Marked improvement in bone metabolism parameters after increasing the dialysate calcium concentration from 2.5 to 3 mEq/L in nonhypercalcemic hemodialysis patients

The optimal dialysate calcium (Ca) concentration for hemodialysis (HD) patients is set at 2.5 mEq/L according to Kidney Disease Outcomes Quality Initiative (K-DOQI) guidelines. This recommendation is opinion-based and could negatively affect secondary hyperparathyroidism. Studies have suggested that a dialysate Ca of 3.0 mEq/L is a compromise between bone protection and cardiovascular risk. The aim of our study was to investigate the effect on bone metabolism parameters after increasing the dialysate Ca concentration from 2.5 to 3.0 mEq/L. The dialysate Ca concentration in our patients was increased from 2.5 to 3.0 mEq/L. Patients with hypercalcemia, normal-high Ca levels with a high Ca-Phosphorus product (Ca x P), excessively suppressed parathyroid hormone (PTH), or a past medical history of calciphylaxis were excluded. Twenty-two patients were studied over 20 weeks. Parathyroid hormone levels decreased significantly (442 +/- 254 vs. 255 +/- 226 pg/mL; p=0.000), without significant changes in serum Ca, P, and Ca x P levels at any sampling point. Better control of secondary hyperparathyroidism allowed us to decrease the paracalcitol dosage in 6 of the 12 patients who had been treated with this drug at the beginning of the study. Other potential factors involved in PTH secretion were not modified. A significant improvement in the rate of patients with 3 or more K-DOQI parameters within the target ranges (8 [36%] vs. 12 [55%]; p=0.026) was observed. In the absence of hypercalcemia or excessively suppressed PTH, an increase from 2.5 mEq to 3.0 mEq/L in dialysate Ca concentration resulted in better control of secondary hyperparathyroidism without affecting Ca, P, and Ca x P levels, thus enabling us to reduce the dosage of vitamin D metabolites.     

Dialysate calcium and calcium/phosphate balance in hemodialysis

The changing pattern of pharmaceutical use in dialysis patients has resulted in several alterations to dialysate calcium concentration over the past 40 years. Non‐calcium–containing phosphate binders and calcimimetics are the most recent examples of drugs that influence the overall calcium balance in dialysis patients. Renal osteodystrophy, vascular disease, and mortality are believed to be linked in patients with chronic kidney disease (CKD), although to date most of the evidence is based only on statistical associations. The precise pathophysiology of vascular calcification in end‐stage renal disease is unknown, but risk factors include age, hypertension, time on dialysis, and, most significantly, abnormalities in calcium and phosphate balance. Prospective studies are required before “cause and effect” can be established with certainty, but it is an active metabolic process with inhibitors and promoters. Serum calcium levels are clearly influenced by dialysate calcium and may therefore play an important role in influencing vascular calcification. Clinical management of hyperphosphatemia is being made easier by the introduction of potent non‐calcium–based oral phosphate binders such as lanthanum carbonate. Short‐term and long‐term studies have demonstrated its efficacy and safety. Vitamin D analogs have been a disappointment in the control of serum parathyroid hormone (PTH) levels, but evidence is emerging that vitamin D has other important metabolic effects apart from this, and may confer survival advantages to patients with CKD. Calcimimetics such as cinacalcet enable much more effective and precise control of PTH levels, but at the cost of a major financial burden. While it is unreasonable to expect that any one of these recent pharmacological developments will be a panacea, they provide researchers with the tools to begin to examine the complex interplay between calcium, phosphate, vitamin D, and PTH, such that further progress is fortunately inevitable.     

