B族维生素在肾移植受者高同型半胱氨酸血症及内皮功能异常治疗中的应用

目的探讨B族维生素治疗肾移植受者高同型半胱氨酸血症效果,对内皮功能的影响。方法将36例接受首次肾移植后的高同型半胱氨酸患者,随机分为两组,观察组18例,口服叶酸5mg/d,维生素B650mg/d及维生素B121000μg/d,连续6个月;对照组18例。分别于治疗前和治疗6个月时观察血肌酐水平和肌酐清除率,平均血压值,血胆固醇、甘油三酯和同型半胱氨酸水平变化,应用彩色多普勒超声测定内皮功能。结果观察组患者治疗后同型半胱氨酸与治疗前相比显著降低[(13±4)μmol/L与(20±5)μmol/L,t=5.3,P<0.01];肱动脉反应性充血时内径变化百分率[(12±5)%与(9±5)%,t=2.9,P<0.01]和含服硝酸甘油后肱动脉内径变化百分率[(18±4)%与(12±5)%,t=3.4,P<0.01]均显著增加。其他指标无显著改变。对照组6个月后各项指标与治疗前相比差异无统计学意义;肱动脉反应性充血时内径变化百分率为(9±6)%,含服硝酸甘油后肱动脉内径变化百分率为(12±5)%,均显著低于观察组(t=2.8,P<0.01;t=3.5,P<0.01)。结论应用叶酸、维生素B6及维生素B12能够有效治疗肾移植受者的高同型半胱氨酸血症,并使内皮功能获得明显改善。     

Atorvastatin improves endothelial function in renal-transplant recipients.

BACKGROUND: Hyperlipidaemia and endothelial dysfunction are common features in cyclosporin A (CsA)-treated renal transplant recipients. Endothelial dysfunction may contribute to the risk of premature atherosclerosis and cardiovascular death in these patients. A beneficial effect of statin therapy beyond cholesterol lowering may be an improvement of endothelial function. The present study was designed to assess the effect of atorvastatin on serum lipids and endothelial function in CsA treated renal transplant recipients. METHODS: This pilot study was an open trial of 4 weeks atorvastatin (10 mg per day) treatment in renal transplant recipients (n=22). All patients received a CsA- and prednisolone-based immunosuppressive regimen. Endothelial function was assessed in the forearm skin microvasculature by acetylcholine stimulation and laser Doppler flowmetry, before and after atorvastatin treatment. Serum lipids, plasma endothelin-1 (ET-1), nitric oxide (NO), and von Willebrand factor (vWF) were also measured. RESULTS: Both total and LDL cholesterol were significantly reduced by 26.8 +/- 8.4 and 41.5 +/- 11.0% respectively, after 4 weeks of treatment. Endothelial function was significantly improved during atorvastatin treatment, area under the flux versus time curve (AUC)(ACh) was 538 +/- 362 AU x min before and 682 +/- 276 AU x min after treatment (P=0.042). Plasma NO levels also showed a borderline significant increase from 49 +/- 30 to 57 +/- 37 micromol/l during the treatment period (P=0.051), though plasma ET-1 (0.37+/-0.08 vs 0.37+/-0.12 fmol/ml) and vW (196+/-57 vs 197+/-37%) were unchanged. CONCLUSION: Atorvastatin lowered serum cholesterol significantly and improved endothelial function in renal transplant recipients after 4 weeks of treatment. Plasma NO levels were increased during atorvastatin treatment, indicating a possible endothelial protective effect through an "endothelial-NO pathway".     

Evidence‐based policy on dietary calcium and vitamin D

The Institute of Medicine's report on calcium and vitamin D makes a positive contribution by grounding its recommendations on the available evidence base. The committee does not substantially change recommended dietary intakes for calcium and modestly increases those for vitamin D based on the need for a median serum 25‐hydroxyvitamin D of 40 nmol/L. They do not support the suggestion that all adults should have levels >75 nmol/L. The committee concludes that current evidence does not support nonskeletal benefits for vitamin D or calcium, and notes that higher intakes of both could have adverse health consequences. The present authors are generally in agreement with these conclusions, with some caveats regarding the evidence base used. However, we believe that the central role of sunlight exposure in determining vitamin D status needs to be explicitly reflected in public policy in this area. © 2011 American Society for Bone and Mineral Research.     

