月见草油抑制草酸钙结晶形成的实验研究

目的了解月见草油在草酸钙结石形成中的作用,为临床治疗提供新的方法与思路。方法雄性SD大鼠60只,随机分为4组,各组15只。C组和D组以月见草油（含γ-亚麻酸9.2%）或葵花籽油（含亚油酸70%）10g/kg灌胃4周后,用诱石剂1%乙二醇（EG）加2%氯化氨喂饮,同时继续以月见草油或葵花籽油灌胃4周,8周后检测各组大鼠肾功能、24h血尿生化指标和肾草酸钙结晶情况;仅饲普通饲料（A组,空白组）和普通饲料加1%乙二醇（EG）加2%氯化氨喂饮（B组,成石组）大鼠作为对照。结果月见草油组肾组织水肿较轻,肾内草酸钙结晶数及肾成石率低于成石组（P〈0.05）,尿枸橼酸较成石组高（P〈0.01）,24h尿钙、尿草酸排泄均低于成石组（P〈0.01）,血尿素氮（P〈0.01）、血肌酐（P〈0.05）低于成石组。结论γ-亚麻酸能有效改善肾功能,减少尿钙及草酸的排泄,抑制实验鼠肾草酸钙结晶形成,在尿石症防治方面可能有一定应用价值。     

草酸钙晶体对大鼠肾小管上皮细胞损伤作用的实验研究

目的 通过研究一水草酸钙晶体粘附于体外培养的Wistar大鼠肾小管上皮细胞后引起的细胞功能变化，探讨尿路结石形成的机制。方法 分离、培养正常雄性Wistar大鼠的肾小管上皮细胞，在原代培养第5天时，将细胞分成3组（空白对照组，草酸组及一水草酸钙组），分别加入正常培养液，含有草酸钠（1、3、5mmol／L）的培养液及含有草酸钠（1、3、5mmol／L）和一水草酸钙晶体（5mmol／L）的培养液，实验8h后利用扫描电镜观察一水草酸钙晶体对肾小管上皮细胞的粘附情况，并分别用比色法测定细胞的钙镁ATP酶和钠钾ATP酶的活性，观察比较细胞功能的变化情况。结果 实验8h后，扫描电镜观察提示一水草酸钙组中有大量一水草酸钙晶体贴附于肾小管上皮细胞表面。①在三个草酸梯度浓度中，草酸组细胞钙镁ATP酶和钠钾ATP酶活性均未见明显下降，与对照组无显著性差异（P〉0．05）；②在三个草酸梯度浓度中，一水草酸钙组细胞钙镁ATP酶和钠钾ATP酶活性均明显下降。与对照组及草酸组有显著性差异（P〈0．05）；③在不同草酸浓度的一水草酸钙组间细胞钙镁ATP酶和钠钾ATP酶活性无显著性差异（P〉0．05）。结论 在高草酸环境下，对体外培养的Wistar大鼠的肾小管上皮细胞产生损伤作用的主要是一水草酸钙晶体而非游离草酸根离子。一水草酸钙晶体粘附于肾小管上皮细胞以后，可以造成细胞的损伤，这一机制可能有助于肾结石的发生。     

中药泽泻不同部位提取物对草酸钙结晶形成影响的体外实验研究

目的：探讨中药泽泻在体外对草酸钙结晶形成的影响。并初步确定其抑制草酸钙结石形成的有效部位。方法：应用种晶技术检测泽泻不同部位的提取物在体外对一水草酸钙晶体生长指数（G）的影响。结果：泽泻乙酸乙酯浸膏高。低剂量组的草酸钙晶体生长指数从32.37%分别降至3.86%,10.01%。结论：中药泽泻乙酸乙酯提取物能明显抑制草酸钙晶体的生长。是泽泻抑制草酸钙结石形成的有效部位。该部位的有效化学活性成分有待于进一步的研究。     

超声引导体外震波碎石术治疗泌尿系结石411例

我院自2001—09至2002—09，对411例泌尿系结石患，经B超引导体外震波碎石治疗，成功率为97．32％。现报告如下。     

草酸与草酸钙晶体损伤肾脏的机制研究进展

尿石症以肾结石多见，是一种严重影响人类健康的常见病和多发病，其中，80％以上的结石成分是草酸钙（CaOx）晶体。近年发现，暴露于高浓度草酸（0x）或CaOx晶体的肾脏上皮细胞会产生活性氧簇（ROS），导致自身损伤，细胞损伤的程度与晶体的浓度和接触晶体的时间成正比，     

