Phosphate Clearance Research Articles

Soluble α-Klotho and Its Relation to Kidney Function and Fibroblast Growth Factor-23

Relations between fibroblast growth factor-23 (FGF-23), soluble α-klotho (s-α-klotho), and kidney function in chronic kidney disease (CKD) are still unclear. Especially the role of s-α-klotho requires further study. Our objectives were to analyze the relation of s-α-klotho to estimated glomerular filtration rate (eGFR), FGF-23, and other parameters of calcium-phosphate metabolism and to investigate the response of s-α-klotho to cholecalciferol. Twenty-four CKD (stage 1-5) patients participated in this 8-week randomized controlled trial (vitamin D and chronic renal insufficiency). Interventions included 40 000 IU cholecalciferol or placebo weekly. S-α-klotho was determined by ELISA with antihuman klotho antibodies 67G3 and 91F1. For all patients, s-α-klotho concentrations did not differ between CKD stages. When patients were subdivided based on FGF-23 concentrations, a positive association of s-α-klotho with eGFR became apparent in patients with lower than median FGF-23 concentrations but not in those above median value. Patients with s-α-klotho below 204 pg/mL showed higher age, lower phosphate clearance, and lower bone-specific alkaline phosphatase compared with patients with higher s-α-klotho. Treatment with cholecalciferol significantly increased 1,25-dihydroxyvitamin D. The increase of FGF-23 had only borderline significance. There was no significant effect of high-dose cholecalciferol administration for 8 weeks on plasma s-α-klotho. CKD patients with s-α-klotho below 204 pg/mL had higher age, lower phosphate clearance, and lower bone-specific alkaline phosphatase. An association of s-α-klotho with eGFR was observed only in the presence of close to normal, but not high, FGF-23 concentrations. Cholecalciferol treatment did not change s-α-klotho concentrations.

Regulation of calcium metabolism in pseudohypoparathyroidism type 1b. From genotype to physiopathology

ObjectivePseudohypoparathyroidism type 1b (PHP1b) results from methylation defects in the maternal GNAS locus. It is implied that the observed hypocalcemia results from impairment of renal vitamin D 1α hydroxylase. This study was undertaken to clarify: (1) How serum concentrations of calcium, phosphate, PTH and 1,25 dihydroxy vitamin D (1,25OH2D) relate to each other in patients with PHP1b; (2) how a mathematical model of calcium metabolism could reproduce the observed findings. PatientsThe study included 139 untreated patients, retrieved from the literature, with simultaneous measurements of Ca, P and PTH of whom 25 had measurements of 1,25OH2D. ResultsMean values and standard errors of the mean (SEM) were: PTH=43pM (3.66); P=2.16mM (0.056); Ca=1.69mM (0.038); 1,25OH2D=84pM (10.9). Phosphate correlated negatively with calcium (R=−0.590; p<0.001) and with age (R=−0.623; p<0.001). No other correlations were observed. The mathematical model simulated closely the biochemical pattern of PHP1b when the clearance of phosphate was reduced to 20%, the clearance of calcium was doubled and the response of 1α hydroxylase was reduced to 30%. Conclusions(1) In PHP1b the concentrations of 1,25OH2D are mostly normal. Therefore, they cannot explain the observed hypocalcemia; (2) hypocalcemia can only be explained by increased fractional excretion of calcium resulting from GNAS haplo-insufficiency at the level of the distal tubule; (3) the use of mathematical models to simulate complex metabolic systems allows the extraction, from clinical data, of insights onto physiopathology that are not accessible to intuition alone.

Potentially life-threatening phosphate diabetes induced by ferric carboxymaltose injection: a case report and review of the literature.

We report the case of a 45-year-old female patient who developed phosphate diabetes after administration of ferric carboxymaltose. Ten days after the second dose, she complained of intense fatigue and blood analysis showed a phosphate plasma level of 0.93 mg/dL with phosphate excretion rate of 23%. She received phosphate supplementation which resulted in phosphate clearance improvement which persisted for two months. We reviewed other cases described in the literature and would draw attention to this rare but potentially life-threatening side effect.

