Role of Vitamin K in CKD: Is Its Supplementation Advisable in CKD Patients?

BACKGROUND: Patients with CKD are at an increased risk of developing vascular calcification (VC) and bone complications which translate into a higher morbidity and mortality. The dephosphorylated and uncarboxylated matrix Gla protein (dp-ucMGP) is considered to be an indicator of vitamin K2 status and correlates with markers of VC. It is activated by γ-glutamyl carboxylase that converts inactive MGP into an active form, and vitamin K2 is a cofactor of this reaction. The active form of MGP is a known inhibitor of arterial wall calcification and plays an important role in bone turnover. Recent studies show poor vitamin K2 status in CKD patients. We aimed to review the literature for the association between vitamin K2 status and calcification and bone disease risk and the efficacy of vitamin K2 supplementation in CKD population. SUMMARY: Most CKD patients, including those on renal replacement therapy, have vitamin K2 deficiency. The dp-ucMGP level, a marker of vitamin K2 status, is decreased by vitamin K2 supplementation in CKD patients, but there is no unequivocal proof that it influences arterial calcification progression and bone complications. Key Messages: CKD population are at risk of vitamin K deficiency. Supplementation of vitamin K2 is safe and improves the serum markers of its deficiency. There is lack of strong evidence that vitamin K2 supplementation slows progression of calcification or reduces the frequency of bone complications. More prospective studies are needed.

Aberrant serum parathyroid hormone, calcium, and phosphorus as risk factors for peritonitis in peritoneal dialysis patients.

Identifying modifiable risk factors of peritoneal dialysis (PD)-related peritonitis is of clinical importance in patient care. Mineral bone disease (MBD) has been associated with mortality and morbidity in end-stage kidney disease (ESKD) patients. However, its influence on PD related peritonitis due to altered host immunity remains elusive. This study investigated whether abnormal biomarkers of MBD are associated with the development of peritonitis in patients undergoing maintenance PD. We conducted a retrospective observational cohort study, analysing data derived from a nationwide dialysis registry database in Taiwan, from 2005 to 2012. A total of 5750 ESKD patients commencing PD therapy during this period were enrolled and followed up to 60 months or by the end of the study period. The patients were stratified based on their baseline serum parathyroid hormone (PTH) levels, calcium (Ca) levels or phosphorus (P) levels, respectively or in combinations. The primary outcome was the occurrence of first episode of peritonitis, and patient outcomes such as deaths, transfer to haemodialysis or receiving renal transplantation were censored. Peritonitis-free survival and the influence of PTH, Ca, P (individual or in combination) on the peritonitis occurrence were analysed. A total of 5750 PD patients was enrolled. Of them, 1611 patients experienced their first episode of peritonitis during the study period. Patients with low PTH, high Ca or low P levels, respectively or in combination, had the lowest peritonitis-free survival. After adjusting for age, sex and serum albumin levels, we found that the combinations of low PTH levels with either high Ca levels or low/normal P levels were significant risk factors of developing peritonitis. Abnormal mineral bone metabolism in maintenance PD patients with low serum PTH levels, in combination with either high Ca levels or low/normal P levels, could be novel risk factors of PD-related peritonitis.

Nutritional vitamin D in CKD: Should we measure? Should we treat?

Vitamin Ddeficiency is frequently present in patients affected by chronic kidney disease (CKD). Experimental studies demonstrated that Vitamin D may play a role in the pathophysiology of diseases beyond mineral bone disorders in CKD (CKD-MBD). Unfortunately, the lack of large and interventional studies focused on the so called "non-classic" effects of 25(OH) Vitamin D supplementation in CKD patients, doesn't permit to conclude definitely about the beneficial effects of this supplementation in clinical practice. In conclusion, treatment of nutritional vitamin D deficiency in CKD may play a central role in both bone homeostasis and cardiovascular outcomes, but there is not clear evidence to support one formulation of nutritional vitamin D over another in CKD.

