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A Series Of Studies On Disorders Of Phosphate Metabolism In Maintenance Hemodialysis Patients

Posted on:2013-08-06Degree:DoctorType:Dissertation
Country:ChinaCandidate:M J WangFull Text:PDF
GTID:1224330395951336Subject:Internal Medicine
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ObjectivesVascular calcification (VC) is very common in dialysis patients. The mechanism responsible are not well understood, but certain factors have been proposed to contribute to this increased calcification risk, including advanced age, time on dialysis, diabetes, hyperphosphatemia, elevated levels of the calcium x phosphorus product and hyperparathyroidism. Phosphate is arguably an important parameter associated with VC and bone mineral disorders in ESRD patients. Serum phosphate concentration is usually effected by a variety of mechanisms including dietary intake, gastrointestinal absorption, urinary excretion, and shifts between the intracellular and extracellular spaces in hemodialysis patients. It is truly a thorny problem for nephrologists to avoid the variability of serum phosphate within the recommended range in hemodialysis patients. However few studies are involved in the relationship between variation of phosphate and VC. The aim of this study was to investigate the variation of serum phosphate and assess the association of phosphate variability with VC in hemodialysis patients.MethodsThis study was performed in77Chinese ESRD patients who had been on3-times per week maintenance hemodialysis(MHD) for at least three years in our dialysis center at Huashan Hospital. Data on demographic, dialysis-specific and clinical characteristics were obtained when the patients were enrolled into this study, as were a variety of biochemical parameters. Serum phosphate, calcium, and PTH were measured every3months at follow-up visit as routine assessment in our unit since January2008. Visit-to-visit variability was defined as the standard deviation (SD) or coefficient of variation (CV=SD/mean). Variability and mean was calculated over all follow-ups and separately over a previous follow-up to the latest follow-up (July2010). Patients were classified into three coronary calcification groups:mild (calcium score=0to10) moderate (calcium score=11to400) and severe (calcium score>400). Ordinally univariate logistic regressions were firstly used to analyze the predictors of coronary artery calcification among the categories of CACs, respectively. Predictors with P≤0.20were included in the ordinally multivariate logistic analysis and the algorithm of backward selection was used to determine the significant variables in the best fitted model.ResultsOverall, the median coronary artery calcium score was168.5(interquartile range,2.5to788.2). Nearly20%of patients had CAC score>900. Older age, male gender, and higher levels of PTH and FGF-23were significantly associated with extent of CAC, whereas high-density lipoprotein cholesterol and was associated negatively with severity of calcium deposition. Variability of serum phosphate (SD-phosphate, CV-phosphate), mean PTH level and mean calcium level in resent18month were significantly related to the extent of CAC. In view of the strong positive correlation between SD of serum phosphate and CV of serum phosphate(r=0.850; P<0.001), these2variables were each entered into separate regression models (Model1and2; Table4), adjusting for the other same confounding covariates. The multiple logistic regression analysis showed that older age (Model1, p=0.003; Model2, p=0.010), male gender (Model1, p=0.002; Model2, p=0.003), higher concentrations of serum FGF-23(Model1, p=0.003; Model2, p<0.001), and SD of serum phosphate(Model1, p=0.007) or CV of serum phosphate(Model2, p=0.011) depending on which variable was entered in the model were significantly associated with higher tertiles of coronary artery calcification.ConclusionsPhosphate variability was first discovered to have a predict value on the calcification of coronary artery. So, reduce the phosphate variability may also be important to protect hemodialysis patients from cardiovascular calcification. PART Ⅱ Assessment of Nutritional Status and Phosphate intake of Hemodialysis PatientsObjectivesDietary intake of phosphate is an important part of the phosphorus metabolism in MHD patients. Phosphate intake is highly related with protein load in diet, which in turn is closely related with the nutritional status. Clinicians often encourage patients to eat more to avoid malnutrition, but the lack of guidance of the nutritionist, often resulting in a variety of metabolic disorders and complications. The nutritional therapy in hemodialysis patients has not received enough attention. Therefore, this study aims to evaluate patients’nutritional status and dietary intake in our HD Center, and to assess the current diet program on the phosphate metabolism in patients.MethodsThis study was performed in94Chinese ESRD patients who had been on3-times per week maintenance hemodialysis(MHD) for at least three months in our dialysis center at Huashan Hospital. Standard socio-demographic characteristics of participants were collected at the entry of the study. The dietary survey was taken on patients for3d with diet records and24h dietary recall. We also made a comprehensive evaluation with physical measurements and biochemical tests. Patients were classified