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.     

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.     

Phosphate‐binding efficacy of crushed vs. chewed lanthanum carbonate in hemodialysis patients

Lanthanum carbonate, a chewable noncalcium‐containing phosphorus (P) binder, is useful for treating secondary hyperparathyroidism in patients who have hypercalcemia and cannot swallow whole tablets. However, some patients cannot chew tablets or prefer to crush and mix them with food. This study was conducted to determine the P‐binding efficacy of crushed lanthanum and compare it with chewed lanthanum in hemodialysis (HD) patients. After a 1‐week washout period, 11 hemodialysis patients (7 men, 4 women) were randomized to receive, in a crossover fashion, lanthanum 1000 mg 3 times daily chewed with meals and lanthanum 1000 mg 3 times daily crushed into a fine powder, mixed with applesauce and taken with meals, for 4 weeks each. Serum P was measured at the end of each washout (baseline) and weekly during treatment. Changes in serum P from baseline for crushed lanthanum were compared with chewed lanthanum using paired sample t test. Administration of crushed lanthanum resulted in a significant reduction in serum P from baseline (P reduction [mg/dL] for crushed lanthanum in week 1: 2.1 ± 0.4, week 2: 1.7 ± 0.5, week 3: 1.7 ± 0.5, week 4: 1.7 ± 0.4, P<0.05). No statistically significant differences were observed in serum P reduction from baseline and serum P attained during treatment with crushed when compared with chewed lanthanum. Crushed lanthanum is effective in reducing serum P and have similar P‐binding efficacy to chewed lanthanum. Crushing lanthanum and mixing it with food can thus be an option for patients who are unable to chew or swallow whole tablets.     

Switch from calcitriol to paricalcitol in secondary hyperparathyroidism of hemodialysis patients: Responsiveness is related to parathyroid gland size

Paricalcitol is more effective than calcitriol in hemodialysis patients (HD) with secondary hyperparathyroidism (SHPT), but it is not effective in some of them. We have investigated the relationship between paricalcitol responsiveness and parathyroid gland (PTG) size. Thirty HD with SHPT treated previously with calcitriol for at least 6 months were switched to paricalcitol (1:4 conversion ratio). Parathyroid gland number and size (maximum longitudinal diameter [MLD] of largest PTG) was measured by ultrasonography. Patients were divided into 2 groups: group A (MLD ≤9.0 mm [17 HD]); and group B (MLD >9.0 mm [13 HD]). They were defined responder if both the last 2 monthly determinations of inhibit parathyroid hormone (iPTH) were within the target (<300 pg/mL) according to National Kidney Foundation Kidney Disease Outcomes Quality Initiative recommendations. Twenty‐six and 20 HD completed 6‐month and 12‐month paricalcitol therapy, respectively. After 6 months of paricalcitol treatment, 23.5% HD of group A and 7.7% of group B were responders. At 12 months, 41.2 % of group A and 7.7% of group B were responders. Throughout paricalcitol therapy, serum calcium and phosphorus concentrations slightly increased in all HD but more significantly in group B. The baseline iPTH and MLD of the largest PTG were significantly correlated with final iPTH levels. Paricalcitol is more effective than calcitriol in SHPT, but the responsiveness to paricalcitol and hypercalcemia are related to PTG size. The measurement of MLD by ultrasonography may be useful for predicting responsiveness to paricalcitol, avoiding an unnecessary and expensive therapy.     

Sternal instability in a hemodialysis patient with secondary hyperparathyroidism

A 77‐year‐old man, 11 years under chronic hemodialysis treatment for chronic renal failure of unknown origin, presented with anterior chest pain, dyspnea with paradoxical breathing, and sternal instability after a simple fall from a standing height. Patient underwent three‐vessel coronary artery bypass grafting 31 months ago. Computed tomography with three‐dimensional volume rendering showed sternal nonunion with a great gap between the two halves of the sternum and at least one fracture in the left half of the sternum. A successful surgical repair followed. Patient suffered from severe secondary hyperparathyroidism for many years. Despite treatment with sevelamer, paricalcitol and cinacalcet, intact parathyroid hormone was 1682 pg/mL. During the last 5 years, serum intact parathyroid hormone remained steadily above 1000 pg/mL. Patient refused parathyroidectomy in the past. We assume that long‐lasting severe hyperparathyroidism contributed to this rare and life‐threatening complication of median sternotomy in our patient, due to the detrimental effect of hyperparathyroidism on bone metabolism and its association with increased incidence of bone fractures and defect in bone fracture healing.     