Seasonal variation of serum 25-hydroxyvitamin D and parameters of bone and mineral disorder in dialysis patients.

BACKGROUND: Vitamin D deficiency is common among dialysis patients and may impact blood concentrations of calcium, phosphorus, intact parathyroid hormone (iPTH), and alkaline phosphatase (ALP). Seasonal variation of serum 25-hydroxyvitamin D [25(OH)D] concentrations has been well established for the general population; however, less is known about circannual variation in 25(OH)D as well as other parameters of mineral and bone disorder among dialysis patients. METHOD: Based on 57,500 serum 25(OH)D measurements collected over two years from January 2009 to December 2010 among 25,025 dialysis patients, we evaluated the circannual variations in serum concentrations of 25(OH)D, calcium, phosphorus, iPTH, and ALP by a linear regression model with a cosinor function for the time period (month). We adjusted for potential confounders including case-mix variables, and ultraviolet index. RESULTS: Serum 25(OH)D concentrations showed significant circannual variation and mean serum 25(OH)D was 3.2 ng/mL higher in summer than in winter. Furthermore, 25(OH)D concentration increased steadily by 1.3 ng/mL per year. While serum calcium concentrations showed statistically significant but clinically negligible seasonal variation (0.02 mg/dL in peak-trough difference), serum phosphorus did not follow such a pattern. Serum iPTH concentrations also showed a modest seasonal variation with 9% higher values in winter than in summer. Concordantly, ALP concentrations in the winter were 2% higher than in the summer time. Seasonal variation of 25(OH)D was greater in male (vs. female), African-American (vs. non-African-American), and younger (vs. older) dialysis patients. CONCLUSION: Serum 25(OH)D and iPTH concentrations show seasonal variation among dialysis patients while the variation in other parameters of mineral and bone disorder was clinically irrelevant, if any. Serum 25(OH)D also showed a gradual increase over time. Clinicians and researchers should be aware of these changes when interpreting laboratory results in dialysis patients.

Response of serum 25(OH)D to Vitamin D and calcium supplementation in school-children from a semi-rural setting in India.

The objectives of this study were to: 1) Determine the impact of varying baseline serum 25OHD on increase in vitamin D concentrations after daily supplementation with vitamin D and calcium (1000 IU + 500 mg respectively) for six months in school-children from a semi-rural setting 2) Test the efficacy of daily vitamin D-calcium supplementation on improvement in serum vitamin D concentrations to ≥75 nmol/L. Data collected from 106 subjects (58 boys, 48 girls), aged 6-12 years, included anthropometric measures like height and weight, body composition analysis, three one-day dietary recalls and sunlight exposure (by questionnaire). Blood was collected at baseline and endline and estimated for serum vitamin D by ELISA technique using standard kits. Classification of Vitamin D status was performed according to the 2011 Endocrine Society Practice Guidelines: vitamin D deficiency - <50 nmol/L; insufficiency - 50.0-74.9 nmol/L; sufficiency - ≥75 nmol/L. Statistical analysis was performed using SPSS software. Mean baseline serum vitamin D concentration was 59.7 ±â€¯11.2 nmol/L; this rose to 79.8 ±â€¯23.3 nmol/L with no significant differences between genders at the two time-points. Inverse relationship was obtained between baseline serum 25(OH)D concentrations and change in serum concentrations after supplementation, implying that with increasing baseline serum concentrations of 25(OH)D, increase in vitamin D levels post supplementation were significantly lower (r = - 0.96, p < 0.0001). Greatest benefit of change in serum vitamin D concentrations after supplementation was experienced by children with basal concentrations of <45 nmol/L. Daily vitamin D supplementation was effective in improving serum 25(OH)D to ≥75 nmol/L in 44% of children. Significantly higher percentage of children who were deficient at baseline (64%) were able to attain serum concentrations of ≥75 nmol/L as compared to children who were vitamin D insufficient (43%) (p < 0.001). Thus, daily supplementation with 1000 IU of vitamin D along with 500 mg of calcium helped in improving serum vitamin D concentrations to ≥75 nmol/L. Children who were vitamin D deficient particularly experienced these benefits.