Clinical Experiences Calcium and phosphate balance in children on home nocturnal hemodialysis (NHD)

Objective: To evaluate and describe biochemical indices of bone metabolism in 4 children on NHD. Method: The children, aged 12, 13, 14, and 16 yrs, have been treated exclusively on NHD for 6, 9, 9, and 15 mos. Subsequently, Pt 1 converted to a hybrid program of 4 nights on home nocturnal plus 1 session of in center conventional HD per week. Biochemical indices of bone metabolism have been collected prospectively. Results: All baseline pre‐dialysis calcium levels were within normal ranges and each patient was started on a dialysis calcium concentration of 3.0 mEq/L. However, over time the number of asymptomatic biochemical hypocalcaemic episodes increased. The dialysate calcium concentration was increased to 3.5 mEq/L in one and decreased to 2.0 mEq/L in another who was hypercalcemic and receiving concurrent calcitonin for bone pain related to osteoporosis. In Pt 1, the dialysate calcium was increased to 3.5 mEq/L during nocturnal and continued on hybrid therapy. Including an evaluation of dietary intake, all 4 patients had a net positive calcium balance, ranging between 9.8 to 23.5 mmol (393–942 mg). A significant reduction in the predialysis phosphate level was observed in all 4 patients, and none required dietary restrictions or the use of phosphate binders within 2 months or vitamin D within 6 months of HND. In addition, phosphate was added to provide a dialysate concentration of 2.4–6.1 mEq/L to prevent hypophosphatemia. This is reflected by significant reductions in intact PTH levels to the desired range (twice the normal range) in all 4, but the level continued to drop to the normal range and below in 2. In Pt 1, after introduction of hybrid therapy, both levels of phosphate and PTH rose, necessitating recommencement of phosphate binders and vitamin D. Likewise, the (Ca × PO₄) dropped and remained <55 in all 4 patients exclusively on NHD, but started to climb in Pt 1 during hybrid therapy. Conclusion: In our cohort of patients, NHD rapidly lowered plasma phosphate and PTH levels. With NHD, additional dialysate phosphate and possibly calcium may be necessary to prevent chronic losses and development of renal osteodystrophy, and caution is required to prevent either oversuppression of PTH and extraskeletal calcification.     

Calcium phosphate metabolism and bone mineral density with nocturnal hemodialysis

An elevated calcium x phosphate product (Ca x P) is an independent risk factor for vascular calcification and cardiovascular death in dialysis patients. More physiological dialysis in patients undergoing nocturnal hemodialysis (NHD) has been shown to produce biochemical advantages compared with conventional hemodialysis (CHD) including superior phosphate (P) control. Benefits of dialysate with greater calcium (Ca) concentration are also reported in NHD to prevent Ca depletion and subsequent hyperparathyroidism, but there are concerns that a higher dialysate Ca concentration may contribute to raised serum Ca levels and greater Ca x P and vascular disease. The NHD program at our unit has been established for 4 years, and we retrospectively analyzed Ca and P metabolism in patients undergoing NHD (8-9 h/night, 6 nights/week). Our cohort consists of 11 patients, mean age 49.3 years, who had been on NHD for a minimum of 12 months, mean 34.3 months. Commencement was with low-flux (LF) NHD and 1.5 mmol/L Ca dialysate concentration, with conversion to high-flux (HF) dialyzers after a period (mean duration 18.7 months). We compared predialysis serum albumin, intact parathyroid hormone, P, total corrected Ca, and Ca x P at baseline on CHD, after conversion to LF NHD and during HF NHD. We also prospectively measured bone mineral density (BMD) on all patients entering the NHD program. Bone densitometry (DEXA) scans were performed at baseline (on CHD) and yearly after commencement of NHD. With the introduction of HF dialyzers, the Ca dialysate concentration was concurrently raised to 1.75 mmol/L after demonstration on DEXA scans of worsening osteopenia. Analysis of BMD, for all parameters, revealed a decrease over the first 12 to 24 months (N = 11). When the dialysate Ca bath was increased, the median T and Z scores subsequently increased (data at 3 years, N = 6). The mean predialysis P levels were significantly lower on LF NHD vs. CHD (1.51 vs. 1.77 mmol/L, p = 0.014), while on HF NHD P was lower again (1.33 mmol/L, p = 0.001 vs. CHD). Predialysis Ca levels decreased with conversion from CHD to LF NHD (2.58 vs. 2.47 mmol/L, p = 0.018) using a 1.5 mmol/L dialysate Ca concentration. The mean Ca x P on CHD was 4.56 compared with a significant reduction of 3.74 on LF NHD (p = 0.006) and 3.28 on HF NHD (p = 0.001 vs. CHD), despite the higher dialysate Ca in the latter. We conclude that an elevated dialysate Ca concentration is required to prevent osteopenia. With concerns that prolonged higher Ca levels contribute to increased cardiovascular mortality, the optimal Ca dialysate bath is still unknown. Better P control on NHD, however, reduces the overall Ca x P, despite the increased Ca concentration, therefore reducing the risk of vascular calcification.     

