Z-BUF-D and Z-BUF-S). RESULTS: Z-BUF-D and Z-BUF-S both significantly reduced potassium levels during CPB. However, Z-BUF-D resulted in a significantly decreased need for supplemental 8.4% sodium bicarbonate administration during CPB (52 mEq ± 48 vs. 159 mEq ± 85, P < 0.01). There were no complications directly attributed to the Z-BUF procedure. CONCLUSION: Z-BUF with dialysate appears to be analternative to Z-BUF with sodium chloride with marked lower utilization of intravenous sodium bicarbonate.

Icodextrin Is Associated with a Lower Mortality Rate in Peritoneal Dialysis Patients.

Background:Icodextrin (ICO) improves fluid removal in peritoneal dialysis (PD) patients. However, whether physiological benefits of ICO translate into patient survival remains unclear. We examine the association of ICO and clinical outcomes.Methods:We identified patients who initiated long-term PD from the National Health Insurance Research Database of Taiwan. We matched ICO users with non-users according to propensity score and survival status when ICO was prescribed. We utilized time-dependent analyses to avoid immortal time bias. Additional competing risk models were utilized for the outcomes except for death. The outcomes of interest were time to death, technique failure, peritonitis, major adverse cardiovascular events (MACE), and hospitalization.Results:A total of 4,914 PD patients were enrolled and 2,836 PD patients (57.7%) were identified as ICO users. The ICO users had significantly better overall survival (hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.63 - 0.86), especially among early ICO users (HR 0.64; 95% CI 0.54 - 0.77, p value for interaction: 0.007). The ICO users were associated with higher risk of peritonitis (subdistribution HR 1.22, 95% CI 1.06 - 1.14) and hospitalization (subdistribution HR 1.14, 95% CI 1.05 - 1.24), considering competing risk of death. However, when considering ICO use as a time-varying covariate, ICO users shared similar risks for technique failure, peritonitis, MACE, and hospitalization as non-users. The effect of ICO on mortality was especially prominent among those early users.Conclusions:After adjustments for immortal time biases, ICO users were significantly associated with approximately 20% reduction in mortality, especially among early users.

Prevention of hypophosphatemia during continuous renal replacement therapy-An overlooked problem.

Hypophosphatemia is a common and potentially serious complication occurring during continuous renal replacement therapy (CRRT). Phosphate supplementation is required in the vast majority of patients undergoing CRRT, particularly beyond the first 48 hours. Supplementation can be provided either as a standalone oral or parenteral treatment or as an additive to CRRT solutions. Each approach has advantages and disadvantages, and clinicians must weigh the individual factors most relevant in their practice setting. Currently there are no consensus protocols for phosphate replacement in CRRT, and many centers replete phosphate in response to hypophosphatemia as opposed to pre-emptively. Repletion protocols have also been challenged in recent years by shortages in injectable phosphate solutions. More recently a commercially available phosphate-containing CRRT solution was approved in the United States, but there has been limited clinical experience with this product. In this review, we present recommendations for phosphate repletion in CRRT to prevent hypophosphatemia, and describe our experience using phosphate-containing CRRT solutions.

Functional and Transcriptomic Characterization of Peritoneal Immune-Modulation by Addition of Alanyl-Glutamine to Dialysis Fluid.

Peritonitis remains a major cause of morbidity and mortality during chronic peritoneal dialysis (PD). Glucose-based PD fluids reduce immunological defenses in the peritoneal cavity. Low concentrations of peritoneal extracellular glutamine during PD may contribute to this immune deficit. For these reasons we have developed a clinical assay to measure the function of the immune-competent cells in PD effluent from PD patients. We then applied this assay to test the impact on peritoneal immune-competence of PD fluid supplementation with alanyl-glutamine (AlaGln) in 6 patients in an open-label, randomized, crossover pilot trial (EudraCT 2012-004004-36), and related the functional results to transcriptome changes in PD effluent cells. Ex-vivo stimulation of PD effluent peritoneal cells increased release of interleukin (IL) 6 and tumor necrosis factor (TNF) α. Both IL-6 and TNF-α were lower at 1 h than at 4 h of the peritoneal equilibration test but the reductions in cytokine release were attenuated in AlaGln-supplemented samples. AlaGln-supplemented samples exhibited priming of IL-6-related pathways and downregulation of TNF-α upstream elements. Results from measurement of cytokine release and transcriptome analysis in this pilot clinical study support the conclusion that suppression of PD effluent cell immune function in human subjects by standard PD fluid is attenuated by AlaGln supplementation.