Serum 25-Hydroxyvitamin D Insufficiency in Search of a Bone Disease.

Context: Vitamin D "insufficiency" and "deficiency" are defined as serum 25-hydroxyvitamin D [25(OH)D] levels <75 and <30 nmol/L, respectively. We aimed to determine whether these values signal hypocalcemia and hypophosphatemia, secondary hyperparathyroidism, high bone remodeling, low areal bone mineral density (aBMD), microstructural deterioration, or reduced matrix mineralization density (MMD) and so suggest whether bone fragility is present. Methods: Concentrations of 25(OH)D, calcium, phosphate, creatinine, and parathyroid hormone (PTH) were measured in 11,855 participants. Serum C-terminal telopeptide of type 1 collagen, procollagen type 1 N-terminal propeptide (P1NP), aBMD, and distal radius microstructure and MMD were measured in a second subset of 150 participants. Results: A breakpoint for calcium, PTH, and alkaline phosphatase was identified at a threshold 25(OH)D level <30 nmol/L. There was no plateau beyond 75 nmol/L. In the subgroup with measurements of bone morphology, no associations were detectable between serum 25(OH)D concentration, aBMD, trabecular density, cortical porosity, or MMD. Among 1439 participants with serum 25(OH)D <30 nmol/L, 6.1% had low serum calcium, 3.4% had low serum phosphate, 6.1% had high alkaline phosphatase, and 34.2% had elevated PTH. Most participants did not have any abnormalities. Conclusion: At a 25(OH)D threshold of ≤30 nmol/L, abnormalities in biochemical features support the notion of a "deficiency" state predisposing to bone disease. However, no deleterious effects were found in participants within an insufficiency threshold of a 25(OH)D level of 30 to 75 nmol/L, which challenges the rationale justifying vitamin D supplementation in these individuals.

Unexpected widespread hypophosphatemia and bone disease associated with elemental formula use in infants and children.

OBJECTIVE: Hypophosphatemia occurs with inadequate dietary intake, malabsorption, increased renal excretion, or shifts between intracellular and extracellular compartments. We noticed the common finding of amino-acid based elemental formula [EF] use in an unexpected number of cases of idiopathic hypophosphatemia occurring in infants and children evaluated for skeletal disease. We aimed to fully characterize the clinical profiles in these cases. METHODS: A retrospective chart review of children with unexplained hypophosphatemia was performed as cases accumulated from various centres in North America and Ireland. Data were analyzed to explore any relationships between feeding and biochemical or clinical features, effects of treatment, and to identify a potential mechanism. RESULTS: Fifty-one children were identified at 17 institutions with EF-associated hypophosphatemia. Most children had complex illnesses and had been solely fed Neocate® formula products for variable periods of time prior to presentation. Feeding methods varied. Hypophosphatemia was detected during evaluation of fractures or rickets. Increased alkaline phosphatase activity and appropriate renal conservation of phosphate were documented in nearly all cases. Skeletal radiographs demonstrated fractures, undermineralization, or rickets in 94% of the cases. Although the skeletal disease had often been attributed to underlying disease, most all improved with addition of supplemental phosphate or change to a different formula product. CONCLUSION: The observed biochemical profiles indicated a deficient dietary supply or severe malabsorption of phosphate, despite adequate formula composition. When transition to an alternate formula was possible, biochemical status improved shortly after introduction to the alternate formula, with eventual improvement of skeletal abnormalities. These observations strongly implicate that bioavailability of formula phosphorus may be impaired in certain clinical settings. The widespread nature of the findings lead us to strongly recommend careful monitoring of mineral metabolism in children fed EF. Transition to alternative formula use or implementation of phosphate supplementation should be performed cautiously with as severe hypocalcemia may develop.

High Prevalence of Suboptimal Vitamin D Status and Bone Loss in Adult Short Bowel Syndrome Even After Weaning Off Parenteral Nutrition.

