尿凝血酶原片断1在肾结石模型大鼠肾组织的表达及其意义

目的　研究尿液中尿凝血酶原片段 1(UPTF1)的来源和UPTF1在肾结石模型大鼠肾组织的表达 ,探讨尿结石形成对肾组织UPTF1表达的影响及其在尿结石形成中的意义。方法用乙二醇和 1α 羟基维生素D3 灌胃制作大鼠肾草酸钙结石模型。采用半定量逆转录聚合酶链反应(RT PCR)检测UPTF1mRNA在结石模型大鼠和正常对照大鼠肾组织中的表达及水平变化。结果　偏光显微镜下结石模型大鼠肾乳头和肾皮质内布满草酸钙晶体 ,肾钙含量、2 4h尿草酸和尿钙分泌量分别为 13 8.3 9mg/g、82 .89μmol和97.3 5 μmol;对照组肾钙含量、2 4h尿草酸和尿钙分泌量分别为 1.5 4mg/g、2 4.2 2 μmol和3 .14 μmol,组间差异均有统计学意义(P <0 .0 1)。UPTF1mRNA在所有大鼠肾组织和肝组织中都有表达 ,但在正常大鼠和肾结石大鼠肾组织中的相对表达量分别为 1.73± 0 .2 5、1.86± 0 .19,两组差异无统计学意义意义 (P >0 .0 5 )。结论　尿液中的UPTF1来源于大鼠肾组织的生物合成 ,可能是草酸钙结石形成的生理性抑制因子 ,从而可以借助实验动物模型为研究UPTF1在尿结石形成中的作用提供了依据。     

转化生长因子在先天性肾积水中的表达研究

目的：探讨先天性肾积水转化生长子因子β1(TGF-β1)mRNA及蛋白表达变化的临床意义。方法：应用免疫组化及原位杂交方法对15例患肾、10例正常肾组织进行染色观察。结果：患肾组织TGF－β1蛋白及mRNA表达均增高,大部分近曲小管、少数肾小球、极少数远曲小管细胞浆内可见TGF－β1蛋白强阳性表达。大部分近曲小管的部分细胞核、极少数肾小球细胞核内可见TGF－β1mRNA的中度阳性表达。患肾肾盂及肾盂输尿管连接处狭窄段肌细胞和间质梭形细胞胞浆及胶原纤维内TGF－β1蛋白及mRNA表达增高。结论：先天性肾积水患肾组织TGF-β1表达增高可能与慢性肾损伤及间质纤维化有关。     

凋亡抑制基因bcl-2在前列腺组织中的表达

目的　探讨前列腺组织中bcl 2基因表达的意义。　方法　采用核酸分子原位杂交技术 ,对 11例胎儿和 2 7例成人尸体前列腺组织、6 0例良性前列腺增生患者前列腺组织中bcl 2基因mRNA表达进行检测。　结果　 9例胎儿前列腺组织bcl 2阳性表达于胚芽上皮细胞 ,其中轻度阳性8例、中度 1例 ,呈弥漫分布 ,染色浅淡。 17例成人正常前列腺组织bcl 2阳性表达于腺上皮基底细胞 ,阳性率 6 3.0 %。分泌细胞阳性表达者 9例 ;高倍镜下见细胞浆染色 ,较淡。 5 0例增生前列腺组织bcl 2阳性表达于腺上皮基底细胞 ,阳性率 83.4 % ;分泌上皮细胞阳性表达 34例 (5 6 .7% ) ;高倍镜下染色均见于细胞浆。增生组前列腺基底细胞、分泌上皮细胞bcl 2阳性表达均高于正常前列腺组 (χ2=4 .36 ,χ2 =4 .0 6 ) ,差别有显著性意义 (P <0 .0 5 ) ;正常前列腺与增生前列腺基底上皮细胞bcl 2阳性表达均高于分泌上皮细胞 (χ2 =7.5 0 ,χ2 =10 .2 0 ) ,差别有显著性意义 (P <0 .0 5 )。　结论　bcl 2基因主要表达于前列腺基底细胞 ,可能在调节前列腺上皮细胞凋亡中有重要作用     

