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.     

Changes in hemoglobin and albumin concentration during nocturnal home hemodialysis

The hemoglobin (Hb) and the serum albumin (S.Alb) concentration commonly rise during seated, conventional thrice-weekly 4 to 4.5 hr hemodialysis (CHD) as a result of rapid fluid removal from the intravascular compartment. Conversely, in long, slow, recumbent nocturnal home hemodialysis (NHHD), the intra-dialytic S.Alb concentration has been shown to fall. In normal human physiology, plasma volume expansion rapidly follows recumbency and is sustained until a resumption of an upright position re-induces plasma volume contraction. The plasma protein dilution of recumbency has been suggested as the mechanism behind this finding in NHHD. Our retrospective analysis of 585 consecutive measurements of predialysis and postdialysis S.Alb and Hb taken from 71 NHHD patients confirmed an intra-dialytic fall in S.Alb (0.99% in alternate night NHHD and 1.4% in 6 nights/week NHHD) compared with an 8.4% rise in a control group of 104 CHD patients (p<0.001). Although the NHHD intra-dialytic Hb rose (3.8% in alternate night NHHD and 2.6% in 6 nights/week NHHD), this rise was significantly greater (8%) in CHD patients (p<0.001), and as physiological data confirm that recumbent dilution for albumin is greater than that for Hb, this may provide the explanation. We conclude that NHHD provides a more physiological volume milieu with the normal physiological dilution mechanisms of recumbency still operating despite the slow, steady volume reduction that accompanied longer hour and more frequent dialysis. These mechanisms are subverted, however, in CHD by the more-aggressive plasma contraction needed to attain adequate control of the intravascular volume in the face of shorter hour, less-frequent dialysis.     

Quality of life and alternate nightly nocturnal home hemodialysis

Hemodialysis has been associated with reduced quality of life (QOL). Small cohort studies of quotidian hemodialysis regimens suggest general QOL and dialysis-related symptoms may improve compared with conventional regimens. An observational cohort study was conducted on 63 patients (age 51.7 ± 12.9 years; 79.4% male; 33.3% diabetes; duration of renal replacement therapy 1.9 [0.7–6.4] years) converted from conventional home hemodialysis (3–5 sessions weekly, 3–6 h/session) to home nocturnal home hemodialysis (NHD) (3–5 sessions weekly, 6–10 h/session). Kidney Disease Quality of Life (KDQOL) and Assessment of Quality of Life instruments and 6-minute–walk tests were applied at baseline and 6 months. Baseline and 6 month surveys were returned by 70% of patients. On KDQOL, significant improvements in general health (P=0.02) and overall health ratings (P=0.0008), physical function (P=0.003), physical role (P=0.018), and energy and fatigue (P=0.027) were documented. There was a trend toward improvement in burden of kidney disease (P=0.05) and emotional role (P=0.066). There was a significant improvement in distance covered in the 6-minute–walk test from 513 m (420.5–576.4) to 536.5 m (459–609), P=0.007. On Assessment of Quality of Life, there was a trend toward improvement in overall utility score from 0.65 (0.39–0.81) to 0.73 (0.46–0.86), P=0.096. After 86.2 patient-years of observation, 23 patients have discontinued NHD (12 transplanted, 5 deceased, 4 psychosocial problems, 1 dialysis access problem, 1 medically unsuitable). Nocturnal home hemodialysis is a sustainable therapy. In addition to improving general QOL, alternate nightly NHD can significantly improve physical functioning as measured by KDQOL and 6-minute–walk tests.     

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.     