Simultaneous formulation of terbinafine and salvia monoterpenes into chitosan hydrogel with testing biological activity of corresponding dialysates against C. albicans yeast.

This work was aimed at a progressive formulation of drugs into chitosan hydrogels. It was taken into consideration that a therapeutic effect of the drugs could be enhanced by a combination of natural compounds with chemical (synthetic) drugs. In this work, sage essential oil (SEO) bicyclic monoterpenes with antiflogistic, antiseptic, and antimycotic properties were combined with terbinafine (TB) having a strong antimycotic activity. Detail optimization of the hydrogel-drugs composition (SEO monoterpenes, TB, chitosan, and polysorbate 80 concentrations), based on permeation experiment and UV absorption/GC-MS analysis of permeated species (eucalyptol, camphor, borneol, thujone, TB) in dialysates, was made. Concerning the active drugs formulation, an optimum concentration of TB was set at the level providing maximum release of the SEO monoterpenes. In vitro activity of the dialysates from the optimized hydrogel was tested against Candida albicans showing that a minimum inhibition concentration was significantly exceeded. The experimental results revealed that the chitosan hydrogel was suitable for the simultaneous formulation of the natural drugs (SEO) with chemical drug (TB) resulting in the preparation with acceptable stability, required gel properties, and significant biological activity. Such preparation should be effective in an antimycotic dermal use.

Effect of Scavenging Circulating Reactive Carbonyls by Oral Pyridoxamine in Uremic Rats on Peritoneal Dialysis.

Pyridoxamine, a reactive carbonyl (RCO) scavenger, can ameliorate peritoneal deterioration in uremic peritoneal dialysis (PD) rats when given via dialysate. We examined the effects of scavenging circulating RCOs by oral pyridoxamine. Rats underwent nephrectomy and 3 weeks of twice daily PD either alone or with once daily oral pyridoxamine. PD solution was supplemented with methylglyoxal, a major glucose-derived RCO, to quench intraperitoneal pyridoxamine. Oral pyridoxamine achieved comparable blood and dialysate pyridoxamine concentrations, suppressed pentosidine accumulation in the blood but not in the mesenterium or dialysate, and reduced the increases in small solute transport and mesenteric vessel densities, with no effects on submesothelial matrix layer thickening or serum creatinine. Thus, reducing circulating RCOs by giving oral pyridoxamine with PD provides limited peritoneal protection. However, orally given pyridoxamine efficiently reaches the peritoneal cavity and would eliminate intraperitoneal RCOs. Oral pyridoxamine is more clinically favorable and may be as protective as intraperitoneal administration.

The Study of Low Calcium Dialysate on Elderly Hemodialysis Patients with Secondary Hypoparathyroidism.

