Modelling of icodextrin hydrolysis and kinetics during peritoneal dialysis.

In peritoneal dialysis, ultrafiltration is achieved by adding an osmotic agent into the dialysis fluid. During an exchange with icodextrin-based solution, polysaccharide chains are degraded by α-amylase activity in dialysate, influencing its osmotic properties. We modelled water and solute removal taking into account degradation by α-amylase and absorption of icodextrin from the peritoneal cavity. Data from 16 h dwells with icodextrin-based solution in 11 patients (3 icodextrin-exposed, 8 icodextrin-naïve at the start of the study) on dialysate volume, dialysate concentrations of glucose, urea, creatinine and α-amylase, and dialysate and blood concentrations of seven molecular weight fractions of icodextrin were analysed. The three-pore model was extended to describe hydrolysis of icodextrin by α-amylase. The extended model accurately predicted kinetics of ultrafiltration, small solutes and icodextrin fractions in dialysate, indicating differences in degradation kinetics between icodextrin-naïve and icodextrin-exposed patients. In addition, the model provided information on the patterns of icodextrin degradation caused by α-amylase. Modelling of icodextrin kinetics using an extended three-pore model that takes into account absorption of icodextrin and changes in α-amylase activity in the dialysate provided accurate description of peritoneal transport and information on patterns of icodextrin hydrolysis during long icodextrin dwells.

Sex Modulates Cardiovascular Effects of Icodextrin-Based Peritoneal Dialysis Solutions.

Background/Aims: Some previous observations have noted that after six months of peritoneal dialysis (PD) treatment with icodextrin solutions, blood pressure (BP) and NT-proBNP tend to return to baseline values. This may be due to accumulation of icodextrin products that exert a colloid osmotic effect, which drives water into the bloodstream, causing the rise in blood pressure. Since icodextrin is metabolized by α-Amylase and its gene copies are lower in females than in males, we hypothesized icodextrin metabolites reach higher concentrations in females and that cardiovascular effects of icodextrin are influenced by sex. Methods: Secondary analysis of a RCT comparing factors influencing fluid balance control in diabetic PD patients with high or high average peritoneal transport receiving icodextrin (n = 30) or glucose (n = 29) PD solutions. Serum icodextrin metabolites, osmolality, body composition and Inferior Vena Cava (IVC) diameter were measured at baseline, and at 6 and 12 months of follow-up. Results: After six months of treatment, icodextrin metabolites showed higher levels in females than in males, particularly G5-7 and >G7, serum osmolality was lower in females. In spite of reduction in total and extracellular body water, ultrafiltration (UF) was lower and IVC diameter and BP increased in females, suggesting increment of blood volume. Conclusion: Females undergoing PD present with higher levels of icodextrin metabolites in serum that may exert an increased colloid-osmotic pressure followed by less UF volumes and increment in blood volume and blood pressure. Whether this could be due to the lesser number of α-Amylase gene copies described in diabetic females deserves further investigation.

Long Peritoneal Dialysis Dwells With Icodextrin: Kinetics of Transperitoneal Fluid and Polyglucose Transport.