BACKGROUND: Previous studies have noticed the high incidence of suboptimal vitamin D (VtD) status and bone loss in short bowel syndrome (SBS) with parenteral nutrition (PN) dependence. However, limited data have focused on adult SBS without PN dependence. Therefore, our objective was to investigate the incidence and risk factors of suboptimal VtD status and bone loss in adult SBS even after weaning off PN. MATERIALS AND METHODS: We performed a prospective study of 60 adult patients with SBS. Serum 25-hydroxyvitamin D (25-OHD) was measured by radioimmunoassay. Bone mineral density (BMD) was measured using dual-energy x-ray absorptiometry (DEXA). Medical records and various laboratory parameters were collected in all participants. RESULTS: Suboptimal VtD status was identified in all individuals, including 3 (5.0%) with VtD insufficiency and 57 (95.0%) with VtD deficiency. Residual small bowel length (B, 0.072, P = .001) and duration of SBS (B, -0.066, P = .020) were both significantly correlated with suboptimal VtD levels. Overall, only 2 patients presented a normal BMD; osteopenia and osteoporosis were noted in 41 (68.3%) and 17 (28.3%) individuals, respectively. Low 25-OHD concentration was associated with a decreased BMD (B, 0.065, P = .029). There were no other demographic characteristics or clinical examinations associated with suboptimal VtD levels and bone loss. CONCLUSION: Suboptimal VtD status and bone loss were common in adult SBS even after weaning off PN. Despite routine oral VtD supplementation, most patients did not achieve satisfactory status. This emphasizes the critical importance of routine surveillance of 25-OHD and BMD, as well as consideration of alternative methods of supplementation after weaning off PN.

Bone status in preterm infant: influences of different nutritional regimens and possible markers of bone disease.

OBJECTIVE: The objective of this study was to evaluate possible influences of parenteral nutrition on growth and bone development in preterms and to search for markers of bone status. STUDY DESIGN: Metacarpus bone transmission time (mc-BTT) was performed at birth, 21 days and 36 weeks of gestational age (GA) in preterms, receiving two different nutritional regimens, together with biochemical analysis. RESULT: A total of 234 patients were studied. Newborns with aggressive nutrition had significantly better growth rate and higher values of mc-BTT until discharge. Mc-BTT at day 21 correlates positively with nutritional intakes and phosphatemia; lower limb length positively correlated with mc-BTT (P<0.01). Newborns with low energy intake in the first week of life (<70 kcal kg(-1) per day) and low serum phosphate level (<1.4 mmol l(-1)) at 21 days had lower mc-BTT at 36 weeks of GA (P<0.01). CONCLUSION: Aggressive parenteral intakes in preterms improve growth and bone status in the short-medium term, suggesting that early nutrition could influence bone development.

Short- and long-term impact of subtotal parathyroidectomy on the achievement of bone and mineral parameters recommended by clinical practice guidelines in dialysis patients: a 12-year single-center experience.

BACKGROUND/AIMS: The short- and long-term impact of parathyroidectomy (PTX) on the parameters of mineral bone disease in dialysis patients with severe secondary hyperparathyroidism (HPT) remains unclear. METHODS: A retrospective chart review of 401 consecutive dialysis patients who underwent subtotal PTX by one surgeon was performed. We checked serum levels of calcium (Ca), phosphorus (P), and intact parathyroid hormone (iPTH) for 3 consecutive days, and then monthly for Ca, P, and tri-monthly for iPTH postoperatively. Patients with available laboratory data within the 1st to 6th postoperative months were included in the short-term follow-up group and those with at least 6 months available data were in the long-term follow-up one. RESULTS: Patients (short-term group, n = 401, and long-term group, n = 94) had severely uncontrolled serum iPTH levels, Ca, P and Ca × P before PTX. In the short-term group, percentages of cases achieving K/DOQI targets for serum Ca, Ca × P, and iPTH and KDIGO ones for serum Ca, P, and iPTH after PTX, significantly improved compared with those before operation (all p < 0.05). In the long-term group (mean follow-up of 43 ± 29 months), the percentage of achieved targets for serum iPTH in both guidelines and for serum Ca and Ca × P in the K/DOQI recommendation also improved postoperatively (all p < 0.05). CONCLUSIONS: Achievements of K/DOQI recommended values for serum Ca, Ca × P, iPTH and KDIGO recommendations for iPTH can be successfully reached by subtotal PTX in medically refractory, secondary HPT in dialysis patients both during short- and long-term follow-ups.