表面活性蛋白A在脂多糖诱导的人肾小管上皮细胞中的表达

目的 研究表面活性蛋白A（SP-A）及其亚型在人肾组织和人肾小管上皮细胞（HK-2）的表达和分布,同时分析脂多糖（LPS）对HK-2细胞中SP-A亚型的 mRNA和蛋白表达的影响。 方法 收集10例人的肾组织,以5例人的肺组织作为对照,同时培养HK-2细胞。免疫组化法检测SP-A在人肾组织的表达部位;RT-PCR法检测SP-A mRNA在人肾组织和HK-2细胞中的表达;限制性内切酶片段长度多态性（RFLP）和测序的方法分析SP-A亚型在HK-2细胞的表达;实时定量PCR法比较SP-A mRNA在人肾组织和在人肺组织中的相对含量;Western印迹法检测人肾组织和HK-2细胞中SP-A蛋白的表达;Western印迹和ELISA法检测人的尿液和HK-2细胞培养上清液中SP-A的分泌量。RT-PCR和Western印迹检测LPS在不同浓度（0、0.1、1、2、5、10 mg/L）作用8 h及5 mg/L LPS在不同时间（0、2、4、8、16、24 h）作用HK-2细胞后,SP-A mRNA和蛋白表达的变化情况。 结果 免疫组化结果显示SP-A主要表达在肾皮质的远曲和近曲小管的肾小管上皮细胞。RFLP和测序的方法均证实HK-2细胞可同时表达SP-A1和SP-A2亚型。实时定量PCR证实SP-A mRNA在人肾组织的表达量仅为肺组织的30%（n = 5）。Western印迹检测到人肾组织和HK-2细胞可表达SP-A蛋白。同时在人的尿液和HK-2细胞培养上清液中也检测到SP-A的分泌,其分泌量分别为（106.614±72.772） nmol/L（n = 30）和（85.533± 58.622） nmol/L（n = 10）。应用1、2、5、10 mg/L的 LPS刺激HK-2细胞8 h后,SP-A1和SP-A2 mRNA及SP-A蛋白表达较0、0.1 mg/L显著升高（P < 0.05）;同时,应用5 mg/L的LPS作用HK-2细胞4、8、16、24 h后, SP-A1和SP-A2 mRNA及SP-A蛋白表达较LPS作用0、2 h显著升高（P < 0.05）。 结论 HK-2细胞能同时表达SP-A1和SP-A2亚型,能产生和分泌SP-A蛋白。SP-A1和SP-A2可能在肾脏的天然免疫和炎性反应调节方面起重要作用。     

胰岛素样生长因子在常染色体显性遗传性多囊肾病发病中的作用

目的研究胰岛素样生长因子-1(IGF-1)在常染色体显性遗传性多囊肾病(ADPKD)发病中的作用。方法采用酶联免疫吸附法测定41例ADPKD患者的血液、囊液及尿液中IGF-1浓度;应用原位杂交及免疫组织化学染色方法检测IGF-1及其受体(IGF-1R)在正常肾组织及ADPKD囊壁组织中的表达分布;采用MTT、流式细胞仪及电镜透视的方法,观察IGF-1对囊肿衬里上皮细胞的促增殖作用。结果41例ADPKD患者囊液中的IGF-1浓度为(162.00±5.06)ng/ml,显著高于血液的(76.00±28.13)ng/ml和尿液中的(62.00±19.18)ng/ml(P<0.01);正常肾组织中IGF-1mRNA、IGF-1的表达主要分布在远端肾小管及集合管,而IGF-1RmRNA、IGF-1R在近端肾小管表达阳性。在ADPKD囊肿组织中的囊壁衬里上皮细胞、平滑肌细胞及间质细胞均有IGF-1、IGF-1R阳性表达。IGF-1、IGF-1R在ADPKD囊肿组织中平均吸光度明显高于正常肾组织中的平均吸光度(P<0.01)。IGF-1在1～50ng/ml范围内显著地促进囊肿衬里上皮细胞的增殖。结论囊液中增多的IGF-1可能来自囊肿衬里上皮细胞及间质细胞合成和分泌,这些细胞通过自分泌和旁分泌,可能刺激囊肿衬里上皮细胞的进一步增殖,刺激囊肿形成和长大,从而参与了ADPKD发病。     