Background and objective: During peritoneal dialysis (PD), the period of effective net peritoneal ultrafiltration during long dwells can be extended by using the colloidal osmotic agent icodextrin but there are few detailed studies on ultrafiltration with icodextrin solution exceeding 12 h. We analyzed kinetics of peritoneal ultrafiltration in relation to icodextrin and its metabolites for 16-h dwells with icodextrin. Design, setting, participants, and measurements: In 20 clinically stable patients (mean age 54 years; 8 women; mean preceding time on PD 26 months), intraperitoneal dialysate volume (VD) was estimated from dilution of 125I-human serum albumin during 16-h dwell studies with icodextrin 7.5% solution. Sodium was measured in dialysate and plasma. In 11 patients, fractional absorption of icodextrin from dialysate, dialysate, and plasma amylase and high and low (Mw <2 kDa) Mw icodextrin fractions were analyzed. Results: Average VD increased linearly with no difference between transport types. At 16 h, the cumulative net ultrafiltration was 729 ± 337 ml (range -18 to 1,360 ml) and negative in only one patient. Average transcapillary ultrafiltration rate was 1.40 ± 0.36 ml/min, and peritoneal fluid absorption rate was 0.68 ± 0.38 ml/min. During 16 h, 41% of the initial mass of icodextrin was absorbed. Plasma sodium decreased from 138.7 ± 2.4 to 136.5 ± 3.0 mmol/L (p < 0.05). Dialysate glucose G2-G7 oligomers increased due to increase of G2-G4 metabolites while G6-G7 metabolites and higher Mw icodextrin fractions decreased. In plasma maltose and maltotriose (G2-G3 metabolites) increased while higher Mw icodextrin oligomers were almost undetectable. Dialysate amylase increased while plasma amylase decreased. Conclusions: Icodextrin resulted in linear increase of VD with sustained net UF lasting 16 h and with no significant difference between peritoneal transport types. In plasma, sodium and amylase declined, G2-G3 increased whereas larger icodextrin fractions were not detectable. In dialysate, icodextrin mass declined due to decrease of high Mw icodextrin fractions while low Mw metabolites, especially G2-G3, increased. The ability of icodextrin to provide sustained UF during very long dwells - which is usually not possible with glucose-based solutions - is especially important in anuric patients and in patients with fast peritoneal transport.

Mechanisms of Crystalloid versus Colloid Osmosis across the Peritoneal Membrane.

Background Osmosis drives transcapillary ultrafiltration and water removal in patients treated with peritoneal dialysis. Crystalloid osmosis, typically induced by glucose, relies on dialysate tonicity and occurs through endothelial aquaporin-1 water channels and interendothelial clefts. In contrast, the mechanisms mediating water flow driven by colloidal agents, such as icodextrin, and combinations of osmotic agents have not been evaluated.Methods We used experimental models of peritoneal dialysis in mouse and biophysical studies combined with mathematical modeling to evaluate the mechanisms of colloid versus crystalloid osmosis across the peritoneal membrane and to investigate the pathways mediating water flow generated by the glucose polymer icodextrin.ResultsIn silico modeling and in vivo studies showed that deletion of aquaporin-1 did not influence osmotic water transport induced by icodextrin but did affect that induced by crystalloid agents. Water flow induced by icodextrin was dependent upon the presence of large, colloidal fractions, with a reflection coefficient close to unity, a low diffusion capacity, and a minimal effect on dialysate osmolality. Combining crystalloid and colloid osmotic agents in the same dialysis solution strikingly enhanced water and sodium transport across the peritoneal membrane, improving ultrafiltration efficiency over that obtained with either type of agent alone.Conclusions These data cast light on the molecular mechanisms involved in colloid versus crystalloid osmosis and characterize novel osmotic agents. Dialysis solutions combining crystalloid and colloid particles may help restore fluid balance in patients treated with peritoneal dialysis.

Copeptin Plasma Levels are Associated with Decline of Renal Function in Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Chronic kidney disease (CKD) is a leading complication of type 2 diabetes mellitus (T2DM) and is considered as a public health problem. Copeptin is a surrogate marker of arginine vasopressin (AVP) system and is proposed as a biomarker of decline renal function. OBJECTIVE: Evaluate whether plasma copeptin levels may be used as a biomarker of decline renal function in patients with T2DM. RESEARCH DESIGN AND METHODS: A total of 480 patients with T2DM and different stages of CKD were included. Plasma levels of copeptin, cystatin-C, and other biochemical parameters were measured. The correlation between copeptin and glomerular filtration rate (GFR), estimated based on plasma cystatin-C levels, was investigated. RESULTS: Plasma copeptin levels were gradually increased from the stage 1-5 of CKD in the patients with T2DM. In univariate linear regression analysis, high plasma levels of copeptin were associated with lower GFR (Standardized ß = -0.535, R2 = 0.287, p <0.0001). This association remained significant even after being adjusted for glucose levels and years of T2DM diagnosis, mean blood pressure, pharmacological treatment, gender, and age. CONCLUSIONS: The results show that high plasma copeptin levels are associated with the decline of renal function in patients with T2DM and, therefore, copeptin may be considered as a biomarker of renal function. Further evaluation of plasma copeptin levels to predict morbidity and mortality of T2DM patients, with or without CKD, has been taken into our consideration.