Mineral and bone disorder in Chinese dialysis patients: a multicenter study.

BACKGROUND: Mineral and bone disorder (MBD) in patients with chronic kidney disease is associated with increased morbidity and mortality. Studies regarding the status of MBD treatment in developing countries, especially in Chinese dialysis patients are extremely limited. METHODS: A cross-sectional study of 1711 haemodialysis (HD) patients and 363 peritoneal dialysis (PD) patients were enrolled. Parameters related to MBD, including serum phosphorus (P), calcium (Ca), intact parathyroid hormone (iPTH) were analyzed. The achievement of MBD targets was compared with the results from the Dialysis Outcomes and Practice Study (DOPPS) 3 and DOPPS 4. Factors associated with hyperphosphatemia were examined. RESULTS: Total 2074 dialysis patients from 28 hospitals were involved in this study. Only 38.5%, 39.6% and 26.6% of them met the Kidney Disease Outcomes Quality Initiative (K/DOQI) defined targets for serum P, Ca and iPTH levels. Serum P and Ca levels were statistically higher (P < 0.05) in the HD patients compared with those of PD patients, which was (6.3 ± 2.1) mg/dL vs (5.7 ± 2.0) mg/dL and (9.3 ± 1.1) mg/dL vs (9.2 ± 1.1) mg/dL, respectively. Serum iPTH level were statistically higher in the PD patients compared with those of HD patients (P = 0.03). The percentage of patients reached the K/DOQI targets for P (37.6% vs 49.8% vs 54.5%, P < 0.01), Ca (38.6% vs 50.4% vs 56.0%, P < 0.01) and iPTH (26.5% vs 31.4% vs 32.1%, P < 0.01) were lower among HD patients, compared with the data from DOPPS 3 and DOPPS 4. The percentage of patients with serum phosphorus level above 5.5 mg/dL was 57.4% in HD patients and 47.4% in PD patients. Age, dialysis patterns and region of residency were independently associated with hyperphosphatemia. CONCLUSIONS: Status of MBD is sub-optimal among Chinese patients receiving dialysis. The issue of hyperphosphatemia is prominent and needs further attention.

Bone microarchitecture is more severely affected in patients on hemodialysis than in those receiving peritoneal dialysis.

We used high-resolution quantitative computed tomography to study the microarchitecture of bone in patients with chronic kidney disease on dialysis. We compared bone characteristics in 56 maintenance hemodialysis (21 women, 14 post-menopausal) and 23 peritoneal dialysis patients (9 women, 6 post-menopausal) to 79 healthy men and women from two cohorts matched for age, body mass index, gender, and menopausal status. All underwent dual-energy X-ray absorptiometry of the spine and hip to measure areal bone mineral density, and high-resolution peripheral quantitative computed tomography of the radius and tibia to measure volumetric bone mineral density and microarchitecture. When compared to their matched healthy controls, patients receiving hemodialysis and peritoneal dialysis had a significantly lower areal bone mineral density in the hip. Hemodialysis patients had significantly lower total, cortical, and trabecular volumetric bone mineral density at both sites. Hemodialysis patients had significantly lower trabecular volumetric bone mineral density and microarchitecture at the tibia than the peritoneal dialysis patients. Overall, peritoneal dialysis patients were less affected, their cortical thickness at the distal tibia being the only significant difference versus controls. Thus, we found more severe trabecular damage at the weight-bearing tibia in hemodialysis compared to peritoneal dialysis patients, but this latter finding needs confirmation in larger cohorts.