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.     

Enhanced solute removal with intermittent, in-center, 8-hour nocturnal hemodialysis

Advances in the dialysis technique and increasing urea Kt/V have not improved outcomes for end‐stage renal disease patients maintained on hemodialysis (HD) therapy. Attention has, thus, focused on enhancing solute removal via prolonged HD sessions. A reduction in the serum levels of phosphorus and β‐2‐microglobulin (B2M) with longer HD treatments has been linked to improved patient outcomes. We have shown that serum phosphorus levels are significantly lowered in patients maintained on thrice‐weekly, in‐center, 8‐hour nocturnal HD performed at a blood flow rate of 400 mL/min. The kinetics of this modality were examined. A total of 8 patients participated in the study (age 45±7 years). Serum creatinine levels decreased from 9.2±1.9 to 3.0±1.0 mg/dL at 8 hours while serum phosphorus decreased from 5.7±1.9 to 2.5±0.7 mg/dL at 8 hours. The initial decrease from predialysis values to 1 hour after the start of HD was significant for both creatinine (P<0.0001) and phosphorus (P<0.001). Serum B2M decreased from 26.8±5.5 mg/L predialysis to 14.9±7.0 mg/L at 8 hours (P<0.01). Dialysate‐side clearances of phosphorus and creatinine were 136±13 and 143±27 cm³/min, respectively. Phosphorus clearances were steadily maintained during the 8‐hour session. A total of 904±292 mg of phosphorus was removed during the 8‐hour treatment, with 501±174 mg (55%) removed during the first 4 hours and the remaining 45% continuously removed during the latter one‐half of the session. The overall calculated B2M clearance was 55.1±40.3 cm³/min using the immediate post‐B2M value and 28.4±34.2 mg/L using the 30‐minute postdialysis value for the calculation. Serum levels of phosphorus and B2M decrease dramatically during an 8‐hour session. Future studies are necessary to determine whether the enhanced solute removal with longer HD sessions translates into an improved outcome for HD patients.     

The individually optimized bolus dose of nadroparin is safe and effective in diabetic and nondiabetic patients with bleeding risk on hemodialysis

The risk of bleeding is a well‐known complication in patients on hemodialysis (HD). The aim of this prospective study was to determine the lowest single bolus dose of low–molecular‐weight heparin nadroparin for safe and effective HD in patients with a bleeding risk. Forty HD patients were divided into 4 subgroups with 10 participants (diabetics with and without a bleeding risk, nondiabetics with and without a bleeding risk). The actual starting bolus dose was decreased by 25% after the initial 4 weeks, further decreased by 25% of the starting dose after 4 weeks, and changed due to extracorporeal circuit clotting in the last 4 weeks. The parameters of coagulation were measured at the beginning, after 2 and 4 h of HD sessions. A significant reduction of nadroparin (first vs. last HD session) was observed in: diabetics with a bleeding risk (49.66 ± 12.33 vs. 28.78 ± 9.60 IU/kg/HD; P<0.001), diabetics without a bleeding risk (50.70 ± 15.23 vs. 33.95 ± 16.97 IU/kg/HD; P<0.001), and nondiabetics with a bleeding risk (61.25 ± 18.68 vs. 32.96 ± 10.06 IU/kg/HD; P<0.001). Altogether, the reduction of the nadroparin dose in these groups was 42.05%; 33.04%, and 46.19%, respectively. Although anti‐Xa at hour 4 at the end of the study was <0.4 IU/mL in our diabetic and nondiabetic patients without a risk of bleeding, serious clottings in the extracorporeal circuit and vascular access thromboses were not found. This study demonstrated for the first time that individually optimized doses of nadroparin are sufficient for safe and effective HD in patients with a bleeding risk.     

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.     