Evaluation of biochemical parameters in calcium oxalate renal stone formers

Background: Calcium oxalate renal stones are the most predominant cases of renal stones, their formation is more complex and no specific cause for the stone can be identified so called 'idiopathic'. This study was designed to analyze the metabolic and biochemical alterations in serum, urine and their relation to pathophysiology of calcium oxalate stone formation Patients and Methods : In this study, individuals have been classified into three groups: Group (A) included (29) apparently healthy persons of non calcium oxalate stone formers aged (20-35 years), group (B) included (16) patients with calcium oxalate renal stone aged (20-35 years) and group(C) included (15) patients with calcium oxalate renal stone aged (40-70 years). Fasting serum, random urine and 24hours urine samples were collected from all individuals to determine urine volume, creatinine clearance, serum and urine levels of calcium, phosphate ,uric acid ,zinc, copper and serum levels of total cholesterol, high density lipoproprotien-cholesterol and urea . Results: Calcium oxalate stone formers group (B) exhibited significantly decreased serum levels of uric acid (P=0.015),zinc (P=0.031) with increased serum level of total cholesterol(P=0.034) when compared to similar age group of healthy control ,group (A). Urinary parameters in calcium oxalate stone formers also showed significantly increased levels of 24-hour urine calcium(P=0.05) and urine calcium: creatinine ratio (P=0.05)when compared to healthy control. While, older age calcium oxalate stone formers, group (C) showed significantly decreased urine volume (P=0.015)with increased kidney stone size(P=0.03) when compared to younger age calcium oxalate stone formers, group (B). Conclusions: Level of urinary calcium and urine volume are the most important urinary factors in enhancing calcium oxalate stone formation. While the observed changes in biochemical measurements of serum in calcium oxalate stone formers may indicate a probable metabolic relation in pathogenesis of this disease.

A compound heterozygous mutation in SLC34A3 causes hereditary hypophosphatemic rickets with hypercalciuria in a Chinese patient

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare metabolic disorder inherited in an autosomal recessive fashion and characterized by hypophosphatemia, short stature, rickets and/or osteomalacia, and secondary absorptive hypercalciuria. HHRH was recently mapped to chromosome 9q34, which contains the gene SLC34A3 which encodes the renal proximal tubular sodium–phosphate cotransporter NaPi-IIc. Here we describe a 29-year-old man with a history of childhood rickets who presented with increased renal phosphate clearance leading to hypophosphatemia, hypercalciuria, low serum parathyroid hormone (PTH), elevated serum 1,25-dihydroxyvitamin D (1,25(OH)2D) and recurrent nephrolithiasis. We performed a mutation analysis of SLC34A3 (exons and adjacent introns) of the proband and his parents to determine if there was a genetic contribution. The proband proved to be compound heterozygous for two missense mutations in SLC34A3: one novel mutation in exon 7 c.571G>C (p.G191R) and one previously identified mutation in exon 13 c.1402C>T (p.R468W). His parents were both asymptomatic heterozygous carriers of one of these two mutations. We also performed an oral phosphate loading test and compared serum phosphate, intact PTH, and intact fibroblast growth factor 23 (iFGF23) in this patient versus patients with other forms of hypophosphatemic rickets, the results of which further revealed that the mechanism of hypophosphatemia in HHRH is independent of FGF23. This is the first report of HHRH in the Chinese population. Our findings of the novel mutation in exon 7 add to the list of more than 20 reported mutations of SLC34A3.

Serum soluble Klotho protein level is associated with residual diuresis in incident peritoneal dialysis patients.

Active vitamin D (1,25-dihydroxyvitamin D₃), PTH, fibroblast growth factor-23 (FGF-23) and Klotho protein are key regulators of phosphate metabolism. Hyperphosphatemia and increased FGF-23 level in patients with end-stage renal disease are associated with increased morbidity and mortality. The relationships among key regulators of phosphate metabolism are still being investigated. FGF-23, the humoral factor involved in phosphate metabolism, is strongly associated with serum phosphorus level. Klotho, a transmembrane protein expressed primarily in renal tubules, functions as an obligatory co-receptor for FGF-23. The soluble form of Klotho, produced by the shedding of the transmembrane protein, is detectable in body fluids. The purpose of the study was to assess if serum soluble alpha-Klotho level was related to phosphate metabolism parameters and residual renal function (RRF) in incident peritoneal dialysis (PD) patients. Thirty-five clinically stable patients 4 to 6 weeks after the onset of PD were included in the study. For each patient, clinical and laboratory data were reviewed. Serum phosphorus concentration, urinary and peritoneal phosphate clearance, serum FGF-23 and soluble Klotho protein concentrations were determined. Serum soluble alpha-Klotho was strongly negatively correlated with 24-hour diuresis (Rs = -0.55, p = 0.004) and renal phosphate clearance (Rs = -0.40, p = 0.049), but not with RRF. Serum soluble Klotho protein concentration is inversely related to residual diuresis and renal phosphate clearance in incident PD patients.