La disminución de triyodotironina se asocia con la elevación del péptido natriurético cerebral N-terminal y con la mortalidad en pacientes en diálisis / Low triiodothyronine is associated with elevation of N-terminal pro-brain natriuretic peptide (NT-proBNP) and mortality in dialysis patients

Antecedentes: La disminución de hormonas tiroideas (HT) y el daño miocárdico son frecuentes en pacientes en diálisis y están asociados con la mortalidad. Sin embargo, poco se conoce de la importancia de las HT como factor de daño miocárdico, como se ha descrito en las enfermedades tiroideas primarias. El objetivo de este estudio fue explorar si existe interacción entre la disminución de triyodotironina total (tT3) y los marcadores de daño miocárdico y la relación de esta interacción entre ambos con la mortalidad, para establecer si el daño cardiovascular es el vínculo entre la disminución de HT y el riesgo de muerte en pacientes con ERC en diálisis. Material y métodos: Se estudiaron los niveles plasmáticos de HT, de marcadores de nutrición, inflamación y de daño al miocardio en 296 pacientes en diálisis peritoneal o en hemodiálisis, a los que se vigiló por 16 meses para conocer la asociación de las variables bioquímicas con la mortalidad. Resultados: En el 45% de los pacientes se encontró tT3 disminuida, lo cual tuvo correlación inversa con la proteína C reactiva (PCR) y con el NT-proBNP y directa con la albúmina y la transferrina. La diabetes, la PCR y la tT3 fueron factores de riesgo para la mortalidad por cualquier causa y la PCR, el NT-proBNP y la tT3 para mortalidad cardiovascular. Conclusiones: Los niveles bajos de tT3 son frecuentes en pacientes en diálisis, se asocian con inflamación, desnutrición y daño miocárdico: este último puede ser el vínculo entre la disminución de HT y la mortalidad por cualquier causa y la mortalidad cardiovascular (AU)

Background: Low thyroid hormone (TH) levels and myocardial damage are common in dialysis patients and are associated with mortality. However, little is known about the role of THs on myocardial damage as has been described in primary thyroid diseases. The aim of this study was to explore the potential relationship between low total triiodothyronine (total T3) and biomarkers of myocardial damage and the effect of their interaction on mortality, to ascertain if cardiovascular damage is the link between low THs and the risk of death in dialysis patients with CKD. Material and methods: TH plasma levels, nutritional markers, inflammation and myocardial damage were studied in 296 patients undergoing peritoneal dialysis or haemodialysis, who were followed up for 16 months to ascertain the association between biochemical variables and mortality. Results: Low total T3 levels were found in 45% of patients, which was inversely correlated with C-reactive protein (CRP) and NT-proBNP, and directly correlated with albumin and transferrin. Diabetes, CRP and total T3 were risk factors for all-cause mortality, and CRP, NT-proBNP and total T3 for cardiovascular mortality. Conclusions: Low total T3 levels are common in dialysis patients and are associated with inflammation, malnutrition and myocardial damage. The latter may be the link between low THs and all-cause and cardiovascular mortality (AU)

Low triiodothyronine is associated with elevation of N-terminal pro-brain natriuretic peptide (NT-proBNP) and mortality in dialysis patients. / La disminución de triyodotironina se asocia con la elevación del péptido natriurético cerebral N-terminal y con la mortalidad en pacientes en diálisis.