尿草酸钙晶体基质蛋白的分离及理化特征

为了进一步了解晶体基质蛋白（ＣＭＰ）的理化特性和其在结石形成中的作用，利用ＤＥＡＥＳｅｐｈａｄｅｘＡ５０、ＳｅｐｈａｄｅｘＧ２００对草酸钙结晶中的基质蛋白进行了分离，并用ＳＤＳＰＡＧＥ、双向电泳和Ｗｅｓｔｅｒｎｂｌｏｔ进行检测。结果表明：ＣＭＰ是草酸钙过饱和方法制备的晶体基质中的主要成分，其分子量为３１０００，等电点为５．０～５．５；Ｗｅｓｔｅｒｎｂｌｏｔ证明与抗人凝血酶原抗体有交叉反应。结果认为ＣＭＰ是活化的人凝血酶原片段     

枸橼酸减轻草酸钙晶体对大鼠肾小管上皮细胞损伤作用的实验研究

目的 通过研究枸橼酸能否减轻一水草酸钙（calcium oxalate monohydrate，COM）晶体对体外培养的Wistar大鼠肾小管上皮细胞造成的损伤，以探讨枸橼酸在尿路结石防治中的作用及其机制。方法分离、培养正常雄性Wistar大鼠的肾小管上皮细胞，在原代培养第5天时，将细胞分成3组（空白对照组、COM组及枸橼酸组），分别于各组培养液中培养2h后用比色法测定各组细胞培养基中丙二醛（malonaldehyde，MDA）的含量及细胞的钙镁ATP酶（Ca`2＋-Mg`2＋-ATPase）和钠钾ATP酶（Na`2＋K`＋-ATPase）的活性。结果①COM组和枸橼酸组细胞Ca2＋-Mg`2＋ATPase和Na`＋＋K`＋-ATPase活性均明显低于对照组（P〈0．05）；②与枸橼酸组相比，COM组细胞Ca`2＋-Mg`2＋-ATPase和a`＋＋K`＋-ATPase活性下降更加明显（P〈O．05）；③COM组和枸橼酸组细胞培养基中MDA的含量均明显高于对照组（P〈O．05）；④与枸橼酸组相比，COM组细胞培养基中MDA的含量更高（P〈O．05）。结论外源性枸橼酸能够减轻一水草酸钙晶体对体外培养的Wistar大鼠肾小管上皮细胞造成的脂质过氧化损伤。     

排石汤对草酸钙泌尿系结石患者尿液成分的影响

目的探讨排石汤对经尿道输尿管镜碎石术(URL)后草酸钙泌尿系结石患者尿骨桥蛋白(OPN)、尿钙、尿草酸钙的影响。方法选取2018年6月至2022年6月在本院收治的80例草酸钙泌尿系结石患者, 随机分为对照组(40例)和观察组(40例)。观察组服用排石汤, 连用3个疗程;对照组给予同等量安慰剂(5%排石汤及食用色素组成)。分别检测两组患者术前、术后第1、7、14、21、28天的尿OPN、尿钙、尿草酸钙含量。结果与术前比较, 术后第7、14、21、28天两组的尿OPN含量均呈上升趋势, 尿钙、尿草酸钙含量均呈下降趋势, 差异均有统计学意义(均P<0.05);但术后第1天与术前比较, 两组的尿OPN、尿钙、尿草酸钙含量比较, 差异均无统计学意义(均P>0.05);而术后第7、14、21、28天, 观察组的尿OPN含量均高于对照组, 尿钙、尿草酸钙含量均低于对照组(均P<0.05)。结论草酸钙泌尿系结石患者URL术后应用排石汤, 对提高尿OPN含量及降低尿钙、尿草酸钙含量有明显帮助。     

