Serum magnesium concentration is an independent predictor of parathyroid hormone levels in peritoneal dialysis patients.

BACKGROUND: Parathyroid hormone (PTH) is a cardinal factor in the pathogenesis of bone disease in the dialysis population. The spectrum of renal osteodystrophy has been reported to have changed during the past years, and adynamic bone disease has emerged as the most common bone disorder in these patients. Continuous ambulatory peritoneal dialysis (CAPD) is considered a risk factor for the development of this condition, and furthermore, the adynamic bone lesion is associated with a state of relative hypoparathyroidism (hypo-PTH). Calcium, vitamin D, and phosphorus play a key role in the control of parathyroid gland function in uremic patients. However, magnesium may also be able to modulate PTH secretion in a way similar to calcium. OBJECTIVE: The aims of this study were (1) to analyze the serum Mg concentration in a large group of CAPD patients, (2) to study the relationship between serum Mg and PTH levels, and (3) to investigate whether this relationship is independent of other factors, such as calcium, phosphorus, and calcitriol, that regulate parathyroid function. PATIENTS AND METHODS: We studied 51 stable patients, aged 23-77 years, under maintenance CAPD for more than 6 months (range 8-48 months). Calcium carbonate was used as a phosphate binder in all patients, and 9 subjects also received aluminum hydroxide. No patient had been previously treated with vitamin D. Biochemical parameters were prospectively evaluated over 6 months, and the mean values were computed. RESULTS: The mean serum Mg was 1.08 +/- 0.19 mmol/L, and hypermagnesemia, defined as a Mg level higher than 1.01 mmol/L, was found in 30 patients (59%). Thirty-one subjects (60%) had an intact PTH (iPTH) level lower than 120 pg/mL and were diagnosed as having relative hypo-PTH. Except for the values of iPTH and alkaline phosphatase, the only difference between the two groups was the serum Mg concentration, which was significantly higher in patients with hypo-PTH (1.16 +/- 0.15 mmol/L vs 0.91 +/- 0.14 mmol/L; p< 0.001). Furthermore, iPTH levels were lower in patients with hypermagnesemia than in subjects with normal serum Mg (69 +/- 49 pg/mL vs 190 +/- 89 pg/mL, p < 0.001). There was a significant correlation between serum Mg and PTH levels (r= -0.70, p< 0.01). After controlling for the effect of other variables by partial correlation analysis, a significant positive association between P and PTH (r= 0.25, p < 0.05), and a negative relationship between Mg and PTH (r= -0.57, p < 0.001) were evident. A forward stepwise multiple regression analysis showed that only P and Mg predicted PTH values (multiple r = 0.59, p < 0.001). CONCLUSIONS: Hypermagnesemia and hypoparathyroidism are frequent in CAPD patients. There is a significant inverse relationship between serum Mg concentration and iPTH levels. Furthermore, this association is independent of the most important factors regulating parathyroid gland function (calcium, phosphorus, and calcitriol). These results suggest that hypermagnesemia may have a suppressive effect on PTH synthesis and/or secretion. Therefore, elevated serum Mg levels may play a role in the pathogenesis of adynamic bone disease.     

Comparative study between intact PTH and fragments of PTH in patients on hemodialysis and CAPD.

Twenty-nine patients on hemodialysis (HD) and 29 patients on continuous ambulatory peritoneal dialysis (CAPD) were studied. Serum calcium and phosphorous levels were similar in the 2 groups. Serum parathyroid hormone (PTH) levels were determined by 4 different methods. Mid-molecule PTH levels were higher in HD (1099.5 +/- 876.8 pmol/L) than in CAPD patients (541.0 +/- 138.8 pmol/L), p less than 0.001, while intact PTH levels were similar. The ratio MM-PTH/Intact PTH was higher in HD (55.2 +/- 29.0) than in CAPD patients (39.0 +/- 20.0), where p less than 0.01. In patients with similar C-PTH, those on CAPD had higher levels of intact PTH (46.0 +/- 27.0 pmol/L) than those in HD (29.3 +/- 29.0 pmol/L), p less than 0.01. The ratio C-PTH/intact PTH was higher in HD (104.9 +/- 39.6) than in CAPD patients (59.3 +/- 32.3), p less than 0.001. The Peritoneal Saturation Index (PSI) of MM-PTH was 23.4 +/- 12%, and it showed a hyperbolic correlation in respect to MM-PTH serum levels. We concluded that CAPD can modify the plasma C-PTH and MM-PTH serum levels by peritoneal losses of these fragments.     

Quantitative ultrasound measurements in diabetic and nondiabetic patients with end-stage renal disease