Quantifying home medication regimen changes and quality of life in patients receiving nocturnal home hemodialysis

Medication regimen simplification may improve adherence in end-stage kidney disease. The effect of nocturnal home hemodialysis (NHHD) on medication burden is unknown. A retrospective pilot study of NHHD patients was conducted. Medication information was collected at baseline, NHHD start, and at 3, 6, 12, 18, and 24 months. SF-36 scores were collected at baseline, 6, 12, and 24 months. The number of medications, pill burden, and number of administrations per day were determined. Medication Regimen Complexity Index was used at each time point as a comparator. Medications for anemia, mineral and bone disorders (MBD), cardiovascular (CV) disease, infection, and vitamins were analyzed for number of medications and pill burden. Thirty-five patients were included. Patients used 10.5 ± 4.4 medications at baseline and 11.8 ± 4.7 at the end of the study (P=NS). Regarding the number of medications, anemia medications, anti-infectives, and vitamins increased; MBD and CV medications decreased by the end of the study. Total pill burden did not change over 24 months, nor did anemia pill burden. Mineral bone disorder and CV pill burden decreased, and vitamins and anti-infective pill burden increased. Daily medication administration times decreased significantly from 5.0 ± 1.5 to 3.6 ± 1.5 by 24 months. Switching to NHHD was associated with a significant increase in Medication Regimen Complexity Index at 24 months (P<0.05). SF-36 scores increased significantly once patients began on NHHD. No measure of medication regimen complexity was correlated with the SF-36 score. Medication burden changes over time after starting NHHD. It is unknown what effect NHHD has on adherence or medication costs, and warrants further study in a prospective comparative investigation.     

Quality of life of end-stage renal disease patients and study on the implementation of nocturnal home hemodialysis in Greece

The aim of this study was to measure the overall health-related quality of life of patients receiving hemodialysis in Greece and to assess willingness, motivation, and concerns about participating in a nocturnal home hemodialysis program. This review measured successfully the quality of life of 146 end-stage renal disease (ESRD) patients undergoing hemodialysis in 10 hemodialysis centers all over Greece and studied the factors that affect their choice to adopt a specific treatment. Physical and mental health status and health-related quality of life, measured by the Kidney Disease Quality of Life Short Form accompanied by the demographic data gathered, provide information that can help to improve ESRD patient care in Greece. A comparison with the Greek general population identifies lower physical functioning scores for the ESRD patients, while the mental functioning scores are comparable with those of the Greek general population. Moreover, it is important to notice the willingness expressed by half of the patients to participate in a potential program of nocturnal home hemodialysis.     

Calcium phosphate formation induced on silica in bamboo

The effect of in vitro induction of calcium phosphate on bamboo surfaces is reported for the first time. Bamboo is studied for biomaterial application due to its elasticity modulus being closer to human bone than other biomaterials. Following an earlier study of cytotoxicity and precipitation of apatite on ground tissue and vascular bundles of bamboo, the composition and function of the minerals in bamboo, especially silica, are considered in the present work. It is found that in both outer and inner surfaces of bamboo culm, there exists some silica. Bamboo elicits an inert response when soaked directly in calcification solution. After the rind of bamboo is treated with sodium hydroxide solution, the silica underneath can induce precipitation of calcium phosphate in an ambient environment. Furthermore, by subsequent grafting with polyethylene glycol (PEG 1000), calcium phosphate induction of bamboo rind can be improved, depending on the concentration of NaOH solution and treatment time. Heat treatment of bamboo can remove the organic materials around the minerals in bamboo, allowing the calcification behaviour of the silica-containing inorganic phase of bamboo in aqueous solution to be studied.     

Effect of phosphate binders on oxidative stress and inflammation markers in hemodialysis patients