高血糖在高草酸尿环境下促进肾草酸钙结石形成的机制研究

目的通过细胞及动物实验,探究高血糖促进草酸钙结石形成的机制。方法八周龄Wistar雄性大鼠(共40只)随机分为4组:阴性对照组、高草酸尿模型组,高血糖模型组,高血糖合并高草酸尿模型组;每组10只。采用q RT-PCR检测在含有不同浓度葡萄糖培养基下HK2细胞中OPN、MCP-1、Cbfa1、BMP-2 m RNA的表达;酶联免疫吸附测定(ELISA)检测OPN与MCP-1在培养基中的浓度;钙盐染色检测各组大鼠肾组织中草酸钙结石晶体;细胞凋亡试验检测各组大鼠肾组织中肾小管上皮细胞凋亡。免疫组织化学染色法(IHC)检测OPN在各组大鼠肾组织中的表达;ELISA检测MCP-1在各组大鼠24小时尿液中的含量。结果高浓度葡萄糖环境中,HK-2细胞的OPN与MCP-1表达上调。高血糖合并高草酸尿模型组肾组织中有大量草酸钙沉积,大量肾小管上皮细胞凋亡,OPN表达显著增加,其尿液中MCP-1总量明显增加,与其他组相比有统计学差异(P0.05)。结论高血糖能促使肾小管上皮细胞炎症趋化因子OPN、MCP-1表达增加。在高草酸尿环境中,高血糖能促进肾小管上皮细胞凋亡及草酸钙结石形成。高血糖可能是通过炎症趋化因子加重局部炎症反应,促进肾小管上皮细胞凋亡及草酸钙结石形成。     

针刺镇痛下体外冲击波碎石术的初步观察

针刺镇痛下施行体外冲击波碎石术（Ｅｘｔｒａｃｏｒｐｏｒｅａｌ Ｓｈｏｃｈ Ｗａｖｅ Ｌｉｔｈｏｔｒｉｐｓｙ，简称ＥＳＷＬ）４０例，另２０例使用镇静镇痛药物作对比。前者镇痛成功率分别为８５％（手法运针）和９０％（电针），后者为８０％。与镇痛有关的并发症，前者仅占１２．５％，后者为６５％。ｘ２检验Ｐ＜０．００５。作者认为，采用针刺镇痛施行ＥＳＷＬ具有安全、有效、易于掌握、并发症少等优点。     

Influence of cranberry juice on the urinary risk factors for calcium oxalate kidney stone formation

Cranberry juice is popular remedy for many ills; apart from the pleasant tasting many people drink it to help in preventing UTIs and stones. Authors from Cape Town (where there is the added benefit of an excellent climate) assessed the influence of cranberry juice on urinary risk factors for calcium oxalate calculi in a randomized crossover trial, showing that it has anti‐lithogenic properties. In the second paper, authors from Jerusalem report on 14 patients with distal ureteric strictures after kidney transplantation, all of whom were treated endourologically. They found transurethral incision of the distal ureteric stricture to be effective.

OBJECTIVE

To investigate the potential influence of cranberry juice on urinary biochemical and physicochemical risk factors associated with the formation of calcium oxalate kidney stones, as this product might affect the chemical composition of urine.

SUBJECTS AND METHODS

Urinary variables were assessed in a randomized cross‐over trial in 20 South African men (students) with no previous history of kidney stones. The first group of 10 subjects drank 500 mL of cranberry juice diluted with 1500 mL tap water for 2 weeks, while the second group drank 2000 mL of tap water for the same period. This was followed by a 2‐week ‘washout’ period before the two groups crossed over. During the experimental phase subjects kept a 3‐day food diary to assess their dietary and fluid intakes; 24‐h urine samples were collected at baseline and on day 14 of the trial periods, and analysed using modern laboratory techniques. Urine analysis data were used to calculate the relative urinary supersaturations of calcium oxalate, uric acid and calcium phosphate. Data were assessed statistically by analysis of variance.

RESULTS

The ingestion of cranberry juice significantly and uniquely altered three key urinary risk factors. Oxalate and phosphate excretion decreased while citrate excretion increased. In addition, there was a decrease in the relative supersaturation of calcium oxalate, which tended to be significantly lower than that induced by water alone.

CONCLUSION

Cranberry juice has antilithogenic properties and, as such, deserves consideration as a conservative therapeutic protocol in managing calcium oxalate urolithiasis.