Effect of the Dialysis Fluid Buffer on Peritoneal Membrane Function in Children

Double-chamber peritoneal dialysis fluids exert less toxicity by their neutral pH and reduced glucose degradation product content. The role of the buffer compound (lactate and bicarbonate) has not been defined in humans. A multicenter randomized controlled trial in 37 children on automated peritoneal dialysis was performed. After a 2-month run-in period with conventional peritoneal dialysis fluids, patients were randomized to neutral-pH, low-glucose degradation product peritoneal dialysis fluids with 35 mM lactate or 34 mM bicarbonate content. Clinical and biochemical monitoring was performed monthly, and peritoneal equilibration tests and 24-hour clearance studies were performed at 0, 3, 6, and 10 months. No statistically significant difference in capillary blood pH, serum bicarbonate, or oral buffer supplementation emerged during the study. At baseline, peritoneal solute equilibration and clearance rates were similar. During the study, 4-hour dialysis to plasma ratio of creatinine tended to increase, and 24-hour dialytic creatinine and phosphate clearance increased with lactate peritoneal dialysis fluid but not with bicarbonate peritoneal dialysis fluid. Daily net ultrafiltration, which was similar at baseline (lactate fluid=5.4±2.6 ml/g glucose exposure, bicarbonate fluid=4.9±1.9 ml/g glucose exposure), decreased to 4.6±1.0 ml/g glucose exposure in the lactate peritoneal dialysis fluid group, whereas it increased to 5.1±1.7 ml/g glucose exposure in the bicarbonate content peritoneal dialysis fluid group (P=0.006 for interaction). When using biocompatible peritoneal dialysis fluids, equally good acidosis control is achieved with lactate and bicarbonate buffers. Improved long-term preservation of peritoneal membrane function may, however, be achieved with bicarbonate-based peritoneal dialysis fluids.

Physiologic volume of phosphorus during hemodialysis: Predictions from a pseudo one‐compartment model

The kinetics of plasma phosphorus concentrations during hemodialysis (HD) are complex and cannot be described by conventional one- or two-compartment kinetic models. It has recently been shown by others that the physiologic (or apparent distribution) volume for phosphorus (Vr-P) increases with increasing treatment time and shows a large variation among patients treated by thrice weekly and daily HD. Here, we describe the dependence of Vr-P on treatment time and predialysis plasma phosphorus concentration as predicted by a novel pseudo one-compartment model. The kinetics of plasma phosphorus during conventional and six times per week daily HD were simulated as a function of treatment time per session for various dialyzer phosphate clearances and patient-specific phosphorus mobilization clearances (K(M)). Vr-P normalized to extracellular volume from these simulations were reported and compared with previously published empirical findings. Simulated results were relatively independent of dialyzer phosphate clearance and treatment frequency. In contrast, Vr-P was strongly dependent on treatment time per session; the increase in Vr-P with treatment time was larger for higher values of K(M). Vr-P was inversely dependent on predialysis plasma phosphorus concentration. There was significant variation among predicted Vr-P values, depending largely on the value of K(M). We conclude that a pseudo one-compartment model can describe the empirical dependence of the physiologic volume of phosphorus on treatment time and predialysis plasma phosphorus concentration. Further, the variation in physiologic volume of phosphorus among HD patients is largely due to differences in patient-specific phosphorus mobilization clearance.

Clinical evaluation of two novel biointact PTH(1–84) assays in hemodialysis patients

