The Expression and Implication of TRPV5,Calbindin-D28k and NCX1 in Idiopathic Hypercalciuria

The expression of calcium epithelium TRPV5, alcium binding protein Calbindin-D28k and Na＋/Ca2＋ exchanger NCX1 was detected in renal distal convoluted tubule, and their effects on urine calcium reabsorption and the possible pathogenic mechanism in idiopathic hypercalciuria （IH） were investigated. Genetic hypercalciuric stone-forming （GHS） rats were chosen as animal models to study urine calcium reabsorption and IH. The cognate female and male rats that had maximal urine calcium were matched to breed next generation. Twelve GHS rats and 12 normal control （NC） SD rats were selected. Western blot and real time quantitative PCR were used to detect the protein and gene expression of TRPV5, Calbindin-D28k and NCX1 respectively. The expression levels of TRPV5 protein and mRNA in GHS rats were significantly lower than in NC rats （P〈0.05）. Western blot revealed that the expression levels of Calbindin-D28k in GHS rats and NC rats were 0.49±0.02 and 0.20±0.01 respectively, with the difference being significant between them （P〈0.05）. By using real time quantitative PCR, it was found that there was no significant difference in Calbindin-28k mRNA expression levels between GHS rats and NC rats （P〉0.05）. There was no significant differ- ence in the NCX1 expression between GHS rats and NC rats （P〉0.05）. It was suggested that TRPV5 and Calbindin-D28k might play an important role in urine calcium reabsorption and IH, but they dif- ferently contributed to the pathogenesis： The down-regulation of TRPV5 decreases urine calcium reabsorption, directly leading to loss of the urine calcium and resulting in hypercalciuria, and the increased Calbindin-D28k expression could relieve, neutralize and decrease intracellular Ca2＋ concentration to maintain calcium balance. NCX1 is not the key protein in urine calcium reabsorption.

Should pediatric idiopathic hypercalciuria be treated with hypocalciuric agents?

BACKGROUND Hypercalciuria is the most common metabolic risk factor for calcium urolithiasis and is associated with bone loss in adult patients.Reduced bone mineral density(BMD)was already described in idiopathic hypercalciuria(IH)children,but the precise mechanisms of bone loss or inadequate bone mass gain remain unknown.Life-long hypercalciuria might be considered a risk to change bone structure and determine low bone mass throughout life.The peak of bone mass should occur without interferences.A beneficial effect of citrate formulations and thiazides on bone mass in adult and pediatric patients with IH have been shown.AIM To evaluate whether pharmacological therapy has a beneficial effect on bone mass in children and adolescents with IH.METHODS This retrospective cohort study evaluated 40 hypercalciuric children nonresponsive to lifestyle and diet changes.After a 2-mo run-in period of citrate formulation(Kcitrate)usage,the first bone densitometry(DXA)was ordered.In patients with sustained hypercalciuria,a thiazide diuretic was prescribed.The second DXA was performed after 12 mo.Bone densitometry was performed by DXA at lumbar spine(L2-L4).A 24-h urine(calcium,citrate,creatinine)and blood samples(urea,creatinine,uric acid,calcium,phosphorus,magnesium,chloride,hemoglobin)were obtained.Clinical data included age,gender,weight,height and body mass index.RESULTS Forty IH children;median age 10.5 year and median time follow-up 6.0 year were evaluated.Nine patients were treated with Kcitrate(G1)and 31 with Kcitrate+thiazide(G2).There were no differences in age,gender,body mass index z-score and biochemical parameters between G1 and G2.There were no increases in total cholesterol,kalemia and magnesemia.Calciuria decreased in both groups after treatment.Lumbar spine BMD z-score increased after thiazide treatment in G2.There was no improvement in G1.CONCLUSION Results point to a beneficial effect of thiazide on lumbar spine BMD z-score in children with IH.Further studies are necessary to confirm the results of the present study.