Diagnosis of pheochromocytoma in a hemodialysis patient through measurement of plasma catecholamines

We report the case of a patient on chronic hemodialysis treatment with paroxysms of severe arterial hypertension accompanied by tachycardia, pallor, sweating and tremor. Measurement of plasma catecholamines revealed norepinephrine level of 4625 pg/mL (reference range 191–225 pg/mL), epinephrine level of 1035 pg/mL (58–76 pg/mL) and dopamine level of 148 pg/mL (50–100 pg/mL). MRI showed a left adrenal mass of 2 cm. After the patient was started on an alpha‐1 adrenergic receptor blocker, she underwent a left adrenalectomy. Anatomopathological examination confirmed the diagnosis of pheochromocytoma. Although urinary testing is not possible in anuric hemodialysis patients, diagnosis of pheochromocytoma can be made through measurement of plasma free metanephrines and/or plasma catecholamines.     

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.     

Malnutrition‐inflammation‐coronary calcification in pediatric patients receiving chronic hemodialysis

Malnutrition, inflammation, and renal osteodystrophy parameters with resultant coronary calcification (CC) are associated with increased cardiovascular mortality in adults. Previous pediatric studies demonstrated CC in children but none assessed for an association between inflammation, malnutrition, renal osteodystrophy, and CC. To assess CC, ultrafast computerized tomogram was obtained for 16 pediatric patients (6 females; median age 17.2 years; range 9.1–21.2 years) receiving hemodialysis for ≥2 months. Inflammation was assessed by serum IL‐6, IL‐8, and C‐reactive protein levels on the day of the computerized tomogram scan; nutrition parameters included serum albumin, cholesterol, the body mass index standard deviation score, and normalized protein catabolic rate. Renal osteodystrophy parameters included time‐averaged serum calcium, phosphorus, total PTH, and calcitriol/calcium dose. Patients received hemodialysis thrice‐weekly; mean single pool Kt/V 1.48±0.13; and mean normalized protein catabolic rate 1.27±0.17 g/kg/day. Five of 16 patients had CC. Patients with CC were older (19.1±2.1 vs. 15.4±3.1 months; P=0.03), had longer dialysis vintage (49.4±15.3 vs. 17.2±10.5 months, P=0.0002), lower serum cholesterol (122±17.7 vs. 160.4±10.6 mg/dL, P=0.02), and higher phosphorus (9.05±1.2 vs. 6.1±0.96 mg/dL, P=0.0001). Mean serum albumin and normalized protein catabolic rate did not differ for patients with CC. All patients had elevated IL‐6 and IL‐8 levels compared with healthy norms; the mean IL‐6, IL‐8, and C‐reactive protein levels were not different in patients with CC. Coronary calcification was prevalent in older children receiving maintenance hemodialysis with a longer dialysis vintage. Worse renal osteodystrophy control and malnutrition (low cholesterol) may contribute to CC development.     

Effect of alternate night nocturnal home hemodialysis on anemia control in patients with end‐stage renal disease

Nocturnal home hemodialysis (NHHD) has shown promising results in various clinical parameters. Whether NHHD provide benefit in anemia management remains controversial. This study aims to investigate whether anemia and erythropoiesis‐stimulating agent (ESA) requirement are improved in patients receiving alternate night NHHD compared with conventional hemodialysis (CHD). In this retrospective controlled study, a clinical data of 23 patients receiving NHHD were compared with 25 in‐center CHD patients. Hemoglobin level, ESA requirement, iron profile, and dialysis adequacy indexes were compared between the two groups. Hemoglobin level increased from baseline of 9.37 ± 1.39 g/dL to 11.34 ± 2.41 g/dL at 24 months (P < 0.001) and ESA requirement decreased from 103.44 ± 53.55 U/kg/week to 47.33 ± 50.62 U/kg/week (P < 0.001) in NHHD patients. ESA requirement further reduced after the first year of NHHD (P = 0.037). Standard Kt/V increased from baseline of 2.02 ± 0.28 to 3.52 ± 0.30 at 24 months (P < 0.001). At 24 months, hemoglobin level increased by 1.98 ± 2.74 g/dL in the NHHD group while it decreased by 0.20 ± 2.32 g/dL in the CHD group (P = 0.007). ESA requirement decreased by 53.49 ± 55.50 U/kg/week in NHHD patients whereas it increased by 16.22 ± 50.01 U/kg/week in CHD patients (P < 0.001). Twenty‐six percent of NHHD patients were able to stop ESA compared with none in the CHD group. Standard Kt/V showed greater increase in the NHHD group. (1.49 ± 0.36 in NHHD vs. 0.18 ± 0.31 in CHD, P = 0.005). NHHD with an alternate night schedule improves anemia and reduces ESA requirement as a result of enhanced uremic clearance. This benefit extended beyond the first year of NHHD.     