Development of a tool for the assessment of calcium and vitamin D intakes in clinical settings

Summary  The study aim was to develop a tool (software and ruler) to assess the dietary calcium and vitamin D intakes in Portugal, and evaluate the usefulness of non-dietary variables as intake predictors. Our findings indicated that is possible to estimate both using three and six food items, respectively, and non-dietary predictors. Introduction  The study aim was to develop a tool to assess the dietary calcium and vitamin D intakes in Portugal, and evaluate the usefulness of non-dietary variables as predictors. Methods  Trained interviewers collected information of 2,414 adults of Porto, Portugal, using a structured questionnaire and a validated semi-quantitative food frequency questionnaire (FFQ). Food items with the highest contribution to the total intake and non-dietary predictors (gender, age and body mass index (BMI)) were selected for the tool. Different statistical approaches were used to predict the intake. A Bland–Altman plot compared the predictions from the tool and the full FFQ. Results  The items selected to predict intake were milk (38%), cheese (12%), yogurt (10%) and gender for calcium and oily fish (39%), canned fish (9%), white fish (7%), eggs (5%), red meat (5%), age and BMI for vitamin D. The Bland–Altman plot showed that the mean differences were 0.0 (limits of agreement = [-220.67; 220.77]) mg/day and 0.0 (limits of agreement = [-1.03; 1.05]) μg/day, respectively for calcium and vitamin D. Conclusion  The equations estimated by the best statistical model to predict the calcium and vitamin D intake allowed for the design of a software and a circular ruler useful in clinical settings.     

Pubertal girls only partially adapt to low dietary calcium intakes.

We evaluated the effects of low calcium in the diets of young adolescent girls. We measured calcium absorption and excretion using stable isotopes. We found partial adaptation to low intakes but a persistent large deficit relative to recommended intakes. Low calcium intakes pose a substantial risk of inadequate calcium retention. INTRODUCTION: A substantial number of adolescent girls in the United States have habitual calcium intakes <500 mg/day (about 40% of the current recommended intake). The ability to adapt to these very low intakes by increasing calcium absorption and decreasing calcium excretion is not known. We sought to determine the effects of recommended (REC-Ca) versus very low (LO-Ca) calcium intakes on calcium absorption and excretion in white and black girls. MATERIALS AND METHODS: Pubertal, but premenarcheal girls, were adapted to low or recommended calcium intakes for at least 2 weeks before each study. Calcium absorption (n = 51) and endogenous fecal calcium excretion (n = 36 of the 51) were determined by dual-tracer stable isotope studies. Subjects were then switched to the other diet for at least 6 weeks, and the study was repeated. RESULTS: Calcium intake was 389 +/- 10 mg/day on LO-Ca and 1259 +/- 35 mg/day on REC-Ca diets. Fractional absorption increased from 44.9 +/- 1.9% on REC-Ca to 63.4 +/- 1.7% on LO-Ca (p < 0.01), but the net calcium absorption remained less than one-half the value on LO-Ca as on REC-Ca. Despite decreases in both endogenous fecal calcium excretion and urinary calcium excretion, net calcium balance was much lower on LO-Ca compared with REC-Ca1 (131 +/- 14 versus 349 +/- 32 mg/day, respectively; p < 0.001). We found significantly lower urinary calcium excretion but not calcium absorption in black girls compared with white girls. CONCLUSIONS: Very low calcium intakes are only partially adapted to by increased absorption and decreased excretion. Very low calcium intakes place both white and black pubertal girls at substantial risk for inadequate calcium retention.     

