Dialysate Ca Research Articles

Personalized Prediction of Short- and Long-Term PTH Changes in Maintenance Hemodialysis Patients.

Background: Personalized management of secondary hyperparathyroidism is a critical part of hemodialysis patient care. We used a mathematical model of parathyroid gland (PTG) biology to predict (1) short-term peridialytic intact PTH (iPTH) changes in response to diffusive calcium (Ca) fluxes and (2) to predict long-term iPTH levels.Methods: We dialyzed 26 maintenance hemodialysis patients on a single occasion with a dialysate Ca concentration of 1.75 mmol/l to attain a positive dialysate-to-blood ionized Ca (iCa) gradient and thus diffusive Ca loading. Intradialytic iCa kinetics, peridialytic iPTH change, and dialysate-sided iCa mass balance (iCaMB) were assessed. Patient-specific PTG model parameters were estimated using clinical, medication, and laboratory data. We then used the personalized PTG model to predict peridialytic and long-term (6-months) iPTH levels.Results: At dialysis start, the median dialysate-to-blood iCa gradient was 0.3 mmol/l (IQR 0.11). The intradialytic iCa gain was 488 mg (IQR 268). Median iPTH decrease was 75% (IQR 15) from pre-dialysis 277 to post-dialysis 51 pg/ml. Neither iCa gradient nor iCaMB were significantly associated with peridialytic iPTH changes. The personalized PTG model accurately predicted both short-term, treatment-level peridialytic iPTH changes (r = 0.984, p < 0.001, n = 26) and patient-level 6-months iPTH levels (r = 0.848, p < 0.001, n = 13).Conclusions: This is the first report showing that both short-term and long-term iPTH dynamics can be predicted using a personalized mathematical model of PTG biology. Prospective studies are warranted to explore further model applications, such as patient-level prediction of iPTH response to PTH-lowering treatment.

High prevalence of biochemical disturbances of chronic kidney disease - mineral and bone disorders (CKD-MBD) in a nation-wide peritoneal dialysis cohort: are guideline goals too hard to achieve?

Introduction:Chronic kidney disease - mineral and bone disorders (CKD-MBD) are common in dialysis patients. Definition of targets for calcium (Ca), phosphorus (P), parathormone (iPTH), and alkaline phosphatase (ALP) and their treatment recommendations, are provided by international guidelines. There are few studies analyzing CKD-MBD in peritoneal dialysis (PD) patients and the impact of guidelines on mineral metabolism control. The aim of our study was to describe the prevalence of biomarkers for CKD-MBD in a large cohort of PD patients in Brazil.Methods:Data from the nation-wide prospective observational cohort BRAZPD II was used. Incident patients were followed between December 2004 and January 2011. According to KDOQI recommendations, reference ranges for total Ca were 8.4 to 9.5 mg/dL, for P, 3.5 to 5.5 mg/dL, for iPTH, 150-300 pg/mL, and for ALP, 120 U/L.Results:Mean age was 59.8 ± 16 years, 48% were male, and 43% had diabetes. In the beginning, Ca was 8.9 ± 0.9 mg/dL, and 48.3% were on the KODQI target. After 1 year, Ca increased to 9.1 ± 0.9 mg/dL and 50.4% were in the KDOQI preferred range. P at baseline was 5.2 ± 1.6 mg/dL, with 52.8% on target, declining to 4.9 ± 1.5 mg/dL after one year, when 54.7% were on target. Median iPTH at baseline was 238 (P25% 110 - P75% 426 pg/mL) and it remained stable throughout the first year; patients within target ranged from 26 to 28.5%. At the end of the study, 80% was in 3.5 meq/L Ca dialysate concentration, 66.9% of patients was taking any phosphate binder, and 25% was taking activated vitamin D.Conclusions:We observed a significant prevalence of biochemical disorders related to CKD-MBD in this dialysis population.

