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.     

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.     

Nocturnal Hemodialysis in Australia

Background: Because home hemodialysis has long been a common Australian support modality, the advent of home‐based nocturnal hemodialysis (NHD) in Canada stimulated the extension of our existing home‐ and satellite‐based conventional hemodialysis (CHD) programs to NHD. As a result, the first government‐funded, home‐based, 6‐nights‐per‐week NHD program in Australia began in July 2001. Methods: Sixteen patients have been trained for NHD; 13 dialyzed at home 8 to 9 hr per night for 6 nights per week, whereas 3 preferred to train for NHD at home using an 8‐ to 9‐hr alternate‐night regime. Results: The program experience to March 1, 2003, was 655 patient‐weeks. Two patients had withdrawn for transplantation and 2 for social reasons, although 1 continues on alternate‐night NHD. There hade been no deaths. Ten patients had dialyzed without partners. All patients ceased phosphate binders at entry. Thirteen of 16 discontinued all antihypertensive drugs. There were no fluid or dietary restrictions. Phosphate was added to the dialysate to prevent hypophosphatemia. Pre‐ and postdialysis urea and phosphate levels were broadly within the normal ranges. All patients reported restorative sleep; similarly partners reported stable sleep patterns and noted improved mood, cognitive function, and marital relationships in their NHD partners. Preliminary cost analyses show that whereas consumables had doubled, and epoetin and iron expenditures had risen by 28.9%, other pharmaceutical costs had fallen by 47%, and nursing wage costs were 48% of the notional cost had these patients remained on CHD. Three patients on NHD were retired, 7 worked full‐time, 3 worked part‐time, and 3 drew disability support, whereas previously on CHD, 3 were retired, 3 had worked full‐time, 3 had worked part‐time, and 7 had drawn disability support. Conclusion: We believe that NHD is viable, safe, effective, and well accepted with significant lifestyle benefits and reemployment outcomes. Although initial setup costs are significant, NHD cost advantage over CHD progressively accrues as program numbers exceed 12 to 15 patients.     

The effect of frequent hemodialysis on matrix metalloproteinases,their tissue inhibitors,and FGF23: Implications for blood pressure and left ventricular mass modification in the Frequent Hemodialysis Network trials

Background: Frequent hemodialysis modifies serum phosphorus, blood pressure, and left ventricular mass (LVM). We ascertained whether frequent hemodialysis is associated with specific changes in biomarker profile among patients enrolled in the frequent hemodialysis network (FHN) trials. Methods: This was a post hoc analysis of biomarkers among patients enrolled to the FHN trials. In particular, we hypothesized that frequent hemodialysis is associated with changes in a specific set of biomarkers which are linked with changes in blood pressure or LVM. Results: Among 332 randomized patients, 243 had biomarker data available. Of these, 124 patients were assigned to 3‐times‐a‐week hemodialysis (94 [Daily Trial] and 30 [Nocturnal Trial]) and 119 patients were assigned to 6‐times‐a‐week hemodialysis (87 [Daily Trial] and 32 [Nocturnal Trial]). Frequent hemodialysis lowered phosphate, blood pressures, LVM, log fibroblast growth factor (FGF)23, and tissue inhibitors of metalloproteinase (TIMP)—2 levels. The fall in phosphate was associated with changes in FGF23 (r = 0.48, P < 0.001) [Daily Trial] and (r = 0.55, P < 0.001) [Nocturnal Trial]) and tended to be associated with changes in systolic blood pressure (r = 0.18, P = 0.057) [Daily Trial] and (r = 0.31, P = 0.04) [Nocturnal Trial]. Within the Daily Trial, changes in MMP2 (r = 0.20, P = 0.034) were associated with changes in LVM. In the Nocturnal Trial, changes in TIMP‐1 (r = 0.37, P = 0.029) and MMP 9 (r = ?0.38, P = 0.01) were associated with LVM changes. MMP2 changes were associated with changes in systolic blood pressure. Conclusions: Reduction of serum phosphate by frequent hemodialysis may modulate FGF23 levels and systolic blood pressure. Markers of matrix turnover are associated with LVM changes. Frequent hemodialysis may affect pathological mediators of chronic kidney disease‐mineral bone‐metabolism disorder.     