ObjectivesIn chronic kidney disease–mineral and bone disorder (CKD-MBD), most treatment decisions are guided by parathyroid hormone (PTH) levels. Here, we aimed at assessing the technical and clinical performance of two novel automated biointact PTH(1–84) assays, from Roche Diagnostics (Ro) and DiaSorin (DS), in hemodialysis patients. Design and methodsWe recorded demographics, dialysis treatment characteristics, pharmacotherapy for CKD-MBD and laboratory work-up. Statistical methods included Passing–Bablok, and multiple linear regression. Results121 patients, dialyzing on average for 3.5years (range: 0.1–22.5), with serum phosphate 1.9±0.6mmol/L (mean±SD), participated in the study. Median serum concentration for intact PTH was 223ng/L (range: 5–2844), and for biointact PTH(1–84) was 136ng/L (Ro; range: 1–1644), respectively 138ng/L (DS; range: 4-1580). Both biointact assays were significantly correlated (r=0.98; Ro=0.87×DS+19.60). Bland–Altmann plots revealed an average bias ±2 SD of 10±27ng/L below 200ng/L, and −32±157ng/L above 200ng/L (Ro minus DS). The variably adjusted association between PTH and serum phosphate was very similar, regardless of the PTH assay, but this was not the case for PTH-derived measures (ratios biointact/intact; differences intact minus biointact). (Log)PTH concentrations as well as serum phosphate were significantly associated with serum creatinine, but only in patients with >0mL urine per day. ConclusionsResults from Roche and DiaSorin biointact PTH(1–84) assays were well correlated, but showed increased deviations at higher concentrations. Biointact PTH(1–84) levels are roughly two third of intact PTH. The association between PTH and serum creatinine may depend on residual renal clearance of PTH and/or serum phosphate.

Efficacy Comparison Between Simple Mixed-Dilution and Simple Mid-Dilution On-Line Hemodiafiltration Techniques: A Crossover Study

Mid-dilution and mixed-dilution on-line hemodiafiltration (OL-HDF) techniques are innovated to overcome the limitations of two standard techniques including predilution and postdilution. Unfortunately, the head-to-head comparisons between these two novel techniques in the same study are still limited. Moreover, the original mid-dilution and mixed-dilution OL-HDF need special dialyzers and special machines. In the present study, simple mid-dilution and simple mixed-dilution OL-HDF were settled with the aim for clinical use in general hemodialysis (HD) centers. The efficacies of uremic toxins removal between both modalities were measured and compared. This prospective randomized crossover study was conducted on 12 stable HD patients undergoing simple mixed-dilution and simple mid-dilution OL-HDF techniques. HD prescriptions were similar in both techniques. The dialysis efficacies were determined by calculating small- (urea, creatinine, and phosphate) and middle-molecule (beta-2 microglobulin [β2M]) removal. Moreover, potential complications such as high transmembrane pressure (TMP) and protein loss were also observed. Simple mixed-dilution OL-HDF provided significantly greater clearances of urea, creatinine, and β2M when compared with the simple mid-dilution OL-HDF techniques. Phosphate clearances in both techniques were comparable. In addition, TMP and dialysate albumin loss were not different. There were no intradialytic complications in both techniques. Simple mixed-dilution OL-HDF could provide greater efficacy for small- and middle-molecule clearances and acceptable potential risks, while phosphate removal is comparable.

Patient-specific phosphorus mobilization clearance during nocturnal and short daily hemodialysis

The kinetics of plasma phosphorus during different hemodialysis (HD) modalities are incompletely understood. We recently demonstrated that a pseudo one-compartment kinetic model including phosphorus mobilization from various body compartments into extracellular fluids can describe intradialytic and postdialytic rebound kinetics of plasma phosphorus during conventional and short 2-hour HD treatments. In this model, individual patient differences in phosphorus kinetics were characterized by a single parameter, the phosphorus mobilization clearance (K(M)). In this report we determined K(M) in patients treated by in-center nocturnal HD (ICNHD) and short daily HD (SDHD) with low dialyzer phosphate clearance. In the ICNHD study, eight patients underwent 8-hour HD treatments where intradialytic and postdialytic plasma samples were collected; K(M) values were determined by nonlinear regression of plasma concentration as a function of time. In the SDHD study, five patients were studied during 28 treatments for approximately 3 hours. Here, K(M) was calculated using only predialytic and postdialytic plasma phosphorus concentrations. Dialyzer phosphate clearances were 134 ± 20 (mean ± SD) and 95 ± 16 mL/min during ICNHD and SDHD, respectively. K(M) values for the respective therapies were 124 ± 83 and 103 ± 33 mL/min, comparable to those determined previously during conventional and short HD treatments of 98 ± 44 mL/min. When results from ICNHD, SDHD, and previous HD modalities were combined, K(M) was directly correlated with postdialytic body weight (r = 0.38, P = 0.025) and inversely correlated with predialytic phosphorus concentration (r = -0.47, P = 0.005). These findings suggest that phosphorus kinetics during various HD modalities can be described by a pseudo one-compartment model.

