肾病综合征患儿血清骨钙蛋白、血钙和24 h尿钙关系研究

目的探讨泼尼松导致骨质疏松的发病机理。方法用患儿自身对照形式将26例原发性肾病(单纯性肾病18例,肾炎性肾病8例)分激素治疗前组和激素足量治疗组两组,测定患儿血清骨钙蛋白、血钙和24h尿钙水平。结果血清骨钙水平在应用激素治疗4～8周后明显低于激素治疗前P<0.001),24h尿钙明显升高(P<0.001),血钙无明显变化;激素治疗后血钙与24h尿钙呈显著负相关(r=-0.536P<0.05)。结论肾病综合征患儿应用泼尼松治疗后骨合成明显下降,24h尿钙排泄增加的原因是骨吸收增强所致。     

用尿脱氧吡啶啉及羟脯氨酸排泄率评价肾病综合征患儿骨吸收功能状况

目的　观察糖皮质激素（激素）对肾病综合征(肾病)患儿骨吸收功能的影响。方法　采用酶联免疫竞争法和分光光度比色法,对68例泼尼松治疗不同阶段的肾病患儿及同龄健康儿童16例尿脱氧吡啶啉（DPD）及羟脯氨酸（HOP）进行检测。结果　（1）激素足量治疗组DPD/肌酐(Cr)为（30±17）nmol/mmol,较正常对照组［（21±5）nmol/mmol］、初发激素治疗前组［(20±8)nmol/mmol］及激素减量治疗组［(20±11)nmol/mmol］均有升高（P均<0.05);（2）与DPD/Cr值变化趋势一致,激素足量治疗组HOP/Cr为［(5.3±2.7)mg/mmol］,与正常对照组［(3.2±1.2)mg/mmol］、初发激素治疗前组［(3.5±0.9)mg/mmol］及激素减量治疗组［(3.7±1.7)mg/mmol］比较差异均有显著意义(P＜0.05,<0.01,<0.05);（3）DPD/Cr与HOP/Cr两指标在正常对照组及肾病各组均呈明显正相关(r=0.64、0.65、0.76、0.78,P均<0.01)。结论　超生理剂量的泼尼松治疗能使肾病患儿骨吸收功能增强,易导致骨质疏松。     

糖皮质激素对肾病综合征患儿骨代谢的影响

目的 探讨糖皮质激素(GC)对肾病综合征(NS)患儿骨代谢的影响.方法 选择30例NS患儿为NS组,予口服泼尼松2 mg·kg-1·d-1,采用中、长程疗法.治疗前及应用GC治疗4周后采集NS患儿静脉血,并留取晨尿,分别测定血Ⅰ型前胶原羧基末端前肽(PICP)、尿脱氧吡啶啉(DPD)排泄率.健康体检的15名学龄前儿童为健康对照组.结果 NS组患儿GC治疗前血清PICP水平、尿DPD排泄率与健康对照组比较,差异均无统计学意义(Pa>0.05);GC治疗后血清PICP水平较治疗前及健康对照组明显降低、尿DPD排泄率较治疗前及健康对照组明显增高,差异均有统计学意义(Pa<0.05).结论 长期应用GC对NS患儿骨骼代谢有潜在的影响.     

糖皮质激素对结核性脑膜炎患儿骨代谢的影响

目的探讨糖皮质激素对结核性脑膜炎患儿骨代谢的影响。方法选择初治结核性脑膜炎30例患儿,观察组予抗结核及糖皮质激素治疗;以同期住院的30例上呼吸道感染患儿作对照组。治疗前和治疗4周分别测定血清Ⅰ型前胶原羧基末端前肽(PICP)和尿脱氧吡啶啉(DPD)。结果结核性脑膜炎患儿激素治疗前血清PICP、尿DPD排泄率和对照组比较均无差异(P均>0.05);激素治疗4周后血清PICP(108.85±46.13)μg/L较治疗前(152.99±44.78)μg/L明显降低,差异有显著性(P<0.01):激素治疗4周后尿DPD的排泄率(28.93±9.27)nmol/L较治疗前(19.94±5.77)nmol/L明显增高,差异有显著性(P<0.01)。结论激素治疗4周即可引起结核性脑膜炎患儿骨形成减少和骨吸收增加。     