     

钙敏感受体活性改变对大鼠泌尿系草酸钙结石形成的影响

目的探讨钙敏感受体（CaSR）活性改变对草酸钙结石形成的影响。方法在实验期间给予乙二醇和氯化铵诱导雄性SD大鼠产生泌尿系草酸钙结石。在造模期间给予不同剂量的CaSR抑制剂（NPS-2390）。实验结束时检测各组大鼠血尿素氮（BUN）、肌酐（Cr）、血磷、血钙、血镁、PTH的含量、24h尿量、尿pH值、尿钙、镁、尿草酸的分泌量,显微镜下观察肾组织切片中草酸钙结晶沉积及病理变化情况及肾脏中CaSR表达情况。从而评价CaSR活性的改变对泌尿系结石形成的影响。结果成石对照组大鼠血BUN、Cr、尿草酸、尿钙较空白组明显升高并且有大量结晶形成,表明建模成功。CaSR抑制剂组较成石对照组甲状旁腺激素（PTH）的分泌增加并且血Ca2＋升高尿钙升高。肾组织病理学检查显示CaSR抑制组的肾脏组织中的草酸钙结晶较成石对照组明显增加,组织病理损伤也较重。结论肾脏中及甲状旁腺中CaSR的表达下降可以导致草酸钙结晶的形成增加。     

Conversion of calcium oxalate to calcium phosphate with recurrent stone episodes

PURPOSE: We have extended our previous observation that the percent occurrence of calcium oxalate stones decreased while that of calcium phosphate stones increased with each new stone event. MATERIALS AND METHODS: The National VA Crystal Identification Center has analyzed veteran patient urinary tract stones from VA hospitals throughout the United States since 1983. We reviewed the composition of 33,198 stones with emphasis on the changes in composition. More than 11,786 stones came from 5,088 recurrent stone formers. Stones were analyzed using high resolution x-ray powder diffraction and Fourier transform infrared spectroscopic techniques. When the stones were investigated as a function of time, it was determined that there was greater variability when samples were more than 30 days apart. RESULTS: The percent occurrence of whewellite, weddelite, apatite, brushite and uric acid in stones increased between 1.0% and 5.9% since our previous study. The percent occurrence of struvite decreased by 2.6%. The percent of calcium oxalate stones decreased while that of calcium phosphate stones increased with each new event. However, the total percent occurrence of all calcium containing stones did not significantly change with recurrent stone events. CONCLUSIONS: Our study suggests a strong trend for the conversion of stone disease from calcium oxalate to calcium phosphate containing stones, which could influence the progression and severity of disease.     

尿液成分对草酸钙结石的影响

目的 探讨尿液成分对草酸钙尿结石形成的影响。方珐 应用红外光谱仪对50份尿结石标本进行成分检测；对16例一水草酸钙（COM）与10例二水草酸钙（COD）尿结石患者的24h尿液进行生化检测，并比较两组生化指标。结果 87．5％的c0M结石患者和90％的c0D结石患者24h尿量减少；COM结石患者尿钙（4．94±2．11）mmol／24h，COD结石患者尿钙（9．43±3．78）mmol／24h；差异有统计学意义（P〈0．01）；COM结石患者尿磷（20．50±8．76）mmol／24h，COD结石患者尿磷（28．38±10．21）mmol／24h，差异有统计学意义（P〈0．05）；87．5％的COM结石患者尿枸橼酸低于正常水平。结论 COD结石患者尿钙、尿磷高于COM结石患者，表明COD结石的形成与高钙尿和高磷尿有关；COM结石的形成可能与低尿枸橼酸有关。     

Parenteral ambroxol treatment causes xanthine and calcium oxalate stones in rats

INTRODUCTION: Ambroxol (ABX) is known to promote bronchial secretion and is used as an expectorant. This study was undertaken to document the connection between ambroxol parenteral treatment and bladder stones in rats. MATERIAL AND METHODS: Forty-five wild rats (Rattus sp.) were divided into three equal groups. Rats from the first and second groups received ABX s.c. during 2 weeks in total doses of 30 mg/kg per 24 h and 60 mg/kg per 24 h, respectively. Rats from the control group received 1 mL of injection solution s.c. One month after the treatment termination, animals were sacrificed and urinary tracts without urethra were dissected. Stones found in the bladders were measured, weighed and chemically analysed. Voiding cystography was performed to exclude pathology of the lower urinary tract. Photo documentation was produced. RESULTS: From the first and second groups, 33% and 47% of rats, respectively, had solitary stones in the bladder. In one case from the second group, there was a huge stone in the bladder and urethra. There were no stones in rats from the control group. The mean length of stones was 1.38 +/- 0.23 mm and 1.41 +/- 0.60 mm in the first and second groups, respectively. Mean stone weight was 1.2 +/- 0.2 x 10(-3) g and 1.44 +/- 0.54 x 10(-3) g. Stones were composed of 67% of xanthine and 33% of calcium oxalate. CONCLUSIONS: Ambroxol parenteral treatment caused xanthine and oxalate stone formation. Attention should be paid to the possibility of urinary stone formation after long-term ABX treatment.     