The potential benefits of dietary and/or supplemental calcium and vitamin D

Osteoporosis is a significant problem in women and men. In addition, as osteoporosis has garnered more attention there should be more attention than ever placed on the potential benefits of calcium and vitamin D. Clinicians need to inform patients that there are numerous healthy dietary sources of calcium and vitamin D. Calcium and vitamin D supplements seem to act synergistically to reduce fracture risk in men and women; therefore, they need to be taken together to impact fracture risk. In addition, almost every randomized trial of an effective osteoporosis drug therapy has utilized calcium and vitamin D to enhance the efficacy of the drug itself. Several forms of calcium supplements are commercially available today and clinicians need to understand the similarities and differences between them. Calcium and vitamin D in moderation also have a good safety profile and may actually have benefits far beyond osteoporosis therapy. For example, calcium may increase high-density lipoprotein (HDL), prevent colon polyps, reduce blood pressure, reduce kidney stone recurrence, and may promote weight loss. Vitamin D may reduce the risk of some cancers, provide an enhanced response to some chemotherapeutic agents, prevent type I diabetes, and may reduce tooth loss along with calcium. Clinicians need to encourage individuals to receive the recommended daily allowance of these two agents because they seem to have an impact on numerous health conditions besides osteoporosis.     

Diagnosis and treatment of prostate cancers in renal-transplant recipients

BACKGROUND: There is no consensus regarding prostate cancer in renal-transplant recipients (RTR). A questionnaire evaluating prostate cancer screening after transplantation and assessing the number, diagnostic modalities, treatment, and outcome of prostate cancer cases was mailed to 22 French renal-transplant centers. RESULTS: Among 1,680 RTR in 1998, 11 (0.65%) cases of prostate cancer were diagnosed, and among the 2,338 recipients followed up, 28 (1%) cases of prostate cancer have been diagnosed and treated. Median ages at diagnosis and at transplantation were 63 and 58, respectively. Clinical stages were T1 50% and T2 25%. Eighteen patients had a Gleason score under 7. At 18 months of mean follow-up, 2 men had died from prostate cancer, and in the curative treatment group, 16 of 17 men were alive with no evidence of disease. CONCLUSIONS: The incidence of prostate cancer in RTR appeared to be higher than expected. Prostate specific antigen (PSA) testing should be performed routinely each year in renal transplantation centers.     

Diagnosis and treatment of prostate cancer in renal-transplant recipients

Introduction  

The incidence and treatment of prostate cancer in male renal-transplant patients has not been extensively evaluated. With the aging of the renal-transplant population, the diagnosis and management of prostate cancer in these patients needs further evaluation.     

Low dose aspirin as prophylaxis against renal-vein thrombosis in renal-transplant recipients.

BACKGROUND: Renal-vein thrombosis (RVT) is an infrequent event that accounts for a high proportion of early renal allograft losses, since graft failure secondary to acute irreversible rejection is now relatively rare. The cause of RVT may be related to technical problems, clotting disorders, diabetes, or cyclosporin, but is often difficult to define. METHODS: This retrospective study was performed to examine the influence of aspirin on the incidence of RVT in cadaveric and living-related renal transplant recipients receiving cyclosporin-based triple immunosuppression. The Oxford Transplant Centre database was used to identify all early (<30 day) non-immunological graft failures and case histories were examined for clinical and pathological evidence of RVT. In July 1991, aspirin (75 mg o.d. starting immediately before and continuing for 1 month post-transplant) was introduced as routine prophylaxis against RVT. Prior to this, aspirin prophylaxis was not used. RESULTS: In the 6-year period from July 1985 to June 1991, there were 27 cases of RVT in 475 transplants (5.6%). In the subsequent 6-year period, there were six cases of RVT in 480 transplants (1.2%) (P:<0.01). CONCLUSION: Although not abolished, this indicates a significant reduction in the incidence of RVT with the addition of low-dose aspirin.     

Validation of a short questionnaire for estimating dietary calcium intakes

Summary

Concern about calcium supplements, and mainly minor side effects (e.g. constipation) impacting on compliance, means that assessing dietary calcium intake is important. There is no suitable biomarker. Compared to food diaries, a short questionnaire was an efficient way of confirming that patients had adequate calcium intakes (>700 or >1,000 mg)

Introduction

Calcium is usually given alongside treatments for osteoporosis, but recent concerns about potential side effects have led to questioning whether supplements are always necessary. It is difficult to assess calcium intake in a clinical setting and be certain that the patient is getting enough calcium. The aim of this study was to determine whether a short questionnaire for estimating dietary calcium intakes in a clinical setting was fit for purpose.

Methods

We assessed dietary calcium intakes using a short questionnaire (CaQ) in patients attending an osteoporosis clinic (n?=?117) and compared them with calcium intakes obtained from a 7-day food diary (n?=?72) and a food frequency questionnaire (FFQ) (n?=?33).