含钙肾结石患者肾组织TRPV5的表达及意义

目的:探讨TRPV5在含钙肾结石患者和正常无结石者肾组织中的表达差异,为寻找尿石症的病因提供理论依据。方法:收集我院2009年6～7月取得的含钙肾结石患者(结石组)和正常无结石者(对照组)肾皮质标本各5例,从形态学、蛋白水平、基因水平分别行免疫组织化学、Western blot和荧光定量PCR技术检测两组标本TRPV5的表达差异。结果:免疫组织化学检测见两组标本的肾远曲小管和集合管上皮细胞均阳性染色,且结石组强度明显低于对照组;Western blot检测结果显示结石组TRPV5蛋白印迹明显弱于对照组,利用Quanti-ty One4.62版软件灰度分析显示两组差异有统计学意义(t=6.433.355,P0.01);结石组TRPV5mRNA表达明显低于对照组(t=5.342.306,P0.05),相对定量显示结石组是对照组的0.248倍。结论:含钙结石患者肾TRPV5蛋白和mRNA的表达明显低于正常无结石者,TRPV5表达的减弱可能是含钙肾结石形成的一个重要因素。     

肿瘤坏死因子α诱导人肾近曲小管上皮细胞C3mRNA表达和蛋白合成及其意义

目的：研究体外培养的人肾脏近曲小管上皮细胞（PTEC）自身以及在肿瘤坏死因子α（TNF－α）诱导下补体第三部分（C3）的基因表达和蛋白合成。方法：用单纯培养或TNF－α诱导培养人肾组织的近曲小管上皮细胞,采用逆转录－聚合酶链反应（RT－PCR）方法测定C3mRNA和酶联免疫法（ELISA）测定C3蛋白。结果：基础状态的人PTEC可表达C3mRNA和合成C3蛋白,并在TNF－α诱导后显著增高,且呈剂量和时间依赖关系。结论：人PTEC自身具有表达C3mRNA和合成C3蛋白的能力,并在TNF－α的诱导下明显上调。     

结缔组织生长因子反义寡核苷酸对肾小管上皮细胞纤溶酶原激活物抑制物1表达的影响

目的探讨结缔组织生长因子(CTGF)反义寡核苷酸(ODN)对转化生长因子β1(TGF-β1)诱导的肾小管上皮细胞纤溶酶原激活物抑制物1(PAI-1)mRNA表达和蛋白产生的影响,以明确CTGF在肾脏细胞外基质(ECM)降解中的作用。方法体外培养人近曲小管上皮细胞(HKC),以脂质体介导方法将CTGF反义ODN转染细胞。以TGF-β1(5μg/L)刺激HKC不同时间后,用逆转录-聚合酶链式反应(RT-PCR)方法检测PAI-1mRNA表达;流式细胞仪法检测胞内PAI-1蛋白合成;Western印迹方法检测HKC分泌到上清中的PAI-1蛋白含量。结果TGF-β1可诱导HKC高表达CTGF和PAI-1。转染后6h,CTGF反义ODN可显著抑制TGF-β1诱导的HKCPAI-1mRNA表达。转染后24h,CTGF反义ODN可明显抑制胞内PAI-1蛋白合成,并减少了HKC分泌到胞外的PAI-1。结论CTGF在肾小管间质纤维化时ECM降解中起了关键调控作用,其反义ODN的导入可能是延缓肾小管间质纤维化的有效手段之一。     