into four DPI groups:<0.8g/kg/d,0.8-1.0g/kg/d,1.0-1.2g/kg/d,≥1.2g/kg/d to observe the effect of DPI on phosphate intake and serum phosphate level.ResultsOf the94patients,54were male and40were female. The mean (±SD) values for measured parameters included a age of58.8±10.3y, a vintage of3.5(1.7,7.3) years, a DPI of1.18±0.53g/d/kg, a DEI level of26.4±12.0kcal/d/kg, a DFI of1.08±0.56g/d/kg, a BMI of21.4±3.2kg/m2, a TSF level of14.5±6.3mm, a MAMC level of21.1±2.9mm, a KT/V of1.39±0.26, a serum albumin level of39.3±3.0g/L, a serum prealbumin level of296.3±59.8g/mL, a hemoglobin level of110.1±16.6g/L, a serum creatinine level of952.6±232.2umol/L, a blood urea nitrogen level of25.6±5.5mmol/L. According to DPI classifications (DPI<0.8,0.8≤DPI<1, 1≤DPI<1.2, DPI≥1.2g/kg/d). the daily phosphate intake and serum phosphate level were581.4mg (464.7mg-699.4mg),687.5mg (558.8mg-806.5mg),878.8mg (804.9mg-919.2mg),1183.lmg(939.8mg-1329.5mg),respectively. The prevalence of malnutrition was2.6%to80.5%according to single indicator of malnutrition.ConclusionsTake all the results of indicators in consideration, the DPI in our patients had reach requirements of KDOQI guideline30-35kcal/d/kg, however, the DEI of80%patients in our center was far less than guideline. According to the albumin level, majority of the patients were in good nutritional status, though50%of the patients had the level of weight, triceps skinfold thickness, arm muscle circumference below the normal. The dietary survey showed that there was a strong correlation between dietary protein intake and dietary phosphate intake and positive relation between serum phosphate level and phosphate intake. PART IIIPhosphate removal model:an observational study of low-flux dialysers in conventional hemodialysis therapyObjectivesPrecise assessing phosphate removal by hemodialysis is important to improve phosphate control in patients on maintenance hemodialysis(MHD). We reported a simple noninvasive model to estimate phosphate removal within4hour hemodialysis.Methods165patients who underwent hemodialysis4hour per session using low-flux dialysers made of polysulfone (1.2m2) or triacetate (1.3m) were enrolled. Blood flows varied from180to300ml/min. Effluent dialysate samples were collected during4-hour HD treatment to measure the total phosphate removal. Pre-dialysis levels of serum phosphate, potassium (K+), hematocrit (Hct), intact parathyroid hormone (iPTH), carbon dioxide combining power (CO2CP), alkaline phosphatase (AKP), clinical and dialysis characteristics were obtained.135observations were randomly selected for model building and the remaining30for model validation.ResultsTotal amount of phosphate removal within4-hour HD was mostly15-30mmol. A primary model (Model1) predicting total phosphate removal was:Tpo4=79.6xC45(mmol/L)-0.023xAge (years)+0.065×Weight(kg)-0.12xCO2CP (mmol/1)+0.05×Clearance (ml/min)-3.44, where C45was phosphate concentration in spent dialysate measured at the45min of HD and Clearance was phosphate clearance of dialyser in vitro conditions offered by manufacturer’s data sheet. Since the parameter CO2CP needed serum sample for measurement, we further derived a noninvasive model (Model2):Tpo4=80.3×C45-0.024xAge+0.07×Weight+0.06xClearance-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.ConclusionsThis study derived a noninvasive model to predict phosphate removal. It applies to patients treated by4-hour hemodialysis under similar conditions. PART IV The effect of residual renal function on phosphate metabolism in hemodialysis patientsObjectivesFibroblast growth factor-23(FGF-23) regulates phosphate metabolism and elevated levels occur in patients with kidney disease and are associated with mortality in maintenance hemodialysis (MHD) patients. Residual renal function (RRF) presumably improves phosphate metabolism in MHD patients. We investigated the role of circulating FGF-23on urinary phosphate excretion and phosphate balance in134MHD patients.MethodsDemographics, laboratory data, and excretion capacity of phosphate were recorded. We used multivariable regression to analyze the relationship of serum phosphate with other factors and of the tubular reabsorption rate of phosphate with other factors.ResultsPatients with high urinary output (>200mL/day) had lower serum phosphate, calcium, iPTH, and FGF-23than patients with low urinary output (<200mL/day). The independent risk factors for elevated serum phosphate were nPNA, iPTH, and FGF-23in patients with low urinary output, and female gender and GFR in patients with high urinary output. The weekly phosphate excretion was300to1500mg in MHD patients with high urinary output, and the tubular reabsorption of phosphate (44%±19%) was nearly50%of the normal level, much lower than that of sodium, chlorine, and calcium which ranged from85%to99%. Elevated circulating FGF-23was significantly associated with decreased tubular phosphate reabsorption after adjusting for GFR and serum phosphate.ConclusionsRRF is associated with significant capacity to excrete phosphate and high levels of FGF-23promote phosphate excretion in remnant nephrons.
Keywords/Search Tags:Maintenance Hemodialysis, Phosphate variability, Cardiovascular calcificationMaintenance Hemodialysis, Nutritional statusMaintenance Hemodialysis, Hyperphosphatemia, Kinetic modeling, Dialyticphosphate removalHemodialysis, Fibroblast growth factor-23
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