The aim of the study was to assess skeletal status in diabetic and nondiabetic subjects with end-stage renal disease (ESRD). One hundred twenty-three patients with ESRD (57 patients with diabetes: 9 type 1 and 48 type 2) and 66 nondiabetic patients were evaluated. Control group comprised 1541 subjects (614 males and 927 females). Diabetes and/or renal insufficiency was the only reason of bone disease and, in control group, no factors known to influence bone metabolism (chronic diseases or prolonged medications) were noted. Skeletal status was evaluated by quantitative ultrasound measurements at the hand phalanges using DBM 1200 (IGEA, Carpi, Italy), which measures amplitude-dependent speed of sound (Ad-SoS [m/s]). Because of some differences in mean age in subgroups of patients and controls, comparisons were performed using values of Z-score. In all diabetic patients, Z-score was significantly higher compared with nondiabetics (p < 0.05). In all type 1 diabetes patients, Z-score was significantly lower than in all nondiabetic patients (p < 0.05) and in patients with type 2 diabetes (p < 0.001). Z-score was also significantly lower in type 2 diabetics than in nondiabetic females (p < 0.00001) but did not differ in males. Comparisons between Z-scores in controls and patients showed that Z-score in nondiabetic females was significantly lower than in female controls (p < 0.000001), and in nondiabetic males--diabetic type 2 males as well as females--Z-score did not differ vs. results in adequate control group. Z-score was significantly lower in patients with diabetes type 1 vs. all controls (p < 0.001). Correlation analysis showed in all nondiabetic patients that Z-score was negatively affected by duration time of dialysis (r = -0.37, p < 0.01) and parathyroid hormone (PTH) serum level (r = -0.35, p < 0.01). In patients with type 1 diabetes, only PTH influenced significantly Z-score (r = -0.76, p < 0.05) and, in patients with type 2 diabetes, no significant correlations were obtained. Subjects with type 1 diabetes seemed to be sensitive for skeletal disturbances in a course of renal insufficiency, whereas subjects with type 2 diabetes did not show such skeletal pathology as shown by ultrasound measurements at hand phalanges.     

Plasma aluminum levels in pediatric dialysis patients: comparison of hemodialysis and continuous ambulatory peritoneal dialysis

Accumulation of aluminum occurs in children with renal failure and can cause anemia, disabling osteodystrophy, and encephalopathy. Effects on bone mineralization are of particular concern in pediatric patients with growth potential. We measured plasma aluminum levels in 36 patients on continuous ambulatory peritoneal dialysis (CAPD) and 22 on hemodialysis under surveillance at a single pediatric center. The levels were above normal in 35 and 21 patients, respectively, and the values correlated with the oral dose of aluminum-containing phosphate-binding medications (r = 0.57; P less than 0.001). Younger and smaller children had higher plasma aluminum levels and also received larger doses of oral aluminum-containing compounds. Mean plasma aluminum levels (57.2 +/- 52.8 and 48.7 +/- 32.1 micrograms/liter, respectively) and the daily oral doses of elemental aluminum (47.3 +/- 37.6 and 39.2 +/- 26.7 mg/kg, respectively) were not statistically different in patients on CAPD and those on hemodialysis. Plasma aluminum levels did not correlate with estimated cumulative oral intake of aluminum, total duration of dialysis, serum calcium and phosphorus concentrations, N-terminal parathyroid hormone levels, or transfusion requirements. Retention of aluminum is common in children undergoing dialysis, correlates with the amount of aluminum administered orally, and results in similar elevations of plasma aluminum with CAPD and hemodialysis. Younger and smaller children are at increased risk for accumulation of aluminum. Alternative methods for control of serum phosphorus are needed in children with end-stage renal disease.     

Correlations among serum calcium, vitamin D and parathyroid hormone levels in the elderly in southern Taiwan

This study correlates serum vitamin D levels to related hormones and dietary intakes among 57 elderly Chinese above the age of 65 who were living in the same community in rural Southern Taiwan (Pingtung) and who had no conditions or drug intake known to interfere with the metabolism of vitamin D. Demographic characteristics, past medical history, medications, and dietary intake were collected via questionnaires. Venous blood samples were collected for analyses of serum 25-hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH) and calcium levels. Our results showed subjects in this study to have normal mean values of serum 25(OH)D, PTH and calcium levels. The mean serum 25(OH)D level was 36.21 (+/- 6.37) ng/ml, the mean serum PTH level 29.24 (+/- 18.62) pg/ml and the mean serum calcium level 9.14 (+/- 0.52) mg/dl. While the mean serum 25(OH)D and calcium values were not found to be significantly different between men and women, the mean serum PTH level was significantly higher in women (33.42 +/- 20.00 pg/ml) than in men (23.07 +/- 14.66 pg/ml) (p <.05), and serum PTH levels were significantly negatively correlated to serum calcium (r = -.33, p <.05) but not 25(OH)D (r = -.21). A higher intake of calcium was significantly associated with higher serum calcium levels (r =.29, p <.05), but not with serum 25(OH)D levels. Results from this study suggested that the elderly people living in Pingtung, a particularly sunny region, had normal serum 25(OH)D levels. The fact that the elderly women studied had higher serum PTH levels and that these levels were negatively correlated to serum calcium levels suggests that a higher PTH level in the elderly women may be related to susceptibility for osteoporosis. In an effort to provide optimal nursing care for the elderly by minimizing hip fractures and related morbidity, further nursing studies are needed to study the effects of the environment, dietary intake and bone metabolism.     