Beyond kidney stones:Why pediatricians should worry about hypercalciuria

The incidence of urolithiasis(UL)is increasing,and it has become more common in children and adolescents over the past few decades.Hypercalciuria is the leading metabolic risk factor of pediatric UL,and it has high morbidity,with or without lithiasis as hematuria and impairment of bone mass.The reduction in bone mineral density has already been described in pediatric idiopathic hypercalciuria(IH),and the precise mechanisms of bone loss or failure to achieve adequate bone mass gain remain unknown.A current understanding is that hypercalciuria throughout life can be considered a risk of change in bone structure and low bone mass throughout life.However,it is still not entirely known whether hypercalciuria throughout life can compromise the quality of the mass.The peak bone mass is achieved by late adolescence,peaking at the end of the second decade of life.This accumulation should occur without interference in order to achieve the peak of optimal bone mass.The bone mass acquired during childhood and adolescence is a major determinant of adult bone health,and its accumulation should occur without interference.This raises the critical question of whether adult osteoporosis and the risk of fractures are initiated during childhood.Pediatricians should be aware of this pediatric problem and investigate their patients.They should have the knowledge and ability to diagnose and initially manage patients with IH,with or without UL.

Bone disease in pediatric idiopathic hypercalciuria

Idiopathic hypercalciuria(IH) is the leading metabolic risk factor for urolithiasis and affects all age groups without gender or race predominance. IH has a high morbidity with or without lithiasis and reduced bone mineral density(BMD), as described previously in pediatric patients as well as in adults. The pathogenesis of IH is complex and not completely understood, given that urinary excretion of calcium is the end result of an interplay between three organs(gut, bone and kidney), which is further orchestrated by hormones, such as 1,25 dihydroxyvitamin D, parathyroid hormone, calcitonin and fosfatonins(i.e., fibroblast growth-factor-23). Usually, a primary defect in one organ induces compensatory mechanisms in the remaining two organs, such as increased absorption of calcium in the gut secondary to a primary renal loss. Thus, IH is a systemic abnormality of calcium homeostasis with changes in cellular transport of this ion in intestines, kidneys and bones. Reduced BMD has been demonstrated in pediatric patients diagnosed with IH. However, the precise mechanisms of bone loss or failure of adequate bone mass gain are still unknown. The largest accumulation of bone mass occurs during childhood and adolescence, peaking atthe end of the second decade of life. This accumulation should occur without interference to achieve the peak of optimal bone mass. Any interference may be a risk factor for the reduction of bone mass with increased risk of fractures in adulthood. This review will address the pathogenesis of IH and its consequence in bone mass.

Ca^(2+)诱导HK-2细胞焦亡及黏附性变化对含钙肾结石形成的分子机制研究

目的探究人肾皮质近曲小管上皮细胞(HK-2)经Ca^(2+)作用后的焦亡经典通路激活及黏附性变化对含钙肾结石形成的作用及机制。方法不同质量浓度的CaCl2(0、0.1、0.5、1.0、2.0、4.0、8.0 g/L)培养HK-2细胞24 h,使用细胞计数试剂盒(CCK-8)及流式细胞凋亡术检测筛选最佳处理浓度。使用透射电镜观察高钙环境下肾小管上皮细胞微结构的变化。在高钙处理后用2,7-二氯荧光素二乙酸酯(DCFH-DA)检测细胞内活性氧(ROS)的产生,并采用实时荧光定量聚合酶链式反应和Western blot法分别检测高钙刺激后HK-2细胞焦亡相关NOD样受体热蛋白结构域相关蛋白3(NLRP3)、胱天蛋白酶1(Caspase-1)、gasderminD(GSDMD)和黏附分子骨桥蛋白(OPN)、CD44的mRNA和蛋白表达水平变化,酶联免疫吸附试验检测白细胞介素(IL)-1β、IL-18和黏附分子单核细胞趋化蛋白1(MCP-1)在高钙刺激后的表达变化。结果Ca^(2+)对HK-2细胞生长具有细胞毒性并且可以促进其凋亡,Ca^(2+)浓度越高,对HK-2细胞生长的毒性越大且凋亡率越高。高钙可以促进HK-2细胞发生细胞膜完整性缺失、内容物释放及胞内大量空泡产生等焦亡样形态学改变。与对照组相比,1.0 g/L及2.0 g/L CaCl2组的ROS表达水平依次升高,焦亡相关基因NLRP3、Caspase-1、GSDMD、IL-1β、IL-18以及黏附相关基因OPN、CD44、MCP-1的mRNA和蛋白表达水平均依次升高(P<0.05)。结论高钙能使HK-2细胞发生氧化应激损伤并产生ROS,从而激活NLRP3炎症小体,进而导致细胞焦亡经典通路的激活和细胞黏附性的增加,最终间接促进肾结石的形成。