OBJECTIVE: The study aimed to study the safety and efficacy of 1.25 mmol/l calcium dialysate on maintenance hemodialysis (MHD) in elderly patients who suffered from secondary hypoparathyroidism. METHODS: Eighty-two elderly patients (ages ≥65) who had been in MHD with dialysate calcium at 1.5 mmol/l over 6 months and had 2 consecutive serum intact parathyroid hormone (iPTH) measurements at level below 100 pg/ml were selected and randomized into 2 groups: treatment group (41 patients, with dialysate calcium at 1.25 mmol/l) and control group (41 patients, still with dialysate calcium at 1.5 mmol/l). Both groups were studied for the duration of 12 months. The changes of serum iPTH, calcium, phosphorus, calcium and phosphorus product and other indicators as well as related adverse reactions were recorded at the following time points: before the study and 1, 3, 6 and 12 months into the study. In addition, the intimal media thickness (IMT) of carotid artery and abdominal aorta calcification score (AACS) were measured in the 0, 6 and 12 months during the study. RESULTS: (1) In the treatment group, the levels of serum corrected calcium, phosphorus and calcium-phosphate product began to decline after 1 month and exhibited further decrease 3 months later. Serum iPTH level increased significantly after 1 month into the study and the trend continued. The above markers stabilized after month 6. Compared with pre-study markers, the changes of the above markers were significant after study (p < 0.05). (2) The average IMT and AACS were evidently decreased during the 6 and 12 months of study in the treatment group. There was statistical significance (p < 0.05) when compared with the above indexes of the pre-study and the control group. (3) In the control group, there were no significant differences in above laboratory markers over the 12-month study period. (4) There was no significant difference in the adverse events observed between the 2 groups. CONCLUSION: Safety of low calcium dialysate (dialysate calcium 1.25 mmol/l) in elderly MHD patients with iPTH <100 pg/ml is good, as well as improving carotid IMT, resistance index and AACS as indexes of vascular calcification in the small study group and warrants further investigation.

New Options for Iron Supplementation in Maintenance Hemodialysis Patients.

End-stage renal disease results in anemia caused by shortened erythrocyte survival, erythropoietin deficiency, hepcidin-mediated impairment of intestinal absorption and iron release, recurrent blood loss, and impaired responsiveness to erythropoiesis-stimulating agents (ESAs). Iron malabsorption renders oral iron products generally ineffective, and intravenous (IV) iron supplementation is required in most patients receiving maintenance hemodialysis (HD). IV iron is administered at doses far exceeding normal intestinal iron absorption. Moreover, by bypassing physiologic safeguards, indiscriminate use of IV iron overwhelms transferrin, imposing stress on the reticuloendothelial system that can have long-term adverse consequences. Unlike conventional oral iron preparations, ferric citrate has recently been shown to be effective in increasing serum ferritin, hemoglobin, and transferrin saturation values while significantly reducing IV iron and ESA requirements in patients treated with HD. Ferric pyrophosphate citrate is a novel iron salt delivered by dialysate; by directly reaching transferrin, its obviates the need for storing administered iron and increases transferrin saturation without increasing serum ferritin levels. Ferric pyrophosphate citrate trials have demonstrated effective iron delivery and stable hemoglobin levels with significant reductions in ESA and IV iron requirements. To date, the long-term safety of using these routes of iron administration in patients receiving HD has not been compared to IV iron and therefore awaits future investigations.

Estudio REFOS: eficacia y seguridad del carbonato de lantano en la práctica clínica en España / REFOS study: Efficacy and safety of Lanthanum Carbonate in clinical practice in Spain

El carbonato de lantano es un potente captor de fósforo que en ensayos clínicos ha mostrado eficacia y seguridad para el manejo de la hiperfosforemia, aunque existen pocos datos en la práctica clínica habitual. El objetivo del estudio fue evaluar, en la práctica clínica habitual, su eficacia y seguridad en pacientes en diálisis. Se recogieron, retrospectivamente, datos de 15 meses de seguimiento, correspondientes a los 3 meses previos al inicio del tratamiento con carbonato de lantano y 12 meses después del inicio. Los datos incluían valores séricos de calcio, fósforo, fosfatasa alcalina, PTH, enzimas hepáticas y hemograma, así como la dosis diaria prescrita de carbonato de lantano, la medicación concomitante, el cumplimiento terapéutico y los eventos adversos. Se incluyeron 674 pacientes, de los cuales completaron el estudio 522. Los abandonos se debieron en mayor medida a trastornos gastrointestinales (26 %) e hipofosfatemia (19 %). El fósforo sérico disminuyó de 6,4 ± 1,7 mg/dl (inicio) a 4,9 ± 1,4 mg/dl (12 meses) (p < 0,001). Al final del seguimiento el 47 % se encontraba dentro del rango de fósforo deseado (3,5-5 mg/dl). No hubo variaciones significativas en el resto de los parámetros. Dosis inicial de carbonato de lantano: 1900 mg/día, y dosis final: 2300 mg/día. Las variables que se asociaron de forma independiente con la fosforemia final fueron el fósforo sérico basal y el cumplimiento terapéutico. Respecto a la seguridad, se observaron 238 efectos adversos leves o moderados que ocurrieron en 117 pacientes, estando el 88 % relacionado con alteraciones gastrointestinales. En conclusión, el carbonato de lantano reduce los valores séricos de fósforo en pacientes en diálisis con un buen perfil de seguridad y aceptable adherencia a este, siendo los trastornos gastrointestinales el efecto adverso más frecuente (AU)