Comparison between different dialysate calcium concentrations in nocturnal hemodialysis

Benefits of dialysate with greater calcium (Ca) concentration are reported in nocturnal hemodialysis (NHD) to prevent Ca depletion and subsequent hyperparathyroidism. Studies with patients dialyzing against 1.25 mmol/L Ca baths demonstrate increases in alkaline phosphatase (ALP) and parathyroid hormone (PTH) and increasing dialysate Ca subsequently corrects this problem. However, whether 1.5 or 1.75 mmol/L dialysate Ca is most appropriate for NHD is yet to be determined, and differences in the effect on mineral metabolism of daily vs. alternate daily NHD have also not been well defined. We retrospectively analyzed mineral metabolism in 48 patients, from 2 institutions (30 at Monash and 18 at Geelong), undergoing home NHD (8 hr/night, 3.5-6 nights/week) for a minimum of 6 months. Thirty-seven patients were dialyzed against 1.5 mmol/L Ca bath and 11 patients against 1.75 mmol/L. We divided patients into 4 groups, based on dialysate Ca and also on the hours per week of dialysis, <40 (1.5 mmol/L, n=29 and 1.75 mmol/L, n=8) or > or =40 (n=4 and 7). We compared predialysis and postdialysis serum markers, time-averaged over a 6-month period, and the administration of calcitriol and Ca-based phosphate binders between 1.5 and 1.75 mmol/L Ca dialysate groups. Baseline characteristics between all groups were similar, with a slightly longer, but nonsignificant, duration of NHD in both 1.75 mmol/L dialysate groups compared with 1.5 mmol/L. The mean predialysis Ca, phosphate, and Ca x P were similar between the 1.5 and 1.75 mmol/L groups, regardless of NHD hr/week. Postdialysis Ca was significantly greater, with 1.75 vs. 1.5 mmol/L in those dialyzing <40 hr/week (2.64+/-0.19 vs. 2.50+/-0.12 mmol/L, p=0.046), but postdialysis Ca x P were similar (2.25+/-0.44 vs. 2.16+/-0.29 mmol(2)/L(2), p=0.60). Parathyroid hormone was also lower with 1.75 vs. 1.5 mmol/L baths in the <40 hr/week groups (31.99+/-26.99 vs. 14.47+/-16.36 pmol/L, p=0.03), although this difference was not seen in those undertaking NHD > or =40 hr/week. Hemoglobin, ALP, and albumin were all similar between groups. There was also no difference in vitamin D requirement when using 1.75 mmol/L compared with the 1.5 mmol/L dialysate. Multivariate analysis to determine independent predictors of postdialysis serum Ca showed a statistically significant positive association with predialysis Ca, dialysate Ca, and total NHD hr/week. An elevated dialysate Ca concentration is required in NHD to prevent osteopenia but differences in serum markers of mineral metabolism between 1.5 and 1.75 mmol/L Ca dialysate in NHD in our study were few. This was similar for patients undertaking NHD <40 or > or =40 hr/week, although differences in the frequency of NHD may also be as important as dialysate Ca with regard to serum Ca levels. With concerns that prolonged higher Ca levels contribute to increased cardiovascular mortality, the optimal Ca dialysate bath is still unknown and further studies addressing bone metabolism with larger NHD numbers are required.     

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.     