长期应用糖皮质激素对慢性血小板减少性紫癜患儿骨代谢的影响

目的探讨长期应用糖皮质激素对慢性血小板减少性紫癜患儿骨代谢的影响以及钙剂和维生素D的干预作用。方法将36例慢性血小板减少性紫癜患儿随机分为干预组(A)和未干预组(B),给予口服泼尼松1.5mg/(kg·d),4～6周后逐渐减量。疗程超过6月。干预组同时给维生素D330万IU1次口服,口服牡蛎碳酸钙75mg,Bid(牡蛎碳酸钙:每片150mg,东盛科技启东盖天力股份有限公司)。每周3天,共6月。治疗前及应用激素4周后采集患儿静脉血,分别测定I型前胶原羧基末端前肽(PICP),尿脱氧吡啶啉(DPD)和DPD排泄率。结果两组患儿糖皮质激素治疗前血清中PICP的浓度、尿中DPD的排泄率无显著性差异(P>0.05);干预组糖皮质激素治疗后血清中PICP的浓度、尿中DPD的排泄率与治疗前相比差异无统计学意义(P>0.05);未干预组糖皮质激素治疗后血清中PICP的浓度较治疗前明显降低、尿中DPD的排泄率较治疗前明显增高,差异均具有统计学意义(P<0.05)。结论长期应用糖皮质激素对慢性血小板减少性紫癜患儿骨骼代谢有潜在的影响,早期干预可以改善。     

糖皮质激素对肾病综合征患儿成骨细胞功能的影响

目的　糖皮质激素是治疗肾病综合征的首选药物。但糖皮质激素可抑制成骨细胞功能,导致骨质疏松。该研究通过检测成骨细胞不同分化阶段的生化指标:I型前胶原羧基端前肽(PICP)、骨钙素(BGP)和总碱性磷酸酶(AKP),探讨糖皮质激素对肾病综合征(NS)患儿成骨细胞功能的影响。方法　测定正常对照组(n=30),未治NS患儿(n=30)和激素治疗后NS患儿(每日泼尼松2mg/kg治疗4 ~8周,n=30)血清PICP、BGP及AKP水平。结果　未治NS患儿血清PICP165 ±56μg/L,BGP15 ±9ng/L水平明显低于正常对照组205 ±81μg/L, 19 ±12ng/L(均P<0. 05),而血清总AKP198 ±71U/L与正常对照组202 ±46U/L比较差异无显著性。激素治疗后NS患儿血清PICP85 ±56μg/L、BGP8±5ng/L、AKP104 ±59 U/L均明显低于未治NS患儿(P<0. 01)。结论　NS患儿本身存在骨合成障碍,大剂量糖皮质激素治疗可进一步抑制NS患儿的成骨细胞合成功能。     

糖皮质激素对肾病综合征患儿成骨细胞功能的影响

目的　糖皮质激素是治疗肾病综合征的首选药物。但糖皮质激素可抑制成骨细胞功能,导致骨质疏松。该研究通过检测成骨细胞不同分化阶段的生化指标:I型前胶原羧基端前肽(PICP)、骨钙素(BGP)和总碱性磷酸酶(AKP),探讨糖皮质激素对肾病综合征(NS)患儿成骨细胞功能的影响。方法　测定正常对照组(n=30),未治NS患儿(n=30)和激素治疗后NS患儿(每日泼尼松2mg/kg治疗4 ~8周,n=30)血清PICP、BGP及AKP水平。结果　未治NS患儿血清PICP165 ±56μg/L,BGP15 ±9ng/L水平明显低于正常对照组205 ±81μg/L, 19 ±12ng/L(均P<0. 05),而血清总AKP198 ±71U/L与正常对照组202 ±46U/L比较差异无显著性。激素治疗后NS患儿血清PICP85 ±56μg/L、BGP8±5ng/L、AKP104 ±59 U/L均明显低于未治NS患儿(P<0. 01)。结论　NS患儿本身存在骨合成障碍,大剂量糖皮质激素治疗可进一步抑制NS患儿的成骨细胞合成功能。     