It has been suggested that phosphate binders may reduce the inflammatory state of hemodialysis (HD) patients. However, it is not clear whether it has any effect on oxidative stress. The objective of this study was to evaluate the effect of sevelamer hydrochloride (SH) and calcium acetate (CA) on oxidative stress and inflammation markers in HD patients. Hemodialysis patients were randomly assigned to therapy with SH (n=17) or CA (n=14) for 1 year. Before the initiation of therapy (baseline) and at 12 months, we measured in vitro reactive oxygen species (ROS) production by stimulated and unstimulated polymorphonuclear neutrophils and serum levels of tumor necrosis factor α, interleukin-10, C-reactive protein, and albumin. There was a significant reduction of spontaneous ROS production in both groups after 12 months of therapy. There was a significant decrease of Staphylococcus aureus stimulated ROS production in the SH group. There was a significant increase in albumin serum levels only in the SH group. In the SH group, there was also a decrease in the serum levels of tumor necrosis factor α and C-reactive protein. Our results suggest that compared with CA treatment, SH may lead to a reduction in oxidative stress and inflammation. Therefore, it is possible that phosphate binders exert pleiotropic effects on oxidative stress and inflammation, which could contribute toward decreasing endothelial injury in patients in HD.     

声电化学法在炭织物表面制备的磷酸钙涂层及其对成骨细胞活性的影响

为了研究炭纤维增强羟基磷灰石(HA)复合材料对骨修复的影响,采用声电化学沉积法在炭纤维织物表面直接制备磷酸钙涂层。电解液为含钙、磷离子的溶液,初始pH值4.7,沉积温度50℃。借助红外光谱、扫描电子显微镜及能谱分析对涂层的结构、形貌、组分就行了研究,并选择人类成骨细胞(MG63)检测了材料的体外细胞相容性。结果表明,超声波的迭加使用改变了磷酸钙沉积层的组分和形貌,与传统的电化学工艺相比更具优势。MTS检测证明,用声电法沉积的磷酸盐涂层更大幅度地提高了成骨细胞的附着和增殖。     

Clinical Experiences High‐flux hemodialysis in the treatment of severe valproic acid overdose: A case report

Introduction:  Hemoperfusion, with or without hemodialysis, has been used to treat patients suffering from severe valproic acid poisoning. We report a patient suffering from severe valproic acid intoxication who was treated effectively with high‐flux hemodialysis alone. Case:  A 20‐year‐old man with a history of bipolar disorder was admitted after having ingested unknown amounts of valproic acid (Depakote®), prednisone, and erythromycin. He was agitated and obtunded but hemodynamically stable initially. Serum valproic acid level was 1,028 μg/mL. Urine toxicology screen as well as serum levels of ethanol, acetaminophen, and acetylsalicylic acid levels were negative. A gastric lavage was followed by activated charcoal instillation. Subsequent myoclonic twitchings that progressed to continuous seizure activity were managed with intravenous lorazepam therapy and endotracheal intubation. Serum valproic acid value measured two hours after admission remained elevated at 1,046 μg/mL. Hemodialysis was performed continuously for 10.5 hours using a high‐flux, polysulfone dialyzer (Polyflux 21S, Fresenius Medical Care, Lexington, MA), a dialyzer blood flow of 200–300 mL/min, and a dialysate flow of 500 mL/min. The therapy brought about a fall in serum valproic acid level to 110 μg/mL and a complete recovery of the patient. Discussion:  Valproic acid (144 Dalton) is 90–95% protein‐bound at therapeutic serum values. However, in the face of an overdose, the unbound fraction rises because of saturation of protein‐binding sites. This unbound fraction is readily dialyzable. We suggest that high‐flux hemodialysis is effective in the treatment of severe valproic acid poisoning.     

Hypertension and left ventricular mass index (L.VMI) in patients on regular hemodialysis (RDT)