P1414THE PREDICTORS OF PARATHYROID HORMONE VARIABILITY IN HEMODIALYSIS PATIENTS

Abstract Background and Aims KDIGO Clinical Practice Guidelines suggest in hemodialysis (HD) patients using a dialysate calcium concentration between 1,25 and 1,5 mmol/L and maintaining serum intact parathyroid hormone (sPTH) levels in the range of approximately 2 to 9 times the upper normal limit for the assay. The aim of the study was to evaluate the predictors of PTH variability in HD patients over a 12 months period. Method The multicenter restrospective study encompassed 398 patients (256M and 142F) with the average age 59,64±13,29 years and the average HD vintage 78,63±64,26 months. Over a 12 months (M0-M12) period: serum calcium (sCa), serum phosphorus (sPi), serum alkaline phosphatase (sAPh), oral calcium-carbonate daily dose, oral calcitriol weekly dose, and dialysate Ca concentration (dCa) were monitored monthly, and sPTH at 6 months. According to PTH assay reference level (18,4-80,1 pg/ml) 3 groups of patients were categorized: patients with low sPTH&amp;lt;160, with target range sPTH =160-721, and with high sPTH&amp;gt;721. For statistical analysis chi-square test, analysis of variance with repeated measures and logistic regression analysis were performed by softver SPSS. Results Over a 12 months period the number of patients with low sPTH significantly decreased, but the number of patients with target range sPTH and high sPTH increased (Chi square=269,45; p&amp;lt;0.001). On the basis of overall pattern of sPTH fluctuation over a 12 months period six subgroups of patients were observed: consistently low in 20,6% of patients, consistently within the target range in 22,1%, consistently high in 14,07%, low-amplitude fluctuation with low and target range sPTH levels (LAL) in 31,4%, low-amplitude fluctuation with target range and high sPTH levels (LAH) in 10,55%, and high-amplitude fluctuation (HA) subgroup with low, target range and high sPTH levels in 1,25%. In 35 patients constantly hemodialyzed over a 12 months period with dCa=1,25 mmol/L due to high sCa the significant increase of sPTH (M0=797±657 vs M12=1030±740 pg/ml; p=0.001) and no significant changes of sCa (M0=2,44± vs M12=2,34± mmol/L; n.s.), sPi (M0=1,81±0,49 vs M12=1,68±0,49 mmol/L; n.s.), Ca-carbonate daily dose (M0=1,88±1,54 vs M12=2,22±1,53 g/d; n.s.) and calcitriol weekly dose (M0=0,84±1,38 vs M12=1,1±1,41 ucg/w; n.s.) were observed. In 24 patients constantly hemodialyzed with dCa=1,75 mmol/L due to low sCa the significant decrease of sPTH (M0=518±582 vs M12=391±530 pg/ml; p=0.037) and no significant changes of sCa (M0=2,17±0,19 vs M12=2,18±0,17 mmol/L; n.s.), sPi (M0=1,3±0,34 vs M12=1,36±0,52 mmol/L; n.s.), Ca-carbonate daily dose (M0=2,53±1,58 vs M12=2,1±1,91 g/d; n.s.) and calcitriol weekly dose (M0=1,33±1,23 vs M12=1,42±1,69 ucg/w; n.s.) were observed. In 195 patients constantly hemodialyzed with dCa=1,5 mmol/L no significant changes of sPTH (M0=388±421 vs M12=434±459 pg/ml; n.s.), sCa (M0=2,29±0,18 vs M12=2,27±0,15 mmol/L; n.s.), sPi (M0=1,48±0,41 vs M12=1,52±0,41 mmol/L; n.s.), Ca-carbonate daily dose (M0=2,42±1,4 vs M12=2,57±1,2 g/d; n.s.) and calcitriol weekly dose (M0=0,47±0,72 vs M12=0,38±0,68 ucg/w; n.s.) were observed. By model of logistic regression analysis dCa=1,75 (OR=8,33), increased sCa (OR=7,7), and presence of diabetes mellitus (OR=2,44) were the most significant predictors of low sPTH&amp;lt;160 (Chi square=116,27; p&amp;lt;0.001), but the increased sCa (OR=6,88), dCa=1,25 (OR=5,08), and the increased sPi (OR=2,72) were the most significant predictors of high sPTH&amp;gt;721 (Chi square=72,475; p&amp;lt;0.001). Conclusion The prolonged use of dCa=1,25 in patients with high sCa led to significant sPTH increase likely due to net negative calcium balance, but prolonged use of dCa=1,75 in patients with low sCa led to significant sPTH decrease likely due to net positive calcium balance.

Phosphate and Calcium Control in Short Frequent Hemodialysis with the NxStage System One Cycler: Mass Balance Studies and Comparison with Standard Thrice-Weekly Bicarbonate Dialysis

Background: Short frequent dialysis with NxStage System One cycler (NSO) has become increasingly popular as home hemodialysis prescription. Short dialysis sessions with NSO might not allow adequate phosphate (P) removal. Methods: Single-session and weekly balances of P and calcium (Ca) were compared in 14 patients treated with NSO (6 sessions/week) and in 14 patients on standard bicarbonate dialysis (BHD). Results: NSO and BHD showed similar plasma P fall, with end-dialysis plasma P slightly lower in BHD (2.2 ± 0.5 vs. 2.7 ± 0.8 mg/dL, p < 0.02). Single-session P removal was lower in NSO, but weekly removal was higher (3,488 ± 1,181 mg vs. 2,634 ± 878, p < 0.003). Plasma Ca increase was lower in NSO, with similar PTH fall. Ca balance varied according to start plasma Ca, dialysate to blood Ca gradient and net ultrafiltration. Conclusions: short, frequent home hemodialysis with NSO, on a 6/week-based prescription, allows higher weekly P removal than BHD. With the dialysate Ca concentration in use (6 mg/dL), total plasma Ca and iCa concentration increase is lower in NSO.