JAK-STAT途径mRNA在肾癌的表达及临床意义

目的研究JAK-STAT途径mRNA在人肾透明细胞癌的表达状况及其临床意义。方法收集人肾细胞癌组织标本20例,良性肾脏组织标本10例。采用RT-PCR的方法测定组织内JAK-STAT信号途经相关基因IFNAR、TYK2、JAK1、STAT1、STAT1、STAT2mRNA的相对表达量,比较肾癌组织和良性肾组织内表达量的差异。结果肾癌组织中JAK1和STAT1相对表达量分别为0.697±0.122和0.333±0.078;良性肾组织内的表达量为0.957±0.103和0.547±0.082。JAK1和STAT1mRNA相对表达量显著低于良性肾脏组织(P0.05)。IFNAR、TYK2、JAK1和STAT2mRNA相对表达量与良性肾脏组织无显著差异。结论肾癌组织JAK1和STAT1mRNA的表达量降低可能是导致干扰素抵抗的潜在原因。     

全反式维甲酸对糖尿病大鼠肾组织Toll样受体4表达的影响

目的观察Toll样受体4（TLR4）在糖尿病大鼠肾脏的表达及全反式维甲酸（ATRA）对肾组织TLR4表达的影响。方法将18只大鼠随机分为对照组（N组）、糖尿病组（DM组）和AT—RA组（T组）,每组6只。DM组和T组用链脲佐菌素诱导糖尿病模型。T组给予ATRA20mg·k^-1·d^-1灌胃8周。于第8周末比较各组大鼠24h尿蛋白量、肌酐清除率（Ccr）、肾质量／体质量比值。逆转录聚合酶链反应（RT-PCR）法检测各组大鼠肾组织TLR4 mRNA的表达。免疫组织化学法检测肾组织TLR4蛋白的表达部位和强度。结果①DM组24h尿蛋白量、Ccr、肾质量／体质量比值均高于正常组,T组尿蛋白量和Ccr较DM组明显降低,差异均有统计学意义（P〈0．01）;②DM组TLR4 mRNA表达高于N组,T组TLR4 mRNA表达高于DM组,差异均有统计学意义（P〈0．01）;③TLR4主要表达于近曲、远曲小管上皮细胞和部分肾小球细胞,DM组TLR4表达高于N组,T组TLR4表达高于DM组,差异均有统计学意义（P〈0.01）。结论ATRA可能通过干预肾组织TLR4表达,从而延缓糖尿病肾脏病进展。     

A study of crystal matrix extract and urinary prothrombin fragment 1 from a stone-prone and stone-free population

South African blacks are immune to urinary calculi whereas whites have an incidence rate similar to that reported in Western societies. Urinary prothrombin fragment 1 (UPTF1) and the crystal matrix extract (CME) from which it is derived have been shown to be potent inhibitors of crystal growth and aggregation in undiluted human urine. The objective of the present study was to isolate CME and UPTF1 from the urines of black and white subjects in order to assess whether either might contribute to the black population's relative stone immunity. CME was isolated from freshly precipitated calcium oxalate (CaOx) crystals and a crystallization study was conducted in synthetic urine. Coulter Counter, ¹⁴C-oxalate deposition, and scanning electron microscopy data demonstrated that the extracts from both race groups strongly inhibited CaOx nucleation. The extract derived from the black subjects inhibited nucleation to a greater extent than that from the whites. A phase conversion from COM to COD in the presence of the extracts, in support of the inhibitory effect of CME, was also observed. Purified UPTF1 isolated from both groups' CME was subjected to rigorous biochemical characterization involving matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry, protein sequencing by Edman degradation, and amino acid analyses. No differences in molecular weight or amino acid sequence and composition were identified. It is suggested that the more potent inhibitory activity of the extract derived from the black subjects might be related to this group's relative stone immunity. Received: 8 August 2000 / Accepted: 16 November 2000     