Lanthanum carbonate is a powerful phosphate binder that has shown efficacy and safety in clinical trials for hyperphosphataemia management, although there are few data in regular clinical practice. The study's objective was to evaluate, in regular clinical practice, its efficacy and safety in patients on dialysis. We retrospectively collected data from 15 months of monitoring, corresponding to 3 months prior to the start of treatment with lanthanum carbonate until 12 months after the start. Results included values of serum calcium, phosphorus, alkaline phosphatase, iPTH, hepatic enzymes and haemogram, as well as the daily-prescribed dose of lanthanum carbonate, the concomitant medication, treatment compliance and adverse events. 647 patients were included of which 522 completed the study. Abandonment, for the most part, was due to gastrointestinal disorders (26%) and hypophosphatemia (19%). Serum phosphorus decreased from 6.4 ± 1.7mg/dl (start) to 4.9 ± 1.4mg/dl (12 months) (P<.001). At the end of the monitoring period, 47% were within the desired phosphorus range (3.5-5mg/dl). There were no significant variations in the remaining parameters. Initial dose of lanthanum carbonate: 1900mg/day; and end dose: 2300mg/day. The variables independently associated with phosphataemia were baseline serum phosphorus and treatment compliance. In relation to safety, we observed 238 slight or moderate adverse effects in 117 patients, with 88% linked to gastrointestinal abnormalities. In conclusion, lanthanum carbonate reduces the serum phosphorus values in patients on dialysis with a good safety profile and acceptable adherence to that profile, with gastrointestinal disorders being the most frequent adverse effect (AU)

Is the dialysate calcium concentration of 1.75 mmol/L suitable for Chinese patients on maintenance hemodialysis?

We studied the effects of increasing the dialysate calcium concentration (DCa) to 1.75 mmol/L on controlling chronic kidney disease-mineral and bone disorder in Chinese patients on maintenance hemodialysis (MHD). We reviewed the data of MHD patients in one center (cohort 1) during prior 10 years and analyzed the risk factors of mortality and transference calcification (TC) in120 MHD patients surviving in 2003 (cohort 2). A multicenter, prospective, parallel-group, controlled trial (cohort 3) was also conducted from January 2011 to December 2012. The DCa at one center was increased from 1.5 to 1.75 mmol/L but was not changed at the other two centers. The clinical outcomes, biochemical parameters, medicine treatments, and TC markers [aortic arch calcification score (AoACS)] were compared between groups. In cohort 1, the annual mean serum iPTH increased significantly over 10 years. In cohort 1, 72 patients survived for 10 years, whose doses of calcium salts and active vitamin D3 and AoACs increased progressively. In cohort 2, the main cause of death was cardiocerebrovascular disease (CCVD) (n = 18, 48.6 %). Male sex and lower serum calcium concentrations were independent risk factors for CCVD mortality. In cohort 3, serum phosphorus, iPTH, and 25(OH)D decreased and serum calcium increased significantly; also, the doses of calcium and vitamin D3 decreased from 2011 to 2012 in the DCa 1.75 group. There were no significant differences in clinical outcomes either between groups or between the two calendar years. Our results indicate that increasing DCa to 1.75 mmol/L can decrease the elevated levels of serum iPTH and phosphorus, reduce the doses of calcium and vitamin D3, and be safe for short periods of time.

Calcitriol decreases TGF-ß1 and angiotensin II production and protects against chlorhexide digluconate-induced liver peritoneal fibrosis in rats.