CKD5D患者骨折风险的相关因素分析

目的探讨CKD5D骨折患者临床特点及风险相关因素。方法 124例CKD5D患者按既往或现在有无骨折的发生,分为骨折组和非骨折组。记录临床资料如年龄、性别、身高、体质量、透析时间、透析方式、体质量指数、高血压、糖尿病病史、服用药物史;实验室检查指标如血红蛋白、红细胞比积、血肌酐、尿素氮血糖、白蛋白、甘油三酯、胆固醇、高密度脂蛋白、低密度脂蛋白、血钠、血钙、血磷、甲状旁腺激素、碱性磷酸酶、25(OH)Vit D;骨密度检查。结果与非骨折组比较,骨折组血液透析比例更高、透析时间更长,血钙、血磷、PTH、AKP更高,骨密度T值、Z值均明显下降。骨折风险的单因素回归分析提示,透析龄长、高钙、高磷、高PTH、高AKP、高25(OH)Vit D与骨折的发生正相关,腹膜透析、使用钙剂与骨折的发生负相关。多因素逐步回归分析提示,高PTH、高AKP与骨折的发生正相关,腰椎骨密度和使用钙剂与骨折的发生负相关。结论低骨密度是骨折发生的重要危险因素,钙剂的使用能减少骨折风险,CKD5D患者高PTH、高AKP应积极干预。     

Serum calcium and phosphorus associate with the occurrence and severity of angiographically documented coronary heart disease, possibly through correlation with atherogenic (apo)lipoproteins.

The associations of serum calcium and phosphorus concentrations as well as other cardiovascular risk factors were investigated in relation to the existence and severity of coronary heart disease (CHD) in 260 clinically stable, angiographically defined CHD patients aged 40-70 years. The subjects were classified as CHD(+) cases if one or more coronary arteries had a significant stenosis (> or =70%) and CHD(-) controls if there was no stenosis (< or =10%) in any artery. The severity of coronary occlusion was scored on the basis of the number and extent of lesions, as normal, mild, moderate or severe. Fasting serum concentrations of electrolytes, lipids and (apo)lipoproteins were determined. The concentrations of serum total calcium (2.41 +/-0.14 vs. 2.33 +/- 0.22 mmol/L, p < or = 0.05), albumin-corrected calcium (2.33 +/- 0.25 vs. 2.23 +/- 0.25 mmol/L, p < or = 0.01), phosphorus (1.32 +/-0.21 vs. 1.25 +/- 0.17 mmol/L, p < or = 0.007) and the ion product of calcium and phosphorus (3.16 +/- 0.58 vs. 2.91 +/- 0.50, p < or =0.0001) were significantly higher in the CHD(+) compared to the CHD(-) group. Patients with CHD compared with controls had increased serum levels of triglyceride, total cholesterol, low-density lipoprotein-cholesterol (LDL-C), apolipoprotein B (apoB), lipoprotein(a) [Lp(a)] and decreased serum levels of high-density lipoprotein (HDL)-C and apoAI. Multiple logistic regression analysis showed strong and significant association between diabetes mellitus (odds ratio, OR = 5.24, p < or = 0.0001), male gender (OR = 8.84, p < or =0.0001), Lp(a) (OR = 1.014, p < or =0.006), hypertension (OR = 2.61, p < or =0.02), apoB (OR = 1.031, p < or =0.001), age (OR = 1.055, p < or =0.003), phosphorus (OR = 2.438, p < or =0.01), albumin-adjusted calcium (OR = 1.532, p < or =0.05), cholesterol (OR = 1.009, p < or =0.05) and the occurrence of CHD. On the basis of bivariate correlation analysis, serum-adjusted calcium was positively correlated with the levels of cholesterol (r = 0.285, p < or =0.0001), LDL-C (r = 0.320, p < or =0.0001), Lp(a) (r = 0.173, p < or = 0.005), apoB (r = 0.237, p < or =0.0001), LDL-C/apoB ratio (r = 0.180, p < or= 0.007), apoAI (r = 0.181, p < or =0.003) and inversely to HDL-C (r = -0.146, p < or =0.02) and HDL-C/apoAI ratio (r = -0.263, p < or =0.0001). Serum phosphorus concentration was a significant correlate of triglyceride (r = 0.199, p < or =0.001) and Lp(a) (r = 0.129, p < or =0.04). The results demonstrated that serum calcium and phosphorus are associated with the prevalence and severity of CHD, probably through correlation with atherogenic lipids and (apo)lipoproteins. Serum calcium and phosphorus and their ion product were also independent risk factors for CHD.     

Sevelamer hydrochloride in peritoneal dialysis patients: results of a multicenter cross-sectional study.