Clinical epidemiology of parathyroidectomy in hemodialysis patients: the USRDS waves 1, 3, and 4 study

Despite advances in the medical management of secondary hyperparathyroidism, parathyroidectomy remains necessary in some end-stage renal disease patients. Observational studies may help with the design of intervention trials. We linked the retrospective Waves 1, 3, and 4 Dialysis Morbidity and Mortality Study datasets to Medicare claims data to identify incident parathyroidectomy in 10,588 Medicare patients receiving hemodialysis in the United States on December 31, 1993. The mean age was 60.0 years, and the mean follow-up 3.6 years. De novo parathyroidectomy incidence was 14.2/1000 patient-years. Considered as quintiles (Q), higher levels of standard bone metabolism variables were associated (p<0.0001) with parathyroidectomy stepwise, such that adjusted hazards ratios (AHR) for Q5 (vs. Q1) were, for calcium (>10.3 mg/dL), 5.09 (3.64-7.10); for phosphorus (>7.5 mg/dL), 2.92 (2.06-4.15); for calcium-phosphorus product (>71 mg2/dL2), 3.32 (2.27-4.85); and for parathyroid hormone (PTH; >480 pg/mL), 13.81 (7.47-25.55). Other antecedent associations included younger age, lower hemoglobin, and longer dialysis vintage, while transplantation, as a time-dependent covariate, was associated with lower hazards ratios. Using interval Poisson analysis, parathyroidectomy was associated with higher mortality risk ratios in the first year, and progressively lower risk ratios subsequently. Demographic variables may modify the risk of parathyroidectomy. Younger patients on long-term hemodialysis may be at a special risk. Parathyroidectomy risk increases stepwise with alterations in bone metabolism variables, suggesting that a single-threshold management approach may not be ideal.     

Survival with short‐daily hemodialysis: Association of time,site, and dose of dialysis

In thrice‐weekly hemodialysis, survival correlates with the length of time (t) of each dialysis and the dose (Kt/V), and deaths occur most frequently on Mondays and Tuesdays. We studied the influence of t and Kt/V on survival in 262 patients on short‐daily hemodialysis (SDHD) and also noted death rate by weekday. Contingency tables, Kaplan‐Meier analysis, regression analysis, and stepwise Cox proportional hazard analysis were used to study the associations of clinical variables with survival. Patients had been on SDHD for a mean of 2.1 (range 0.1–11) years. Mean dialysis time was 12.9 ± 2.3 h/wk and mean weekly stdKt/V was 2.7 ± 0.5. Fifty‐two of the patients died (20%) and 8‐year survival was 54 ± 5%. In an analysis of 4 groups by weekly dialysis time, 5‐year survival continuously increased from 45 ± 8% in those dialyzing <12 hours to 100% in those dialyzing >15 hours without any apparent threshold. There was no association between Kt/V and survival. In Cox proportional hazard analysis, 4 factors were independently associated with survival: age in years Hazard Ratio (HR)=1.05, weekly dialysis hours HR=0.84, home dialysis HR=0.50, and secondary renal disease HR=2.30. Unlike conventional HD, no pattern of excessive death occurred early in the week during SDHD. With SDHD, longer time and dialysis at home were independently associated with improved survival, while Kt/V was not. Homedialysis and dialysis 15+ h/wk appear to maximize survival in SDHD.     

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

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

Inappropriately elevated endothelin‐1 plays a role in the pathogenesis of intradialytic hypertension

