Combination therapy with sevelamer hydrochloride and calcium carbonate in Japanese patients with long-term hemodialysis: alternative approach for optimal mineral management

Calcium (Ca) overload by Ca-containing phosphorus (P) binder has been suggested to be implicated in the pathogenesis of soft tissue and vascular calcification, which contribute to increased morbidity and mortality of cardiovascular disease in patients undergoing dialysis. Recently, a noncalcium P binder, sevelamer hydrochloride (sevelamer), has become available in Japan. However, Japanese patients undergoing dialysis might be less tolerant of sevelamer treatment, and it is likely to cause hypocalcemia because their dietary Ca intake is less than that in European and American patients. We evaluated the effects of combination therapy with sevelamer and calcium carbonate (CC) on mineral metabolism in Japanese hemodialysis patients, as an alternative form of P management. A total of 210 hemodialysis patients were enrolled, and were given a small dose of sevelamer (0.75-1.5 g/day) on CC treatment. Sevelamer dose was gradually increased, while CC decreased during 24 weeks. Five patients discontinued sevelamer treatment because of severe constipation, anorexia, and parathyroidectomy for severe secondary hyperparathyroidism. After 24 weeks, the dose of sevelamer was significantly increased to 3.29 g/day (initial dose: 1.47 g/day), while CC was decreased by 54%. Adjusted serum Ca significantly decreased (9.63 +/- 0.57-9.45 +/- 0.67 mg/dL; P = 0.0012), although serum P increased (5.89 +/- 1.32-6.25 +/- 1.32 mg/dL; P = 0.017). Serum intact PTH (iPTH) significantly increased in patients with a low or normal iPTH level (< or =300 pg/mL), while it did not change in patients with secondary hyperparathyroidism (>300 pg/mL). The results suggest that the therapeutic regimen is more tolerant and reduces Ca load in Japanese hemodialysis patients while avoiding hypocalcemia. In addition, the mitigated Ca overload could improve PTH hyposecretion in patients with adynamic bone disease, which is associated with soft tissue calcification and higher mortality in uremia.     

Effects of serum calcium, phosphorous, and intact parathyroid hormone levels on survival in chronic hemodialysis patients in Japan

Disturbances in bone mineral metabolism are common in chronic hemodialysis (HD) patients and often underlie morbid conditions and mortality; however, no large epidemiological study for Asian dialysis patients has been performed. We analyzed the database of the Japanese Society for Dialysis Therapy registry. In this study, data from patients who were on HD at the end of 2000 was compiled. The Cox's proportional hazard analysis was carried out to evaluate the significance of the impact of variables related to bone mineral metabolism on survival after adjusting for possible confounding variables. The study period was three years, and a cohort of 27 404 HD patients was studied. The hazard ratios were 1.098 (P = 0.0129) for serum calcium levels ranging 10.0-10.9 mg/dL, and 1.243 (P = 0.0001) for serum calcium levels >11.0 mg/dL when the reference serum calcium level range was 9.0-9.9 mg/dL. Similarly, the hazard ratios were significantly higher in a serum phosphorous level of 5.0 mg/dL than for the reference serum phosphorous level range of 4.0-4.9 mg/dL. For intact parathyroid hormone (iPTH), the hazard ratios were significantly small (<119 pg/mL) when the reference iPTH level range was 180-359 pg/mL. However, the hazard ratio did not increase when the iPTH level increased to >360 pg/mL. Results showed that disturbances in bone mineral metabolism, such as those involving serum calcium, phosphorous, and iPTH, have a significant impact on survival in Japanese dialysis patients.     