Results

Mean (SD) daily calcium intakes from the CaQ were 836 (348)?mg; from the diaries, 949 (384)?mg; and from the FFQ, 1,141 (387)?mg. The positive predictive value (PPV) was >80 % for calcium cut-offs?>?700 mg and 70 % for cut-offs?>?1,000 mg. The calcium intakes for the false positives results were not far below the cut-off. For 1,200 mg, the PPV was 67 % or less.

Conclusion

The CaQ is an adequate tool for assessing whether a patient has daily calcium intakes above 700 or 1,000 mg; if below these cut-offs, it is possible that the patient still has enough calcium in the diet, which could be clarified by questioning the patient further. As there were few patients with calcium intakes above 1,200 mg a day, the CaQ cannot be recommended as a tool for confirming higher dietary calcium intakes.     

Health-related quality of life among renal-transplant recipients in Japan

BACKGROUND: This study had four goals: (1) to evaluate an index of health-related quality of life (HQOL) among renal-transplant recipients in Japan, (2) to compare HQOL of renal-transplant recipients with that of the Japanese population as a whole, and (3,4) to study associations of HQOL with renal function and with the time since transplantation. METHODS: Questionnaires were distributed to 570 subjects. All were outpatients, were 16 years old or older, and were studied at least 1 year after they had received their latest renal transplant. HQOL was assessed with the Short Form 36-item health survey. Subjects' physicians provided data on renal function. Associations of HQOL with serum creatinine concentration and with the time since transplantation were evaluated by logistic regression. RESULTS: The response rate was 83%. Data from patients with diabetes and from those who had had at least two renal transplants were excluded; data from 395 recipients were analyzed. On the physical functioning, general health perception, vitality, and social functioning scales, the patients' scores were significantly lower than the Japanese national-norm scores. General health perception was particularly low. Serum creatinine concentrations were associated with general health perception, vitality, and social functioning. Longer times since transplantation were associated with better social functioning. CONCLUSIONS: Although social and physical functioning may improve after transplant surgery, a low self-rating of general health seemed to remain. The rarity of renal transplantation in Japan and other psychosocial factors may explain the low self-rating of general health in Japanese renal-transplant recipients.     

Epidemiology of systemic mycoses among renal-transplant recipients in India

BACKGROUND: Systemic mycoses have a high impact on tropical renal-transplant recipients. METHODS: Data from 1,476 primary renal-transplant recipients was prospectively recorded from 1986 to 2000 at a single center. Cumulative incidence of systemic mycoses, its time of occurrence, risk factors, outcome, and postmortem findings in 30 patients with systemic mycoses were analyzed. RESULTS: A total of 110 episodes of systemic mycoses occurred in 98 patients. The fungal genera Aspergillus, Cryptococcus, and Candida constituted 61% of pathogens, 45% localizing to the lungs. Cytomegalovirus (CMV) disease caused a 5-fold and chronic liver disease a 2-fold increase in systemic mycoses. Tuberculosis (TB) with or without nocardiosis was a significant coinfection. Cyclosporine (CsA) was associated with nearly a 4-fold risk of systemic mycoses less than 6 months from the time of transplantation as compared with prednisolone+azathioprine (PRED+AZA) therapy. Overall, the probability of survival with systemic mycoses was 73.4%, 60.8%, 39.5%, and 25.6% and was 92.5%, 87.5%, 80.0%, and 75.5% without systemic mycoses at 1, 2, 5, and 10 years, respectively (P<0.0001). An extended Cox model with time-independent and dependent covariates showed greater than 15 times the risk of death among those who develop systemic mycoses. Similarly, Posttransplantation (postTX) TB+/-Nocardiosis, preTX TB, CMV disease, diabetes mellitus, PTDM, chronic liver disease (>40 months), and Pred+AZA immunosuppression (>2 years) had 3.5, 1.5, 2.9, 1.9, 1.4, 1.6, 2.3 times the risk for death, respectively, as compared with those who did not have those risk factors. CONCLUSIONS: There is a recent predominance of Aspergillus among the transplant recipients. The risk factors for systemic mycoses are CMV disease, chronic liver disease, and hyperglycemia, and TB is an important coinfection. Systemic mycoses increased in the early postTX period with CsA. The risk factors for death are systemic mycoses, CMV disease, chronic liver disease (>40 months), diabetes mellitus, and Pred+AZA immunosuppression (>2 years). Overall, the probability of survival with systemic mycoses was poor; however, survival has recently improved.     