Hypercalciuria switches Ca^(2+) signaling in proximal tubular cells,induces oxidative damage to promote calcium nephrolithiasis

Proximal tubule(PT)transports most of the renal Ca^(2+),which was usually described as paracellular(passive).We found a regulated Ca^(2+)entry pathway in PT cells via the apical transient receptor potential canonical 3(TRPC3)channel,which initiates transcellular Ca^(2+)transport.Although TRPC3 knockout(−/−)mice were mildly hypercalciuric and displayed luminal calcium phosphate(CaP)crystals at Loop of Henle(LOH),no CaP+calcium oxalate(CaOx)mixed urine crystals were spotted,which are mostly found in calcium nephrolithiasis(CaNL).Thus,we used oral calcium gluconate(CaG;2%)to raise the PT luminal[Ca^(2+)]o further in TRPC3−/−mice for developing such mixed stones to understand the mechanistic role of PT-Ca^(2+)signaling in CaNL.Expectedly,CaG-treated mice urine samples presented with numerous mixed crystals with remains of PT cells,which were pronounced in TRPC3−/−mice,indicating PT cell damage.Notably,PT cells from CaG-treated groups switched their mode of Ca^(2+)entry from receptor-operated to store-operated pathway with a sustained rise in intracellular[Ca^(2+)]([Ca^(2+)]i),indicating the stagnation in PT Ca^(2+)transport.Moreover,those PT cells from CaG-treated groups demonstrated an upregulation of calcification,inflammation,fibrotic,oxidative stress,and apoptotic genes;effects of which were more robust in TRPC3 ablated condition.Furthermore,kidneys from CaG-treated groups exhibited fibrosis,tubular injury and calcifications with significant reactive oxygen species generation in the urine,thus,indicating in vivo CaNL.Taken together,excess PT luminal Ca^(2+)due to escalation of hypercalciuria in TRPC3 ablated mice induced surplus CaP crystal formation and caused stagnation of PT[Ca^(2+)]i,invoking PT cell injury,hence mixed stone formation.

Renal calcification in children with renal tubular acidosis:What a paediatrician should know

Renal tubular acidosis(RTA)can lead to renal calcification in children,which can cause various complications and impair renal function.This review provides pediatricians with a comprehensive understanding of the relationship between RTA and renal calcification,highlighting essential aspects for clinical manage-ment.The article analyzed relevant studies to explore the prevalence,risk factors,underlying mechanisms,and clinical implications of renal calcification in children with RTA.Results show that distal RTA(type 1)is particularly associated with nephrocalcinosis,which presents a higher risk of renal calcification.However,there are limitations to the existing literature,including a small number of studies,heterogeneity in methodologies,and potential publication bias.Longitudinal data and control groups are also lacking,which limits our understanding of longterm outcomes and optimal management strategies for children with RTA and renal calcification.Pediatricians play a crucial role in the early diagnosis and management of RTA to mitigate the risk of renal calcification and associated complications.In addition,alkaline therapy remains a cornerstone in the treatment of RTA,aimed at correcting the acid-base imbalance and reducing the formation of kidney stones.Therefore,early diagnosis and appropriate therapeutic interventions are paramount in preventing and managing renal calcification to preserve renal function and improve long-term outcomes for affected children.Further research with larger sample sizes and rigorous methodologies is needed to optimize the clinical approach to renal calcification in the context of RTA in the pediatric population.

The CALVIH Study: How to Handle Renal Stones in Persons Living with HIV1?