Peritoneal phosphate removal varies by peritoneal dialysis regimen: an underestimated parameter of phosphate control

The optimization of phosphate (P) removal by peritoneal dialysis (PD) is often underestimated. Our objective was to investigate peritoneal P clearance and its relationship with standard adequacy targets, hyperphosphatemia and automated PD (APD) parameters. Dialysis dose, P clearances (24-hour urine and effluent samples), estimated percentage of diffusive P removal and peritoneal transport rate (PET) were evaluated in 77 adult prevalent PD patients. Total P removal strongly correlated with residual renal function parameters, dissociated from peritoneal Kt/V urea (r=-0.36; p=0.02) and creatinine clearance (r=-0.32; p<0.0001). A correlation of P clearance with net ultrafiltration was not found. Among the variables studied, only renal and peritoneal P clearances were significantly lower in hyperphosphatemic patients. In APD, peritoneal phosphate clearance was positively correlated with 4-hour dialysate to plasma creatinine ratio (r=0.46; p=0.039). Slow transporters had higher peritoneal P clearances under continuous ambulatory PD (CAPD) regimens. Hyperphosphatemia was significantly associated with a lower number of APD cycles and shorter nightly therapy time, with insufficient dwell time individualization. P peritoneal clearance is a modifiable parameter of P control in PD regimens and an additional adequacy target. Prescription skills are recommended in APD patients, particularly in anurics, to take into account peritoneal transport rate.

Phosphate removal model: An observational study of low‐flux dialyzers in conventional hemodialysis therapy

Precise assessing phosphate removal by hemodialysis (HD) is important to improve phosphate control in patients on maintenance HD. We reported a simple noninvasive model to estimate phosphate removal within a 4-hour HD. One hundred sixty-five patients who underwent HD 4 hours per session using low-flux dialyzers made of polysulfone (1.2 m(2)) or triacetate (1.3 m(2)) were enrolled. Blood flows varied from 180 to 300 mL/min. Effluent dialysate samples were collected during the 4-hour HD treatment to measure the total phosphate removal. Predialysis levels of serum phosphate, potassium, hematocrit, intact parathyroid hormone, total carbon dioxide (TCO(2)), alkaline phosphatase, clinical and dialysis characteristics were obtained. One hundred thirty-five observations were randomly selected for model building and the remaining 30 for model validation. Total amount of phosphate removal within the 4-hour HD was mostly 15-30 mmol. A primary model (model 1) predicting total phosphate removal was Tpo(4) = 79.6 × C(45) (mmol/L) - 0.023 × age (years) + 0.065 × weight (kg) - 0.12 × TCO(2) (mmol/L) + 0.05 × clearance (mL/min) - 3.44, where C(45) was phosphate concentration in spent dialysate measured at the 45 minute of HD and clearance was phosphate clearance of dialyzer in vitro conditions offered by manufacturer's data sheet. Since the parameter TCO(2) needed serum sample for measurement, we further derived a noninvasive model (model 2):Tpo(4) = 80.3 × C(45) - 0.024 × age + 0.07 × weight + 0.06 × clearance - 8.14. Coefficient of determination, root mean square error, and residual plots showed the appropriateness of two models. Model validation further suggested good and similar predictive ability of them. This study derived a noninvasive model to predict phosphate removal. It applies to patients treated by 4-hour HD under similar conditions.

Multiscale Physiology‐Based Modeling of Mineral Bone Disorder in Patients With Impaired Kidney Function

A physiologically based, multiscale model of calcium homeostasis and bone remodeling was used to describe the impact of progressive loss of kidney function over a typical 10-year course of chronic kidney disease (CKD), including the evolution of secondary hyperparathyroidism (HPT) caused by diminished renal phosphate clearance and increased plasma phosphate. An important sequela of HPT is marked elevations in bone resorption and loss of bone mineral density (BMD). Clinically, this CKD-related disease state is described as mineral bone disorder, or CKD-MBD. A multiscale physiologic model previously had been shown to describe CKD-MBD-related clinical changes in phosphate, parathyroid hormone (PTH), and calcitriol. The authors have extended the model to link bone remodeling markers with BMD elimination (0.000145 h(-1)) and formation rates. The composite model predicted lumbar spine BMD losses, relative to baseline, at months 28 (glomerular filtration rate = 58 mL/min), 50 (39 mL/min), and 120 (16 mL/min) of approximately -0.98%, -3.0%, and -6.5%, respectively, compared to the observed BMD values in corresponding renal function groups, scaled to a 100-mL/min baseline, of -0.5%, -4.0%, and -8.1%, respectively. In addition, simulated interventions with a hypothetical calcimimetic agent and calcitriol are provided to show the utility of this model as a platform for evaluating therapeutics.