Peritoneal fibrosis is a major complication of peritoneal dialysis that can lead to ultrafiltration failure. This study investigates the protective effects of calcitriol on chlorhexidine digluconate-induced peritoneal fibrosis in rats. Peritoneal fibrosis was induced in Sprague-Dawley rats by daily administration of 0.5mL 0.1% chlorhexidine digluconate in normal saline via peritoneal dialysis for 1week. Rats received daily intravenous injections of calcitriol (low-dose, 10ng/kg; or high-dose, 100ng/kg) for 1week. After 7days, conventional 4.25% Dianeal (30mL) was administered via peritoneal dialysis over 4h. Peritoneal solute transport was calculated from the dialysate concentration relative to its concentration in the initial infused dialysis solution (D4/D0 glucose) for glucose, and the dialysate-to-plasma concentration ratio (D4/P4 urea) at 4h for urea. Rats were then sacrificed and the liver peritoneum was harvested for immunohistochemical analysis via microscopy. After dialysis, the D4/P4 Urea level was reduced; increases were observed in the D4/D0 glucose level and the levels of active transforming growth factor-ß1 and angiotensin II in serum and dialysate; the liver peritoneum and muscle peritoneum was markedly thickened, and the expression of α-SMA, fibronectin, collagen, vascular endothelial growth factor, angiotensin II, transforming growth factor-ß1, and phosphorylated Smad2/3 (P-Smad2/3)-positive cells in the liver peritoneum was elevated in the peritoneal fibrosis group compared with the vehicle group. Calcitriol decreased the serum and dialysate active transforming growth factor-ß1 and angiotensin II level, decreased the thickness of the liver peritoneum and muscle peritoneum, and decreased the expression of α-SMA, fibronectin, collagen, vascular endothelial growth factor, angiotensin II, transforming growth factor-ß1, and P-Smad2/3-positive cells in liver peritoneum cells. High-dose calcitriol exhibited better protective effects against peritoneal fibrosis than did the lower dose. Calcitriol protected against chlorhexidine digluconate-induced peritoneal fibrosis in rats by decreasing transforming growth factor-ß1 and angiotensin II production.

Bioenergetic gain of citrate anticoagulated continuous hemodiafiltration--a comparison between 2 citrate modalities and unfractionated heparin.

PURPOSE: To determine bioenergetic gain of 2 different citrate anticoagulated continuous hemodiafiltration (CVVHDF) modalities and a heparin modality. MATERIALS AND METHODS: We compared the bio-energetic gain of citrate, glucose and lactate between 29 patients receiving 2.2% acid-citrate-dextrose with calcium-containing lactate-buffered solutions (ACD/Ca(plus)/lactate), 34 on 4% trisodium citrate with calcium-free low-bicarbonate buffered fluids (TSC/Ca(min)/bicarbonate), and 18 on heparin with lactate buffering (Hep/lactate). RESULTS: While delivered CVVHDF dose was about 2000 mL/h, total bioenergetic gain was 262 kJ/h (IQR 230-284) with ACD/Ca(plus)/lactate, 20 kJ/h (8-25) with TSC/Ca(min)/bicarbonate (P < .01) and 60 kJ/h (52-76) with Hep/lactate. Median patient delivery of citrate was 31.2 mmol/h (25-34.7) in ACD/Ca(plus)/lactate versus 14.8 mmol/h (12.4-19.1) in TSC/Ca(min)/bicarbonate groups (P < .01). Median delivery of glucose was 36.8 mmol/h (29.9-43) in ACD/Ca(plus)/lactate, and of lactate 52.5 mmol/h (49.2-59.1) in ACD/Ca(plus)/lactate and 56.1 mmol/h (49.6-64.2) in Hep/lactate groups. The higher energy delivery with ACD/Ca(plus)/lactate was partially due to the higher blood flow used in this modality and the calcium-containing dialysate. CONCLUSIONS: The bioenergetic gain of CVVHDF comes from glucose (in ACD), lactate and citrate. The amount substantially differs between modalities despite a similar CVVHDF dose and is unacceptably high when using ACD with calcium-containing lactate-buffered solutions and a higher blood flow. When calculating nutritional needs, we should account for the energy delivered by CVVHDF.