Background: Renal stone (RS) is a highly prevalent disease in our societies and is mostly secondary to lifestyle habits. HIV1 patients often experience RS, although specific risk factors are not known. Despite other priorities, comprehensive work-up should be offered to avoid recurrences (50% risk in 5 years). Purpose and Methods: The aim of the study is to describe how to handle RS in persons living with HIV1 and to suggest how the understanding of mechanisms involved in stone composition helps customize therapy and prevent recurrences. We prospectively performed a complete work-up in a cohort of 23 prevalent HIV1 patients referred to our highly-specialized center by HIV physicians. Results: Inclusion was secondary to a colic episode with spontaneous elimination of the stone (74%), bilateral (67%), not obstructive (67%);53% underwent urologic interventions. Mean age was 34 ± 16 years old and BMI was 22.5 ± 3 (one-third with metabolic syndrome). History of RS showed only one episode (22%), >one (74%) or >4 (4%). Estimated GFR was 78 ± 24 ml/min/1.73m2 (mean Cr 101 ± 24 μmol/L), and 5 were classified CKD stage 3. Stone analysis was only available for 7 patients and in 6/7 patients, and calcium metabolism was fully explored (2 absorptive hypercalciuria, 4 renal primitive hypercalciuria). Retained mechanism for RS was uric acid dependent for one, oxalic acid dependent for three and calcium dependent for three. Very few patients were exposed to known environmental risk factors for RS, 3 were/had been exposed to darunavir and 3 to atazanavir, 1 to efavirenz, 1 to acetazolamide, 2 to allopurinol. Conclusion: RS in HIV1 patients is mostly not related to ARV. Understanding of renal stone composition is critical to prevent recurrences by offering specific dietetic counselling and therapy. The role of HIV physicians is important due to the high prevalence of RS in the context of HIV disease.

云南德宏州傣族人群CaSR基因SNP与含钙肾结石和高钙尿的关联性

目的研究云南德宏州傣族人群CaSR基因多态性与含钙肾结石和高钙尿的相关性。方法云南德宏州的傣族含钙肾结石患者为实验组,云南德宏州的体检健康傣族人群为对照组,抽静脉血进行CaSR基因3个SNP位点rs7652589、rs1801725、rs1042636测定,结石组研究对象行24 h尿钙值测定,进行基因相关对比分析。结果rs7652589位点纯合AA型基因者与AA+GG基因者在含钙肾结石的发生对比分析,差异具有统计学意义(P<0.05)。rs1042636位点的GG型基因者的24 h尿钙值与AA和AG基因型者对比,差异具有统计学意义(P<0.05)。rs7652589位点GG型基因者24 h尿钙与AA和AG型基因者对比,差异具有统计学意义(P<0.05)。结论云南德宏州傣族人群中CaSR基因上的rs7652589位点多态性与含钙肾结石和高钙尿的发生有关,rs1042636位点的GG型基因与傣族高钙尿发生相关,rs7652589位点GG型基因可能是该民族发生高钙尿和含钙肾结石的候选基因。

特发性高钙尿症患者维生素D受体基因多态性研究及其临床意义

目的 :探讨维生素D受体 (VDR)等位基因多态性与特发性高钙尿症的关系 ,并分析其临床意义。方法 :筛选 36例特发性高钙尿症患者 ,采用PCR -RFLP法检测其VDR基因的Taq1、Apa1、FokⅠ多态性 ,并分析其与特发性高钙尿症的相关性。结果 :特发性高钙尿症组与健康组之间 ,启动子FokⅠ等位基因各基因型频率存在显著性差异 (P <0 .0 5 ) ,基因型为ff型者 2 4h尿钙含量显著高于同组的其它基因型 (P <0 .0 5 )。Apa1、Taq1基因多态性在两组之间并无显著差异。结论 :特发性高钙尿症与VDR基因启动子Fok1等位基因多态性有关 ,而与VDR基因Apa1和Taq1多态性无关 ,ff型等位基因有可能成为特发性高钙尿症的遗传标志基因。