BACKGROUND: Low thyroid hormone (TH) levels and myocardial damage are common in dialysis patients and are associated with mortality. However, little is known about the role of THs on myocardial damage as has been described in primary thyroid diseases. The aim of this study was to explore the potential relationship between low total triiodothyronine (total T3) and biomarkers of myocardial damage and the effect of their interaction on mortality, to ascertain if cardiovascular damage is the link between low THs and the risk of death in dialysis patients with CKD. MATERIAL AND METHODS: TH plasma levels, nutritional markers, inflammation and myocardial damage were studied in 296 patients undergoing peritoneal dialysis or haemodialysis, who were followed up for 16 months to ascertain the association between biochemical variables and mortality. RESULTS: Low total T3 levels were found in 45% of patients, which was inversely correlated with C-reactive protein (CRP) and NT-proBNP, and directly correlated with albumin and transferrin. Diabetes, CRP and total T3 were risk factors for all-cause mortality, and CRP, NT-proBNP and total T3 for cardiovascular mortality. CONCLUSIONS: Low total T3 levels are common in dialysis patients and are associated with inflammation, malnutrition and myocardial damage. The latter may be the link between low THs and all-cause and cardiovascular mortality.

Effect of icodextrin on heart rate variability in diabetic patients on peritoneal dialysis.

INTRODUCTION: Spectral analysis of heart rate variability is a noninvasive method for evaluating autonomic cardiovascular dysfunction under various clinical conditions, such as in dialysis patients, in whom an imbalance between the sympathetic and parasympathetic nervous system appears to be an important risk factor for sudden cardiovascular death and arrhythmia. ♢ OBJECTIVE: We compared the effect of icodextrin-based dialysis solution, an option that allows for better metabolic and fluid overload control, with that of glucose-based dialysis fluid on sympathetic and parasympathetic activity in the heart, as assessed by heart rate variability, in diabetic patients on peritoneal dialysis (PD). ♢ METHODS: This secondary analysis uses data from a randomized controlled trial in diabetic PD patients with high or high-average peritoneal transport using icodextrin-based (ICO group, n = 30) or glucose-based (GLU group, n = 29) solutions for the long dwell. All patients underwent 24-hour electrocardiographic Holter monitoring at baseline, and at 6 and 12 months of follow-up. ♢ RESULTS: We observed no significant differences between the groups in most of the variables analyzed, although values were, in general, below reference values. In the ICO group, total power and both low- and high-frequency power in normalized units increased, but the percentage of RR intervals with variation of more than 50 ms declined over time; in the GLU group, all those values declined. Plasma catecholamine levels were higher at baseline and declined over time. ♢ CONCLUSIONS: These results indicate a partial recovery of sympathetic activity in the ICO group, probably because of better extracellular fluid control and lower exposure to glucose with the use of icodextrin-based dialysis solutions.

Dialysis adequacy indices and body composition in male and female patients on peritoneal dialysis.

OBJECTIVES: Creatinine clearance scaled to body surface area (BSA) and urea KT/V normalized to total body water (TBW) are used as indices for peritoneal dialysis (PD) adequacy. We investigated relationships of indices of dialysis adequacy (including KT/V, KT, clearance, dialysate over plasma concentration ratio) and anthropometric and body composition parameters (BSA, TBW, body mass index (BMI), weight, height, fat mass (FM), and fat-free mass (FFM)) in male and female patients on continuous ambulatory peritoneal dialysis. METHODS: Ninety-nine stable patients (56 males) performed four 24-hr collections of drained dialysate for four dialysis schedules with three daily exchanges of glucose 1.36% and one night exchange of either: 1) glucose 1.36%, 2) glucose 2.27%, 3) glucose 3.86% or 4) icodextrin 7.5%. RESULTS: KT and dialysate over plasma concentration ratio, CD/CP, for urea and creatinine were similar for males and females and, in general, did not depend on body-size parameters including V (= TBW), which means that the overall capacity of the transport system in females and males is similar. However, after normalization of KT to V or 1.73/BSA yielding KT/V and creatinine clearance, Cl(1.73/BSA), respectively, the normalized indices were substantially higher in females than in males and correlated inversely with body-size parameters, especially in males. CONCLUSIONS: As KT/V depends strongly on body size, treatment target values for KT/V should take body size and therefore also gender into account. As KT is less influenced by body size, body composition and gender, KT should be considered as a potential auxiliary index in PD.