The aim of this study is to investigate the effects of endogenous vasoactive substances on the occurrence of intradialytic hypertension (IDH) in patients during maintenance hemodialysis. Thirty‐four maintenance hemodialysis patients were enrolled in this trial, and 17 of them were diagnosed with IDH (defined as an increase in blood pressure of at least 10 mmHg during or immediately after a hemodialysis session), while 17 age‐matched and sex‐matched controls without IDH were selected for a retrospective comparison. We collected patients' blood samples before and after a dialysis session and measured the plasma levels of N‐terminal fragment brain natriuretic peptide, renin, angiotensin‐II, aldosterone (ALD), angiotensin‐converting enzyme (ACE), endothelin‐1 (ET‐1), nitric oxide (NO), norepinephrine (NOR), and adrenomedullin. The post‐dialysis serum ET‐1 concentrations were significantly higher (4.09 ± 2.06 vs. 2.75 ± 1.34 pg/mL, P < 0.05), while the post‐dialysis ratio of NO to ET‐1 was lower (17.79 ± 5.65 vs. 24.78 ± 12.04, P < 0.05) in IDH patients compared with the control group. Post‐dialysis ALD and NOR values were significantly lower (P < 0.01) and ACE levels were significantly higher (P < 0.01) than the pre‐dialysis concentrations only in the control and not in the IDH group. All other measured factors did not differ significantly between the groups and between pre‐dialysis and post‐dialysis determinations. Compared with blood angiotensin‐II, ALD, ACE, NOR, adrenomedullin, N‐terminal fragment brain natriuretic peptide, and NO status, inappropriately elevated ET‐1 plasma concentrations may play a predominant role in the pathogenesis of IDH.     

Comparison of serum albumin,C‐reactive protein and carotid atherosclerosis as predictors of 10‐year mortality in hemodialysis patients

Serum albumin, C‐reactive protein (CRP), and the intima‐medial thickness of the common carotid artery (CA‐IMT) are associated with clinical outcomes in hemodialysis (HD) patients. However, it remains unclear which parameters are more reliable as predictors of long‐term mortality. We measured serum albumin, CRP, and CA‐IMT in 206 HD patients younger than 80 years old, and followed them for the next 10 years. One hundred sixty‐eight patients (age: 57 ± 11 years, time on HD: 11 ± 7 years) were enrolled in the analyses. We divided all patients into three tertiles according to their albumin levels, and conducted multivariate analyses to examine the impact on 10‐year mortality. Seventy‐three (43.5%) patients had expired during the follow‐up. Serum albumin was significantly lower in the expired patients than in the surviving patients (3.8 ± 0.3 vs. 4.0 ± 0.3, P<0.01), while CRP (4.7 ± 5.0 vs. 2.8 ± 3.5 g/L, P=0.01) and CA‐IMT (0.70 ± 0.15 vs. 0.59 ± 0.11 mm, P<0.01) were significantly higher in the expired group. The multivariate analysis revealed that there was a significantly higher risk for total mortality in HD patients with serum albumin <3.8 g/dL (odds ratio 5.04 [95% CI: 1.30–19.60], P=0.02) when compared with those with albumin >4.1 g/dL. In contrast, CRP and CA‐IMT did not associate with total death. It follows from these findings that serum albumin is more superior as a mortality predictor compared with CRP and CA‐IMT in HD patients.     

Antibiotic lock: In vitro stability of gentamicin and sodium citrate stored in dialysis catheters at 37 °C

Catheter‐related bacteremia (CRB) is a major cause of morbidity and mortality especially among patients receiving hemodialysis. Antibiotic lock therapy represents a promising technique in the treatment of CRB. Several studies have evaluated antibiotics in combination with heparin as an interdialytic locking solution for prophylaxis of CRB. The objective of this study was to evaluate the stability of gentamicin and sodium citrate in hemodialysis catheters as an interdialytic lock. Solutions containing gentamicin 2.5 mg/mL and sodium citrate 40 mg/mL (4%) were prepared individually and in combination. The solutions were instilled into dialysis catheters and stored at 37 °C for 96 h. Samples were withdrawn randomly from catheter lumens at 24‐hour intervals for 4 days and stored at ?20 °C until analysis. The samples were analyzed with validated, stability‐indicating HPLC assays. The luminal concentration of gentamicin 2.5 mg/mL, sodium citrate 40 mg/mL (4%), and the combination was determined on study days 0, 1, 2, 3, and 4. When gentamicin was combined with sodium citrate and stored at 37 °C in dialysis catheters, the solution showed no decrease in either the gentamicin or the sodium citrate concentrations over the 96‐hour study period. The percent of the original concentration at 96 h was 102.4±1.03 for gentamicin and 102.9±1.25 for citrate (P=0.5556). The combination of gentamicin 2.5 mg/mL and sodium citrate 40 mg/mL (4%) can be retained in hemodialysis catheters for at least 96 h at 37 °C with no evidence of degradation.