Bioaccessibility of calcium, iron and magnesium in residues of citrus and characterization of macronutrients

The aim of this study was to estimate bioaccessibility of Ca, Fe and Mg in residues of orange, lime, and their mixture, in order to evaluate the effects of cooking in water on mineral bioaccessibility and also to determine the composition of macronutrients and myo-inositol phosphate content. The citrus samples contained on average 9.53g/100 g moisture, 6.09g/100 g protein, 3.23g/100g ash, 3.15g/100g lipids, 34.26g/100g insoluble fiber, 27.88g/100g soluble fiber and 25.64g/100g carbohydrates. The percentage of soluble and dialyzable minerals ranged from 19.36 to 77.33% and from 5.59 to 69.06% for Fe, from 33.34 to 60.84% and 14.71 to −26.13% for Ca, and from 29.95 to 94.20% and 34.42 to 62.51%, for Mg, respectively. It was verified that cooking influenced the minerals bioaccessibility and increased the dialyzable fraction of Fe and Mg, but decreased the fraction of Ca dialysate, except to orange. No myoinositol phosphate esters were detected. The Principal Component Analysis allowed the separation of different types of citrus residues, but did not discriminate the raw and cooked samples. This study pointed the potential of citrus residue to be used for human consumption and contribute to the necessary dietary minerals and macronutrients, with high content of soluble and insoluble fibers.

Mineral metabolism and cardiovascular disease in CKD.

The mineral bone disorder of CKD, called Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD), has a major role in the etiology and progression of cardiovascular disease in CKD patients. Since the main emphasis in CKD-MBD is on three categories (bone abnormalities, laboratory abnormalities, and vascular calcifications), we have routinely accepted ectopic cardiovascular calcifications as a central risk factor in the pathophysiology of CKD-MBD for cardiac events. However, recent compelling evidence suggests that some CKD-MBD-specific factors other than vascular calcification might contribute to the onset of cardiovascular disease. Most notable is fibroblast growth factor-23 (FGF23), which is thought to be independently associated with cardiac remodeling. Slow progression of cardiac disorders, such as vascular calcification and cardiac remodeling, characterizes cardiac disease due to CKD-MBD. In contrast, fatal arrhythmia may be induced when QT prolongation occurs with CKD-MBD treatment, such as with lower Ca dialysate or the use of calcimimetics. Sudden onset of fatal cardiac events, such as heart failure and sudden cardiac death, due to fatal arrhythmia would be another distinctive phenomenon of CKD-MBD. This may be defined as CKD-MBD-specific cardiac complex syndrome.

Mineral bone disorder and its management among hemodialysis patients in the Gulf Cooperation Council: Initial findings from the dialysis outcomes and practice patterns study (2012-2015).

The prospective cohort Dialysis Outcomes and Practice Patterns Study (DOPPS) initiated data collection in national samples of hemodialysis (HD) units (total of 41 study sites) in all six Gulf Cooperation Council (GCC) countries (Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and the United Arab Emirates) in late 2012. Here, we report initial results regarding mineral bone disorders (MBDs) and its management in the GCC countries. Forty-one randomly selected HD facilities, treating >23 HD patients each, were sampled and represent care for >95% of GCC HD patients. Descriptive results for the GCC countries based on a random sample of 20-30 HD patients in each study facility. Initial results for the GCC are from 931 HD patients treated at 41 dialysis units (ranging from 1 unit in Bahrain to 21 in Saudi Arabia). Results are presented as weighted estimates, accounting for the sampling fraction in each unit. Baseline descriptive statistics (e.g., mean, median, or percentage), weighted by facility sampling fraction were calculated for the study sample. For analyses examining the percent of facility patients having (a) serum phosphorus >6.0 mg/dL or (b) parathyroid hormone (PTH) >600 pg/mL, analyses were restricted to facilities having at least 10 HD patients with a reported serum phosphorus or PTH measurement, respectively. Logistic regression analyses of the indicated binary outcomes were based on the use of generalized estimating equations and were adjusted for GCC country, patient age category (<45 years, 45-65 years, and >65 years old), sex, and whether the patient was diagnosed with diabetes mellitus. Logistic models accounted for clustering of patients within facilities, assuming an exchangeable working correlation matrix. Mean age of HD patients in the GCC countries was 53 years vs. 61-64 years in the three other DOPPS regions. MBD markers showed slightly lower mean serum Calcium in the GCC countries, similar mean serum phosphorus, and intermediate median PTH levels compared with the three other DOPPS regions. Among GCC countries, the country mean value of MBD markers ranged from 8.6-9.0 mg/dL for serum calcium, 4.4-5.4 mg/dL for serum phosphorus, whereas median PTH ranged from 163-389 pg/mL. Similar to other DOPPS regions, PTH was higher among patients who were younger or without diabetes, and serum phosphorus was lower with older age (P <0.001 for each). History of parathyroidectomy was lower in the GCC countries versus other regions but did not differ when adjusted for age and dialysis vintage. Among treatments used for managing MBD, the GCC countries showed one of the highest uses of cinacalcet (24%) and phosphorus binder use (81%), whereas intravenous Vitamin D use (24%) was slightly higher than that in EURANZ. A much larger fraction of HD patients in the GCC countries had a dialysate calcium bath ≥3.5 mEq/L (43%) versus 0-4% in the three other DOPPS regions. Although many aspects of MBD management and MBD marker achievement are similar in the GCC countries to that seen in other DOPPS study regions, large variability was seen across countries and facilities in the GCC. Mean serum calcium was lower in the GCC despite the much greater use of dialysate Ca of ~3.5 mEq/L which may be due to the relatively low use of vitamin D and higher cinacalcet use, meriting further study. Future work will focus on GCC facility HD practices and patient characteristics most strongly related to the achievement of MBD target levels and associated outcomes.

