HISTOPATHOLOGIC DETERMINANTS OF HUMAN NEPHROLITHIASIS

人类肾结石的组织病理学决定因素

• 批准号: 7311588
• 负责人: ANDREW P EVAN
• 金额: $ 4.82万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7311588
• 关键词: apatites; computed axial tomography; cystine; histopathology; hydroxyapatites; hyperparathyroidism; immunocytochemistry; infrared spectrometry; jejunectomy /duodenectomy /ileectomy; lithotripsy; nephrolithiasis; osteoblasts; oxalates; pathologic process; polymerase chain reaction; renal tubule; stomach /intestine bypass; swine; urine acidity

Our histopathologic studies performed during the previous grant period have characterized the histopathological and mineral composition in three groups of stone formers: common idiopathic calcium oxalate stone formers, patients with stones due to intestinal bypass surgery for obesity and brushite stone formers (as well as non-stone formers) to test the hypothesis that Randall's plaque, calcium phosphate deposits in kidneys of patients with calcium renal stones, arise in unique anatomical regions of the kidney, their formation conditioned by specific stone-forming pathophysiologies. We were amazed at the finding, in that, each group of stone formers had a different and unique histopathologic pattern of crystal desposition while all intraparenchymal and interstitial sites of crystalline material were hydroxyapatite, yet another surprise. Because we were so highly successful in the last funding period in identifying a clear set of surgical/ morphological/metabolic characteristics in these three different groups of human stone formers (CaOx, intestinal bypass for obesity and brushite) and will extend these analyses to new groups of stone formers: apatite (including RTAs) stone formers, primary hyperparathyroidism with kidney stones, ileostomy with kidney stones, cystine stone formers, uric acid stones, bariatric patients with stones and CaOx stone formers with high urine pH (> pH 6.3) using histopathology,mu CT, and mu FTIR. In addition, we will seek to test a new set of hypotheses concerning the mechanisms of stone formation. First, we will test the hypothesis that the progression of HA accumulation occurs along a specific segment of the loops of Henle, the thin descending limb. Second, the mechanism of crystal particle formation and coalescence in the common CaOx patients will be determined by quantitative TEM and tetracycline studies. Third, test the hypothesis that there are candidate proteins that either promote or inhibit crystal nucleation and growth within the papillary interstitium or tubular lumens. This will be done using TEM immunohistochemical analysis to define the interaction of osteopontin, prothrombin fragment 1,fetuin-A and bikunin on interstitial and the plaque-stone interface. Fourth, we will use RT-PCR techniques to detect transcripts for the presence of osteoblast-like activity. Lastly, we will examine the idea that a loss of fluid pH control in the inner medullary collecting ducts due to SWL injury may result in an alkalization of the bulk urine and, therefore, give insights into the mechanisms of stone formation in brushite stone disease.

我们在上一个赠款期间进行的组织病理学研究表征了 histopathological and mineral composition in three groups of stone formers: common idiopathic calcium oxalate stone formers, patients with stones due to intestinal bypass surgery for obesity and brushite stone formers (as well as non-stone formers) to test the hypothesis that Randall's plaque, calcium phosphate deposits in kidneys of patients with calcium renal stones, arise in unique anatomical regions of the kidney, their formation以特定的石材形成病理生理为条件。我们对发现的发现感到惊讶，因为每一组石材形成者都有一种不同且独特的组织病理学模式的晶体贬低，而晶体材料的所有内核层面和间质部位都是羟基磷灰石，又是另一个惊喜。因为我们在最后一个资金期间非常成功，以确定一套清晰的外科手术/ morphological/metabolic characteristics in these three different groups of human stone formers (CaOx, intestinal bypass for obesity and brushite) and will extend these analyses to new groups of stone formers: apatite (including RTAs) stone formers, primary hyperparathyroidism with kidney stones, ileostomy with kidney stones, cystine stone formers, uric acid stones, bariatric patients with stones and CaOx stone formers with high使用组织病理学，MU CT和MU FTIR的尿液pH（> pH 6.3）。此外，我们将寻求测试有关石材形成机理的新假设。首先，我们将检验以下假设 HA积累的进展沿着亨勒环的特定段，薄的降肢。其次，普通CAOX患者中晶体颗粒形成和聚结的机制将由定量TEM和四环素研究确定。第三，检验以下假设：有候选蛋白可以促进或抑制乳头状间质或管状腔内内晶体成核和生长。这将使用TEM免疫组织化学分析来定义骨桥蛋白，凝血酶蛋白片段1，Fetuin-A和Bikunin在间隙和斑块 - 石界面上的相互作用。第四，我们将使用RT-PCR技术来检测成骨细胞样活性的转录本。最后，我们将研究以下想法：由于SWL损伤，由于SWL损伤而导致的内部髓质收集导管的流体丧失可能导致散装尿液的碱化，因此可以深入了解Brushite Stone病中石材形成机制。