泼尼松治疗肾病综合征患儿血清骨钙蛋白的动态变化

目的 通过测定泼尼松治疗肾病综合征患儿血清骨钙蛋白水平，了解患儿成骨细胞的功能变化。方法 实验分四组：激素治疗前组、激素足量治疗组、激素减量治疗组和对照组，测定4组血清骨钙蛋白含量。结果 在应用泼尼松治疗前血清骨钙蛋白水平已明显低于对照组(P＜0．01)，足量激素治疗后继续显著下降(P＜0．001)；而在激素减量治疗期间，血清骨钙蛋白水平渐升高，又与对照组相比无显著差异(P＞0．05)。结论 肾病综合征患儿血清骨钙蛋白随尿排出体外，应用激素治疗后患儿成骨细胞功能受到显著抑制，导致血清骨钙蛋白水平的降低；而采取隔日应用激素维持治疗阶段对患儿的成分细胞影响较小。     

小儿原发性肾病综合征足量糖皮质激素治疗前后血尿白介素-6检测及其临床意义

目的：白介素-6(IL-6)是原发性肾病综合征有肯定意义的细胞因子之一。该文探讨原发性肾病综合征患儿足量糖皮质激素治疗前后血、尿白细胞介素-6水平变化及其临床意义。方法：初治的原发性肾病综合征患儿38例,分别于足量激素治疗前和足量激素治疗8周后(或尿蛋白转阴2周后)用ELISA方法检测血、尿中白细胞介素-6的水平。比较激素敏感组和激素耐药组血、尿白细胞介素-6的含量。结果：激素治疗前,激素敏感组和激素耐药组血IL-6分别为118.74±31.18 ng/L和129.62±28.14 ng/L,均较对照组35.13±16.21 ng/L显著升高(P<0.05),激素敏感组和激素耐药组之间比较差异无显著性(P>0.05)。在激素治疗前激素敏感组和激素耐药组尿IL-6分别为14.19±4.87 ng/L和22.54±5.35 ng/L,均较对照组3.62±1.87 ng/L显著升高(P<0.05),而激素耐药组和激素敏感组比较差异有显著性(P<0.05)。激素治疗8周后,激素敏感组血、尿IL-6分别为41.68±18.94 ng/L和5.11±1.31 ng/L,均较治疗前显著降低(P<0.05),与对照组比较差异无显著性,而激素耐药组血、尿IL-6水平分别为115.53±24.65 ng/L,20.74±3.21 ng/L,与治疗前比较差异无显著性(P>0.05)。结论：血、尿IL-6对原发性肾病综合征激素敏感性的判断和预后估计有一定的参考价值。     

中性粒细胞明胶酶相关脂质转运蛋白在儿童原发性肾病综合征尿液中的表达及意义

目的：研究中性粒细胞明胶酶相关脂质转运蛋白（NGAL）在原发性肾病综合征患儿尿中的水平及其意义。方法：原发性肾病综合征初治患儿34例,经口服泼尼松足量治疗4周尿蛋白未转阴患者归入糖皮质激素耐药型肾病综合征（SRNS）组,尿蛋白转阴患者归入糖皮质激素敏感型肾病综合征（SSNS）组。所有病例在口服泼尼松治疗前、治疗1周、2周、3周、4周时分别收集晨起中段尿,采取ELISA法检测尿液NGAL浓度,同时测得尿中肌酐(Cr)值,采用尿Cr排出量来校正单次尿NGAL水平,比较两组间尿NGAL与Cr比值的表达差异。结果：与SRNS组比较,SSNS组病例尿标本中NGAL/Cr比值在泼尼松治疗3、4周时明显下降（P＜0.05）;与SRNS组比较,SSNS组病例尿标本中β2-MG/Cr比值在泼尼松治疗4周时才开始明显下降。SSNS与SRNS两组病例尿NGAL/Cr与尿蛋白/Cr比值呈正相关(r=0.510,P＜0.01)。ROC曲线下分析结果显示,用药3周后尿NGAL/Cr诊断截点为0.043时,敏感度和特异度分别为100%和79.2%。结论 ：SRNS患儿尿液中NGAL/Cr比值持续维持于高水平,而SSNS患儿尿液中NGAL/Cr比值在泼尼松治疗后逐渐下降,且其下降时间早于β2 MG/Cr比值,提示动态监测尿液中NGAL/Cr比值,有助于早期判断原发性肾病综合征的泼尼松治疗效应。     