Reduction of Dialysate Calcium Level Reduces Progression of Coronary Artery Calcification and Improves Low Bone Turnover in Patients on Hemodialysis.

Exposure to high Ca concentrations may influence the development of low-turnover bone disease and coronary artery calcification (CAC) in patients on hemodialysis (HD). In this randomized, controlled study, we investigated the effects of lowering dialysate Ca level on progression of CAC and histologic bone abnormalities in patients on HD. Patients on HD with intact parathyroid hormone levels ≤300 pg/ml receiving dialysate containing 1.75 or 1.50 mmol/L Ca (n=425) were randomized to the 1.25-mmol/L Ca (1.25 Ca; n=212) or the 1.75-mmol/L Ca (1.75 Ca; n=213) dialysate arm. Primary outcome was a change in CAC score measured by multislice computerized tomography; main secondary outcome was a change in bone histomorphometric parameters determined by analysis of bone biopsy specimens. CAC scores increased from 452±869 (mean±SD) in the 1.25 Ca group and 500±909 in the 1.75 Ca group (P=0.68) at baseline to 616±1086 and 803±1412, respectively, at 24 months (P=0.25). Progression rate was significantly lower in the 1.25 Ca group than in the 1.75 Ca group (P=0.03). The prevalence of histologically diagnosed low bone turnover decreased from 85.0% to 41.8% in the 1.25 Ca group (P=0.001) and did not change in the 1.75 Ca group. At 24 months, bone formation rate, trabecular thickness, and bone volume were higher in the 1.25 Ca group than in the 1.75 Ca group. Thus, lowering dialysate Ca levels slowed the progression of CAC and improved bone turnover in patients on HD with baseline intact parathyroid hormone levels ≤300 pg/ml.

Calcium-phosphate and parathyroid intradialytic profiles: A potential aid for tailoring the dialysate calcium content of patients on different hemodialysis schedules.

Severe hyperparathyroidism is a challenge on hemodialysis. The definition of dialysate calcium (Ca) is a pending issue with renewed importance in cases of individualized dialysis schedules and of portable home dialysis machines with low-flow dialysate. Direct measurement of calcium mass transfer is complex and is imprecisely reflected by differences in start-to-end of dialysis Ca levels. The study was performed in a dialysis unit dedicated to home hemodialysis and to critical patients with wide use of daily and tailored schedules. The Ca-phosphate (P)-parathyroid hormone (PTH) profile includes creatinine, urea, total and ionized Ca, albumin, sodium, potassium, P, PTH levels at start, mid, and end of dialysis. "Severe" secondary hyperparathyroidism was defined as PTH > 300 pg/mL for ≥3 months. Four schedules were tested: conventional dialysis (polysulfone dialyzer 1.8-2.1 m(2) ), with dialysate Ca 1.5 or 1.75 mmol/L, NxStage (Ca 1.5 mmol/L), and NxStage plus intradialytic Ca infusion. Dosages of vitamin D, calcium, phosphate binders, and Ca mimetic agents were adjusted monthly. Eighty Ca-P-PTH profiles were collected in 12 patients. Serum phosphate was efficiently reduced by all techniques. No differences in start-to-end PTH and Ca levels on dialysis were observed in patients with PTH levels < 300 pg/mL. Conversely, Ca levels in "severe" secondary hyperparathyroid patients significantly increased and PTH decreased during dialysis on all schedules except on Nxstage (P < 0.05). Our data support the need for tailored dialysate Ca content, even on "low-flow" daily home dialysis, in "severe" secondary hyperparathyroid patients in order to increase the therapeutic potentials of the new dialysis techniques.