The impact of dietary calcium intake and vitamin D status on the effects of zoledronate

Summary

We investigated whether baseline dietary calcium intake or vitamin D status modified the effects of zoledronate. Neither variable influenced the effect of zoledronate on bone mineral density, bone turnover, or risk of acute phase reaction, suggesting that co-administration of calcium and vitamin D supplements with zoledronate may not always be necessary.

Introduction

Calcium and vitamin D supplements are often co-administered with bisphosphonates, but it is unclear whether they are necessary for therapeutic efficacy or minimizing side effects of bisphosphonates. We investigated whether baseline dietary calcium intake or vitamin D status modified the effect of zoledronate on bone mineral density (BMD) or bone turnover at 1 year, or the risk of acute phase reactions (APR).

Methods

Data were pooled from two trials of zoledronate in postmenopausal women without vitamin D deficiency in which calcium and vitamin D were not routinely administered. The cohort (zoledronate n?=?154, placebo n?=?68) was divided into subgroups by baseline dietary calcium intake (<800 vs. ≥800 mg/day) and vitamin D status [25-hydroxyvitamin D (25OHD) <50 vs. ≥50 nmol/L, and <75 nmol/L vs. ≥75 nmol/L] and treatment?×?subgroup interactions tested.

Results

There were 52, 86, and 36 % of the zoledronate group and 64, 94, and 46 % of the placebo group that had dietary calcium intake ≥800 mg/day, 25OHD ≥50 nmol/L, and 25OHD ≥75 nmol/L, respectively. There were no significant interactions between treatment and either baseline dietary calcium or baseline vitamin D status for lumbar spine BMD, total hip BMD, the bone turnover markers P1NP and β-CTx, or the risk of an APR. There was also no three-way interaction between baseline dietary calcium intake, baseline vitamin D status, and treatment for any of these variables.

Conclusions

Baseline dietary calcium intake and vitamin D status did not alter the effects of zoledronate, suggesting that co-administration of calcium and vitamin D with zoledronate may not be necessary for individuals not at risk of marked vitamin D deficiency.     

Supplementation of vitamin D and calcium: advantages and risks.

Calcium and the vitamin D hormonal system are both essentialfor the development and maintenance of skeletal health [1].Calcium plays a vital role in neuromuscular function, many enzyme-mediatedprocesses, blood clotting and in providing rigidity to the skeletonby virtue of its phosphate salts. Over 99% of the body's calciumis stored in the bone, where, apart from providing mechanicalstrength, it serves as a mineral reservoir that can be drawnupon to maintain normal plasma calcium. Its non-structural rolesrequire the strict maintenance of ionized calcium concentrationin tissue fluids, at the expense of the skeleton if necessary,and therefore it is the skeleton which is at risk if the supplyof calcium falls short of the requirement     

A prospective study of the physician effect on blood pressure in renal-transplant recipients.

BACKGROUND: Physician presence results in elevated blood pressure (BP) in the general population. The determinants of this phenomenon in renal-transplant recipients are not known. METHODS: We prospectively evaluated BP changes with physician presence in 231 stable adults with graft survival > or =1 year. A nurse measured timed sitting BP by Korotkoff phase I and V sounds before physician entry, during physician presence and upon exit. The haemoglobin, creatinine, weight, immunosuppressive drug dosage and/or level, and anti-hypertensive medication profile were recorded. Paired Student's t-test with Bonferroni correction and multiple linear regression analysis were used to examine BP changes. Characteristics of patients with change in mean arterial BP > or =+10 mmHg (n=55, "high") were compared with those with change < or =+5 mmHg (n=132, "low") by chi-square or Wilcoxon rank sum test as appropriate. A group of 100 recipients served as controls in whom BP was measured thrice without physician presence on any occasion. A multivariate analysis was performed for the combined groups controlling for physician entry as a predictor variable. RESULTS: In the study group, systolic BP (mean+/-SE) rose by 4.2+/-0.8, diastolic BP by 3.5+/-0.5 and mean arterial BP by 3.5+/-0.5 mmHg in physician presence. The BP returned to baseline with exit (P<0.001 for each). Higher haemoglobin and creatinine demonstrated a trend towards influencing the physician-induced rise in diastolic BP. The "high" sub-group demonstrated a shorter time to the second BP measurement in physician presence (P=0.03) and a trend towards morning measurements (P=0.08). In the control group, systolic BP declined by 3.2+/-0.9 mmHg from the first to the second measurement, with a further decline of 2.4+/-0.6 mmHg from the second to third measurements. Diastolic BP did not change. In the combined multivariate analysis, physician entry was an independent predictor of BP change (P=0.0001). CONCLUSIONS: Renal-transplant recipients demonstrate a significant physician effect on BP despite adequate experience with post-transplant clinic visits and BP-altering medication. This population deserves further evaluation through ambulatory BP monitoring.     