透析液钙离子浓度对维持性血液透析患者血全段甲状旁腺激素的影响

目的评价不同钙离子浓度的透析液对维持性血液透析(MHD)患者血全段甲状旁腺激素(iPTH)的影响,分析血钙、磷和钙磷乘积与iPTH之间的相关性。方法对2006年1月至3月,上海交通大学医学院附属新华医院肾内科门诊35例长期使用钙离子浓度为1·75mmol/L的透析液进行维持性血液透析的患者,于透析前留取血标本进行血Ca2 、P3-、iPTH测定,并计算钙磷乘积后,改为钙离子浓度为1·25mmol/L或1·50mmol/L的透析液进行维持性血液透析,3个月后于透析前再次留取血标本进行血Ca2 、P3-、iPTH测定,并计算钙磷乘积。结果与使用钙离子浓度为1·75mmol/L透析液比较,使用钙离子浓度为1·25mmol/L或1·50mmol/L透析液3个月后,MHD患者血Ca2 、P3-、钙磷乘积差异无显著性意义,P>0·05,血iPTH明显升高,P<0·01。血iPTH与Ca2 呈显著性负相关,r=-0·45,P<0·01;与P3-及钙磷乘积无相关性,r分别为0·13和-0·03,均P>0·05。结论1·25mmol/L或1·50mmol/L的低钙透析液可以升高MHD患者血清iPTH水平。     

The influences of method of calcium correction and the timing of blood collection on application of the K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Japan

We investigated the treatment of renal osteodystrophy (ROD) in Japan and problems concerning the K/DOQI Guidelines. The subjects were 3698 hemodialysis patients (2328 males and 1370 females) with a mean age of 61.4 years. On average, they had been on hemodialysis for 8.34 years. The serum phosphorus level was <3.5 mg/dL in 5% of the subjects, 3.5-5.5 mg/dL in 49%, 5.6-7.0 mg/dL in 33%, and >7.0 mg/dL in 13%. The serum calcium level was <8.4 mg/dL in 16% of the subjects, 8.4-9.5 mg/dL in 47%, 9.5-10.2 mg/dL in 22%, and >10.2 mg/dL in 15%. The intact PTH level was <150 pg/mL in 57%, 150-300 pg/mL in 27%, and >300 pg/mL in 16% of the patients. The first problem is that correcting Ca is not always performed in clinical fields. The uncorrected calcium level was 9.14+/-0.92 mg/dL, while the corrected calcium level [Ca = Ca + 0.8 x (4-Alb)] was 9.26+/-0.93 mg/dL (P < 0.05). The second problem is that the timing of blood collection is not described in the K/DOQI Guidelines. Subjects with a serum phosphorus level >7.0 mg/dL at 3 days after the previous dialysis were selected for assessment. In these patients, the midweek serum phosphorus level (7.13+/-0.15 mg/dL) at was significantly lower than that (8.11+/-0.15 mg/dL) at the beginning of the next week (P < 0.001). These results suggest that it is necessary to specify the timing of measurement and the method of Ca correction when guidelines for management of ROD are established in the future.     

Effect of age on serum immunoreactive parathyroid hormone and its biological effects

Immunoreactive parathyroid hormone (iPTH) levels, nephrogenous cAMP (ncAMP), and tubular maximum phosphate reabsorption (TmP) were measured in 10 young and 12 healthy volunteers. The fasting urinary calcium to creatinine ratio (Ca:Cr) was also quantitated as an index of bone resorption. Aging was attended by increased iPTH levels (6.9 +/- 0.8 vs. 3.4 +/- 0.4 mu leq/ml; P less than 0.01) as well as increased ncAMP levels (2.48 +/- 0.28 vs. 1.12 +/- 0.21 nmol/100 ml glomerular filtrate; P less than 0.005) and decreased TmP (2.9 +/- 0.2 vs. 4.1 +/- 0.2 mg/100 ml glomerular filtrate; P less than 0.005), indicating that the increased iPTH levels reflected the biological effects of the hormone. A significant positive correlation of iPTH and ncAMP and a significant negative correlation of iPTH and TmP were observed. The Ca:Cr was increased in the older volunteers (0.10 +/- 0.02 vs. 0.05 +/- 0.01; P less than 0.05). The elderly subjects had significantly decreased daily calcium ingestion, serum phosphate and albumin, and creatinine clearance. Our findings suggest that the increased biological effects of PTH in the elderly subjects may contribute to the increases in Ca:Cr and bone loss that occur with age.     