Hemodynamic Behavior During Hemodialysis: Effects of Dialysate Concentrations of Bicarbonate and Potassium

Background/Aims: Ultrafiltration that occurs during hemodialysis (HD) promotes profound alterations in a relatively short period of time. The dialysate content of bicarbonate (DBic) and potassium (DK) may have impact over intradialytic hemodynamics, which goes beyond ultrafiltration, and its impact was evaluated in a prospective cohort. Methods: 30 patients under HD were submitted to hemodynamic assessment (HA) at the beginning and at the end of HD sessions, through a non-invasive method. Serum minus dialysate potassium concentration was expressed as K-Gap. Cardiac index (CI) and peripheral arterial resistance (PAR) variation (post-HD minus pre-HD) were expressed as ΔCI and ΔPAR. Dialysate content of sodium and calcium were expressed as DNa and DCa, respectively. Results: Mean DNa, DK and DBic were, respectively, 136.4 ± 1.1, 2.1 ± 0.6 and 38.2 ± 2.1 mEq/L. In 15 patients, DCa was >1.5 mmol/L and in the other 15 patients ≤ 1.5 mmol/L. The K-Gap ranged from 1.4 to 5.1 mEq/l (median 3.0 mEq/L). There was a reduction in post-HD CI and systolic blood pressure (ΔCI = -0.72l/min/m² and -11.3±15.1mmHg, respectively, p<0.001 for both). Conversely, PAR increased (ΔPAR = 272dyn.s/cm⁵, p<0.001). Lower post-HD CI was was associated to higher DBic (p=0.0013) and lower K-Gap (p=0.026). In multivariate analysis, ΔCI was dependent on DBic and K-Gap, whereas ΔPAR was dependent on dialysate calcium during HD. Conclusion: We confirmed that Na and Ca dialysate content exerts and important role on hemodynamic during HD. In addition, our findings pointed out that higher dialysate concentrations of bicarbonate and potassium promote lower cardiac performance at the end of hemodialysis session.

Dialysate Calcium Concentration and the Risk of Sudden Cardiac Arrest in Hemodialysis Patients

The optimal dialysate calcium concentration to maintain normal mineralization and reduce risk of cardiovascular events in hemodialysis patients is debated. Guidelines suggest that dialysate Ca concentration should be lowered to avoid vascular calcification, but cardiac arrhythmias may be more likely to occur at lower dialysate Ca. Concurrent use of QT-prolonging medications may also exacerbate arrhythmic risk. This study examined the influence of serum Ca, dialysate Ca, and QT interval-prolonging medications on the risk of sudden cardiac arrest in a cohort of hemodialysis patients. This case-control study among 43,200 hemodialysis patients occurred between 2002 and 2005; 510 patients who experienced a witnessed sudden cardiac arrest were compared with 1560 matched controls. This study examined covariate-adjusted sudden cardiac arrest risk associations with serum Ca, dialysate Ca, serum dialysate Ca gradient, and prescription of QT-prolonging medications using logistic regression techniques. Patients assigned to low Ca dialysate<2.5 mEq/L were more likely to be exposed to larger serum dialysate Ca gradient and had a greater fall in BP during dialysis treatment. After accounting for covariates and baseline differences, low Ca dialysate<2.5 mEq/L (odds ratio=2.00, 95% confidence interval=1.40-2.90), higher corrected serum Ca (odds ratio=1.10, 95% confidence interval=1.00-1.30), and increasing serum dialysate Ca gradient (odds ratio=1.40, 95% confidence interval=1.10-1.80) were associated with increased risk of sudden cardiac arrest, whereas there were no significant risk associations with QT-prolonging medications. Increased risk of sudden cardiac arrest associated with low Ca dialysate and large serum dialysate Ca gradients should be considered in determining the optimal dialysate Ca prescription.

Effect of Lower Calcium Dialysate on Laboratory Abnormalities in Chronic Kidney Disease–Associated Mineral and Bone Disorder

Increased vascular calcification, possibly due to the biochemical problem of calcium (Ca) and phosphate excess, has been associated with cardiovascular disease in patients with end stage renal disease. The use of a lower dialysate Ca concentration (<2.50 mEq/L) has been postulated as one of the methods to prevent long-term Ca accumulation. Concern, however, has been raised over the possibility that using a low Ca dialysate may lead to an increase in the intact parathyroid hormone concentration and therefore the need for higher doses of vitamin D analogs. This may thus mitigate the much desired long-term benefits. With an aim to decrease the total Ca load in our patients, the standard dialysate Ca concentration in our outpatient dialysis center was decreased from 2.5 to 2.25 mEq/L in September 2009. We found that the use of a lower Ca dialysate in our maintenance hemodialysis patients led to a significant reduction in the mean serum Ca concentration without a significant increase in serum parathyroid hormone levels or an increase in vitamin D analogs/Ca-based phosphate binder dose requirements. Further prospective studies are needed to assess the impact of this intervention on long-term cardiovascular morbidity and mortality.

Dialysate calcium individualisation: a pending issue.