Vitamin A antagonizes calcium response to vitamin D in man.

For unknown reasons, the highest incidence of osteoporosis is found in northern Europe. In these populations, the sunlight exposure is limited and the vitamin A intake is high. The interaction between vitamin A and D has been the subject of several in vitro and animal studies. We have studied the acute effects of vitamin A and D on calcium homeostasis in 9 healthy human subjects. We compared the effect of (i) 15 mg of retinyl palmitate, (ii) 2 microg of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], (iii) 15 mg of retinyl palmitate plus 2 microg of 1,25(OH)2D3, and (iv) placebo in a double-blind crossover study. The subjects took vitamin preparations at 10:00 p.m. and the following day blood samples were collected five times from 8:00 a.m. to 4:00 p.m. Serum levels of 1,25(OH)2D3 and retinyl esters increased (1.7-fold and 8.3-fold, respectively; p < 0.01). As expected, serum calcium (S-calcium) increased (2.3%; p < 0.01) and S-parathyroid hormone (PTH) decreased (-32%; p < 0.05) after 1,25(OH)2D3 intake. In contrast, retinyl palmitate intake resulted in a significant decrease in S-calcium when taken alone (-1.0%; p < 0.05) and diminished the calcium response to 1,25(OH)2D3 after the combined intake (1.4%; p < 0.01). S-PTH was unaffected by retinyl palmitate. No significant changes in serum levels of the degradation product of C-telopeptide of type I collagen (CrossLaps), or U-calcium/creatinine levels were found. In conclusion, an intake of vitamin A corresponding to about one serving of liver antagonizes the rapid intestinal calcium response to physiological levels of vitamin D in man.     

Prophylactic deoxyspergualin treatment in living-related renal-transplant recipients transfused with donor-specific blood

BACKGROUND: Deoxyspergualin (DSG) prophylaxis has improved long-term graft survival in living-related renal-transplant recipients transfused with donor-specific blood (DST). We examined the influence of acute rejection (AR) on graft survival in these patients. METHODS: The study groups consisted of either historic control recipients without DSG (group A, n=64, 1985-1989) and recipients with DSG as the initial immunosuppressive agent (group B, n=76, 1989-1995). Both groups received DST from a one-haplotype identical donor and were treated with cyclosporine-based immunosuppression. Rejection was classified into accelerated rejection (Acc, within 5 days), AR (from 6 days-3 months), and late AR (LAR, from 4 months-1 year). RESULTS: Overall 5-year graft survival rates were significantly higher in group B than group A (89.5 vs. 73.4%, P=0.0070). Each group was then subdivided on the basis of whether or not they had an episode of Acc, AR, or LAR. In group A, 5-year graft survival rate was not affected the presence or absence of Acc (75.0 vs. 73.1%), and it was influenced significantly by the presence or absence of AR (50.0 vs. 85.7%, P=0.0012) or LAR (46.7 vs. 81.6%, P<0.0001). In group B, 5-year graft survival did not change significantly by the presence or absence of Acc (100 vs. 88.7%), AR (81.8 vs. 92.6%), or LAR (81.0 vs. 92.7%). CONCLUSIONS: Prophylactic use of DSG in living-related renal-transplant recipients treated with DST improves long-term graft survival, even in patients with AR episodes.