Is serum phosphorus control related to parathyroid hormone control in dialysis patients with secondary hyperparathyroidism?

ABSTRACT: BACKGROUND: Elevated serum phosphorus (P) levels have been linked to increased morbidity and mortality in dialysis patients with secondary hyperparathyroidism (SHPT) but may be difficult to control if parathyroid hormone (PTH) is persistently elevated. We conducted a post hoc analysis of data from an earlier interventional study (OPTIMA) to explore the relationship between PTH control and serum P. METHODS: The OPTIMA study randomized dialysis patients with intact PTH (iPTH) 300-799 pg/mL to receive conventional care alone (vitamin D and/or phosphate binders [PB]; n = 184) or a cinacalcet-based regimen (n = 368). For patients randomized to conventional care, investigators were allowed flexibility in using a non-cinacalcet regimen (with no specific criteria for vitamin D analogue dosage) to attain KDOQITM targets for iPTH, P, Ca and Ca x P. For those assigned to the cinacalcet-based regimen, dosages of cinacalcet, vitamin D sterols, and PB were optimized over the first 16 weeks of the study, using a predefined treatment algorithm. The present analysis examined achievement of serum P targets ([less than or equal to]4.5 and [less than or equal to]5.5 mg/dL) in relation to achievement of iPTH [less than or equal to] 300 pg/mL during the efficacy assessment phase (EAP; weeks 17-23). RESULTS: Patients who achieved iPTH [less than or equal to] 300 pg/mL (or a reduction of [greater than or equal to]30% from baseline)were more likely to achieve serum P targets than those who did not, regardless of treatment group. Of those who did achieve iPTH [less than or equal to] 300 pg/mL, 43% achieved P [less than or equal to]4.5 mg/dL and 70% achieved P [less than or equal to]5.5 mg/dL, versus 21% and 46% of those who did not achieve iPTH [less than or equal to] 300 pg/mL. Doses of PB tended to be higher in patients not achieving serum P targets. Patients receiving cinacalcet were more likely to achieve iPTH [less than or equal to]300 pg/mL than those receiving conventional care (73% vs 23% of patients). Logistic regression analysis identified lower baseline P, no PB use at baseline and cinacalcet treatment to be predictors of achieving P [less than or equal to]4.5 mg/dL during EAP in patients above this threshold at baseline. CONCLUSIONS: This post hoc analysis found that control of serum P in dialysis patients was better when serum PTH levels were lowered effectively, regardless of treatment received. Clinicaltrials.gov identifier NCT00110890.     

Serum Phosphate and Calcium Should Be Primarily and Consistently Controlled in Prevalent Hemodialysis Patients

Mineral metabolism affects mortality in hemodialysis patients and is identified by imbalances in serum phosphate (P), calcium (Ca), and parathyroid hormone (PTH). We examined associations between annual mineral values (P, Ca, PTH) and mortality in a 3‐year cohort (Dec 2006–2009) of 128 125 hemodialysis patients using three models, that is, baseline, time‐dependent and time‐average Cox models. We also examined associations between achieved Japanese guideline targets (P: 3.5?6.0 mg/dL, corrected Ca 8.4?10.0 mg/dL, intact PTH 60?180 mg/dL) and all‐cause survival to elucidate which parameter should be controlled as a priority. High and low serum P (>6.0 or ≤3.5 mg/dL), high Ca (>9.5 mg/dL), higher PTH (>300 pg/mL) and lower PTH (≤60 pg/mL) were significantly associated with high mortality in all three models (P < 0.01). When we examined the association between combination of mineral targets and mortality, patients who achieved all targets simultaneously (20% of subjects, reference) showed lowest mortality. Those who achieved both P and Ca targets showed the same mortality as the reference group. Those who only met P target had a lower risk of death (hazard ratio = 1.17) compared to those that achieved Ca or PTH target (1.41, 1.47, respectively). As time of achieving P and Ca targets increased, all‐cause mortalities diminished incrementally, significantly. Mineral metabolism disorder would lead to high mortality in prevalent hemodialysis patients. Among mineral values, P would be the strongest predictor for high mortality. Consistent achievement of P and Ca targets would lead to good survival.     