Treatment of severe metastatic calcification in hemodialysis patients

Soft tissue and vascular calcifications are commonly present in uremic patients secondary to disturbances in calcium and phosphate balance and secondary to hyperparathyroidism. We report a uremic patient who developed uncontrolled hyperparathyroidism rapidly within 6 months after commencing hemodialysis (HD) therapy, with clinical presentations of tumoral calcinosis, calciphylaxis, and myocardial calcifications. After treatment with a low-calcium dialysate, non–calcium-containing phosphate binders, and parathyroidectomy, a dramatic resolution of soft tissue calcification was achieved. However, there was relatively little change in the vascular and other visceral calcifications over the 3-month observation period. This case highlights an unusual and rapid development of tertiary hyperparathyroidism, the importance of tight calcium/phosphate control in uremic patients, the potential hazards of a high calcium concentration dialysate, and the dangers of the overzealous use of active vitamin D therapy in HD patients with uncontrolled hyperparathyroidism.     

Looking at calcimimetics impact on hypercalcemia of immobilization: hypotheses and a case study

For the treatment of secondary hyperparathyroidism (HPTH-II) in dialysis patients and hypercalcemia in patients with parathyroid carcinoma. Calcimimetics are a new class of drugs approved in the European Community and the United States by the Food and Drug Administration that were designed to suppress parathyroid hormone (PTH) levels with a simultaneous reduction in serum calcium and phosphorus levels, and calcium phosphorus product (Ca x P). Hypocalcemia is a frequent finding during the correction phase of the HPTH-II with calcimimetics. By contrast, the appearance of a hypercalcemia has yet to be described. In this paper, we report a case of severe hypercalcemia of immobilization in a 40-year-old hemodialyzed woman treated by cinacalcet HCl for a severe HPTH-II (PTH>1,000 pg/mL). A kidney transplantation recipient 1983 to 1995, she was diagnosed with Charcot-Marie Tooth disease in 1991. She had multiple orthopedic interventions for kidney-related osteoarticular problems probably favored by the kidney graft and the immunosuppressive treatment. While she was receiving the maximum dose of 180 mg/day of cinacalcet HCl and PTH at 443 pg/mL, she needed to be hospitalized for a right hip prothesis. Two weeks after the intervention she developed a symptomatic hypercalcemia of 3.57 mmol/L which was resistant to several measures including lowering the calcium concentration in the dialysate, withdrawing all vitamin D and calcium supplementation and the administration of calcitonin. Her serum calcium level was finally stabilized in the 2.37-2.95 mmol/L by administration of a single intravenous dose of pamidronate. This observation illustrates that the pharmacological activation of the parathyroid CaR and other putative CaR on bone cells by calcimimetics did not protect against the occurrence of hypercalcemia of immobilization favored by a severe HPTH-II in a hemodialysis patient.     

The effects of nocturnal compared with conventional hemodialysis on mineral metabolism: A randomized‐controlled trial

Hyperphosphatemia is common among patients receiving dialysis and is associated with increased mortality. Nocturnal hemodialysis (NHD) is a long, slow dialytic modality that may improve hyperphosphatemia and disorders of mineral metabolism. We performed a randomized‐controlled trial of NHD compared with conventional hemodialysis (CvHD); in this paper, we report detailed results of mineral metabolism outcomes. Prevalent patients were randomized to receive NHD 5 to 6 nights per week for 6to 10 hours per night or to continue CvHD thrice weekly for 6 months. Oral phosphate binders and vitamin D analogs were adjusted to maintain phosphate, calcium and parathyroid hormone (PTH) levels within recommended targets. Compared with CvHD patients, patients in the NHD group had a significant decrease in serum phosphate over the course of the study (0.49 mmol/L, 95% confidence interval 0.24–0.74; P=0.002) despite a significant reduction in the use of phosphate binders. Sixty‐one percent of patients in the NHD group compared with 20% in the CvHD group had a decline in intact PTH (P=0.003). Nocturnal hemodialysis lowers serum phosphate, calcium‐phosphate product and requirement for phosphate binders. The effects of NHD on PTH are variable. The impact of these changes on long‐term cardiovascular and bone‐related outcomes requires further investigation.     