Stability of continuous renal replacement therapy solutions after phosphate addition: an experimental study.

The incidence of hypophosphatemia is high in critically ill children on continuous renal replacement therapy (CRRT) and the addition of phosphate supplements to the replacement and dialysis fluids reduces the frequency of hypophosphatemia. The objective of this study was to determine the in vitro stability of the CRRT solutions after phosphate addition. Three different concentrations of phosphate, 2.5, 4.6 and 7.7 mg/dL, in the replacement and dialysis fluids were analyzed. The pH, glucose, total calcium, phosphate, and magnesium were determined before adding the phosphate and at 2, 24, and 48 h after its addition. The bags were macroscopically observed for possible precipitation. After addition of the phosphate, its concentration remained stable and there were no significant changes in the concentrations of the other components. There were no visible signs of precipitation up to 48 h. The addition of phosphate to the CRRT fluids at concentrations of up to 7.7 mg/dL does not cause problems with precipitation or instability of the mixture.

Electrolysed-reduced water dialysate improves T-cell damage in end-stage renal disease patients with chronic haemodialysis.

BACKGROUND: T-cell damage by increased oxidative stress in end-stage renal disease (ESRD) patients undergoing chronic haemodialysis (HD) led to the increased T-cell apoptosis and the alteration of surface markers and Th1/Th2 ratio in CD4(+) T lymphocytes. Antioxidant electrolysed-reduced water (ERW) was used as the dialysate in ESRD patients undergoing chronic HD to test for improved oxidative stress-related T-cell apoptosis, alterations of surface markers and intracellular cytokine profile. METHODS: We evaluated apoptosis formation by annexin V, CD25-related surface markers, and cytokine ratio of Th1/Th2 in CD4(+) T lymphocytes and Tc1/Tc2 in CD8(+) T lymphocytes of 42 ESRD patients haemodialysed with ERW for 1 year. RESULTS: In comparison to 12 healthy individuals, the ESRD patients had more T-cell apoptosis and less CD3(+), CD4(+) and CD8(+) T cells and CD25/CD69/CD94/CD3(+) phenotypes at baseline. Lower intracellular IL-2 and IFN-gamma levels in the Th1/CD4(+) and Tc1/CD8(+) cells and higher intracellular IL-4, IL-6 and IL-10 levels in the Th2/CD4(+) and Tc2/CD8(+) cells were also noted in the ESRD patients. After a 1-year ERW treatment, the patients had a decrease in T-cell apoptosis and increases in CD3(+), CD4(+) and CD8(+) cell numbers and CD25/CD69/CD94/CD3(+) phenotypes in the T cells. The intracellular IL-2 and IFN-gamma levels in the Th1/Tc1 cells significantly (P < 0.05) increased and the intracellular IL-4, IL-6 and IL-10 levels in the Th2/Tc2 cells decreased. Furthermore, the Th1/Th2 and Tc1/Tc2 cytokine ratios were improved toward a normal status. CONCLUSION: One-year ERW treatment effectively ameliorated T-cell apoptosis, altered CD25-related surface markers and intracellular cytokine profile in the HD patients.

Intravenous iron sucrose changes the intraperitoneal homeostasis.

BACKGROUND/AIMS: Intravenous iron infusion is the accepted way of supplementation of that compound in uremic patients. The aim of the study was to evaluate whether this treatment affects intraperitoneal homeostasis in patients on peritoneal dialysis. METHODS: Blood and peritoneal dialysate samples were collected from 10 patients treated with continuous ambulatory peritoneal dialysis who were given 100 mg iron sucrose (IS) intravenously. Systemic and peritoneal permeability as well as transperitoneal transport were studied. The effect of spent dialysate was tested in vitro on human peritoneal mesothelial cells (MCs). RESULTS: Dialysate total iron was increased (+19%, p < 0.01) during intravenous infusion of IS. Immediately after infusion the concentration of 8-OHdG was increased in plasma (+10%, p < 0.01) and in dialysate (+5%, p < 0.05). IS infusion caused a transient decrease in peritoneal permeability to protein (-42%, p < 0.05) and glucose (-30%, p < 0.01) and a reduction in dialysate cell count (-58%, p < 0.05). During the exchange dialysate hyaluronan was increased by 27% (p < 0.01). Spent dialysate, tested ex vivo on cultured MC, induced oxidative stress (+39%, p < 0.01), slowed their proliferation (-20%, p < 0.01), and stimulated MCP-1 synthesis (+46%, p < 0.01). Iron content in MCs exposed to dialysate obtained after IS infusion was increased by 32% (p < 0.01). CONCLUSION: Intravenous infusion of IS causes oxidative stress and inflammation within peritoneal MCs which may impair viability of the peritoneum.