Effect of different doses of vitamin D on osteocalcin and deoxypyridinoline in preterm infants

Background: Metabolic bone disease of prematurity is a common problem in preterm infants. The aim of the present paper was to measure the effect of vitamin D, in order to see the relation between vitamin D and urinary excretion of deoxypyridinoline (DPD), serum osteocalcin (OC), calcium (Ca), inorganic phosphorus (P), and alkaline phosphatase (ALP). Methods: Three different doses of vitamin D, 200 IU/kg (group 1, 11 infants), 400 IU/kg (group 2, 15 infants) and 800 IU/kg bodyweight/day (group 3, 11 infants), were administered to a total of 37 preterm infants between 15th day of birth until the 30th day of birth. Results: There were no significant differences in levels of serum Ca and P before and after vitamin D supplementation in all groups. Serum ALP levels were increased in all but significantly only in groups 1 and 3. Serum OC levels were also increased in each group by the treatment. Urinary DPD excretion was increased gradually by the increase in vitamin D intake, but it was significant only in group 3. Conclusion: High dose of vitamin D supplementation might accelerate bone turnover and increased urinary DPD levels might reflect increased bone resorption. To the best of the authors’ knowledge this is the first study comparing the effects of different vitamin D dose, by the means of urinary collagen cross‐links, on bone turnover in preterm infants.     

Biochemical markers of bone turnover,intact serum parathyroid hormone and renal calcium excretion in patients with pseudohypoparathyroidism and hypoparathyroidism before and during vitamin D treatment

In addition to the well-documented hyporesponsiveness of the kidney, resistance to parathyroid hormone (PTH) has been postulated for bone in pseudohypoparathyroidism type I (PHP). In some of these patients reduced bone density and even frank osteitis fibrosa suggest osteoclastic overactivity. To address the possibility that the skeletal system of patients with PHP may be affected by their increased PTH secretion we measured intact serum PTH and three biochemical markers of bone turnover in a large number of patients with PHP (n=20). The results were compared with subjects with low (hypoparathyroidism, HP, n=29), normal (controls, n=31) and high (primary hyperparathyroidism, 1°HPT, n=13) PTH secretion. Both markers of osteoblastic bone formation, alkaline phosphatase activity and osteocalcin concentration in serum, and one index of osteoclastic bone degradation, the urinary hydroxyproline/creatinine ratio (OH-P/Cr), were decreased in HP and increased in 1°HPT, whereas only OH-P/Cr was elevated in patients with PHP. Although intact serum PTH was significantly more increased in PHP than in 1°HPT, the markers of bone turnover were not significantly different in these two groups, suggesting some bone resistance in the patients with PHP. In these subjects intact serum PTH was elevated even at normocalcaemia during vitamin D treatment with a negative correlation with the respective serum calcium concentration (r=–0.69, P<0.001), indicating an elevated set-point for the suppression of their parathyroid glands. OH-P/Cr was negatively related to serum calcium in PHP, it normalized in most patients during normocalcaemia induced by vitamin D treatment. The urinary calcium excretion remained normal in the patients with PHP but was markedly elevated in patients with HP after the serum calcium levels had normalized during vitamin D therapy. In conclusion, the present and other studies suggest that the resistance to PTH in patients with PHP is mainly limited to the proximal kidney tubule and that the tendency to increased bone degradation implies either some response of the remodelling bone system to PTH or the result of marked secondary hyperparathyroidism overcoming a partial resistance of bone cells. The aim of vitamin D treatment in patients with PHP should therefore be an elevation of the serum calcium concentration into the high normal-range in order to suppress PTH secretion and thus bone degradation. In these patients the parathyroid glands are less sensitive to circulating calcium levels.Abbreviations AHO Albright's hereditary osteodystrophy - AMP adenosine monophosphate - AP alkaline phosphatase activity - Ca calcium - Ca/Cr urinary calcium/creatinine ratio - Cr creatinine - HP hypoparathyroidism - 1°HPT primary hyperparathyroidism - OH-P/Cr urinary hydroxyproline/creatinine ratio - PHP pseudohypoparathyroidism - PTH parathyroid hormone - SDS standard deviation score     