Use of 3‐hour daily hemodialysis and paricalcitol in patients with severe secondary hyperparathyroidism: A case series

Patients with poor metabolic control receiving conventional hemodialysis are at risk for developing severe secondary hyperparathyroidism. We postulated that daily hemodialysis may be effective at controlling parathyroid hormone (PTH) in the setting of severe secondary hyperparathyroidism by improving the control of hyperphosphatemia and allowing increased use of vitamin D analogs. We present 5 patients with severe secondary hyperparathyroidism (median iPTH=1783 pg/mL) who were treated with 3‐hour daily hemodialysis (3 hours × 6 times a week). Daily hemodialysis, at 1 year, was associated with a 70.4% reduction in median PTH (1783 pg/mL [interquartile range: 1321–1983]–472 pg/mL [334, 704], P<0.001). Additionally, there was an increase in paricalcitol dose from 0 mcg/d to 10.8 (2.00, 11.7) mcg/d, a 39% reduction in calcium × phosphorus product (80.3 ± 26.8–48.9 ± 14.0, P<0.01), a 52% reduction in serum phosphorus (9.90 ± 2.34–4.75 ± 0.79 mg/dL, P<0.0001), and a 17.6% increase in serum calcium (8.18 ± 2.04–9.62 ± 0.93 mg/dL, P<0.01). Three‐hour daily hemodialysis with the use of high‐dose paricalcitol is associated with improved control of severe secondary hyperparathyroidism.     

Intradialytic changes of serum magnesium and their relation to hypotensive episodes in hemodialysis patients on different dialysates

Magnesium is a crucial mineral, involved in many important physiological processes. Magnesium plays a role of maintaining myocardial electrical stability in hemodialysis patients. Intradialytic hypotension is a common complication of dialysis and it is more common with acetate dialysate. The significance of the intradialytic changes of magnesium and their relation to parathyroid hormone (PTH) level and calcium changes during dialysis, and their relation to hypotensive episodes during dialysis are interesting. The aim of this work is to investigate the intradialytic changes of serum magnesium in chronic hemodialysis patients with different hemodialysis modalities and the relation to other electrolytes and to PTH, and also the relation to intradialytic hypotension. The present study was conducted on 20 chronic renal failure patients. All patients were on regular hemodialysis thrice weekly 4 hr each using acetate dialysate (group I). To study the effect of an acetate-based dialysate vs. a bicarbonate-based dialysate on acute changes of magnesium, calcium, phosphorus, and PTH during a hemodialysis session, the same patients were shifted to bicarbonate dialysis (group II). All patients were subjected to full history and clinical examination, predialysis laboratory assessment of blood urea nitrogen (BUN), serum creatinine, albumin, and hemoglobin, serial assessment of magnesium, calcium, phosphorus, and parathyroid hormone at the start of the hemodialysis session, 2 hr later, and at the end of the session, blood pH, and electrocardiogram (ECG) presession and postsession. All patients were urged to fix their dry weight, diet, and current medications. None of the patients had diabetes, neoplasia, liver disease, or cachexia, nor had they been recently on magnesium-containing drugs or previously parathyroidectomized. Hemodialysis sessions were performed by volumetric dialysis machines using the same electrolyte composition. Magnesium level significantly increased in the bicarbonate group at the end of dialysis (0 hr: 2.73+/-0.87, 2 hr: 3.21+/-1.1, and at 4 hr: 5.73+/-1.45 mg/dL, p value <0.01), while it significantly decreased in the acetate group (0 hr: 3.00+/-0.58, 2 hr: 2.26+/-0.39, 4 hr: 1.97+/-0.33 mg/dL, p value <0.01). Calcium level significantly increased in the bicarbonate group (p=0.024) but not in the acetate group. Phosphorus level significantly decreased in both acetate and bicarbonate groups. PTH level did not significantly change in either group, p value > or =0.05. Blood pH significantly increased, changing from acidic to alkaline pH, with both modalities of hemodialysis. ECG showed no significant changes during sessions with either type of dialysate. Hypotension was significantly higher in group I compared with group II (p=0.01), and this hypotension was positively correlated with a decrease in serum magnesium level in group I. Intradialytic changes in serum magnesium have no correlation with intradialytic changes in serum calcium or with PTH level. However, it was significantly correlated with hypotension during the dialysis session, especially with acetate dialysate. Further investigations are needed to determine whether or not this is true in patients using bicarbonate dialysis.     