Calcium is one of the key elements to consider in patients on dialysis due to its relationship with cardiovascular risk. The introduction of non-calcium-based phosphate binders and calcimimetics has changed the setting for pre-dialysis serum calcium in recent years from 9.5-10.5mg/dl to 8.5-9.5mg/dl. To assess more accurately the changes in calcium (Ca) during haemodialysis sessions and to individualise prescriptions, the aim of this study was to assess the intradialytic changes of two different dialysate Ca concentrations before and after hemodialysis and their implications in controlling calcium-phosphate metabolism. We analysed 98 patients with a mean age of 59.3 ± 15 years, 68 of which were men and 30 women. Each patient received two HD sessions with two different dialysate Ca concentrations: 2.5 mEq/l (Ca25 group) or 3.0 mEq/l (Ca30 group). Pre- and post-dialysis Ca, phosphorus (P) and PTH were determined, and associated medications were recorded. For a more individualised analysis, patients were divided into four subgroups of Ca<8.5mg/dl, 8.5-9.0mg/dl, 9.0-9.5mg/dl, and >9.5mg/dl, according to pre-dialysis serum calcium levels. There were no differences in pre-dialysis values of Ca: 8.81 ± 0.65 (CA25) and 8.88 ± 0.61 (CA30), P: 4.01 ± 1.3 (CA25) and 4.19 ± 1.2 (CA30), or PTH: 352 ± 288 (CA25) and 369 ± 310 (CA30). Post-dialysis Ca and PTH did not change significantly with CA25 dialysate, although there was a significant post-dialysis Ca increase to 10.2 ± 0.6 (P<.001) accompanied by a decrease in post-dialysis PTH (181 ± 227, P<.001) with CA30. However, with CA25 dialysate, when different subgroups of pre-dialysis Ca were analysed: <8.5mg/dl (30.6%), 8.5-9.0mg/dl (31.6%), 9.1-9.5mg/dl (23.5%) and >9.5mg/dl (14.3%) we observed a Ca increase during the session in the <8.5 (P<.001) and 8.5-9.0 (P<.01) subgroups. Ca was unchanged in the 9.1-9.5 group and Ca decreased when the initial Ca values were >9.5mg/dL (P<.01). A Ca increase (P<.001) and a decrease in PTH (P<.01) were observed in all subgroups with CA30 dialysate. A total of 42% of patients were taking calcimimetics, 47% paricalcitol, and 32% calcium-based phosphate binders, although these drugs were not linked with pre- or post-dialysis Ca levels in or dialysate treatment. We concluded that the prescription of Ca dialysate needs to be individualised based on pre- and post-dialysis Ca values and the need for an increase, decrease, or no changes in post-dialysis calcium in relation to the clinical condition of the patient's phosphorous-calcium metabolism.

Achievements in CKD-MBD guidelines targets: is there a progress in the implementation practice?

Guidelines should help the practicing nephrologists to reduce the variability in diagnostic and treatment strategies, and achieve the best possible patients' outcomes. The aim of our study was to look at the treatment strategies and the shortcomings in the implementation of the chronic kidney disease mineral and bone disorder (CKD-MBD) KDOQI guidelines in dialysis units across the Republic of Macedonia in 2009, and to analyze trends with regard to our previous analysis from 2005. A questionnaire was sent in 2009 to all dialysis units in our country for data concerning CKD-MBD in dialysis patients. This study included 742 patients, comparable with the reply we got on the same our 2005 survey, with a total of 588 patients. We collected the last 6 months mean values of biochemical parameters [calcium (Ca), phosphate (P), and intact parathyroid hormone (iPTH)], as well as treatment data including dialysate Ca concentration, phosphate binding agents, and vitamin D doses. The majority of patients in both surveys had values within the target ranges for all parameters, except for iPTH, which was <150 pg/ml in most patients, in both reports. Compared to the 2005 study, in 2009 we found a significantly improved control of all four biochemical parameters, but a greater proportion of patients within guidelines targets was found only for serum Ca (79 vs. 67.4%, P<0.05). Treatment with low Ca dialysate concentration of 1.25 mmol/L continued to be an underused option (3.7 vs. 6.1%), while the 1.75 mmol/L was still the standard dialysate in the majority of patients (57.7 vs. 64.2%). The dose of calcium carbonate was significantly reduced (2.77±1.71 vs. 3.06±1.54, P<0.01) in 2009 compared to 2005. The mean of the achieved targets increased significantly in 2009 (2.33±1.05 vs. 2.13±1.03, P<0.01). There was an improved control of all bone and mineral parameters in our dialysis units, following the publication of the CKD-MBD KDOQI guidelines. In order to improve the iPTH values, a more frequent use of low Ca dialysate (1.25 mmol/L) and of non-calcium-based phosphate binders in this small subset of patients should be implemented, as recommended by the guidelines. Individualization of the CKD-MBD management may be successful, even when newer treatment options are not available. Finally, the guidelines implementation process should be a continuous and self-monitored process, with the help of periodic surveys.