Influence of sevelamer on mineral metabolism and hyperparathyroidism in Japanese hemodialysis patients

In June 2003, sevelamer hydrochloride became widely available in Japan and was expected to control hyperphosphatemia in hemodialysis patients without inducing hypercalcemia. To evaluate the impact of sevelamer therapy on mineral metabolism, we recruited 954 hemodialysis patients from 21 renal units just before the general release of sevelamer in Japan. The serum calcium, phosphate, and parathyroid hormone levels determined on enrollment were compared with those later measured in June 2004. Sevelamer was prescribed for 169 of the 859 patients for whom data were available in 2004. The mean calcium level, phosphate level, and calcium x phosphate product were all significantly reduced during the 12-month study period, but the intact parathyroid hormone (iPTH) level did not change. As a result, the percentage of patients who achieved a calcium x phosphate product of <55 mg(2)/dL(2) was significantly increased, but there were no changes in that of patients who achieved the target ranges for phosphate (3.5-5.5 mg/dL) or iPTH (150-300 pg/mL). Among sevelamer-treated patients, iPTH significantly increased, and this change was more marked in the patients with an initial iPTH level <150 pg/mL. Sevelamer was useful for reducing the serum calcium level and calcium x phosphate product, but hyperphosphatemia and hyperparathyroidism were not improved in our study population at 12 months after the release of sevelamer. A decrease in the calcium load might result in the exacerbation of hyperparathyroidism. However, among patients with relative hypoparathyroidism, sevelamer therapy may be beneficial for the prevention of adynamic bone disease.     

Sevelamer hydrochloride improves hyperphosphatemia in hemodialysis patients with low bone turnover rate and low intact parathyroid hormone levels

Sevelamer improves hyperphosphatemia without increasing the calcium load. However, it remains unknown whether sevelamer restores bone metabolism in hemodialysis patients with low bone turnover osteodystrophy and hypoparathyroidism. We investigated the changes in serum intact parathyroid hormone (iPTH) and bone metabolic marker levels after replacing calcium carbonate with sevelamer in these patients. We also conducted stratified analysis based on patient background and multivariate analysis to determine the factors affecting these parameters. During sevelamer replacement therapy, serum calcium and phosphate concentrations, and the calcium phosphate product were measured at 0, 1, 3, and 6 months. Serum iPTH, bone alkaline phosphatase and osteocalcin concentrations were measured at 0 and 6 months. In hemodialysis patients (71 men and 46 women, 63 +/- 12 years old) serum calcium levels and the calcium phosphate product decreased significantly at 1 month. Serum iPTH, bone alkaline phosphatase and osteocalcin levels increased significantly at 6 months. Increases in serum iPTH concentrations were observed in all stratified groups. Significant increases in serum bone alkaline phosphatase and osteocalcin concentrations were found only in the relative hypoparathyroidism group (iPTH levels > or =51.5 pg/mL, the median pretreatment level). Multivariate analysis showed that the factors affecting change in serum iPTH level are baseline serum iPTH, baseline calcium level (> or =9.5 mg/dL), and dialysis duration of 10 years or longer. Sevelamer appears useful for the treatment of hyperphosphatemia in these patients. Particularly, in the relative hypoparathyroidism group, the iPTH secretory response is probably enhanced and bone turnover may have been improved as a result of reducing the calcium load.     