Background:  Because of high incidence of acquired renal cyst and renal malignancy, it is suggested that spontaneous renal rupture more frequently occurs in patients receiving long‐term hemodialysis than in the general population. This study was performed to evaluate the clinical characteristics of spontaneous renal rupture in hemodialysis patients. Methods:  This retrospective study enrolled 12 hemodialysis patients who developed spontaneous renal rupture. We investigated primary renal disease, duration of dialysis, clinical symptoms and signs, radiologic findings, treatment modalities, and histologic findings. Result:  The mean age of the patients was 54 ± 10 years old and the number of male was 9. Primary renal disease consisted of autosomal dominant polycystic kidney disease (PCKD)(n = 5), chronic glomerulonephritis (n = 2), diabetic nephropathy (n = 1), hypertensive nephropathy (n = 1), unknown cause (n = 3). Presenting symptoms and signs were sudden onset of flank pain in 9 patients and gross hematuria with mild flank pain in 3 patients. Mean duration from initiation of hemodialysis to development of spontaneous renal rupture was 53 ± 36 months. Abdominal computed tomography showed subcapsular or perinephric hematoma in all patients. Of the 7 non‐PCKD patients, 6 patients had multiple acquired renal cysts. Surgical exploration was undertaken in 9 patients. Pathologic examination demonstrated small sized renal cell carcinoma in 2 of 9 patients. Three patients were only treated with conservative management including blood transfusion. All 12 patients recovered without recurrence. Conclusion:  This study demonstrated that genetic or acquired renal cyst was an important cause of spontaneous renal rupture in hemodialysis patients and presenting manifestations were sudden onset of flank pain and gross hematuria.     

Calcium phosphate formation on plasma immersion ion implanted low density polyethylene and polytetrafluorethylene surfaces

The flexible structure of polymers has enabled them to be useful in a wide variety of medical applications due to the possibility to tailor their properties to suit desired applications. For a long time, there has been an increasing interest in utilizing polymers as matrices for calcium phosphate-based composites with applications in hard tissue implants. On the other side, polymers with application as heart valves, urea catheters and artificial vessels present a case where the formation of minerals (namely calcification) should be avoided. The modification of polymer surfaces by various ion beam treatments for reducing the calcification, as for example plasma immersion ion implantation (PIII), is well known and has a long time effect. This work is part of a wider investigation of the ability of plasma immersion ion implanted polymers to induce calcium phosphate formation from an aqueous solution resembling the human blood plasma. In the experiment described in this paper, topographical and chemical changes were inserted on the surfaces of two conventional polymers (low density polyethylene and polytetrafluorethylene) by PIII with nitrogen ions, and under conditions mimicking the natural mineral formation processes. The effect of the plasma modification on the calcium phosphate nucleation and growth from the aqueous solution was ambiguous. We suppose that the complex combination of surface characteristics influenced the ability of the plasma treated polymer films to induce the formation of a calcium phosphate layer.     

Microhardness studies on calcium hydrogen phosphate (brushite) crystals

Vicker's and Knoop microhardness studies were carried out on grown calcium hydrogen phosphate dihydrate (CaHPO₄·2H₂O) crystals over a load range of 10-50 g. The Vickers (H_V) and Knoop (H_K) microhardness numbers for the above loads were found to be in the range of 94-170 kg/mm² and 28-35 kg/mm² respectively. It was also found that these numbers increased with increase in load. The Mayer's index (n) was found to be greater than 1.6 showing soft-material characteristics. The fracture toughness values (K_c), determined from measurements of crack length, were estimated to be 6 ± 0.5 × 10³ kg m^−3/2 and 4.5 ± 0.5 × 10³ kg m^−3/2 at 25 g and 50 g respectively. The brittleness indices (B_i) were found as 2.3 ± 0.1 × 10⁴ m^−1/2 for 25 g and 3.7 ± 0.1 × 10⁴ m^−1/2 for 50 g. Using Wooster's empirical relation, the elastic stiffness coefficient (c₁₁) has been calculated from Vicker's hardness values as 4.8 ± 0.5 × 10¹⁵ Pa for 10 g, 9.7 ± 0.5 × 10¹⁵ Pa for 25 g and 13.3 ± 0.5 × 10¹⁵ Pa for 50 g. The Young's modulus was calculated as 1.5 ± 0.1 × 10¹⁰ N m⁻² from Knoop microhardness values.     