未成年人尿钙与肌酐比值测定及其意义

目的 :探讨未成年人尿钙 /肌酐 (Ca2 + / Cr)比值的分布特征、影响因素及其对高钙尿症的诊断价值。 方法 :对上海1833例 3～ 18岁未成年人行尿钙、尿 Cr普查测定 ,15 4例行 2 4h尿钙定量分析。结果 :尿 Ca2 + / Cr值呈偏态分布 ,其第 95百分位数为 0 .2 85 ,与性别无关 ,但不同年龄和地区之间略有差异。对高钙尿症诊断的敏感性为 98.9% ,特异性为 5 9.0 %。结论 :尿 Ca2 + / Cr测定是一简便而实用的高钙尿症筛选试验 ,其标准应考虑受检对象的年龄和所在地区的影响。

特发性高钙尿肾结石患者肾乳头组织中Runx2、Osterix的表达

目的研究成骨样细胞转录因子Runx2、Osterix在特发性高钙尿(idiopathic hypercalciuria,IH)肾结石患者肾乳头组织中的表达,以及IH患者结石形成的发病机制。方法筛选华中科技大学同济医学院附属同济医院IH肾结石患者8例(IH组),排除各种已知影响血清钙或者尿钙的继发疾病;另选取同期因肾肿瘤或非结石所致的无功能肾需要行肾切除术的患者8例作为对照(NC组)。取16例患者肾乳头组织标本若干,采用实时荧光定量PCR和Western blot检测Runx2和Osterix mRNA以及蛋白的表达水平。结果 IH组Runx2mRNA表达量为(1.437±0.115),而NC组Runx2mRNA表达量为(1.037±0.027),两组间差异有统计学意义(P<0.05);IH组与NC组Osterix mRNA的表达量分别为(1.826±0.462)和(1.030±0.072),差异有统计学意义(P<0.05)。Western blot检测Runx2蛋白在NC组和IH组表达分别为(1.585±0.389)和(1.642±0.395),差异无统计学意义。Osterix蛋白在NC组和IH组表达量分别为(1.138±0.143)和(1.621±0.164),差异有统计学意义(P<0.05)。结论 IH肾结石患者肾乳头Runx2和OsterixmRNA表达增强为间质异位钙化特征,结石形成的病理过程可能与正常骨发生机制生理过程类似。

高钙离子诱导人肾小管上皮细胞表达MCP-1和HMGB1

目的:观察体外培养的人肾小管上皮细胞在高钙离子环境下细胞损伤及炎性因子MCP-1和HMGB1的表达。方法:体外培养人肾小管上皮细胞(HK-2细胞),使用Ca Cl_2配制成不同钙离子浓度的溶液作为刺激剂,实验分为正常对照组(正常培养液)、Ca Ⅰ组(5 mmol/L Ca^(2+)液)、Ca Ⅱ组(10 mmol/L Ca^(2+)液)和Ca Ⅲ组(15 mmol/L Ca^(2+)液)。各组细胞分别培养至3 h、6 h、9 h时,采用MTT法检测细胞活力。培养6 h时,采用4',6-二脒基-2-苯基吲哚(DAPI)进行细胞凋亡染色,观察各组细胞凋亡情况;同时收集细胞培养上清液,采用ELISA法分别检测各组细胞上清液过氧化氢(H_2O_2)和8-异前列烷(8-IP)浓度,微量酶标仪法检测各组细胞上清液乳酸脱氢酶(LDH)活性。此外,培养6 h时收集各组细胞,采用real-time PCR法检测细胞MCP-1和HMGB1的mRNA表达情况;并收集各组细胞上清液,采用ELISA法检测其MCP-1和HMGB1的含量。结果:随着细胞培养液中钙离子浓度的增加,细胞活力抑制率和细胞凋亡明显增加。LDH活性、细胞上清液H_2O_2的浓度和8-IP的含量在Ca Ⅰ组、Ca Ⅱ组和Ca Ⅲ组均较正常对照组高(P<0.05)。real-time PCR的结果显示,与对照组比较,3个钙离子诱导组细胞MCP-1和HMGB1的mRNA表达水平升高,差异有统计学显著性(P<0.05)。此外,3个钙离子诱导组细胞上清液MCP-1和HMGB1含量均较正常组高(P<0.05)。结论:本研究结果提示,高钙离子可诱导人肾小管上皮细胞出现氧化应激损伤,同时细胞高表达MCP-1和HMGB1。由MCP-1和HMGB1引发的炎症反应可能是高钙尿参与结石形成的重要机制。