Effect of Calcium Carbonate Combined With Calcitonin on Hypercalcemia in Hemodialysis Patients

This short‐term study assessed the efficacy and safety of calcium carbonate combined with calcitonin in the treatment of hypercalcemia in hemodialysis patients. Patients (n = 64) on hemodialysis for chronic kidney disease for more than 6 months were included based on total serum calcium more than 10.5 mg/dL. All patients were randomized (1 : 1) to receive calcium carbonate combined with calcitonin (Group I) or lanthanum carbonate (Group II) for 12 weeks. Blood levels of calcium, phosphorus and intact parathyroid hormone (iPTH) were measured every month, bone mass density (BMD) and coronary artery calcium scores (CACS) were measured at 3 months. During the study period, serum calcium decreased from 10.72 ± 0.39 to 10.09 ± 0.28 mg/dL (P < 0.05), serum phosphorus decreased from 6.79 ± 1.05 to 5.46 ± 1.18 mg/dL (P < 0.05), and serum iPTH levels in the Group I and Group II were not significantly different from the baseline. There were no significant differences in CACS in either group. There were no significant differences in the BMD values between Group I and baseline. In Group II, the BMD values at the lumbar spine and femoral neck were significantly lower than those before the trial and significantly lower than the corresponding values of Group I (P < 0.05). Calcium carbonate combined with calcitonin and lanthanum carbonate were equally effective in the suppression of hypercalcemia in hemodialysis patients. There were no serious treatment‐related adverse events in treatment with calcium carbonate combined with calcitonin.     

Proteinuria as a risk factor for cardiovascular disease and mortality in older people: a prospective study

BACKGROUND: The prognostic significance of proteinuria in older people is not well defined. We examined the associations between proteinuria and incident coronary heart disease, cardiovascular mortality, and all-cause mortality in older people.SUBJECTS AND METHODS: Casual dipstick proteinuria was determined in 1,045 men (mean [+/- SD] age 68 +/- 7 years) and 1,541 women (mean age 69 +/- 7 years) attending the 15th biennial examination of the Framingham Heart Study. Participants were divided by grade of proteinuria: none (85.3%), trace (10.2%), and greater-than-trace (4.5%). Cox proportional hazards analyses were used to determine the relations of baseline proteinuria to the specified outcomes, adjusting for other risk factors, including serum creatinine level.RESULTS: During 17 years of follow-up, there were 455 coronary heart disease events, 412 cardiovascular disease deaths, and 1,214 deaths. In men, baseline proteinuria was associated with all-cause mortality (hazards ratio [HR] = 1.3, 95% confidence interval [CI] 1.0 to 1.7 for trace proteinuria; HR = 1.3, 95% CI 1.0 to 1.8 for greater-than-trace proteinuria; P for trend = 0.02). In women, trace proteinuria was associated with cardiovascular disease death (HR = 1. 6, 95% CI 1.1 to 2.4), and all-cause mortality (HR = 1.4, 95% CI 1.1 to 1.7).CONCLUSION: Proteinuria is a significant, although relatively weak, risk factor for all-cause mortality in men and women, and for cardiovascular disease mortality in women.     

Predictor of poor coronary collaterals in chronic kidney disease population with significant coronary artery disease

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.     

Effect of transdermal testosterone treatment on serum lipid and apolipoprotein levels in men more than 65 years of age