Severe Cortical and Trabecular Osteopenia in Secondary Hyperparathyroidism

Background: Peripheral quantitative computed tomography (pQCT) provides real volumetric bone density values, not only of the total, but also of trabecular and cortical bone, separately. In addition, it provides data on bone geometry that can be related to the risk of fracture. Methods: Total, cortical, and trabecular volumetric bone mineral densities (BMD), as well as the main geometric parameters (cross‐sectional area, cortical area, trabecular area, and cortical thickness) were assessed by pQCT at the distal radius in 24 hemodialysis patients affected by severe secondary hyperparathyroidism (PTH, mean ± SD: 1444 ± 695 pg/mL). The strength‐strain index (SSI), a biomechanical parameter describing bone fragility, was also determined. Results: Compared with a control group of 64 healthy age‐matched subjects, volumetric BMD (mg/cm³) was significantly reduced in all patients (total BMD: 243 ± 87 vs. 405 ± 138, cortical BMD: 605 ± 218 vs. 856 ± 204, trabecular BMD: 95 ± 51 vs. 182 ± 75). Cortical area and cortical thickness showed significant modifications, while cross‐sectional area did not. SSI was significantly reduced (547 ± 125 vs. 927 ± 306 mm³). PTH levels showed a significant inverse correlation with cortical BMD (r = ?0.56), cortical thickness (r = ?0.46), cortical area (r = ?0.61), and SSI (r = ?0.54). Quantitative analysis of bone demonstrated cortical porosity. Conclusions: In dialysis patients with severe secondary hyperparathyroidism, pQCT showed a significant cortical osteopenia, associated with geometric and mechanical bone impairment. Interestingly, we also found a comparable deficit of trabecular bone, which may be related to the very high PTH levels. Generalized cortical thinning, intracortical porosity and cortical‐endosteal resorption (“trabecularization” of the cortical bone) are major determinants of reduced bone strength, which may be quantitated by pQCT.     

Solute kinetics with short-daily home hemodialysis using slow dialysate flow rate

"NxStage System One^™" is increasingly used for daily home hemodialysis. The ultrapure dialysate volumes are typically between 15 L and 30 L per dialysis, substantially smaller than the volumes used in conventional dialysis. In this study, the impact of the use of low dialysate volumes on the removal rates of solutes of different molecular weights and volumes of distribution was evaluated. Serum measurements before and after dialysis and total dialysate collection were performed over 30 times in 5 functionally anephric patients undergoing short-daily home hemodialysis (6 d/wk) over the course of 8 to 16 months. Measured solutes included β₂ microglobulin (β₂M), phosphorus, urea nitrogen, and potassium. The average spent dialysate volume (dialysate plus ultrafiltrate) was 25.4±4.7 L and the dialysis duration was 175±15 min. β₂ microglobulin clearance of the polyethersulfone dialyzer averaged 53±14 mL/min. Total β₂M recovered in the dialysate was 106±42 mg per treatment (n=38). Predialysis serum β₂M levels remained stable over the observation period. Phosphorus removal averaged 694±343 mg per treatment with a mean predialysis serum phosphorus of 5.2±1.8 mg/dL (n=34). Standard Kt/V averaged 2.5±0.3 per week and correlated with the dialysate-based weekly Kt/V. Weekly β₂M, phosphorus, and urea nitrogen removal in patients dialyzing 6 d/wk with these relatively low dialysate volumes compared favorably with values published for thrice weekly conventional and with short-daily hemodialysis performed with machines using much higher dialysate flow rates. Results of the present study were achieved, however, with an average of 17.5 hours of dialysis per week.     