Arsenic removal by adsorption on iron(III) phosphate

Under natural conditions, arsenic is often associated with iron oxides and iron(III) oxidative capacity towards As(III) is well known. In this study, As(III) and As(V) removal was performed using synthesised iron(III) phosphate, either amorphous or crystalline. This solid can combine (i) As(III) oxidation by iron(III) and (ii) phosphate substitution by As(V) due to their similar properties. Results showed that adsorption capacities were higher towards As(III), leading to Fe2+ and HAsO4(2-) leaching. Solid dissolution and phosphate/arsenate exchange led to the presence of Fe3+ and PO4(3-) in solution, therefore various precipitates involving As(V) can be produced: with Fe2+ as Fe3(AsO4)2.8H2O(s) and with Fe3+ as FeAsO4.2H2O(s). Such formations have been assessed by thermodynamic calculations. This sorbent can be a potential candidate for industrial waste treatment, although the high release of phosphate and iron will exclude its application in drinking water plants.     

Morphosynthesis of Calcium Carbonate in Poly(vinylalcohol)

In situ synthesis of calcium carbonate particles has been carried out in poly(vinylalcohol) solution and physical gels under free drift conditions. A multitude of morphologies, ranging from spherulites to helical structures of calcite, are produced by systematically varying the polymer concentration both in solution as well as in gels.     

Calcium phosphate silicate ceramics for heavy metal immobilization and antibacterial activity in waste water

In the present work we have prepared a hydroxyapatite (HA)–silica porous ceramic material for the immobilization of heavy metals (Pb, Cd, Zn). This material, shaped as Raschig rings, is obtained by extrusion starting from urban and industrial wastes. Additionally, it has been proved that when Ag or Cu is added over the rings surfaces, these ceramics also have a bactericidal activity.     

Rb ion-exchange profile in potassium titanyl phosphate (KTP)

The Rb depth profiles in KTP as a function of ion-exchange duration in rubidium nitrate (RbNO₃) melts with small concentrations of Ba(NO₃)₂ in the melt have been studied by using Rutherford backscattering (RBS). The data indicate that small Ba concentrations have a major effect on the incorporation of Rb and its distribution in the KTP. The results also show the effect of the Ba impurity in Rb ion-exchange is a function of the duration of exchange and varies substantially as the impurity concentration increases. The ion-exchange of pure Rb shows a possible formation of a diffusion barrier which leads to a lesser near-surface concentration as the exchange duration increases. A small concentration of Ba removes this diffusion barrier.     

The carbon footprints of home and in‐center maintenance hemodialysis in the United Kingdom

Climate change presents a global health threat. However, the provision of healthcare, including dialysis, is associated with greenhouse gas emissions. The aim of this study was to determine the carbon footprints of the differing modalities and treatment regimes used to deliver maintenance hemodialysis (HD), in order to inform carbon reduction strategies at the level of both individual treatments and HD programs. This was a component analysis study adhering to PAS2050. Emissions factors were applied to data that were collected for building energy use, travel and procurement. Thrice weekly in‐center HD has a carbon footprint of 3.8 ton CO₂ Eq per patient per year. The majority of emissions arise within the medical equipment (37%), energy use (21%), and patient travel (20%) sectors. The carbon footprint of providing home HD varies with the regime. For standard machines: 4 times weekly (4 days, 4.5 hours), 4.3 ton CO₂ Eq; 5 times weekly (5 days, 4 hours), 5.1 ton CO₂ Eq; short daily (6 days, 2 hours), 5.2 ton CO₂ Eq; nocturnal (3 nightly, 7 hours), 3.9 ton CO₂ Eq; and nocturnal (6 nightly, 7 hours), 7.2 ton CO₂ Eq. For NxStage equipment: short daily (5.5 days, 3 hours), 1.8 t CO₂ Eq; 6 nightly nocturnal (2.1 ton CO₂ Eq). The carbon footprint of HD is influenced more by the frequency of treatments than by their duration. The anticipated rise in the prevalence of home HD patients, dialyzing more frequently and for longer than in‐center patients, will increase the emissions associated with HD programs (despite reductions in patient travel emissions). Emerging technologies, such as NxStage, might offer a solution to this problem.