BACKGROUND: Sevelamer hydrochloride is a phosphate binder widely employed in hemodialysis patients. Until now, information about its efficacy and safety in peritoneal dialysis patients has been scarce. PATIENTS AND METHODS: In September 2005 a cross-sectional study of demographic, biochemical, and therapeutic data of patients from 10 peritoneal dialysis units in Catalonia and the Balearic Islands, Spain, was conducted. RESULTS: We analyzed data from 228 patients. At the time of the study, 128 patients (56%) were receiving sevelamer. Patients receiving sevelamer were younger (p < 0.01), showed a longer period of time on dialysis (p < 0.01), and had a lower Charlson Comorbidity Index (p < 0.01). Serum calcium and intact parathyroid hormone levels were not different between the two groups, while phosphate levels <5.5 mg/dL were observed more frequently in patients not receiving sevelamer (79% vs 61%, p < 0.01). Serum total cholesterol (167 +/- 41 vs 189 +/- 42 mg/dL, p < 0.01) and low density lipoprotein (LDL) cholesterol (90 +/- 34 vs 109 +/- 34 mg/dL, p < 0.01), but not high density lipoprotein cholesterol or triglycerides, were lower in sevelamer-treated patients. Moreover, sevelamer-treated patients displayed a higher serum albumin (38 +/- 5 vs 36 +/- 4 g/L, p < 0.01) and a lower C-reactive protein (4.9 +/- 12.8 vs 8.8 +/- 15.7 mg/L, p < 0.01). Blood bicarbonate levels <22 mmol/L were observed more frequently in patients receiving sevelamer (22% vs 5%, p < 0.01). Logistic regression analysis adjusting by confounding variables confirmed that sevelamer therapy was associated with serum total cholesterol <200 mg/dL [relative risk (RR): 2.77, 95% confidence interval (CI): 1.44 - 5.26, p = 0.002] and blood bicarbonate <22 mmol/L (RR: 8.5, 95% CI: 2.6 - 27.0, p < 0.001), but not with serum phosphate >5.5 mg/dL, calcium-phosphate product >55 mg(2)/dL(2), serum albumin <35 g/L, or C-reactive protein >5 mg/L. CONCLUSIONS: This uncontrolled cross-sectional study in peritoneal dialysis patients showed that sevelamer hydrochloride treatment allows an adequate serum phosphate level in about 60% of patients and significantly reduces total and LDL-cholesterol levels. Since this treatment is associated with metabolic acidosis in 22% of patients, we recommend close monitoring of bicarbonate levels in this group of patients until the clinical significance of this result is clarified.     

Earlier onset and greater severity of disordered mineral metabolism in diabetic patients with chronic kidney disease

OBJECTIVE

Disordered mineral metabolism is a common complication of chronic kidney disease (CKD) and a novel risk factor for CKD progression, cardiovascular disease, and mortality. Although diabetes is the leading cause of CKD and is associated with worse clinical outcomes than other etiologies, few studies have evaluated mineral metabolism in CKD according to diabetes status.

RESEARCH DESIGN AND METHODS

Using the Chronic Renal Insufficiency Cohort Study, we tested the hypothesis that diabetes is independently associated with lower serum calcium and higher serum phosphate, parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23).

RESULTS

Compared with participants without diabetes (n = 1,936), those with diabetes (n = 1,820) were more likely to have lower estimated glomerular filtration rate (eGFR), lower serum albumin, and higher urinary protein excretion (all P < 0.001). Unadjusted serum phosphate, PTH, and FGF23 levels were higher and calcium was lower among those with compared with those without diabetes (all P < 0.001). After multivariate adjustment, diabetes remained a significant predictor of serum phosphate, PTH, and FGF23 but not calcium. The eGFR cut point at which 50% of participants met criteria for secondary hyperparathyroidism or elevated FGF23 was higher in participants with diabetes compared with those without (PTH: eGFR 30–39 vs. 20–29, P < 0.001; FGF23: eGFR 50–59 vs. 40–49, P < 0.001).

CONCLUSIONS

Disordered mineral metabolism begins earlier in the course of CKD and is more severe among CKD patients with compared with those without diabetes. Future studies should explore mechanisms for these differences and whether they contribute to excess risks of adverse clinical outcomes among diabetic patients with CKD.An estimated 25.8 million people in the U.S. suffer from diabetes, a leading risk factor for cardiovascular disease (CVD) and the most common cause of chronic kidney disease (CKD) (1,2). Although improved understanding of diabetes-related complications has led to advances in clinical management of affected individuals, recent studies show that even with delivery of optimal care, high risks of CVD and CKD persist (3). Moreover, compared with patients without diabetes, those with diabetes experience faster progression to end-stage renal disease (ESRD) and higher rates of CVD events and mortality (2). Thus, identifying novel pathophysiologic mechanisms that may contribute to these differences and can be targeted for intervention is a critical priority for diabetes and CKD management.Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD) refers to the clinical syndrome of laboratory abnormalities, bone disease, and extraskeletal calcification, including the arterial system (4). Among the earliest manifestations of CKD-MBD are vitamin D deficiency, disordered calcium and phosphate homeostasis, and secondary elevations of parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23). Mounting experimental and epidemiologic data support these alterations in mineral metabolism as novel risk factors for ESRD, CVD, and mortality (5,6). The evidence is especially strong for elevated serum phosphate and FGF23, which independently predict risks of CKD progression, CVD, and mortality (7,8). Differences in mineral metabolism according to diabetes status have been described in patients with ESRD (9,10), but a detailed characterization of the syndrome according to diabetes status is lacking in earlier stages of CKD. We measured mineral metabolites in baseline samples from 3,756 participants in the Chronic Renal Insufficiency Cohort (CRIC) Study, a racially and ethnically diverse prospective CKD cohort with a high prevalence of diabetes. We hypothesized that individuals with diabetes would have more severe abnormalities of mineral metabolism at comparable levels of renal dysfunction than patients without diabetes (lower serum calcium, higher serum phosphate, PTH, and FGF23 levels).     

Short-term effects of low-calcium dialysis solutions on calcium mass transfer, ionized calcium, and parathyroid hormone in CAPD patients.