Fibroblast Growth Factor 23 in Patients Undergoing Peritoneal Dialysis

Fibroblast growth factor 23 (FGF23) is an independent risk factor for mortality in patients with ESRD. Before FGF23 testing can be integrated into clinical practice of ESRD, further understanding of its determinants is needed. In a study of 67 adults undergoing peritoneal dialysis, we tested the hypothesis that longer dialysis vintage and lower residual renal function and renal phosphate clearance are associated with higher FGF23. We also compared the monthly variability of FGF23 versus parathyroid hormone (PTH) and serum phosphate. In unadjusted analyses, FGF23 correlated with serum phosphate (r = 0.66, P < 0.001), residual renal function (r = -0.37, P = 0.002), dialysis vintage (r = 0.31, P = 0.01), and renal phosphate clearance (r = -0.38, P = 0.008). In adjusted analyses, absence of residual renal function and greater dialysis vintage associated with higher FGF23, independent of demographics, laboratory values, peritoneal dialysis modality and adequacy, and treatment with vitamin D analogs and phosphate binders. Urinary and dialysate FGF23 clearances were minimal. In three serial monthly measurements, within-subject variability accounted for only 10% of total FGF23 variability compared with 50% for PTH and 60% for serum phosphate. Increased serum phosphate, loss of residual renal function, longer dialysis vintage, and lower renal phosphate clearance are associated with elevated FGF23 levels in ESRD patients undergoing peritoneal dialysis. FGF23 may be a more stable marker of phosphate metabolism in ESRD than PTH or serum phosphate.

Haemodiafiltration versus High-Flux Haemodialysis: Effects on Phosphate Control and Erythropoietin Response

Introduction: Haemodiafiltration (HDF) has been reported to improve erythropoietin (EPO) responsiveness and phosphate clearance. We prospectively audited the effect of HDF on EPO dosages, weight and serum phosphate. Methods: 34 patients dialyzing on Tu/Th/Sa switched to HDF, and 44 dialyzing on M/W/F remained on high-flux haemodialysis (HD) and were followed for 12 months. Results: Dialysis adequacy (Kt/V start HDF 1.56 ± 0.03 vs. HD 1.58 ± 0.04 and 12 months 1.55 ± 0.03 vs. 1.59 ± 0.03), haemoglobin (start 11.7 ± 0.3 vs. 11,8 ± 0.2 g/dl and end 11.5 ± 0.1 vs. 11.3 ± 0.3 g/dl), weight (start 69.8 ± 2.4 vs. 67.8 ± 2.5 kg and end 67.4 ± 2.5 vs. 66.1 ± 2.3 kg), or EPO prescription (start 83 (61–186) vs. 123 (71–225) IU/kg/weeks and 12 months 142 (48–188) vs. 124 (59–223) IU/kg/weeks) did not differ. There were no differences in serum albumin, CRP, calcium and parathyroid hormone. Serum beta-2-microglobulin (B₂M) decreased with HDF (32.7 ± 1.9 vs. 28.1 ± 1.1 mg/l, p < 0.01), but not with HD (31.6 ± 1.4 vs. 31.5 ± 1.1 mg/l). Serum phosphate fell with HDF (start 1.48 ± 0.08 vs. 1.57 ± 0.07 mmol/l (p = NS); 3 months 1.35 ± 0.07 vs. 1.61 ± 0.08; 6 months 1.34 ± 0.06 vs. 1.57 ± 0.06, and 12 months 1.36 ± 0.07 vs. 1.67 ± 0.07, all p < 0.05). Conclusion: HDF did not lead to weight gain or improved EPO responsiveness in this prospective observational study. However, predialysis serum phosphate and B₂M fell with HDF.

Intrarenal hemodynamics and impaired tubular functions in patients with systemic lupus erythematosus

Система комплексной поддержки и сопровождения научного журнала Elpub позволяет запустить двуязычный сайт журнала со встроенной системой электронной редакции в соответствии с лучшими издательскими практиками, а так же предусматривает техническую и методическую поддержку со стороны специалистов НЭИКОН.