Interventions for bone disease in children with chronic kidney disease.

BACKGROUND: Bone disease is common in children with chronic kidney disease (CKD) and when untreated may result in bone deformities, bone pain, fractures and reduced growth rates. OBJECTIVES: To investigate the benefits and harms of interventions for preventing and treating bone disease in children with CKD. SEARCH STRATEGY: The Cochrane Renal Group's specialised register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, reference lists and abstracts were searched without language restriction. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing different interventions used to prevent or treat bone disease in children with CKD stages 2-5D compared with placebo, no treatment or other agents were included. Studies examining different routes or frequency of treatment were also included. DATA COLLECTION AND ANALYSIS: Data were extracted by two authors. The random-effects model was used and results were reported as risk ratios or risk differences for dichotomous outcomes and mean differences for continuous outcomes with 95% confidence intervals. MAIN RESULTS: Fifteen RCTs (369 children) were identified. Compared with oral calcitriol, intraperitoneal calcitriol significantly reduced the level of serum parathyroid hormone (PTH) but there were no significant differences in bone histology or other biochemical measures (2 RCTs). There were no significant differences detected in growth, PTH, serum calcium or phosphorus between daily versus intermittent calcitriol (3 RCTs). Vitamin D therapy significantly reduced PTH levels compared with placebo or no treatment. The number of children with hypercalcaemia did not differ significantly between groups (4 RCTs). No significant differences were detected in growth rates, bone histology or biochemical parameters between calcitriol and either dihydrotachysterol or ergocalciferol (2 RCTs). Though fewer episodes of hypercalcaemia were reported with sevelamer, no significant differences were detected in serum calcium, phosphorus and PTH levels between calcium-containing phosphate binders and either aluminium hydroxide or sevelamer (4 RCTs). AUTHORS' CONCLUSIONS: Bone disease, assessed by changes in PTH levels, is improved by all vitamin D preparations. However no consistent differences between routes of administration, frequencies of dosing or vitamin D preparations have been demonstrated. Though fewer episodes of high calcium levels occurred with the non calcium-containing binder, sevelamer, compared with calcium-containing binders, there were no differences in serum phosphorus and calcium overall and phosphorus values were reduced to similar extents. All RCTs were small with few data available on patient-centred outcomes (growth, bone deformities) and limited data on biochemical parameters resulting in considerable imprecision of results thus limiting the applicability to care of children with CKD.

[Effect of Chinese herb medicine compound on bone loss in rats under 3 weeks simulated weightlessness: preliminary study].

OBJECTIVE: To investigate the effect of Chinese herb medicine compound on bone lose in rats under 3 weeks simulated weightlessness, and to observe the synergistic action of other ingredients in the compound on calcium. METHODS: Thirty male Wistar rats were divided into 3 groups: control group, tail-suspend group, tail-suspend and medicine group which took Chinese herb medicine compound (contains Radix Rehmanniae Praeparata, Radix Achyranthis Bidentatae, Radix Astragali, Radix Angelicae Sinensis, Concha Ostreae prepared by acetic acid) by gastric administration. After 3 weeks simulated weightlessness, serum calcium (Ca), phosphorus (P), bone mineral density (BMD) and content (BMC), bone mechanical properties (MEC) were observed. RESULTS: At the end of the experiment, serum Ca and P increased significantly (P<0.01), BMD and BMC of posterior body decreased significantly (P< 0.01) in tail suspend rats, compared with in the control group. In rats of tail suspended and medicine group, the increase degree of serum Ca and P were smaller, BMD and BMC of posterior body increased significantly (P<0.01 or 0.05), and MEC also tend to increase. CONCLUSION: Bone mass of posterior body lose significantly, with mechanical property significantly decrease in rats after 3 weeks simulated weightlessness. Chinese herb medicine compound is effective to prevent the change of bone. Simple calcium supplement can not prevent simulated weightlessness induced bone loss, therefore other ingredients in the compound may perform synergistic action to calcium (Concha Ostreae prepared by acetic acid).