Patients on CAPD using calcium carbonate (CaCO3) as phosphate binder might benefit from low-calcium (Ca) concentration dialysis solutions; however, no data are available for the effects of this regimen on Ca metabolism. We studied 10 patients on stable CAPD regimens with standard dialysis solutions (Ca 7 mg/dL) who were taking CaCO3 to control hyperphosphatemia (mean daily doses 4.5 +/- 2.4 g). Hypercalcemic episodes had been recorded in 6 patients. Standard dialysis solutions were replaced with solutions containing 5 mg/dL of Ca. Calcium and phosphate peritoneal mass transfer (MT), serum concentrations of total Ca, ionized Ca (Ca++), phosphate, intact PTH, and mid-molecular PTH, were evaluated before and 48 hours after change of dialysate. The switch to low-Ca solutions was accompanied by significant changes in calcium mass transfer (Ca MT) (+9.84 +/- 48.22 versus -96.74 +/- 48.32 mg/day, p less than .001). Ca MT was significantly (p less than .05) correlated with the serum/dialysate Ca gradient. There was no difference in phosphate MT. Serum Ca++ significantly (p less than .05) decreased from 5.20 +/- 0.32 to 4.88 +/- 0.36 mg/dL, and intact PTH significantly increased (81.5 +/- 139 versus 112.4 +/- 168 pg/mL, p less than .05). It is concluded that dialysis solutions with Ca 5 mg/dL result in a negative peritoneal Ca MT and can be useful to prevent and treat hypercalcemia in CAPD patients taking CaCO3 as phosphate binder. A careful monitoring of ionized calcium, PTH, and phosphate is suggested when an extensive and long-term use of this solution is considered.     

CRP、IL-18在慢性肾脏病患者中的表达及与CKD-MBD进展的关系

目的研究微炎症状态标志物C反应蛋白(CRP)、白细胞介素(IL)-18在慢性肾脏病(CKD)患者中的表达及与慢性肾脏病-矿物质和骨异常(CKD-MBD)进展的关系。方法将该院2016年1月至2019年6月收治的113例CKD患者纳为研究对象,根据美国肾脏病基金会(NKF-K/DOQI)相关标准,将其分为CKD1~2期组(22例)、CKD3期组(46例)、CKD4期组(30例)及CKD5期组(15例)。统计各组患者CKD-MBD发生率,检测患者血清CRP、IL-18及血清钙(Ca)、磷(P)、甲状旁腺激素(PTH)水平,分析不同分期患者血清CRP、IL-18水平与Ca、P、PHT的相关性。结果113例CKD患者中共59例发生CKD-MBD(52.21%),CKD-MBD发生率在CKD1~2、CKD3、CKD4、CKD5期组间呈依次上升趋势。血清CRP、IL-18水平在CKD1~2、CKD3、CKD4、CKD5期组间呈依次上升趋势,组间差异有统计学意义(P<0.05)。CKD3、CKD4、CKD5期组Ca水平差异无统计学意义(P>0.05),但3组Ca水平均明显高于CKD1~2期组(P<0.05),血清P及PTH水平在CKD1~2、CKD3、CKD4、CKD5期组间均呈依次上升趋势,组间差异有统计学意义(P<0.05)。相关性分析提示,CKD5期组患者血清CRP、IL-18水平与血清Ca呈负相关(r=-0.372、-0.369,P<0.05),与血清P及PTH呈正相关(r=0.421、0.253,0.433、0.272;P<0.05)。结论CKD患者CKD-MBD发生率较高,其微炎症状态与CKD-MBD密切相关,两者可能通过相互作用促进CKD发展。     

Effect of indapamide on urinary calcium excretion in patients with and without urinary stone disease

BACKGROUND: Indapamide is an antihypertensive agent similar to thiazides, but with some different effects. Thiazide and thiazide-like diuretics are useful in preventing recurrent urinary stone formation due to their hypocalciuric effects. OBJECTIVE: To determine the hypocalciuric and other effects on certain laboratory parameters of indapamide 1.5 mg in different patient groups. METHODS: Four groups of patients recruited from urology and nephrology outpatient departments were experiencing non-hypercalciuric urinary stone disease (group 1), idiopathic hypercalciuria (group 2), urinary stone disease with hypercalciuria (group 3), and essential hypertension (group 4). In all patients, fasting serum uric acid, calcium, sodium, potassium, cholesterol, triglyceride, parathyroid hormone (PTH) values, and morning second-spot urine calcium and creatinine levels were assessed before and 8 weeks after treatment with indapamide. RESULTS: Urinary calcium excretion was reduced significantly in all groups: group 1 from 0.10 +/- 0.02 to 0.07 +/- 0.03 (mean +/-SD; 30% reduction; p < 0.001), group 2 from 0.30 +/- 0.15 to 0.15 +/- 0.10 (50% reduction; p < 0.001), group 3 from 0.35 +/- 0.15 to 0.20 +/- 0.10 (43% reduction; p < 0.001), and group 4 from 0.10 +/- 0.03 to 0.08 +/- 0.02 (20% reduction; p < 0.0010). These results should be interpreted with caution since no control group was included in this study. Mean serum uric acid and triglyceride levels were significantly increased, and mean PTH and potassium levels and diastolic and systolic blood pressure were significantly decreased in all groups. Few temporary adverse effects, such as dizziness and fatigue, were noticed and none of them caused discontinuation of treatment. CONCLUSIONS: Indapamide 1.5 mg/day is effective in decreasing calciuria in patients with non-hypercalciuric urinary stone disease, idiopathic hypercalciuria, urinary stone disease with hypercalciuria, and essential hypertension. This could be achieved with few adverse effects similar to those of thiazides and indapamide 2.5 mg. Indapamide decreased the PTH levels in all groups. Long-term clinical benefits of these effects should be evaluated prospectively with further randomized studies.     