PURPOSE: Because the effects of androgen replacement on lipoprotein levels are uncertain, we sought to determine the effect of transdermal testosterone treatment on serum lipid and apolipoprotein levels in elderly men. SUBJECTS AND METHODS: One hundred and eight healthy men more than 65 years of age who had serum testosterone concentrations >1 SD below the mean for young men were randomly assigned to receive either testosterone (54 men; 6 mg/day) or placebo (54 men) transdermally in a double-blind fashion for 36 months. Serum concentrations of lipids and apolipoproteins were measured, and cardiovascular events recorded. RESULTS: Serum total cholesterol concentrations decreased in both the testosterone-treated men and placebo-treated men, but the 3-year mean (+/- SD) decreases in the two groups (testosterone treated, -17 +/- 29 mg/dL; placebo treated, -12 +/- 38 mg/dL) were not significantly different from each other (P = 0.4). Similarly, serum low-density lipoprotein (LDL) cholesterol levels decreased in both treatment groups, but the decreases in the two groups (testosterone treated, -16 +/- 24 mg/dL; placebo treated, -16 +/- 33 mg/dL) were similar (P = 1.0). Levels of high-density lipoprotein (HDL) cholesterol, triglycerides, and apolipoproteins A-I and B did not change. Lipoprotein(a) levels increased in both groups by similar amounts (testosterone treated, 3 +/- 9 mg/dL; placebo treated, 4 +/- 6 mg/dL; P = 1.0). The number of cardiovascular events was small and did not differ significantly between the testosterone-treated men (9 events) and the placebo-treated men (5 events) during the 3-year study (relative risk = 1.8; 95% confidence interval: 0.7 to 5.0). CONCLUSIONS: As compared with placebo, transdermal testosterone treatment of healthy elderly men for 3 years did not affect any of the lipid or apolipoprotein parameters that we measured. The effect of testosterone treatment on cardiovascular events was unclear, because the number of events was small.     

Effect of parathyroid hormone levels on carotid intima-media thickness after renal transplantation.

BACKGROUND: The present study aimed to investigate the intact parathyroid hormone (iPTH)-dependent evolution of common carotid intima-media thickness (CC IMT) in renal transplant recipients (RTR) within a 12-month follow-up, ie, before (E0) and 3 months (E3), 6 months (E6), and 12 months after renal transplantation (RTX). METHODS: A total of 55 normotensive patients, aged 47 +/- 1.7 years, underwent a RTX. The graft function was stable (clearanceCockroft >60 mL/min and S-creatinine <2.5 mg/dL) in all patients throughout the follow-up. RESULTS: In 67% of the RTR, the iPTH levels were classified as high at E0 (E6: 63%; E6: 49%; E12: 67%). The plasma iPTH levels decreased after RTX (P < .01). The arterial blood pressure remained stable. The CC IMT was positively and independently correlated with age (P < .01), gender (P < .01), and iPTH levels (P < .01). CONCLUSIONS: Normalization of iPTH levels is associated with a significant intima-media thickness (IMT) reduction. The increased IMT in renal transplant recipients may contribute to the high cardiovascular morbidity and mortality in patients with end-stage renal failure.     

Large and small artery compliance changes during hemodialysis

BACKGROUND: Cardiovascular disease is the major cause of mortality and morbidity in patients undergoing hemodialysis. Reduced arterial compliance is an independent predictor of cardiovascular mortality in end stage renal disease and can be measured noninvasively using pulse wave analysis technology. METHODS: Ten chronic hemodialysis patients were evaluated using pulse wave analysis to determine large and small vessel compliance before hemodialysis, midway through the treatment, and at the end of the treatment. Serum calcium was measured before and after hemodialysis. RESULTS: No significant changes in systolic blood pressure (BP), diastolic BP, pulse pressure, or heart rate occurred during hemodialysis. A significant decrease in small vessel compliance (C2) occurred during the treatment, with the mean C2 decreasing from 5.6 +/- 2.7 mL/mm Hg x 10 predialysis to 3.3 +/- 1.5 mL/mm Hg x 10 midway through the treatment (P = .04) and to 3.9 +/- 4.3 mL/mm Hg x 10 at the end of the dialysis treatment. There was no significant change in large vessel compliance (C1). Serum calcium increased significantly during the dialysis treatment from 8.0 +/- 1.2 mg/dL to 9.8 +/- 0.9 mg/dL (P = .003). CONCLUSIONS: Significant decreases in small artery compliance occur without systolic or diastolic BP changes during routine hemodialysis. A significant increase in serum calcium also occurred during hemodialysis. Measurements of arterial compliance during hemodialysis may be an important tool to identify patients with vascular responses, which may place them at greater risk for cardiovascular disease.     