The association of vitamin D use with hypercalcemia and hyperphosphatemia in hemodialysis patients: a case–crossover study

Elevated levels of phosphorus (P) and calcium (Ca) have been shown in observational studies to be associated with an increased risk of adverse clinical outcomes including mortality. Vitamin D sterols have been shown to increase the risk of hypercalcemia and hyperphosphatemia in clinical trials. We sought to explore these risks in real-world clinical practice. We employed a case-crossover design, which eliminates confounding by non-time-varying patient characteristics by comparing, within each patient, vitamin D doses before the event with those at an earlier period. Using this method, we estimated the risk of hypercalcemic (Ca ≥ 11 g/dL) and hyperphosphatemic (P ≥ 8 g/dL) events for patients at different dose quartiles of vitamin D relative to patients not on a vitamin D sterol. There was a dose-dependent association between vitamin D dose quartile and risk of hypercalcemia or hyperphosphatemia. In adjusted analyses, each increase in vitamin D quartile was associated with a multiple of hypercalcemia risk between 1.7 and 19 times compared with those not on vitamin D and a multiple of hyperphosphatemia risk between 1.8 and 4. Use of vitamin D sterols is associated with an increased risk of hypercalcemic and hyperphosphatemic events in real-world clinical practice. Other potential predictors of these events, such as phosphate binder use and dialysate Ca levels, were not examined in this analysis.

Management of hypophosphatemia in nocturnal hemodialysis with phosphate-containing enema: A technical study

Hypophosphatemia is observed in patients undergoing nocturnal hemodialysis. Phosphate is commonly added to the dialysate acid bath, but systematic evaluation of the safety and reliability of this strategy is lacking. The objectives of this study were 4-fold. First, we determined whether predictable final dialysate phosphate concentrations could be achieved by adding varying amounts of Fleet® enema. Second, we assessed the stability of calcium (Ca) and phosphate dialysate levels under simulated nocturnal hemodialysis conditions. Third, we assessed for Ca-phosphate precipitate. Finally, we evaluated whether dialysate containing Fleet® enema met the current sterility standards. We added serial aliquots of enema to 4.5 L of dialysate acid concentrate and proportioned the solution on Gambro and Althin/Baxter dialysis machines for up to 8 hours. We measured dialysate phosphate, Ca, pH, and bicarbonate concentrations at baseline, and after simulated dialysis at 4 and 8 hours. We evaluated for precipitation visually and by assessing optical density at 620 nm. We used inoculation of agar to detect bacteria and Pyrotell reaction for endotoxin. For every 30 mL of Fleet® (1.38 mmol/mL of phosphate) enema added, the dialysate phosphate concentration increased by 0.2 mmol/L. There were no significant changes in dialysate phosphate, Ca, pH, and bicarbonate concentrations over 8 hours. No precipitate was observed in the dialysate by optical density measures at 620 nm for additions of up to 90 mL of enema. Bacterial and endotoxin testing met sterility standards. The addition of Fleet® enema to dialysate increases phosphate concentration in a predictable manner, and no safety problems were observed in our in vitro studies.

Calcium Mass Balances in Bicarbonate Hemodialysis

Dialysate calcium (Ca) concentration should be viewed as part of the integrated therapeutic regimen to control renal osteodystrophy and maintain normal mineral metabolism. The goals of this integrated approach are to keep the patient in a mild positive Ca mass balance (CaMB), to maintain normal serum Ca levels, to control plasma parathyroid hormone values to two to three times above normal levels, and to avoid soft-tissue calcifications. Thus, a correct net CaMB during hemodialysis (HD) is crucial in the treatment of renal osteodystrophy. Very few studies have been published which measured CaMBs in bicarbonate HD. This is mainly due to the technical difficulties in achieving an accurate measurement of CaMBs owing to the need for the collection of the total spent dialysate or of a proportional aliquot of it. Whereas no doubt exists about the fact that an inlet dialysate Ca concentration (CaD) of 1.75 mmol/L leads to a positive CaMB, more controversial is this issue, when dealing with a CaD of 1.50 mmol/L and, even more, when dealing with a CaD of 1.25 mmol/L. Another important issue is the appropriate CaD in long-hour slow-flow nocturnal HD. Finally, which CaMB should we study: ionized CaMB or total CaMB? This issue is largely discussed in the review.