Vitamin D and bone health in adults with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) patients have chronic pancreatic insufficiency leading to malabsorption of fat-soluble vitamins, including vitamin D which can contribute to poor skeletal health and respiratory function. OBJECTIVE: This study evaluated the prevalence of vitamin D insufficiency and its impact on bone and respiratory health in adults with CF. DESIGN AND MEASUREMENTS: This was a retrospective study in which data were collected from medical records over a 2-year period. Data included patient demographics, lung function, biochemical data, bone mineral densities, X-rays and ascertainment of use of vitamin supplements. Data were collected from medical records at a single accredited CF Center. Serum 25-hydroxyvitamin D [25(OH)D] levels and bone mineral density studies were also collected. PATIENTS: A total of 185 adults with CF were identified with a mean age of 29 +/- 9 years. RESULTS: The prevalence of vitamin D insufficiency [25(OH)D < 75 nmol/l] was 76%. Mean serum 25(OH)D concentrations were 58.8 +/- 30 nmol/l. Use of specific vitamin D supplementation was protective against vitamin D insufficiency whereas use of multivitamins was not. There was a small, but significant, positive association between serum 25(OH)D and FEV(1) per cent predicted after controlling for age, gender, BMI and race (R(2) = 0.30, P < 0.001). A high prevalence (27%) of vertebral fractures was detected on lateral chest X-ray. CONCLUSIONS: The prevalence of vitamin D insufficiency and poor skeletal health is high in the US CF population. Vitamin D status appears to be positively associated with lung function. Prospective studies to examine the impact of correction of vitamin D insufficiency on skeletal and lung health in adult CF are warranted.

[Serum hyaluronic acid, tumor necrosis factor -alpha, vascular endothelial growth factor, NO, and Se levels in adult patients with Kashin-Beck disease].

OBJECTIVE: To investigate the association of serum levels of hyaluronic acid (HA), tumor necrosis factor-alpha (TNF-alpha), vascular endothelial growth factor (VEGF), NO, and Se with the clinical manifestations in adult patients with Kashin-Beck disease (KBD). METHODS: Total 216 adults were selected for KBD screening from the KBD-prevalent areas in Yongshou county and the non-KBD areas of Chang'an county, Xi'an city, ShaanXi Province. According to the National Diagnostic Criteria of Kashin-Beck Disease in China, the diagnoses of KBD was established in 25 adult patients (11 men and 14 women, average age of 47.88+/-11.16 years), and 20 healthy control subjects from the KBD areas (8 men and 12 women, average age of 47.85+/-12.05 years) and 20 from the non-KBD areas (8 men and 12 women, average age of 47.45+/-11.24 years) were also selected to serve as controls. There was no significant difference in the average age and gender distribution between the 3 groups. The serum levels of HA, TNF-alpha, VEGF, NO and Se were measured by enzyme-linked immunosorbent assay, nitrate reductase method and griphite furnace atomic absorption spectrometry. RESULTS: Serum NO level was significantly higher in KBD group (41.7+/-21.89 micromol/L) than in the health controls from KBD areas (17.1+/-13.01 micromol/L) and non-KBD areas (17.58+/-11.48 micromol/l, F=13.11, df=2, P<0.001). Serum TNF-alpha level in KBD group (32.7+/-3.55 pg/ml) was significantly higher than that in the control subjects from the non-KBD areas (30.95+/-2.22 pg/ml, F=3.672, df=2, P=0.031), but similar with the control subjects from the KBD areas (32.7+/-3.55 pg/ml). Serum TNF-alpha and NO levels were identified as the indices that differed between adult KBD patients and the controls from both KBD and non-KBD areas by differential analysis (the function of differentiation was 0.062xNO+0.173xTNF -7.218). CONCLUSION: Serum TNF-alpha and NO levels are significantly increased in adult KBD patients and are associated with the clinical manifestations of KBD.