[Erytrocyte membrane change due to the chemical treatment studied with atomic force microscopy]. / Zastosowanie mikroskopii sil atomowych do badan zmian w blonie erytrocytów wywolanych czynnikami chemicznymi.

The influence of some selected pharmacological compounds on the structure of human erythrocytes (red blood cells, RBCs) has been studied by means of an atomic force microscopy (AFM). The imaging has been done both in the air environment on the fixed cells, and in the liquid (physiological conditions). It was shown that RBCs are very sensitive to osmotic changes in the solution. Increased NaCl concentration in the solution to a value higher than 0.9% leads to the characteristic changes of the erythrocyte from a discoid-like shape to a very irregular one, the so-called "echinocyte", with a lot of ledges. After exposition on nifedipin the modification of the erythrocyte surface morphology was observed. Based on the contact and non-contact AFMs study the consecutive stages of RBCs surface modification were observed. Scanning electron microscopy pictures of erythrocytes were presented for comparison.

Pharmacokinetics of calcitriol and maxacalcitol administered into peritoneal dialysate bags in peritoneal dialysis patients.

OBJECTIVES: It is well known that injection of calcitriol (CT) or maxacalcitol (OCT) is very effective in hemodialysis patients with secondary hyperparathyroidism (2HPT). However, it is difficult to use these drugs with peritoneal dialysis (PD) patients with 2HPT because these drugs must be injected two or three times per week. The objective of the present study was to evaluate the stability of physiological activities of CT and OCT in PD bags and to determine the CT or OCT dosage for intraperitoneal (IP) administration. MATERIALS AND METHODS: We added CT 1.5 microg or OCT 10 microg to Dianeal PD-2 (approximate pH = 5.0, calcium = 0.87 mmol/L; Baxter,Tokyo, Japan), Midpeliq 250 (approximate pH = 7.0, Ca = 1.0 mmol/L;Terumo Corporation, Tokyo, Japan), and Peritoliq 250 (approximate pH = 5.5, Ca = 1.0 mmol/L; Terumo Corp.). Dialysis solutions were collected from the PD bags at 0, 1, 4, 8, 12, 24, 48, and 72 hours after addition of CT and OCT. The activities of CT and OCT in the dialysis effluent were measured by radioimmunoassay. The levels of serum and effluent OCT after a single IP administration of 10 microg OCT were examined in 4 PO patients with advanced 2HPT. RESULTS: Although the levels of CT and OCT in PD bags made of polyvinyl resins decreased by 70% - 75% immediately after injection, levels in PD bags made of polypropylene resins decreased only slightly. The concentration of CT mixed into the acidic solution in glass containers was stable; the decreased concentration of CT in the PD solution might be due to adsorption onto polyvinyl resins. The maximum serum concentration after IP administration of 10 microg OCT was 750 pg/mL after 5 minutes, and remained at 500 pg/mL at 60 minutes. These results show good peritoneal transport of OCT but not rapid disappearance, unlike intravenous administration. CONCLUSIONS: If peritoneal administration of vitamin D derivatives is contemplated, it is important to select the composition of PD bag resins, type of vitamin D analog, and time lag to use when deciding the dosage of injectable vitamin D preparations, such as OCT or CT, for IP administration to PD patients. It appears that IP administration in overnight dwells might be useful for PD patients as a complementary vitamin D preparation.