The role of glycoproteins in calcium oxalate crystal development

OBJECTIVE: To assess the effects of a glycoprotein (mucine) on calcium oxalate crystal development in different conditions and situations, to clarify some of its possible effects. MATERIALS AND METHODS: Crystallization was assessed using a batch system in presence of mucine suspensions, by kinetic-turbidimetric measurements, and using a flow system in the presence of retained agglomerates of mucine, evaluating the precipitated calcium oxalate. RESULTS: In batch conditions low mucine concentrations (<15 mg/L) inhibited calcium oxalate nucleation and higher concentrations (<250 mg/L) inhibited calcium phosphate nucleation, whereas at high concentrations there was also promotion. The presence of an aggregate of mucine in the flow system provoked calcium oxalate monohydrate crystallization at 0.691 microg/h per mg of mucine. In flow conditions pyrophosphate at 11.5 micromol/L caused a decrease of 84% in the calcium oxalate crystallized on mucine, 1.32 mmol/L of citrate a decrease of a 83%, 20 mg/L of pentosan polysulphate a decrease by 80%, and 7.58 micromol/L phytate totally prevented the crystallization of calcium oxalate on mucine. CONCLUSION: All substances inhibiting calcium oxalate crystallization with the capacity to interact with calcium ions also have crystallization promoting properties when they are at sufficiently high concentrations, because of their capacity to form agglomerates or the insolubility of their calcium salts.     

Intestinal oxalate absorption is higher in idiopathic calcium oxalate stone formers than in healthy controls: measurements with the [(13)C2]oxalate absorption test

PURPOSE: We assessed the importance of oxalate hyperabsorption for idiopathic calcium oxalate urolithiasis, oxalate absorption in healthy volunteers and recurrent calcium oxalate stone formers was compared. MATERIALS AND METHODS: The [(13)C2]oxalate absorption test, a standardized, radioactivity-free test, was performed. On 2 days 24-hour urine was collected and an identical standard diet containing 800 mg Ca daily was maintained. On the morning of day 2 a capsule containing 0.37 mmol sodium [(13)C2]oxalate was ingested. A total of 120 healthy volunteers (60 women and 60 men) and 120 patients (30 women and 90 men) with idiopathic CaOx urolithiasis (60% or greater CaOx) were tested. RESULTS: Mean intestinal oxalate absorption in the volunteers was 8.0 +/- 4.4%, and in the patients was 10.2 +/- 5.2% (p <0.001). There was no significant difference in mean absorption values between men and women within both groups. A high overlap between the absorption values of volunteers and patients was found. Only in the patient group did absorption values greater than 20% occur. Oxalate absorption correlated with oxalate excretion in the patients, r = 0.529 (p <0.01) and in the volunteers, r = 0.307 (p <0.01). CONCLUSIONS: In high oxalate absorbers dietary oxalate has a significant role in oxalate excretion and, therefore, increases the risk of calcium oxalate stone formation.     