Assessment of phosphorus and calcium metabolism and its clinical management in hemodialysis patients in the community of Valencia.

AIM: The objective of the study was to determine the situation concerning mineral metabolism and bone disease in hemodialysis (HD) patients living in the community of Valencia (Spain), as well as the clinical practices for bone disease control in relation to the laboratory targets recommended in the National Kidney Foundation Dialysis Outcomes Quality Initiative (K/DOQI) guidelines. METHODS: In December 2003, a cross-sectional study was performed including 2392 patients (1485 males and 907 females) from 43 different centers in the council of Valencia (the entire HD population). Mean age was 65.8 +/- 14 yrs. Cut-off levels for the study of calcium, phosphorus, calcium-phosphorus product (Ca x P) and parathyroid hormone (PTH) were performed following the recommendations of the K/DOQI guidelines. RESULTS: The mean values for calcium were 9.57 +/- 0.7 mg/dL, phosphorus 4.97 +/- 1.5 mg/dL, intact PTH (iPTH) 297 +/- 353 pg/mL, Ca x P 47.5 +/- 15 mg2/dL2. Hypocalcemia (<8.4 mg/dL) was present in 5% of patients, whereas 17.8% of patients presented hypercalcemia (>10.2 mg/dL), 60.3% of whom received vitamin D. Hypophosphoremia (<3.5 mg/dL) was present in 16% of patients, and 29% of patients presented hyperphosphoremia (>5.5 mg/dL). Ca x P was <55 mg2/dL2 in 73% of patients. Thirty one percent of patients presented secondary hyperparathyroidism (HPTH >300 pg/mL), being severe in 12% (>600 pg/mL); 43% of patients presented iPTH <150 pg/mL. Only 7.3% of patients achieved the four recommendations provided in the K/DOQI guidelines. Vitamin D treatment was administered in 48% of patients. CONCLUSIONS: The population undergoing dialysis in the community of Valencia achieved targets based on the clinical recommendations of the K/DOQI guidelines as follows: 45% of patients achieved targets for calcium, 55% for phosphorus, 73% for Ca x P and 26% for iPTH levels. Surprisingly, only 7.3% of patients achieved all four targets.

Does the phosphate binder lanthanum carbonate affect bone in rats with chronic renal failure?

Adequate control of phosphate levels remains an important issue in patients with chronic renal failure (CRF). Lanthanum carbonate has been proposed as a new phosphate binder. Previous studies have shown a high phosphate binding capacity (>97%) and low gastrointestinal absorption of lanthanum, without serious toxic side effects in the presence of a normal renal function (NRF). Because of lanthanum's physicochemical resemblance to calcium, the possible effects of it on bone have to be considered. The aim of this study was to investigate the effects of lanthanum carbonate on bone histology in NRF and CRF rats after oral administration of the compound with doses of 100, 500, or 1000 mg/kg per d for 12 wk. Bone histomorphometry showed that CRF animals that received vehicle developed secondary hyperparathyroidism. Urinalysis of lanthanum-loaded CRF animals showed a dose-dependent decrease in urinary phosphorus excretion, which was clearly more pronounced in the CRF groups compared with NRF animals. Phosphatemia, however, remained normal. Lanthanum carbonate administration induced a dose-dependent decrease in bone formation rate and increase in osteoid area in CRF animals. Three of seven animals in the CRF-1000 group and one of eight animals in the NRF-100 group were classified as having a mineralization defect. The number of cuboidal osteoblasts, however, was not affected, indicating that bone changes were not due to a toxic effect of lanthanum on the osteoblast. Furthermore, lanthanum concentrations in the femur remained low and did not correlate with histomorphometric parameters. These findings suggest that the administration of high doses of phosphate binder (1000 mg/kg per d lanthanum carbonate), in combination with decreased 25-(OH) vitamin D(3) in the uremic state, resulted in phosphate depletion and followed by an increased mobilization of phosphorus out of bone and/or reduced incorporation into bone. There was no evidence that lanthanum had a direct toxic effect on osteoblasts.