Effects of dopamine on leptin release and leptin gene (OB) expression in adipocytes from obese and hypertensive patients.

BACKGROUND: A reduction of dopaminergic (DAergic) activity with increased prolactin levels has been found in obese and hypertensive patients, suggesting its involvement as a pathophysiological mechanism promoting hypertension. Similarly, leptin action increasing sympathetic activity has been proposed to be involved in mechanisms of hypertension. The aim of this study was to analyze the effects of DA, norepinephrine (NE), and prolactin on leptin release and leptin gene (OB) expression in adipocytes from obese and hypertensive patients. METHODS: Leptin release and OB gene expression were analyzed in cultured adipocytes from 16 obese and hypertensive patients treated with DA (0.001, 0.01, 0.1, and 1.0 µmol/L), NE (1.0 µmol/L), insulin (0.1 µmol/L), and prolactin (1.0 µmol/L), and from five nonobese and normotensive controls treated with DA (1 µmol/L), NE (1 µmol/L), insulin (0.1 µmol/L), and prolactin (1.0 µmol/L). RESULTS: A dose-related reduction of leptin release and OB gene messenger ribonucleic acid expression under different doses of DA was observed in adipocytes from obese hypertensive patients. Whereas prolactin treatment elicited a significant increase of both leptin release and OB gene expression, NE reduced these parameters. Although similar effects of DA and NE were observed in adipocytes from controls, baseline values in controls were reduced to 20% of the value in adipocytes from obese hypertensive patients. CONCLUSION: These results suggest that DAergic deficiency contributes to metabolic disorders linked to hyperleptinemia in obese and hypertensive patients.

Cardiovascular and renal effects of bromocriptine in diabetic patients with stage 4 chronic kidney disease.

OBJECTIVE: The objective of this study was to investigate the effect of bromocriptine (BEC) on left ventricular mass index (LVMI) and residual renal function (RRF) in chronic kidney disease (CKD) patients with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: A 6-month double-blind randomized controlled trial was conducted in 28 patients with T2D and stage 4 CKD with increased LVMI. Fourteen patients received BEC (2.5 mg, initially 1 tablet with subsequent increase to three times a day) and 14 received a placebo (PBO; initially 1 tablet with subsequent increase to three times a day). Cardiovascular changes were assessed by monitoring 24 h ambulatory blood pressure, two-dimensional-guided M-mode echocardiography, and N-terminal brain natriuretic peptide (NT-proBNP) plasma levels. RRF was evaluated by creatinine clearance and cystatin-C plasma levels. RESULTS: Both BEC and PBO groups decreased blood pressure-but the effect was more pronounced in the BEC group. Average 24 h, diurnal and nocturnal blood pressures, and circadian profile showed improved values compared to the PBO group; LVMI decreased by 14% in BEC and increased by 8% in PBO group. NT-proBNP decreased in BEC (0.54 ± 0.15 to 0.32 ± 0.17 pg/mL) and increased in PBO (0.37 ± 0.15 to 0.64 ± 0.17 pg/mL). Creatinine clearance did not change in the BEC group and decreased in the PBO group. CONCLUSIONS: BEC resulted in a decrease on blood pressure and LVMI. BEC also prevented the progression of CKD while maintaining the creatinine clearance unchanged.