Evaluation of nutritional status and factors related to malnutrition in children on CAPD.

OBJECTIVE: The aim of this study was to investigate the nutritional status of children on continuous ambulatory peritoneal dialysis (CAPD) and to relate it to the dose of dialysis and serum levels of inflammatory cytokines and insulin-like growth factor-1 (IGF-1). PATIENTS: 17 CAPD patients (8 girls, 9 boys; mean age 13.1 +/- 3.5 years, median 15 years) were included in the study. Anthropometric measurements and serum albumin levels were used in the evaluation of nutritional status. Serum interleukin (IL)-1beta, IL-6, tumor necrosis factor alpha, and IGF-1 levels were determined in all CAPD patients and in a healthy control group. Weekly Kt/V and creatinine clearance (CCr) were measured to determine adequacy of dialysis. RESULTS: The mean dialysis period was 23.7 +/- 15.2 months (median 23 months). Anthropometric measurements and serum albumin level were as follows: height 130.2 +/- 15.6 cm, height standard deviation score (HtSDS) -4.2 +/- 2.4, body mass index (BMI) 16.3 +/- 1.6 kg/m2, body mass index standard deviation score (BMISDS) -0.8 +/- 0.9, triceps skinfold thickness (TST) 4.2 +/- 1.4 mm, midarm circumference (MAC) 16.21 +/- 2.3 cm, upper arm muscle area (AMA) 1799.1 +/- 535.7 mm2, upper arm fat area (AFA) 334.5 +/- 143 mm2, and serum albumin 3.1 +/- 0.7 g/dL. The BMI was above the fifth percentile in all patients; TST and MAC were below the fifth percentile in 14 patients (82.4%) and 10 patients (58.8%) respectively. The AMA was below the fifth percentile in 8 patients; however, the AFA was below the fifth percentile in all patients. Mean serum albumin level was under 3.5 g/dL in 70.5% of the children. We found significant positive correlations between BMI and Kt/V (r = 0.69, p < 0.01), CCr (r = 0.64, p < 0.05), and IL-6 (r = 0.61, p < 0.01). There was an inverse correlation between BMISDS and dialysis period (r = -0.58, p < 0.05); and between IL-6 and serum albumin (r = -0.49, p < 0.05). A significant positive correlation between BMISDS and serum IGF-1 level (r = 0.62, p < 0.01) was noted. We also found a significant positive correlation between serum IGF-1 level and both HtSDS (r = 0.57, p < 0.05) and TST (r = 0.52, p < 0.05). Significant positive correlations between AFA and CCr and IGF-1 were also noted (both r = 0.56, p < 0.05). CONCLUSION: Although many factors may be responsible for malnutrition and growth retardation, we found that prolonged period of dialysis, inadequate dialysis, and low IGF-1 levels are the most important risk factors in CAPD patients.     

Quantitative ultrasound in monitoring of skeletal status in adults with end-stage renal disease

The aim of the longitudinal study was to assess skeletal status in 29 subjects (18 males and 11 females) with end-stage renal disease (ESRD) being on regular hemodialysis. Control group consisted of 494 healthy subjects (305 males and 189 females). Skeletal status was evaluated by quantitative ultrasound measurements at the hand phalanges using DBM Sonic 1200 (IGEA, Carpi, Italy), which measures amplitude-dependent speed of sound (Ad-SoS, in m/s), performed three times: at the baseline, six and 12 months later. A precision expressed in root mean square-CV% was 0.72% in males and 0.43% in females. The values of Ad-SoS, T-score and Z-score at the baseline were significantly lower than in controls (p < 0.05). The mean values of Ad-SoS decreased over a period of observation; in the whole group from 1979 +/- 106 m/s to 1928 +/- 105 m/s, p < 0.0001, in males from 2003 +/- 93 m/s to 1949 +/- 111 m/s, p < 0.001 and in females from 1940 +/- 121 m/s to 1894 +/- 108 m/s, p < 0.05. Ad-SoS Z-scores dropped significantly over a period of the study in whole group (-1.14 +/- 1.64 to -2.08 +/- 2.26, p < 0.01), in males (-0.63 +/- 1.44 to -1.74 +/- 2.29, p < 0.0001) and in females nonsignificant decrease was observed. Using the least significant change (LSC) values for skeletal measurement, a decrease in Ad-SoS was noted in 15 subjects (52%). The values of PTH were over a normal limit. In the whole group main factors negatively influencing current Ad-SoS values were duration of dialysis, age and PTH. The skeletal status in subjects with ESRD on hemodialysis was seriously affected, and longitudinal measurements showed its aggravation over a time of the study.     