肾性甲状旁腺功能亢进症甲状旁腺全切加前臂移植31例临床分析

目的总结31例尿毒症继发性甲状旁腺功能亢进症(以下简称甲旁亢)行甲状旁腺全切加前臂移植的临床经验。方法回顾性分析1996-2005年我院肾科行甲状旁腺全切加前臂移植者31例的临床特点、相关内科处理及疗效。结果 31例患者为长期血液透析者(平均透析9.2年),26例有骨痛,11例有骨折,25例有皮肤瘙痒,14例有转移性钙化。(2)31例患者血甲状旁腺激素(iPTH)平均为(1811±879)ng/L;颈部 B 超及发射型计算机体层摄影术均证实有增生肿大的甲状旁腺2～4枚,内科治疗均失败。(3)31例患者均做甲状旁腺全切加前臂移植术,术后症状明显改善。iPTH 快速下降至200 ng/L 以下。高钙、高磷恢复至正常水平,碱性磷酸酶逐步下降。随访最长时间9年,目前 iPTH、钙、磷正常。结论严重肾性甲旁亢对内科治疗失败者应及时行甲状旁腺全切加前臂移植治疗,疗效可靠。     

Relation between serum uric acid and risk of cardiovascular disease in essential hypertension. The PIUMA study

The question of serum uric acid as an independent risk factor in subjects with essential hypertension remains controversial. For up to 12 years (mean, 4.0) we followed 1720 subjects with essential hypertension. At entry, all subjects were untreated and all were carefully screened for absence of cardiovascular disease, renal disease, cancer, and other important disease. Outcome measures included total cardiovascular events, fatal cardiovascular events, and all-cause mortality. During 6841 person-years of follow-up there were 184 cardiovascular events (42 fatal) and 80 deaths from all causes. In the 4 quartiles of serum uric acid (division points: 0.268, 0.309, and 0.369 mmol/L [4.5, 5.2, and 6.2 mg/dL] in men; 0.190, 0.232, and 0.274 mmol/L [3.2, 3.9, and 4.6 mg/dL] in women), the rate (per 100 person-years) of cardiovascular events was 2.51, 1.48, 2.66, and 4.27, that of fatal cardiovascular events was 0.41, 0.33, 0.38, and 1.23, and that of all-cause deaths was 1.01, 0.55, 0.93, and 2.01, respectively. The relation between uric acid and event rate was J-shaped in both genders. After adjustment for age, gender, diabetes, total cholesterol/HDL cholesterol ratio, serum creatinine, left ventricular hypertrophy, ambulatory blood pressure, and use of diuretics during follow-up, uric acid levels in the highest quartile were associated with increased risk for cardiovascular events (relative risk, 1.73; 95% CI, 1.01 to 3.00), fatal cardiovascular events (relative risk, 1.96; 95% CI, 1.02 to 3.79), and all-cause mortality (relative risk, 1.63; 95% CI, 1.02 to 2.57) in relation to the second quartile. In untreated subjects with essential hypertension, raised uric acid is a powerful risk marker for subsequent cardiovascular disease and all-cause mortality.     

Cholesterol 2001. Rationale for lipid-lowering in older patients with or without CAD

Statin treatment of men and women age > or = 50 with coronary artery disease (CAD) and hypercholesterolemia reduces the risk of all-cause mortality, cardiovascular mortality, coronary events, coronary revascularization, stroke, and intermittent claudication. The target serum low-density lipoprotein (LDL) cholesterol level is < 100 mg/dL in older patients with CAD, prior stroke, peripheral arterial disease, or extracranial carotid arterial disease and serum LDL cholesterol > 125 mg/dL despite diet therapy. Statins are also effective in reducing cardiovascular events in older persons with hypercholesterolemia but without cardiovascular disease. Consider using statins in patients age 50 to 80 without cardiovascular disease, serum LDL cholesterol > 130 mg/dL, and serum high-density lipoprotein (HDL) cholesterol < 50 mg/dL.     