Calcium mass balances during standard bicarbonate hemodialysis and long-hour slow-flow bicarbonate hemodialysis

Dialysate calcium (Ca) concentration should be viewed as part of the integrated therapeutic regimen to control renal osteodystrophy and maintain normal mineral metabolism. Thus, a correct ionized calcium mass balance (Ca++MB) during hemodialysis (HD) is crucial in the treatment of renal osteodystrophy. The GENIUS single-pass batch dialysis system (Fresenius Medical Care, Germany) consists of a closed dialysate tank of 90 L; it offers the opportunity of effecting mass balances of any solute in a very precise way. The present study has a crossover design: 11 stable anuric HD patients underwent 2 bicarbonate HD sessions, 1 of 4 hours (4h) and the other of 8 hours (8h) in a random sequence, always at the same interdialytic interval, at least 1 week apart. The GENIUS system and high-flux FX80 dialyzers (Fresenius Medical Care, Germany) were used. The volume of blood and dialysate processed, volume of ultrafiltration and dialysate Ca concentrations (1.50 mmol/L) were prescribed to be the same. Trends of plasma Ca++, blood pH and bicarbonates during dialysis, as well as Ca++MBs were determined. Plasma parathyroid hormone (PTH) levels at the start and end of the 2 treatments were measured. Ca++MBs (mean ± SD) were +284.6 ± 137.4 mg and +297.7 ± 131.6 mg (p=0.307) in the 4h and 8h treatments, respectively. No single session out of the 22 had a negative Ca++MB for the patient. Mean plasma Ca++, blood pH and bicarbonate levels were not statistically significantly different when comparing the start and end of the sessions of the 2 treatments. Mean plasma Ca++, blood pH and bicarbonate levels increased significantly along the time points in both 4h and 8h HD sessions (repeated measures ANOVA: p<0.0001). Mean plasma PTH levels were not statistically significantly different when comparing the start and end of the sessions of the 2 treatments. The differences between predialysis and postdialysis plasma PTH levels were not statistically significantly different either in 4h or 8h sessions (Wilcoxon's test: p=NS), even though a trend toward lower postdialysis plasma PTH levels was observed in both 4h and 8h treatments. Our data show incontrovertibly that, when dialyzing with a dialysate Ca concentration of 1.50 mmol/L, 4h standard bicarbonate HD and 8h slow-flow bicarbonate HD always achieve a quite similar positive Ca++MB for the patients.

Vascular calcifications and renal osteodystrophy in chronic hemodialysis patients: what is the relationship between them?

Vascular calcifications (VCs) and renal osteodystrophy (ROD) are frequently seen together and represent the major causes of morbidity and mortality in hemodialysis (HD) patients. Some studies suggest a pathogenic link between them, but there is no consensus as yet regarding this issue. The main objective of our study was to establish whether there is any relation between VCs and ROD in our HD patients. We evaluated the prevalence of VCs and ROD and the relationship between VCs and some clinical and biochemical characteristics of HD patients. We examined radiological signs of VCs and ROD on hands and pelvis bone radiographs in 81 chronic HD patients, and we calculated a VC score on this basis. We found a significant relation between radiological signs of ROD and those of VC (P=0.019). The patients with ROD had a higher mean VC score (P=0.02). By linear regression, the VC score correlated directly with serum calcium (Ca), phosphorus (P), intact parathyroid hormone (iPTH) and CaxP product and inversely with serum albumin. The logistic regression model revealed that ROD, male gender and treatment with calcium salts were predictive of VCs development. There were no associations between VCs and age, HD vintage, diabetes, dialysate Ca concentration, vitamin D treatment, spKt/V, URR and C-reactive protein (CRP) levels. There seems to be a pathogenetic link between bone and artery diseases in chronic HD patients. Both VCs and ROD have a high prevalence. ROD, male gender and treatment with calcium salts are risk factors for VCs.

Calcium and Magnesium Flux in Automated Peritoneal Dialysis

Calcium and magnesium balance in continuous ambulatory peritoneal dialysis (CAPD) has been extensively studied with several of the different formulations of fluid available. Calcium and magnesium balance in automated PD (APD) is less well studied and the effect on Ca and Mg flux is unknown. Data on glucose polymer solutions are also lacking. This prospective observational study was undertaken to examine mass transfer of Ca and Mg in APD patients. 12 patients on APD were studied for two 24-hour periods using, alternately, 1.75 mmol/L and 1.25 mmol/L Ca (Dianeal PD1 and Dianeal PD4; Baxter Healthcare, Newbury, UK) 1.36% glucose-based dialysis fluid for the 9-hour overnight dialysis, followed by a 15-hour daytime dwell of glucose polymer-based fluid (icodextrin). Serum ionized Ca, serum Mg, and dialysate Ca and Mg concentrations were measured at the beginning and end of each period. Mass transfer was calculated as millimoles per exchange. During rapid overnight exchanges with Dianeal PD1 and PD4, mass transfer of Mg and Ca did not show significant correlations with serum levels when using PD1 fluid; however, mass transfer of Mg, but not Ca, was significantly correlated to serum levels when using PD4 fluid. During the long dwell with icodextrin, dialysate drain volume was the most significant factor determining the flux of both Ca and Mg. Mass transfer of Ca and Mg in APD patients using conventional dialysis fluid was not related to drain volume in this study, which differs to studies in CAPD. Flux of Ca and Mg during icodextrin use was found to be dependent on ultrafiltration rate and not dialysate or serum concentration.