慢性肾脏病5期与5D期患者血清矿物质及骨代谢异常调查

目的比较慢性肾脏病(CKD)5期与5D期患者血清矿物质及骨代谢异常(MBD)状况。方法回顾性分析240例终末期肾脏病患者的临床资料。根据血液透析情况将患者分为CKD5期组(非透析)和CKD5D期组(已透析),比较2组血清矿物质及骨代谢相关指标(血清钙、磷、全段甲状旁腺素、碱性磷酸酶等),评估血钙、血磷和甲状旁腺激素的达标情况。结果CDK5D期组患者血清全段甲状旁腺素(iPTH)、校正血钙、钙磷乘积、血清白蛋白高于CKD5期组,估算肾小球滤过率(eGFR)低于CKD5期组,差异均有统计学意义(P<0.01)。CKD5期组、CDK5D期组患者高磷血症发生率分别为83.75%、91.25%,低钙血症发生率分别为31.25%、17.50%,高钙血症发生率分别为1.88%、30.00%,高甲状旁腺激素发生率分别为37.50%、63.75%。结论终末期肾脏病患者伴有严重的钙、磷和甲状旁腺激素指标异常,CKD5期患者突出表现为高磷、低钙和高甲状旁腺激素。CKD5D期患者的CKD-MBD状况并未因血液透析而得到改善,反而变得更加严重,突出表现为高磷、高钙和高甲状旁腺激素。     

Lack of relationship between serum and gallbladder bile calcium in patients with gallstone disease

BACKGROUND: Recent studies suggest that alternation in serum calcium influences the level of gallbladder bile ionized calcium (Ca2+). Theoretically, this could increase the risk of calcium precipitation in the gallbladder. METHODS: We therefore measured serum and gallbladder bile minerals in patients with gallstones (n = 27) and without (n = 10, controls). The serum samples were taken just prior to induction of anaesthesia and gallbladder bile was aspirated before any manipulation of the gallbladder. RESULTS: The active molality of Ca2+ in gallbladder bile was not statistically significant different between cases and controls (0.44 +/- 0.16 vs. 0.40 +/- 0.10 mmol/kg), whereas pH was significantly lower (6.94 +/- 0.31 vs. 7.36 +/- 0.28, p < 0.0001) and cholesterol higher (4.37 +/- 2.70 vs. 1.79 +/- 1.33 mmol/l; p < 0.01) in gallbladder bile obtained from cases. Serum Ca2+ at actual pH, magnesium and phosphate were significantly higher among cases than in controls. Gallbladder bile active molality of Ca2+ was significantly correlated with bile total calcium in both groups (r = 0.72; p < 0.001 and r = 0.91; p < 0.001, respectively). In controls only, we observed a positive relationship between serum Ca2+ at actual pH and the active molality of Ca2+ in bile (r = 0.61; p < 0.05). CONCLUSION: Our study demonstrates that Ca2+ in gallbladder bile does not differ between cases and controls. The lack of correlation between serum and gallbladder bile constituents in cases compared to controls suggests that changes in calcium equilibration between bile and serum in patients with gallstone disease might be of importance for the formation of gallstones.     

Aluminum-induced de novo bone formation in the beagle. A parathyroid hormone-dependent event.

To examine the influence of osteoblast function on aluminum-induced neo-osteogenesis in the mammalian species, we compared the effects of aluminum in sham-operated and thyroparathyroidectomized (TPTX) beagles. TPTX dogs received sufficient calcium carbonate and calcitriol to maintain normal plasma calcium and calcitriol levels, but developed evidence of decreased osteoblast recruitment and activity, including diminished osteoid-covered trabecular bone surface (3.22 +/- 0.21 vs. 10.95 +/- 1.30%) and a decreased osteoblast number (27.8 +/- 8.1 vs. 139.0 +/- 26.0/mm). Administration of aluminum (1.25 mg/kg i.v., three times/wk) increased the serum aluminum levels in both sham (1,087.0 +/- 276.0 vs. 2.7 +/- 0.8 micrograms/liter) and TPTX animals (2,786.0 +/- 569.0 vs. 3.6 +/- 0.8 micrograms/liter) above normal but did not alter the plasma calcium, creatinine, or PTH from control levels in either sham or TPTX dogs. After 8 wk of therapy, however, bone biopsies from sham-operated beagles displayed evidence of neo-osteogenesis including an increased bone volume (47.0 +/- 1.0 vs. 30.4 +/- 0.9%) and trabecular number (4.1 +/- 0.2 vs. 3.2 +/- 0.2/mm). Much of the enhanced volume resulted from deposition of poorly mineralized woven bone (9.9 +/- 2.7%). In contrast, biopsies from aluminum-treated TPTX animals exhibited significantly less evidence of ectopic bone formation. In this regard, bone (35.5 +/- 1.7%) and woven tissue volume (1.4 +/- 0.8%) as well as trabecular number (3.3 +/- 0.1/mm) were significantly less than those of the aluminum-treated controls. These observations illustrate that aluminum reproducibly stimulates neo-osteogenesis and induces a positive bone balance. However, this effect apparently depends on the availability of a functional osteoblast pool which, if depleted by TPTX, limits the expression of aluminum-induced new bone formation.     

Evidence that blood ionized calcium can regulate serum 1,25(OH)2D3 independently of parathyroid hormone and phosphorus in the rat.