Peritoneal Membrane Phosphate Transport Status

Phosphate control impacts dialysis outcomes. Our aim was to define peritoneal phosphate transport in peritoneal dialysis (PD) and to explore its association with hyperphosphatemia, phosphate clearance (PPhCl), and PD modality. Two hundred sixty-four patients (61% on continuous ambulatory PD [CAPD]) were evaluated at month 12. PPhCl was calculated from 24-hour peritoneal effluent. Phosphate (Ph) and creatinine (Cr) dialysate/plasma (D/P) were calculated at a 4-hour 3.86% peritoneal equilibration test. D/PPh correlated with D/PCr. PPhCl correlated better with D/PPh than with D/PCr. Prevalence of hyperphosphatemia (>5.5 mg/dl) was 30%. In a multiple regression analysis, only residual renal function was independently, negatively associated with hyperphosphatemia; in anuric patients, only D/PPh was an independent factor predicting hyperphosphatemia. D/PPh was 0.57 ± 0.10, and according to this, 16% of the patients were fast, 31% were fast-average, 35% were slow-average, and 17% were slow transporters. PPhCl was 37.5 ± 11.7 L/wk; it was lower in the slow transporter group (31 ± 14 L/wk). Among fast and fast-average transporters, PPhCl was comparable in both PD modalities. In comparison to automated PD, CAPD was associated with increased PPhCl among slow-average (36 ± 8 versus 32 ± 7 L/wk) and slow transporters (34 ± 15 versus 24 ± 9 L/wk). In hyperphosphatemic, particularly anuric, patients, optimal PD modality should consider peritoneal phosphate transport characteristics. Increasing dwell times and transfer to CAPD are effective strategies to improve phosphate handling in patients with inadequate phosphate control on automated PD.

Akt/PKB‐sensitive proximal tubular glucose and phosphate transport

Akt/PKB stimulates the glucose carrier GLUT4. Here we explored whether Akt directly regulates Na+‐coupled transport of glucose (by SGLT1) or phosphate (by NaPiIIa). Immunohistochemistry showed that Akt2 is expressed in proximal renal tubules. According to dual electrode voltage clamp experiments the coexpression of Akt increased the glucose‐induced current in SGLT1‐expressing and the phosphate‐induced current in NapiIIa‐expressing Xenopus oocytes. Renal transport was further studied using Akt2 deficient (akt2−/−) and wild type mice (akt2+/+). akt2−/− mice suffered from glucosuria which was partially due to increased plasma glucose levels but was not observed in akt2+/+ mice made similarly hyperglycemic as akt2−/− mice by fructose feeding pointing to defective renal tubular glucose reabsorption. Glucose‐induced depolarization was significantly smaller in isolated perfused renal tubules from akt2−/− than from akt2+/+ mice. In addition, the phosphate clearance was higher in akt2−/− than in akt2+/+ mice despite a significantly decreased plasma PTH and enhanced 1,25‐dihydroxyvitamin D3 concentration and a tendency of lower plasma phosphate. Bone density was significantly reduced in akt2−/− mice. In conclusion, Akt plays a role in the regulation of renal glucose and phosphate transport contributing to the maintenance of phosphate balance and adequate mineralization of bone.

Phosphate Elimination in Modalities of Hemodialysis and Peritoneal Dialysis

Hyperphosphatemia is highly prevalent in hemodialysis (HD) and peritoneal dialysis (PD) patients and is a major risk factor for cardiovascular mortality. Elimination of inorganic phosphate by dialysis is a cornerstone of the management of hyperphosphatemia. Phosphate clearance during HD is affected by various factors of dialysis prescription, such as blood and dialysate flow rate, dialyzer membrane surface area and ultrafiltration volume. Phosphate mass removal can be improved by hemodiafiltration, increased dialysis frequencies and extended treatment times. Short daily or extended daily or 3 times weekly nocturnal HD allow higher phosphate mass removal and potentially complete discontinuation of phosphate binder medication. In PD, phosphate mass removal appears to be correlated with peritoneal creatinine but not urea clearance. In hyperphosphatemic PD patients, the decision on the optimal PD modality should be based on peritoneal creatinine and ideally also on peritoneal phosphate transport characteristics.