Reaching targets for mineral metabolism clinical practice guidelines and its impact on outcomes among Mexican chronic dialysis patients.

BACKGROUND AND AIMS: An increasing number of studies have been published concerning meeting targets of clinical guidelines for different aspects of the diagnosis and treatment of patients with end-stage renal disease. Most of these studies have shown that guideline recommendations are not always satisfied, and results outside target limits have been associated with high rates of mortality and morbidity. The objective of this study was to analyze the frequency of reaching mineral and bone metabolism-related guideline targets and its impact on clinical outcomes in Mexican chronic dialysis patients. METHODS: A cohort of prevalent peritoneal dialysis (PD) and hemodialysis (HD) patients were analyzed at baseline and followed for at least 16 months. Patients were on continuous ambulatory peritoneal dialysis (CAPD), automated peritoneal dialysis (APD), and HD and contracted HD modalities where patients received HD sessions outside institution facilities. RESULTS: We studied 753 patients. The percentage of patients within target limits for phosphorus was 35%, for calcium 32%, and for PTH 12%. The most frequent pattern was hyperphosphatamia, hypercalcemia, and low PTH. This was even more frequent in CAPD patients, probably due to the high percentage of diabetic patients. Hypercalcemia was found as an independent risk factor for mortality. CONCLUSIONS: The most important results suggest that guideline recommendations are not usually satisfied and that hypercalcemia, in addition to other traditional risk factors, is associated with high mortality rates. The study also detected some opportunities to improve the quality of treatment by reducing the calcium content of dialysis solutions and reducing the use of calcium carbonate as a phosphate binder.

Threefold peritoneal test of osmotic conductance, ultrafiltration efficiency, and fluid absorption.

BACKGROUND: Fluid removal during peritoneal dialysis depends on modifiable factors such as tonicity of dialysis fluids and intrinsic characteristics of the peritoneal transport barrier and the osmotic agent-for example, osmotic conductance, ultrafiltration efficiency, and peritoneal fluid absorption. The latter parameters cannot be derived from tests of the small-solute transport rate. We here propose a simple test that may provide information about those parameters. METHODS: Volumes and glucose concentrations of drained dialysate obtained with 3 different combinations of glucose-based dialysis fluid (3 exchanges of 1.36% glucose during the day and 1 overnight exchange of either 1.36%, 2.27%, or 3.86% glucose) were measured in 83 continuous ambulatory peritoneal dialysis (CAPD) patients. Linear regression analyses of daily net ultrafiltration in relation to the average dialysate-to-plasma concentration gradient of glucose allowed for an estimation of the osmotic conductance of glucose and the peritoneal fluid absorption rate, and net ultrafiltration in relation to glucose absorption allowed for an estimation of the ultrafiltration effectiveness of glucose. RESULTS: The osmotic conductance of glucose was 0.067 ± 0.042 (milliliters per minute divided by millimoles per milliliter), the ultrafiltration effectiveness of glucose was 16.77 ± 7.97 mL/g of absorbed glucose, and the peritoneal fluid absorption rate was 0.94 ± 0.97 mL/min (if estimated concomitantly with osmotic conductance) or 0.93 ± 0.75 mL/min (if estimated concomitantly with ultrafiltration effectiveness). These fluid transport parameters were independent of small-solute transport characteristics, but proportional to total body water estimated by bioimpedance. CONCLUSIONS: By varying the glucose concentration in 1 of 4 daily exchanges, osmotic conductance, ultrafiltration efficiency, and peritoneal fluid absorption could be estimated in CAPD patients, yielding transport parameter values that were similar to those obtained by other, more sophisticated, methods.

Genetic damage in patients with chronic kidney disease, peritoneal dialysis and haemodialysis: a comparative study.