This study asks whether arterial blood ionized calcium concentration (Ca++) can regulate the serum level of 1,25-dihydroxy-vitamin D3 [1,25(OH)2D3] independently of serum phosphorus and parathyroid hormone (PTH). We infused either PTH (bovine 1-34, 10 U/kg body wt/h) or saline into awake and unrestrained rats for 24 h, through a chronic indwelling catheter. PTH raised total serum calcium and arterial blood ionized calcium, yet serum 1,25(OH)2D3 fell from 35 +/- 6 (mean +/- SEM, n = 10) with saline to 12 +/- 3 pg/ml (n = 11, P less than 0.005 vs. saline). To determine if the decrease in serum 1,25(OH)2D3 was due to the elevated Ca++, we infused PTH into other rats for 24 h, along with varying amounts of EGTA. Infusion of PTH + 0.67 micron/min EGTA reduced Ca++, and 1,25(OH)2D3 rose to 90 +/- 33 (P less than 0.02 vs. PTH alone). PTH + 1.00 micron/min EGTA lowered Ca++ more, and 1,25(OH)2D3 increased to 148 +/- 29 (P less than 0.01 vs. saline or PTH alone). PTH + 1.33 micron/min EGTA lowered Ca++ below values seen with saline or PTH alone, and 1,25(OH)2D3 rose to 267 +/- 46 (P less than 0.003 vs. all other groups). Thus, during PTH infusion lowering Ca++ with EGTA raised 1,25(OH)2D3 progressively. There were no differences in serum phosphorus concentration or in arterial blood pH in any group infused with PTH. The log of serum 1,25(OH)2D3 was correlated inversely with Ca++ in all four groups infused with PTH (r = -0.737, n = 31, P less than 0.001), and also when the saline group was included (r = -0.677, n = 41, P less than 0.001). The results of this study indicate that serum 1,25(OH)2D3 may be regulated by Ca++ independent of PTH and serum phosphorus levels in the rat. Since 1,25(OH)2D3 regulates gastrointestinal calcium absorption, there may be direct feedback control of 1,25(OH)2D3, by its regulated ion, Ca++.     

Effect of valsartan on erythropoietin and hemoglobin levels in stage III-IV chronic kidney disease patients

Angiotensin-converting enzyme inhibitors (ACEIs) were accepted as a potential cause of inadequate epoetin response in chronic kidney disease (CKD) patients. We aimed to determine the effects of valsartan, an angiotensin receptor blocker (ARB), on serum ertyhropoietin levels and on certain biochemical and haematological parameters in hypertensive CKD patients. Twenty-two stage III-IV CKD patients (mean age; 56.8 +/- 8.9 years, 12 male 10 female) were included in the study. Before initiating the treatment, current anti-hypertensive treatments (if any) were discontinued, and blood samples were collected after a washout period of 3 weeks. Valsartan 80 mg/day was started, and additional anti-hypertensive agents were given according to study protocol if needed. One way Anova and paired t-tests were used for statistical comparisons. Serum blood urea nitrogen (BUN), creatinine, uric acid, potassium, haemoglobin and erythropoietin values were measured, and glomerular filtration rates were calculated before and 3, 6 and 90 days after valsartan treatment, a significant reduction in EPO level was observed at 3rd (19.6 +/- 24.0 vs. 13.8 +/- 8.5, p = 0.010), 6th (12.1 +/- 7.6, p = 0.009), and 90th days (8.3 +/- 5.4, p = 0.007). When pre-treatment values were compared with 90th day results, no significant change was observed in terms of hgb, htc, serum BUN, creatinine, uric acid, potassium, and GFR values. In conclusion, valsartan, an ARB, did not decrease haemoglobin levels in stage III-IV CKD patients despite significant reduction in serum erythropoietinlevels, so ARBs may be preferred to ACEIs in CKD patients when indicated.     

Do serum aluminum levels reflect underlying skeletal aluminum accumulation and bone histology before or after chelation by deferoxamine?

Patients undergoing dialysis may accumulate tissue aluminum burdens, and are at risk of developing two aluminum-associated syndromes, namely dialysis osteomalacia and encephalopathy. We address the clinical usefulness of serum aluminum levels in the diagnosis of dialysis osteomalacia. Twenty-four patients, 15 with dialysis osteomalacia and nine with clinically apparent secondary hyperparathyroidism, had serum aluminum levels measured before and after a standard infusion of a chelating agent, deferoxamine (DFO). Baseline serum aluminum levels were regarded as "high" (greater than 133 micrograms/L) if they exceeded 1 SD above the mean (74 micrograms/L) for a larger population of 152 patients undergoing routine hemodialysis. All patients had a bone biopsy for assessment of aluminum deposits by a specific histochemical stain. High serum aluminum levels had a diagnostic sensitivity of 60% in predicting those patients ultimately shown to have dialysis osteomalacia associated with histochemical evidence of aluminum accumulation in bone biopsy specimens; however, 40% of patients with histologic evidence of dialysis osteomalacia would have been missed if only serum aluminum had been used as a diagnostic test. Serum aluminum levels (+/- SEM) were 194 +/- 31 micrograms/L in patients with dialysis osteomalacia and 120 +/- 42 micrograms/L in those with secondary hyperparathyroidism (P greater than 0.05). Serum aluminum levels rose in all patients after DFO infusion to peak levels of 664 +/- 110 and 514 +/- 90 micrograms/L in patients with osteomalacia and hyperparathyroidism, respectively. However, neither the peak serum aluminum level nor its increment after DFO infusion distinguished between patients with osteomalacia and secondary hyperparathyroidism more effectively than did the baseline serum aluminum level.(ABSTRACT TRUNCATED AT 250 WORDS)