Beneficial effects of nocturnal hemodialysis in a hemodynamically unstable patient with AL‐amyloidosis

We present a patient with primary systemic AL‐amyloidosis, who stabilized hemodynamically on nocturnal hemodialysis (NHD). The NHD allowed a significant reduction in ultrafiltration rates which likely underlies the procedural tolerability. It also provided an increase in urea clearance, better control of serum phosphorus levels without the use of any binders, and normalization of blood pressure despite the discontinuation of all antihypertensive agents. Given the autonomic derangements associated with AL‐amyloidosis pathophysiology and the clinical benefits of NHD on hemodynamic stability, the use of intensive hemodialysis may be considered for the management of patients with unstable hemodynamic profiles.     

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.     

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.     

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 m²), 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.     

Rationale and study design of a three‐period, 58‐week trial of ferric citrate as a phosphate binder in patients with ESRD on dialysis

Chronic kidney disease associated mineral and bone disorders arise as a result of aberrant bone mineral metabolism in patients with advancing levels of renal dysfunction and end‐stage renal disease. One of the cornerstones of treatment is the use of phosphate‐binding agents. We describe the rationale and study design for a clinical trial to assess the safety and efficacy of ferric citrate as a phosphate binder. This trial is a three‐period, international, multicenter, randomized, controlled clinical trial to assess the safety and efficacy of ferric citrate as a phosphate binder, consisting of a 2‐week washout period, a 52‐week safety assessment period in which subjects are randomized to ferric citrate or active control, and a 4‐week efficacy assessment period in which subjects randomized to ferric citrate in the safety assessment period are randomized to ferric citrate or placebo. Eligible subjects include end‐stage renal disease patients who have been treated with thrice‐weekly hemodialysis or peritoneal dialysis for at least 3 months in dialysis clinics in the United States and Israel. Primary outcome measure will be the effect of ferric citrate vs. placebo on the change in serum phosphorus. Safety assessments will be performed by monitoring adverse events, concomitant medication use, and sequential blood chemistries (including iron parameters, phosphorus, and calcium). This three‐period trial will assess the efficacy of ferric citrate as a phosphate binder. If proven safe and efficacious, ferric citrate will likely provide an additional phosphate binder to treat chronic kidney disease associated mineral and bone disorders.     

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.     

Development and utility of a multi‐dimensional grid to assess individual mineral metabolism control in hemodialysis patients: A potential aid for therapeutic decision making?

A grid was developed to evaluate control of serum calcium, phosphate, and parathyroid hormone levels in hemodialysis patients, based on guideline recommendations (National Kidney Foundation Kidney Disease Outcomes Quality Initiative and Canadian Society of Nephrology), and its face validity was examined in a representative sample of Canadian patients. A retrospective chart review was undertaken in hemodialysis patients from 7 Canadian units. Patients >18 years, on hemodialysis for ≥12 months, and ≥3 parathyroid hormone levels measured ≥1 month apart were included. The grid classified mineral metabolism control as optimal, suboptimal, or poor (mean of 3 measurements). Medication use, hospitalization, and Emergency Department visits were evaluated in relation to grid occupancy. A second comparative analysis of grid occupancy was undertaken on prevalent hemodialysis cases in British Columbia in 2008. Data from 268 patients (mean age 62.3 years) were analyzed. Using National Kidney Foundation Kidney Disease Outcomes Quality Initiative guidelines, 17.5%, 28.8%, and 53.7% of patients had optimal, suboptimal, and poor control, respectively, of all 3 parameters (calcium, phosphate, and parathyroid hormone). Using Canadian Society of Nephrology criteria, optimal, suboptimal, and poor control rates were 6.3%, 4.2%, and 89.5%, respectively. Poor control was a possible or a probable cause of hospitalization or Emergency Department attendance in 8 patients. Data from British Columbia in 2008 (n=1858) show optimal, suboptimal, and poor control rates of 15.8%, 24.5%, and 59.7%, respectively. Poor mineral metabolism control among Canadian hemodialysis patients is not showing improvement. The therapeutic grid is a valid tool and may help guide therapeutic decisions, quality control initiatives, and patient counseling. http://www.ukidney.com/bone‐and‐mineral‐metabolism‐resource .     