Patients with chronic kidney disease (CKD) have signs of genomic instability and, as a consequence, extensive genetic damage, possibly due to accumulation of uraemic toxins, oxidative stress mediators and other endogenous substances with genotoxic properties. We explored factors associated with the presence and background levels of genetic damage in CKD. A cross-sectional study was performed in 91 CKD patients including pre-dialysis (CKD patients; n = 23) and patients undergoing peritoneal dialysis (PD; n = 33) or haemodialysis (HD; n = 35) and with 61 healthy subjects, divided into two subgroups with the older group being in the age range of the patients, serving as controls. Alkaline comet assay and cytokinesis-block micronucleus assay in peripheral blood lymphocytes were used to determine DNA and chromosome damage, respectively, present in CKD. Markers of oxidative stress [malondialdehyde (MDA), advanced glycation end products (AGEs), thiols, advanced oxidation protein products and 8-hydroxy-2'-deoxyguanosine] and markers of inflammation (C-reactive protein, interleukin-6 and tumour necrosis factor alpha) were also measured. Micronucleus (MN) frequency was significantly higher (P < 0.05) in the CKD group (46±4‰) when compared with the older control (oC) group (27.7±14). A significant increase in MN frequency (P < 0.05) was also seen in PD patients (41.9±14‰) versus the oC group. There was no statistically significant difference for the HD group (29.7±15.6‰; P = NS) versus the oC group. Comet assay data showed a significant increase (P < 0.001) of tail DNA intensity in cells of patients with CKD (15.6±7%) with respect to the total control (TC) group (11±1%). PD patients (14.8±7%) also have a significant increase (P < 0.001) versus the TC group. Again, there was no statistically significant difference for the HD group (12.5±3%) compared with the TC group. Patients with MN values in the upper quartile had increased cholesterol, triglycerides, AGEs and MDA levels and lower albumin levels. Multiple logistic regression analysis showed that male gender, diabetes and treatment modality were independently associated with higher levels of DNA damage. Our results suggest that oxidative stress, diabetes, gender and dialysis modality in CKD patients increased DNA and chromosome damage. To confirm these data, prospective clinical trials need to be performed.

Intima media thickness in children undergoing dialysis.

BACKGROUND: Uremic vasculopathy, including vascular calcification, increases the risk for cardiovascular disease and mortality in chronic kidney disease (CKD) patients. We have investigated the prevalence and factors associated with vasculopathy in children undergoing peritoneal dialysis (PD) or hemodialysis (HD) in a single center. METHODS: Common carotid intima media thickness (cIMT) and its relation with demographics, biochemical parameters and medication was analyzed in 60 patients (mean age 12.9 ± 3.4 years; 27 girls) treated with PD (n = 31) or HD (n = 29) for 34 ± 34 months. Patients were divided into two groups: normal cIMT and increased cIMT. RESULTS: Mean levels of calcium, phosphate and calcium/phosphate product were in the normal range, the but parathyroid hormone level, 729 ± 670 pg/mL, was higher than the National Kidney Foundation Kidney Disease Outcome Quality Iniative (K/DOQI) recommendations. Twenty-nine patients had increased cIMT, which was associated with time on dialysis of >2 years, hypercalcemia, higher daily dose of calcitriol and HD (vs. PD). In the multivariate analysis, accounting for time on dialysis, HD persisted as a risk for increased cIMT. CONCLUSIONS: The prevalence of increased cIMT in children on dialysis is similar to that reported in adults with CKD and increased with time on dialysis. HD was associated with increased cIMT, independently of time on dialysis; however, the results should be interpreted with caution due to the possible impact of confounding factors. These results underline the need to monitor and, if possible, prevent and treat increased cIMT in children on dialysis.

Ultrafiltration and dialysis adequacy with various daily schedules of dialysis fluids.