Citrate vs. acetate dialysate on intradialytic heparin dose: A double blind randomized crossover study

Introduction Citrate containing dialysate has a calcium‐binding anticoagulant effect compared to standard acetic acid containing dialysate. We performed a randomized, double‐blind, crossover trial in maintenance HD patients to determine if citrate dialysate (“citrate”) safely allows for a lower cumulative heparin dose (“heparin dose”). Methods Intradialytic heparin was adjusted to the minimum during a 2‐week run‐in phase. Patients remaining on heparin at the end of the run‐in phase were then randomized to two weeks of HD with acetate dialysate (“acetate”) followed by two weeks of citrate (sequence 1) or two weeks of citrate followed by two weeks of acetate (sequence 2). We estimated a minimum of 14 patients are required to show a 30% reduction in heparin dose per HD session with citrate compared with acetate. Twenty‐five patients entered the run‐in phase, 20 were randomized, and 19 completed the study. Findings The mean heparin dose was reduced by 19% (656 units, 95% CI ?174 to ?1139 units, P = 0.011) in the acetate group, and 30% (1046 units 95% CI ?498 to 1594 units, P < 0.001) in the citrate group. There was no difference in the mean heparin dose reduction between the two dialysates (P > 0.05). The intradialytic ionized calcium in the citrate group was lowered by 0.10 mmol/L (95% CI 0.07 to 0.14 mmol/L, P < 0.001), and remained unchanged in the acetate group. Discussion Although citrate is a safe alternative to acetate, it does not result in additional heparin dose reduction.     

Treating mineral metabolism disorders in patients undergoing long hemodialysis: A search for an optimal strategy

In hemodialysis (HD) patients, mineral metabolism (MM) disorders have been associated with an increased mortality rate. We report the evolution of MM parameters in a stable HD population undergoing long hemodialysis by performing an annual cross-sectional analysis for every year from 1994 to 2008. The therapeutic strategy has changed: the dialysate calcium concentration has decreased from a mean of 1.7 ± 0.1 to 1.5 ± 0.07 mmol/L and has been adapted to parathyroid hormone serum levels (from 1 to 1.75 mmol/L). The use of calcium-based and aluminum-based phosphate binders has decreased and they have been replaced by sevelamer; alfacalcidol has partly been replaced by native vitamin D. The percentage of patients with a parathyroid hormone serum level between 150 and 300 pg/mL has increased from 9% to 67% (P<0.001); the percentage of patients with phosphataemia between 1.15 and 1.78 mmol/L has increased from 39% to 84% (P<0.001). The percentage of those with albumin-corrected calcemia between 2.1 and 2.37 mmol/L has increased from 29% to 61% (P<0.001), and that of patients with a calcium-phosphorous product (Ca × P) level >4.4 mmol/L decreased from 8.8% to 2% (P=0.02). Although patients undergo long and intensive HD treatment, MM disorders are common. However, an appropriate strategy, mostly consisting of native vitamin D supplementation, progressive replacement of calcium-based phosphate binders with non–calcium-based ones, and individualization of dialysis session duration and dialysate calcium concentration, would result in a drastic improvement.     

Intensive In-Center Hemodialysis for Children: A Case for Longer Dialysis Duration

Background:  Children with renal failure need their dialysis time optimized. Although traditional surrogate markers of outcome in pediatric patients have been growth and development, increasing attention is being focused on cardiovascular risk factors, such as hypertension, volume overload, malnutrition, and elevated calcium (Ca) and phosphorus (P) levels. We have previously shown catch-up growth without growth hormone, in children undergoing long intermittent hemodialysis. Recently we analyzed retrospectively cardiovascular risk factors in patients treated with this regimen.
Methods:  Patients starting dialysis between 1997 and 2001 and on dialysis at least 6 months were evaluated. Charts were reviewed for Ca, P, parathyroid hormone (PTH), albumin, hemoglobin and blood pressure levels, Ca intake, blood pressure medications, dialysis time, and clearance and ultrafiltration rates. Means were calculated for 6- month intervals, up to 36 months.
Results:  Mean equilibrated dialyzer Kt/V _urea ranged from 1.9 to 2.1, and mean weekly dialysis time for oliguric patients varied from 14.8 to 16.3 hr, with average hourly ultrafiltration rates from 0.3 to 0.4 L. Mean values for P and Ca × P were below 1.8 mM and 4.4 mmol   ² /L ² , respectively. Mean hemoglobin levels were 115 to 126 g/L, albumin 39 to 41 g/L, and PTH 156 to 231 pg/mL. Most patients had normal predialysis blood pressures.
Conclusions:  In this pediatric cohort, intensive center hemodialysis was associated with excellent growth, nutrition, Ca, P, and anemia control and reasonable blood pressure values. Large multicenter studies are needed to better determine optimal dialysis therapy for children.     