The Effect of Frequent and Occasional Dialysis-Associated Hypotension on Survival of Patients on Hemodialysis

Hyperphosphatemia and poor uremia control are established cardiovascular risk factors in patients with end-stage renal disease (ESRD) associated with impaired endothelial dependent and independent vasodilation (EDV and EIV). Nocturnal hemodialysis [6 × 8 h/week] augments dialysis dose and offers normal phosphate (Pi) balance. We hypothesized that NHD would restore EDV (endothelial function) and EIV (vascular smooth muscle cell function) by simultaneously improving uremia and Pi control. 2 groups of ESRD patients (mean age 41 ± 2 years) stratified according to their baseline plasma Pi levels (normal Pi <1.8 mM, high Pi >1.8 mM) were studied. Dialysis dose (Kt/V per session), plasma Pi, blood pressure (BP) and brachial artery responses to reactive hyperemia (EDV), and sublingual nitroglycerin (EIV) were examined before, 1 and 2 months after conversion from conventional hemodialysis (CHD) [3 × 4 h/week] to NHD. After 2 months, NHD increased dialysis dose (from 1.24 ± 0.06 to 2.04 ± 0.08; p = 0.02) and lowered BP (from 140 ± 5/82 ± 3 to 119 ± 1/71 ± 3, p = 0.01) in all patients. In patients with adequate Pi control during CHD, EDV was normalized after 1 month of NHD. In contrast, in the high Pi group, 1 month of NHD was sufficient to reduce plasma phosphate levels, but 2 months of NHD was required for EDV to improve.  

     

Efficacy and safety of Cinacalcet on secondary hyperparathyroidism in Chinese chronic kidney disease patients receiving hemodialysis

Introduction Secondary hyperparathyroidism (SHPT) develops in patients with chronic renal failure. Cinacalcet hydrochloride has been used successfully in U.S., Europe, and Japan in the treatment of SHPT, while maintaining serum levels of calcium and phosphorus. The efficacy and safety profile of Cinacalcet treatment vs. conventional treatments has been of great interest in clinical practice. In this recent phase III study conducted in China, efficacy and safety of a calcimimetic agent, Cinacalcet (Kyowa Hakko Kirin Co., Ltd.), were assessed for SHPT treatment in stable chronic renal disease patients on hemodialysis. Methods In this double‐blind, multicenter, placebo‐controlled, randomized phase III study, 238 subjects were enrolled in 12 centers and randomly divided into a Cinacalcet group and a placebo group. The percentage of patients achieving a serum parathyroid hormone (PTH) level ≤250 pg/mL was the primary efficacy end point. Serum calcium and phosphorus levels were measured. Adverse events and serious adverse events were recorded, and causal analysis performed. Findings In primary analysis, 25.4% of the Cinacalcet group and 3.5% of the placebo group achieved the primary end point (PTH ≤250 pg/mL). Calcium and phosphorus levels and calcium–phosphorus product were lower in the Cinacalcet group compared with the placebo group. Eleven serious adverse events were reported and considered to be not related to study drugs. Mild to moderate hypocalcemia and reduced calcium levels were reported and considered to be Cinacalcet related. Discussion This phase III study demonstrated that Cinacalcet is effective and well tolerated in treating SHPT in Chinese chronic kidney disease patients on hemodialysis, and in a patient population with much higher baseline PTH levels.     