Dialysis regimens for continuous ambulatory peritoneal dialysis (CAPD) patients vary with the need for fluid removal, but also because of concerns about the local and systemic consequences of high glucose exposure. The implications of various regimens for dialysis adequacy--that is, fluid and small-solute removal--are not always clear. We therefore analyzed ultrafiltration (UF) and adequacy indices for 4 different combinations of dialysis fluid. Collections of 24-hour dialysate and urine were carried out in 99 patients on CAPD. On 4 separate occasions, each patient performed 4 exchanges in 24 hours, including 3 daily exchanges with 1.36% glucose and 1 night exchange with either 1.36% glucose (G1 schedule), 2.27% glucose (G2 schedule), 3.86% glucose (G3 schedule), or icodextrin (Ico schedule). Weekly, total, and dialysis Kt/V and KT were calculated for both urea and creatinine. The mean values of urea Kt/V and KT were significantly lower for the G1 schedule than for the G3 and Ico schedules. The adequacy indices for overnight application of 3.86% glucose and icodextrin were similar. Using dialysis fluids with 1.36% and 2.27% glucose overnight reduces glucose exposure, but those schedules may provide inadequate UF and small-solute removal in some patients (UF < 1 L daily, Kt/V < 1.7).

An update on peritoneal dialysis solutions.

Peritoneal dialysis (PD) has achieved its current position as the most commonly used home-based dialysis therapy--and with patient survival equal to that seen with hemodialysis--despite the use of glucose-based dialysis solutions with high concentrations of glucose, glucose degradation products and lactate, high osmolality, and low pH, features that are harmful both for the peritoneum and the patient. Newer PD solutions with alternative buffers, a higher pH and fewer glucose degradation products, or ones that contain icodextrin or amino acids as osmotic agents, have been introduced in many countries and have been shown to improve peritoneal membrane health and viability. Icodextrin solution enhances fluid and sodium removal, and the once-daily use of icodextrin and/or amino acid solutions can lessen the harmful effects caused by the exposure of the peritoneal membrane to glucose. However, whether the newer PD solutions improve patient survival over the older solutions is not clear. Use of PD therapy, with or without the newer PD solutions, is associated with an improvement in patient survival that is equivalent to that obtained with hemodialysis. Therefore, the conventional glucose-based solutions--despite their known negative features--continue to have a well-established role in PD therapy, particularly in the many countries where the newer PD solutions are not easily available.

Vascular calcification inhibitors in relation to cardiovascular disease with special emphasis on fetuin-A in chronic kidney disease.

The mortality rate is extremely high in chronic kidney disease (CKD), primarily due to the high prevalence of cardiovascular disease (CVD) in this patient group. Apart from traditional Framingham risk factors, evidences suggest that nontraditional risk factors, such as inflammation, oxidative stress, endothelial dysfunction, and vascular calcification also contribute to this extremely high risk of CVD. Disturbance in the mineral metabolism, especially in the ions of Ca and PO4, are linked to enhanced calcification of blood vessels. Although the mechanism(s) of this enhanced calcification process are not fully understood, current knowledge suggests that a large number (and an imbalance between them) of circulating promoters and inhibitors of the calcification process, that is, fetuin-A (or alpha 2-Heremans-Schmid glycoprotein, AHSG), matrix-Gla protein (MGP), osteoprotegerin (OPG), osteopontin (OPN), bone morphogenetic proteins (BMPs), and inorganic pyrophosphate (PPi), are involved in the deterioration of vascular tissue. Thus, an imbalance in these factors may contribute to the high prevalence of vascular complications in CKD patients. Among these mediators, studies on fetuin-A deserve further attention as clinical studies consistently show that fetuin-A deficiency is associated with vascular calcification, all-cause and cardiovascular mortality in CKD patients. Both chronic inflammation and the uremic milieu per se may contribute to fetuin-A depletion, as well as specific mutations in the AHSG gene. Recent experimental and clinical studies also suggest an intriguing link between fetuin-A, insulin resistance, and the metabolic syndrome.