小儿Dent病临床特征和基因突变分析

目的探讨小儿Dent病的临床特征和分子遗传学特点。方法以2例拟诊的Dent病患儿及其家系中的女性为研究对象。盐析法从外周血白细胞提取基因组DNA,PCR扩增CLCN5基因所有的编码序列,PCR产物直接测序。结果2例患儿均有小分子量蛋白尿和高钙尿症,其中1例有肾脏钙化,2例肾功能均正常。在这2个家系发现了2个CLCN5基因的突变,分别为L594fsX595和R637X,其中L594fsX595为新发现的突变。结论持续性小分子量蛋白尿和高钙尿症是国内小儿Dent病的主要临床特征,并证实了我国Dent病患儿存在CLCN5基因的突变。

大鼠低摄钙相关性高草酸尿症模型的建立

目的建立大鼠低摄钙相关性高草酸尿症模型并进行初步探讨。方法健康雄性SD大鼠24只,用随机区组设计法分为低剂量钙组、中等剂量钙组及高剂量钙组,连续喂养3 d,各组大鼠在3 d内分别依次给予剂量递减的饮食钙。测量大鼠每天的24 h尿量、尿草酸浓度、尿肌酐浓度并计算24 h尿草酸总排泄量。其中,尿草酸浓度用高效液相色谱法检测,尿肌酐浓度用自动生化分析仪检测。结果 24 h尿草酸总排泄量随时间变化而变化(F=7.893,P<0.01);时间因素与分组因素之间无交互作用(F=1.142,P>0.05);24 h尿草酸总排泄量随分组变化而变化(F=3.565,P<0.05)。3组大鼠第3天的24 h尿草酸总排泄量均显著高于第1天(P<0.05)。结论通过控制饮食钙摄入水平,成功建立了大鼠低摄钙相关性高草酸尿症模型。

维生素D受体在特发性高钙尿症发病机制中的作用

特发性高钙尿症(idiopathic hypercalciuria,IH)是病因未明的尿钙增多而血清钙正常的钙代谢异常,是尿路结石形成的重要危险因素。患者肠道钙吸收增加、骨再吸收增加及肾尿钙再吸收减少而导致高钙尿。目前利用动物模型对该病发病机制进行了较深入的研究,发现维生素D受体(Vitamin D receptor,VDR)基因多态性、VDR表达增加及其调控蛋白的异常在IH基本的发病机制中起重要作用。

羟乙膦酸钠对实验性高钙尿症的防治作用及其机制

目的 :观察骨吸收抑制剂羟乙膦酸钠对实验性高钙尿症的防治作用 ,并探讨其可能机制。 方法 :建立大鼠实验性高钙尿症模型 ,观察羟乙膦酸钠治疗后 2周和 4周的尿钙 ,Ca2 + / Cr,NAG/ Cr,以及肾和十二指肠 Ca2 + - ATP酶 (钙泵 )的变化。结果 :2周时尿钙 ,Ca2 + / Cr,血 AL P虽有所升高 ,但 4周时尿钙 ,Ca2 + / Cr,NAG/ Cr及血 AL P均显著下降 (P<0 .0 1) ,2 4h尿钙定量与尿 NAG/ Cr值呈正相关 ;而靶组织钙泵活性无显著改变。 结论 :骨吸收抑制剂具降尿钙和保肾作用 ,其机制不依赖钙泵活性的改变。