Achieving targets for bone and mineral metabolism: the impact of cinacalcet HCl in clinical practice

Achieving the K/DOQI targets for bone and mineral metabolism has proven difficult with the use of vitamin D analogues and phosphate binders. The introduction of cinacalcet HCl provided a new tool with a novel therapeutic mechanism of action. The purpose of this study was to evaluate the effect of the introduction of combination algorithm for managing secondary hyperparathyroidism (SHPT) on phosphorus, calcium, and biointact parathyroid hormone (PTH). The 61 patients who dialyzed in the facility from January 2004 (baseline) and who remained in the facility as of April 2005 (follow-up) were included in the study. In the baseline period, 37 (61%) of the patients received paricalcitol at some time during the 3-month observation period. In the follow-up period, 19% or 31% of the patients received cinacalcet HCl. Of those not receiving cinacalcet HCl, 67% had PTH at or below target, 17% were felt to be noncompliant with oral meds, 7% had low calcium, and 10% either could not get the medication or were not switched to the combination pathway. Compared with the baseline period, the percent of patients who met the PTH target increased from 19.7% to 37.7%, p<0.05. The percent of patients meeting all 4 targets increased from 14.8% to 24.6%, although this did not reach statistical significance. The introduction of cinacalcet HCl into a treatment algorithm for management of SHPT resulted in a significant increase in the percentage of patients achieving the PTH target while maintaining the other mineral metabolism targets.     

Association of mineral metabolism factors with all-cause and cardiovascular mortality in hemodialysis patients: the Japan dialysis outcomes and practice patterns study

Abnormalities in mineral metabolism have been linked to mortality in hemodialysis (HD) patients. We postulated that these abnormalities would have a particularly large deleterious impact on deaths due to cardiovascular causes in Japan. This study describes the recent status of abnormal mineral metabolism, significant predictors, and potential consequences in the Dialysis Outcomes and Practice Patterns Study (DOPPS), Phases 1 and 2, in Japan. Major predictor variables were patient demographics, comorbidities, and laboratory markers of mineral metabolism such as albumin-adjusted serum calcium (calciumAlb), phosphorus, and intact PTH (iPTH). In a cross section of 3973 Japanese HD patients in DOPPS I and II, a large faction had laboratory values outside of the recommended Kidney Disease Outcomes Quality Initiative (K/DOQI) guideline range for serum concentrations of phosphorus (51% of patients above upper target range), calciumAlb (43.7% above), calcium-phosphorus (Ca x P) product (41.1% above), and iPTH (18.6% above). All-cause mortality was significantly and independently associated with calciumAlb (relative risk [RR]=1.22 per 1 mg/dL, p=0.0005) and iPTH (RR=1.04 per 100 pg/mL, p=0.04). Cardiovascular mortality was significantly associated with calciumAlb (RR=1.28, p=0.02), phosphorus (RR=1.13 per 1 mg/dL, p=0.008), Ca x P product (RR=1.07 per 2 mg(2)/dL(2), p=0.002), and PTH (RR=1.08, p=0.0001). This study expands our understanding of the relationship between altered mineral metabolism and mortality outcomes, showing slightly stronger associations with cardiovascular causes than observed for all-cause mortality. These findings have important therapeutic implications for Japanese HD patients.     

Cervical tumoral calcinosis with secondary hyperparathyroidism in a chronic hemodialysis patient

Tumoral calcinosis is an uncommon and severe complication of chronic renal failure. It is generally associated with the presence of a high‐serum calcium‐and‐phosphorus product. We report here a case of a patient on maintenance hemodialysis who presented with progressively increasing, solitary, tumor‐like swelling over the nape of the neck. A 50‐year‐old female on thrice weekly maintenance hemodialysis for the last 3 years presented with a small swelling over the nape of the neck that had been progressively increasing over the last 1 year to cricket ball size. The patient was investigated and diagnosed as having tumoral calcinosis. The metastatic calcification occurring in the patient was most likely related to high calcium × phosphate product with coexistent secondary hyperparathyroidism possibly aggravated by vitamin D therapy. The patient was treated with withdrawal of vitamin D therapy, strict control of serum phosphate levels with noncalcemic phosphate binders, and subtotal parathyroidectomy. The neck swelling started decreasing in size after 2 months of parathyroidectomy and there was marked clinical improvement with drop in serum parathormone levels, over a period of 6 months. After 2 years of parathyroidectomy, the neck swelling again started increasing in size with increase in serum parathormone levels. The patient was treated with cinacalcet and the neck swelling gradually decreased in size along with control of serum parathormone and phosphate levels.     