儿童急性淋巴细胞白血病化疗前后骨代谢研究

目的 　研究急性淋巴细胞白血病 (ALL)患儿化疗前后骨代谢状况。方法 　对 32例ALL患儿化疗前及化疗缓解后 3个月、1 2个月分别测定血清Ⅰ型胶原羧基端前肽 (PICP)、尿脱氧吡啶啉 (deoxypyridinoline ,DPD)排泄率并行骨骼X线检查 ,同期健康体检儿童 30例设为对照组。结果 　治疗前PICP及尿DPD排泄率较对照组增高 ,治疗后 3个月、1 2个月PICP较治疗前及对照组降低 ,尿DPD排泄率较治疗前下降 ,但仍高于对照组 ,经t检验 ,差异具有显著性 (P <0 0 1 )。结论 　ALL患儿治疗前存在骨质溶解 ,骨质吸收 ;化疗缓解后出现骨形成障碍 ,仍存在骨质吸收 ,可能与化疗药物应用有关。     

窒息新生儿尿中尿酸/肌酐比值的变化及意义

目的：探讨尿中尿酸/肌酐比值的变化在新生儿窒息及窒息后肾损伤中的意义。方法：对38例足月窒息新生儿(轻度窒息13例，重度窒息25例)和15例正常新生儿的尿中尿酸/肌酐比值及反映肾损伤指标N-乙酰-β-D-氨基葡萄糖苷酶(NAG)活性和β2-微球蛋白 (β2-MG)水平进行了检测。结果：与正常组［(0.56±0.20)，(2.73±2.50) U/L，(0.10±0.01) mg/L］相比，轻度窒息组尿中尿酸/肌酐比值、NAG，β2-MG水平［(1.19±0.53)，(10.34±8.72) U/L，(2.80±1.95) mg/L］显著升高(P<0.01)，重度窒息组尿中上述指标［(2.60±1.23)，(26.53±10.54) U/L，(5.05±2.19) mg/L］也显著升高(P<0.01)，且重度窒息组高于轻度窒息组(P<0.01)。在窒息组内，尿酸/肌酐比值与Apgar评分呈显著负相关关系(r为-0.63，P<0.01)，与NAG活性及β2-MG水平之间均呈显著正相关关系(r分别为 0.62，0.89，P<0.01)。结论：窒息新生儿尿中有较高的尿酸/肌酐比值，该比值有望成为反映新生儿窒息程度和窒息后肾损伤的早期指标。     

Renal osteodystrophy in children undergoing continuous ambulatory peritoneal dialysis

This paper describes a retrospective evaluation of the course of renal bone disease in 14 children undergoing treatment with continuous ambulatory peritoneal dialysis (CAPD) for an average of 11.9 +/- 1.5 months (mean +/- SE). The patients were divided in two groups according to the changes in serum alkaline phosphatase activity during the period of observation: five patients had alkaline phosphatase activity that decreased or was relatively stable (group I), and nine patients exhibited a rising serum alkaline phosphatase activity (group II). Serial radiological examinations showed adequate control of renal osteodystrophy in the patients of group I, whereas the patients of group II had no improvement or worsening of their bone disease. Group I had higher serum calcium and lower parathyroid hormone levels than group II at the end of period of observation despite similar dosage of vitamin D metabolite. The progression of bone disease was not related to the duration of CAPD or type of previous treatment for end stage renal disease. The observation that the radiological manifestations of secondary hyperparathyroidism were prevented in patients whose serum calcium levels were frequently above 2.62 mmol/liter (group I) while serum calcium levels between 2.25 and 2.50 mmol/liter in group II patients failed to lead to regression of secondary hyperparathyroidism is consistent with the existence of altered "set-point" regulation of the parathyroid gland in children undergoing CAPD.     