4种大鼠肾草酸钙结石模型的比较

目的筛选简便、快捷、成石效果好的SD大鼠肾草酸钙结石的造模方法。方法分别采用目前普遍使用的2种大鼠肾草酸钙结石的模型复制方法和2种改良的造模方法进行造模,并设立空白对照组,造模结束后采集每组大鼠24h尿量及血清,比较大鼠24h尿量、尿Ca2＋、尿Mg2＋、尿pH、尿草酸（0x）及血尿素氮（BUN）、肌酐（cr）、P、Ca2＋、Mg2＋,肾脏病理切片HE染色后光学显微镜下观察和比较各组大鼠肾脏病理改变及草酸钙结晶的沉积情况。结果E组[1％乙二醇＋2％氯化铵＋10％葡萄糖（48d）]在光学显微镜下草酸钙结晶沉积较传统组C组明显增多（P〈0．05）,但有30％大鼠死亡,血肌酐在5组大鼠中最高。D组[1％乙二醇＋2％氯化铵＋10％葡萄糖（28d）]较传统组C组草酸钙结晶沉积明显增多（P〈0．05）,并且造模时间短,大鼠存活率高（80％）,E组与D组相比结晶形成量无统计学意义（P〉0．05）,B组[1％乙二醇（28d）3肾脏中无肾结晶形成,仅有轻微的肾脏病理学改变,大鼠无死亡,肌酐不高。空白对照组无结晶形成,无病理改变。结论用1％乙二醇＋2％氯化铵＋10％葡萄糖诱导28天复制肾草酸钙结石模型的效果好,并且花费时间短,大鼠存活率高,建议选用。     

瘦猪肉餐对草酸钙结石患者尿生化的影响

目的研究瘦猪肉餐对一水草酸钙（calciumoxalate monohydrate,COM）与二水草酸钙（calciumoxalate dehydrate,COD）结石患者尿生化的影响,探讨草酸钙结石形成的机制。方法正常人、COM与COD结石患者各6例,共18例同予以煮瘦猪肉350g食用,收集实验日晨5-7时2h尿为样本,餐后各留3次2h尿标本,测定尿pH值和尿晶体成分浓度;采用SPSS软件对检测结果进行方差分析。结果三组受试者瘦猪肉餐后尿钙、尿酸和尿草酸排泄逐渐增加,而尿量、尿pH值和尿枸橼酸降低;瘦肉餐前后比较,COM与COD结石患者尿pH值、尿枸橼酸、尿钙和尿草酸有显著性差异（P〈0.05）,尿酸排泄有极显著性差异（P〈0.01）;对照组,尿钙、尿酸排泄均有显著性差异（P〈0.05,P〈0.01）。结论大量饮食猪瘦肉可导致尿pH值和尿晶体成分变化,可能是尿结石形成的重要原因之一。     

The urinary response to an oral oxalate load in recurrent calcium stone formers

PURPOSE: Dietary oxalate may contribute up to 50% to 80% of the oxalate excreted in urine. We studied the urinary response to an oral oxalate load in male and female idiopathic recurrent calcium oxalate stone formers with and without mild hyperoxaluria to evaluate the potential pathophysiological significance of dietary oxalate. MATERIALS AND METHODS: A total of 60 recurrent calcium stone formers underwent an oral oxalate load test. Urine samples were obtained after an overnight fast. Each patient then received an oral oxalate load (5 mM. sodium oxalate dissolved in 250 ml. distilled water) and 3, 2-hour urine samples were obtained 2, 4 and 6 hours after the oxalate load. We compared the response to the oxalate load in patients with and without mild hyperoxaluria, and in male and female patients without hyperoxaluria. RESULTS: The peak urinary response occurred 4 hours after the oral oxalate load in all patients. Those with mild hyperoxaluria had a mean fasting urinary oxalate-to-creatinine ratio +/- SE of 0.027 +/- 0.003 and a mean peak urinary oxalate-to-creatinine ratio of 0.071 +/- 0.006. In comparison, patients with normal oxalate excretion had a fasting and peak urinary oxalate-to-creatinine ratio of 0.018 +/- 0.001 and 0.056 +/- 0.004, respectively (p <0.05). The mean 6-hour increment for urinary oxalate excretion after the oxalate load for patients with hyperoxaluria versus those with normal urinary oxalate excretion was 17.2 +/- 1.9 versus 12.1 +/- 0.98 mg. (p <0.05). In the subset of patients with normal urinary oxalate excretion mean 6-hour cumulative urinary oxalate excretion was 16.8 +/- 1.3 and 13.3 +/- 1.4 mg. in males and females, respectively (p not significant). CONCLUSIONS: Recurrent calcium stone formers with mild hyperoxaluria have higher fasting urinary oxalate and an exaggerated urinary response to an oral oxalate load compared with recurrent calcium stone formers with normal urinary oxalate excretion. Men and women stone formers without hyperoxaluria excrete similar fractions of an oral oxalate load. Increased gastrointestinal absorption and renal excretion of dietary oxalate may be a significant pathophysiological mechanism of stone formation in patients with mild hyperoxaluria.