Effect of incident nocturnal home hemodialysis versus incident continuous ambulatory peritoneal dialysis on employment rate,clinical, and laboratory outcomes: A 1‐year retrospective observation study

Introduction: While studies demonstrated favorable outcomes of nocturnal home hemodialysis (NHHD), direct comparison on employment rate, clinical and laboratory outcomes between the NHHD and continuous ambulatory peritoneal dialysis (CAPD) had not been previously performed. Methods: A 1‐year retrospective observation study was performed in 20 incidents alternate night NHHD and 81 incident CAPD patients of Chinese ethnicity, who were sex, diabetic status, and Charlson comorbidity index matched, but not age due to our center's age limit for NHHD enrollment. The primary outcome was the difference in employment rate at 1 year. Secondary outcomes included differences in clinical parameters (weight, blood pressure, number of antihypertensive medication, dosage of phosphate binders, and erythropoietin stimulating agent) and laboratory parameters (residual renal function, mineral metabolic markers, hemoglobin). Findings: NHHD subjects were 5 years younger than CAPD patients, and they had higher employment rate (80% vs. 33.3%, P < 0.01) at 1 year, with age‐adjusted odds ratio for employment was 6.10 (95% confidence interval 1.77–20.99, P = 0.04). They consumed less aluminum‐based phosphate binder (0 vs. 1800 mg, P < 0.01), but showed no significant disparities in other clinical parameters. Residual renal function in both groups declined comparably, nonetheless NHHD group had lower serum phosphate (1.37 vs. 1.71 mmol/L, P = 0.01) and calcium phosphate product (3.13 vs. 4.12 mmol²/L², P < 0.01), with similar hemoglobin levels. Discussion: NHHD appeared to offer higher employment rate, lower dosage of aluminum‐based phosphate binder and mineral metabolic markers at 1 year compared with CAPD in Hong Kong.     

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.     

Hyperprolactinemia in end‐stage renal disease and effects of frequent hemodialysis

Introduction: End‐stage renal disease is associated with elevations in circulating prolactin concentrations, but the association of prolactin concentrations with intermediate health outcomes and the effects of hemodialysis frequency on changes in serum prolactin have not been examined. Methods: The FHN Daily and Nocturnal Dialysis Trials compared the effects of conventional thrice weekly hemodialysis with in‐center daily hemodialysis (6 days/week) and nocturnal home hemodialysis (6 nights/week) over 12 months and obtained measures of health‐related quality of life, self‐reported physical function, mental health and cognition. Serum prolactin concentrations were measured at baseline and 12‐month follow‐up in 70% of the FHN Trial cohort to examine the associations among serum prolactin concentrations and physical, mental and cognitive function and the effects of hemodialysis frequency on serum prolactin. Findings: Among 177 Daily Trial and 60 Nocturnal Trial participants with baseline serum prolactin measurements, the median serum prolactin concentration was 65 ng/mL (25th–75th percentile 48–195 ng/mL) and 81% had serum prolactin concentrations >30 ng/mL. While serum prolactin was associated with sex (higher in women), we observed no association between baseline serum prolactin and age, dialysis vintage, and baseline measures of physical, mental and cognitive function. Furthermore, there was no significant effect of hemodialysis frequency on serum prolactin in either of the two trials. Discussion: Serum prolactin concentrations were elevated in the large majority of patients with ESRD, but were not associated with several measures of health status. Circulating prolactin levels also do not appear to decrease in response to more frequent hemodialysis over a one‐year period.