高钙尿症和低镁血症在Bartter综合征和Gitelman综合征分型中的临床价值

目的评价血镁和尿钙水平在Bartter综合征(Bartter syndrome,BS)和Gitelman综合征(Gitelman syn-drome,GS)中鉴别诊断的价值。方法选取北京儿童医院临床诊断为BS和GS患儿72例,以尿钙/肌酐>0.2作为高钙尿症的标准,以血镁<0.8 mmol/L作为低镁血症的标准,对72例患儿进行分组,比较高钙尿症组与尿钙正常组、低镁血症组与血镁正常组发病年龄、生长发育指标和电解质水平的差异。结果 72例患儿中,男52例,女20例;年龄2个月至15.5岁,平均(5.55±4.59)岁。患儿就诊时常无典型的症状,以发热咳嗽(25.0%)、生长发育迟缓/矮小(22.2%)、呕吐(18.1%)、四肢无力(13.9%)为主。高钙尿症组患儿年龄低于尿钙正常组[(2.64±2.95)岁vs.(7.76±4.49)岁,P=0.00];体重的标准差积分值(standard deviation score,SDS)低于尿钙正常组,分别为(-2.57±1.11)SDS和(-1.59±1.26)SDS(P=0.005),但身高和BMI的SDS值2组间差异无统计学意义。血镁正常组患儿体重和BMI的SDS值低于低镁血症组,分别为(-2.42±1.60)SDS vs.(-1.42±1.13)SDS(P=0.005),(-1.82±1.77)SDS vs.(-0.82±1.37)SDS(P=0.018);且血镁正常组患儿年龄也低于低镁血症组,分别为(3.78±4.14)岁和(7.66±4.47)岁(P=0.00)。结论年龄是BS患者的危险因素。小年龄患儿出现高钙尿症,常伴有BMI降低和发育落后,但血镁水平正常;低镁血症易出现在大年龄患儿,且预后相对较好。通过检测尿钙和血镁水平,可有助于BS和GS患者亚型的分析并提供个体化诊疗。

舒林酸对实验性高钙尿症的防治作用

目的：观察新型非类固醇类抗炎药—舒林酸对实验性高钙尿症的防治作用，探讨其可能机制。 方法：建立大鼠实验性高钙尿症模型，观察舒林酸治疗后２ 周和４ 周尿 Ｃａ 、尿 Ｃａ／ Ｃｒ 、尿 Ｎ Ａ Ｇ／ Ｃｒ 以及肾和十二指肠 Ｃａ２ ＋ Ａ Ｔ Ｐ 酶（ 钙泵） 的变化。 结果：２ 周和４ 周时尿 Ｃａ 、尿 Ｃａ／ Ｃｒ 、尿 Ｎ Ａ Ｇ／ Ｃｒ 及肾和十二指肠 Ｃａ２ ＋ Ａ Ｔ Ｐ 酶均显著下降（ Ｐ＜ ００１） ，２４ｈ 尿钙定量与尿 Ｎ Ａ Ｇ／ Ｃｒ 值呈正相关（ Ｐ＜ ００１） 。 结论：舒林酸对高钙尿症具降尿钙和保肾作用，其机制可能与下调维生素 Ｄ 靶组织钙泵活性有关。

CLDN16基因突变致家族性低镁血症高钙尿症伴肾钙质沉着症基因型与表型特点分析

目的探讨以严重佝偻病为主要表现的CLDN16基因突变致家族性低镁血症高钙尿症伴肾钙质沉着症(FHHNC)的基因型与临床表型特点。方法回顾性分析1例以严重佝偻病为主要表现的FHHNC患儿的临床资料及相关检查结果,并进行家系调查及基因测序。结果体格检查示患儿发育落后,特殊面容(鼻梁塌平、眼距宽、颈短),鸡胸,四肢弯曲畸形,肘关节及膝关节膨大,被动盘腿坐位。实验室检测结果示血钙、血镁降低,尿钙升高,25-羟基维生素D降低。影像学检查结果示骨骼系统异常。全外显子基因测序提示患儿CLDN16基因存在“错义变异C.647G>A,p.Arg216His(纯合子)”,患儿父母携带该位点变异(杂合子)。结合相关检查结果明确诊断为FHHNC。结论FHHNC由CLDN16/CLDN19基因突变引起,以低镁血症、高钙尿症、肾钙质沉着症以及进行性慢性肾功能衰竭为特征,可伴佝偻病等骨骼系统异常。全外显子基因测序可辅助诊断FHHNC。