Intensive weight loss combining flexible dialysis with a personalized,ad libitum,coach‐assisted diet program. A “pilot” case series

Obesity is a growing problem on dialysis. The best approach to weight loss has not been established. The risks of malnutrition may offset the advantages of weight loss. Personalized hemodialysis schedules, with an incremental approach, are gaining interest; to date, no studies have explored its potential in allowing weight loss. This case series reports on combining flexible, incremental hemodialysis, and intensive weight loss. Setting: a small Dialysis Unit, following incremental personalized schedules (2–6 sessions/week, depending on residual function), tailored to an equivalent renal clearance >12 mL/min. Four obese and two overweigh patients (5 male, 1 female; age: 40–63 years; body mass index [BMI] 31.1 kg/m²) were enrolled in a coach‐assisted weight loss program, with an “ad libitum” approach (3–6 foods/day chosen on the basis of their glycemic index and glycemic load). The diet consists of 8 weeks of rapid weight loss followed by 8–12 weeks of maintenance; both phases can be repeated. This study measures weight loss, side effects, and patients' opinions. Over 12–30 months, all patients lost weight (median ?10.3 kg [5.7–20], median ΔBMI–3.2). Serum albumin (pre‐diet 3.78; post‐diet 3.83 g/dL), hemoglobin (pre‐diet 11; post‐diet 11.2 g/dL), and acid–base balance (HCO₃ pre‐diet: 23.3; post‐diet: 23.4 mmol/L) remained stable, with decreasing needs for erythropoietin and citrate or bicarbonate supplements. Calcium‐phosphate‐parathyroid hormone (PTH) balance improved (PTH‐pre 576; post 286 pg/mL). Three out of 4 hypertensive patients discontinued, 1 decreased antihypertensives. None experienced severe side effects. Patient satisfaction was high (9 on a 0–10 analog scale). Personalized, incremental hemodialysis schedules allow patient enrollment in intensive personalized weight loss programs, with promising results.     

Severe hypercalcemia caused by Milk‐Alkali syndrome requiring urgent hemodialysis – Tums by the ton

An increased frequency of the Milk‐Alkali syndrome in the last several years has been noticed related to increasing use of calcium carbonate as a phosphate binder in CKD patients, as an antacid or as calcium supplementation. We present a case of severe hypercalcemia secondary to Milk‐Alkali syndrome that precipitated acute renal failure requiring urgent hemodialysis. A 59-year‐old male with history of hypertension, diabetes mellitus, and acid reflux presented to the ER with confusion, lethargy, nausea, vomiting, and diarrhea. His family relayed a history of recent indigestion and relief with Tums. He was taking several tablets at short intervals to self‐treat the indigestion. At the time of presentation, patient was confused and noted to be dehydrated. Lab findings were significant for elevated BUN/Cr‐ 121 mg/dl/11.1 mg/dl (baseline Cr 1.1 mg/dl few months ago), bicarbonate 38 mg/dl, calcium 16.7 mg/dl, ionized Ca of 1.76 mmol/L, iPTH 10 pg/ml, PTHrP 0.7 pg/ml. Medical management with intravenous fluids and furosemide showed no improvement in renal failure, or calcium level. Patient was then started on hemodialysis with 2.0 mmol/L calcium in the dialysate the next day. There was gradual improvement in patient's mental status, calcium values, and renal failure over the ensuing 2 weeks.
Discussion and Conclusions:  The diagnosis of Milk‐Alkali syndrome is made on the basis of history. Metabolic abnormalities involved in this syndrome are hypercalcemia with low to normal PTH and Vit. D levels, renal failure, and metabolic alkalosis. Failed medical management required acute dialysis in this patient. Acute hemodialysis in such a case could be life saving. Due to increasing use of calcium carbonate for dyspepsia and osteoporosis, patients should be made aware of these severe, potentially life-threatening adverse effects.