Effects of 12 months rhGH treatment on bone and collagen turnover in children with constitutional growth delay

Serum bone Gla protein (BGP), marker of osteoblast function, serum carboxyterminal cross-linked telopeptide of type I collagen (ICTP) and urinary free deoxypyridinoline (DPD), markers of bone resorption, and the aminoterminal propeptide of type III procollagen (PIIINP), marker of type III collagen turnover, were determined in eight prepubertal children (8 males, age range 7-9.6 yr, Tanner stage I) with constitutional growth delay (CGD), before and after 6-12 months of treatment with rhGH (Saizen, Serono, 0.6 IU/kg/week, s.c.). Serum BGP (mean+/-SD: 15.4+/-1.7 ng/ml), ICTP (9.4+/-1.6 ng/ml) and urinary DPD/creatinine (11.3+/-1.7 nmol/mmol) levels were significantly lower (p<0.02, p<0.0001 and p<0.02, respectively) in children with CGD than in healthy age-matched controls (BGP: 18.9+/-3.6 ng/ml, ICTP: 14.3+/-2.6 ng/ml, DPD: 20.7+/-10.0 nmol/mmol), while PIIINP levels of patients were similar to those recorded in controls (6.3+/-0.7 vs 6.7+/-2.3 ng/ml, respectively). Serum BGP, urinary free DPD/creatinine and PIIINP levels significantly increased after 6 (BGP: 20.9+/-2.1 ng/ml, p<0.0001; DPD/creatinine: 16.3+/-3.6 nmol/mmol, p<0.001; PIIINP: 8.1+/-1.6 ng/ml, p<0.005) and 12 months (BGP: 19.2+/-2.0 ng/ml, p<0.0001; DPD/creatinine: 19.7+/-5.1 nmol/mmol, p<0.001; PIIINP: 8.8+/-1.9 ng/ml, p<0.002) of GH treatment. Serum ICTP levels did not significantly change after 6 months (10.6+/-2.1 ng/ml), while a significant increase (p<0.002) was evident after 12 months of therapy (13.6+/-1.3 ng/ml). Our study shows that BGP, ICTP and DPD/creatinine levels are significantly reduced in children with CGD, thus indicating the presence of low bone turnover in this form of short stature. Since GH treatment is able to reactivate bone remodeling and increase collagen synthesis, it is tempting to speculate that a partial GH-IGF-I defect (i.e. locally at bone level) might be one of the factors involved in determining the biochemical alterations of bone metabolism found in this clinical condition.     

Efficacy of recombinant human growth hormone in children with juvenile rheumatoid arthritis and growth failure

Ten patients with juvenile rheumatoid arthritis (JRA) and growth failure were treated with recombinant human growth hormone (GH) for 1 to 3 years at a dosage of 0.57 IU/kg/wk. All the patients had been on prednisone at a mean dosage of 4.12 mg p.o. daily. GH was low in one patient, two patients had a borderline level and seven patients had adequate response to provocative tests or post-sleep measurement. Serum IGF-I was found to be low in five of six patients. Mean growth velocity increased from 2.45 cm/yr to 4.79 cm/yr after 1 year's treatment with GH (P<0.004). Six patients continued on GH treatment for a second year and continued to have a better growth velocity, with a mean of 5.43 cm/yr (P<0.014). Two patients entered puberty during the second year of GH treatment. This study demonstrates the potential beneficial effect of GH treatment in patients with JRA with growth failure of systemic onset or polyarticular onset who are on prednisone. Further study is needed to determine the long-term effect of GH treatment on ultimate height.