Serum potassium and risk of cardiovascular disease: the Framingham heart study

BACKGROUND: Published studies of the association between serum potassium concentration and risk for cardiovascular disease in community-based populations have reported conflicting results. We sought to determine the association between serum potassium concentration and cardiovascular disease risk in the Framingham Heart Study. METHODS: A total of 3151 participants (mean age, 43 years; 48% men) in the Framingham Heart Study who were free of cardiovascular disease and not taking medications affecting potassium homeostasis had serum potassium levels measured (1979-1983). Proportional hazards models were used to determine the association of serum potassium concentration at baseline with the incidence of cardiovascular disease at follow-up. RESULTS: During mean follow-up of 16 years, 313 cardiovascular disease events occurred, including 46 cardiovascular disease-related deaths. After adjustment for age, serum potassium level was marginally associated with risk of cardiovascular disease (hazard ratio [HR] per 1 mg/dL increment, 1.03; 95% confidence interval [CI], 1.00-1.05; P =.02). However, after further adjustment for multiple confounders, serum potassium level was not significantly associated with cardiovascular disease risk (HR, 1.00; 95% CI, 0.98-1.03). There were no significant associations between serum potassium level and cardiovascular disease-related death in either age- and sex-adjusted models (HR, 1.06; 95% CI, 0.99-1.12) or multivariable-adjusted models (HR, 1.04; 95% CI, 0.97-1.11). CONCLUSION: In our community-based sample of individuals free of cardiovascular disease and not taking medications that affect potassium homeostasis, serum potassium level was not associated with risk of cardiovascular disease.     

Effects of calcitriol on type 5b tartrate-resistant acid phosphatase and interleukin-6 in secondary hyperparathyroidism

BACKGROUND/AIMS: Secondary hyperparathyroidism (SHP) is characterized by high bone turnover and elevated serum bone remodeling markers. Elevation of serum interleukin-6 (IL-6) levels is also characteristic of end-stage renal disease. This study investigates the effects of intravenous calcitriol on serum bone resorptive markers, namely, type 5b tartrate-resistant acid phosphatase (TRACP5b) and IL-6 in patients with SHP. METHODS: Intravenous calcitriol therapy was given for 16 weeks to 24 patients on maintenance hemodialysis with plasma intact parathyroid hormone (iPTH) levels >300 pg/ml. Blood was drawn at baseline and every 4 weeks for 16 weeks for determination of the levels of biochemical parameters, iPTH, IL-6 and bone remodeling markers, including bone-specific alkaline phosphatase (bAP) and TRACP5b. RESULTS: Only 21 patients responded to the calcitriol therapy, with significant decrements in serum iPTH after 4 weeks of therapy and thereafter. After 16 weeks of calcitriol therapy, 21 patients had significant decrements in serum iPTH (707.9 +/- 317.8 vs. 205.0 +/- 63.1 pg/ml, p < 0.01). Prior to treatment, a significant correlation was found between increased levels of serum iPTH and IL-6 levels (r = 0.45, p < 0.05). After treatment, there was also a significant and parallel lowering of levels of serum iPTH, IL-6 (8.52 +/- 3.59 vs. 7.24 +/- 2.81 pg/ml, p < 0.01), bAP (54.68 +/- 36.17 vs. 24.55 +/- 13.84 U/l, p < 0.01) and TRACP5b (3.41 +/- 1.89 vs. 1.80 +/- 0.55 U/l, p < 0.01). Our results additionally showed significant positive correlationsbetween baseline levels of serum IL-6 and those of iPTH, bAP and TRACP5b. After 16 weeks of calcitriol treatment, the correlation between IL-6 and iPTH levels lost significance but levels of serum IL-6, bAP and TRACP5b remained significantly correlated. CONCLUSIONS: Elevated levels of serum IL-6 and bone remodeling markers, namely, bAP and TRACP5b which are common features of SHP, are effectively suppressed by calcitriol therapy. This indicates that hyperparathyroidism not only accelerates bone remodeling but may also aggravate inflammation in patients on maintenance hemodialysis.