The hole truth: intracrystalline proteins and calcium oxalate kidney stones

The ultimate aim of our research is to understand the role of macromolecules in the formation of human kidney stones, particularly their interactions with calcium oxalate (CaOx) crystals. The invariable association of stones with proteins raises the possibility that proteins play a role in their formation, similar to the role of proteins in healthy biomineralization. Do these proteins induce mineralization? Are they merely a response to the disease process? Or are they protective molecules that were overwhelmed by mineral supersaturation? A protein of particular interest is fragment 1 (F1) of prothrombin. We have shown that mRNA for prothrombin is present in the kidney. Because the F1 fragment of prothrombin present in urine is slightly different from that found in the blood, we refer to this protein as "urinary prothrombin fragment 1" (UPTF1). Available evidence suggests that the kidney manufactures the protein for protection against stone disease and that the protein has a directive role in stone formation. We now have evidence that proteins are interred within CaOx crystals precipitated from human urine, where it is distributed in continuous channels. These proteins could facilitate crystal deconstruction and removal after attachment to the renal epithelium and endocytosis. We suspect that the formation of CaOx crystals in the urine is a normal process designed to permit harmless disposal of an excess of calcium, oxalate, or both. The incorporation of proteins provides a second line of defense against stone formation by enabling the destruction and removal of retained crystals. Understanding the basic molecular strategies by which plants produce protein-containing CaOx crystals may provide insight into human CaOx stone formation.     

Effects of oxalate exposure on Madin-Darby canine kidney cells in culture: renal prothrombin fragment-1 mRNA expression

It has been suggested that renal tubular cell damage induced by oxalic acid, one of the components of urinary calculi, may be involved in a variety of ways in the development of urolithiasis. During our study on a calculus related protein, renal prothrombin fragment-1 (RPTF-1), we noted that this is an inflammation related substance that mediates an acute inflammatory reaction, one of the original roles of prothrombin. RPTF-1 is a part of prothrombin that is a coagulation factor known to be expressed in the renal tubule. We examined whether oxalic acid may cause cytotoxic effects on tubular epithelial cells and whether such chemical stimulation may promote the translation of RPTF-1 mRNA into RPTF-1 proteins. We used Madin-Darby canine kidney (MDCK) cells derived from the distal tubule of a dog kidney. In this study, the effects of oxalic acid in culture solution at different concentrations on cytotoxicity were assessed using a MTT assay. The location of active oxygen species was identified using dichlorofluorescein diacetate. After the prothrombin sequence of RPTF-1 was confirmed in MDCK cells, RPTF-1 mRNA expression was determined by RT-PCR. The gene sequence of the same promoter area was ligated, and a luciferase sequence was inserted downstream of the vector. The target sequence was transfected into MDCK cells and the relation between oxalic acid and prothrombin promoter was examined. In addition, the variable expression of RPTF-1 mRNA was quantitatively compared depending on oxalic acid concentrations using real-time PCR. When cytotoxicity was investigated, cells were not damaged but, by contrast, were stimulated and activated under oxalic acid below a certain concentration. The relation between cytotoxicity on the cultured MDCK cell membrane and active oxygen species was confirmed. Luminescence in MDCK cells containing the luciferase gene was detected by the addition of oxalic acid, which activated the prothrombin promoter. A part of the prothrombin gene sequence in the MDCK cells was detected and an increase in the expression of RPTF-1 mRNA in MDCK cells by the addition of oxalic acid was confirmed using real-time PCR. Increased expression of prothrombin by adding oxalic acid has already been demonstrated in previous studies. In this study, however, RPTF-1 mRNA was promoted by oxalic acid and a direct association between oxalic acid and RPTF-1 is indicated. This finding shows that increased oxalic acid in urine induces the expression of RPTF-1 in tubular epithelial cells and thereby causes the generation of active oxygen species.     

Heterozygous prothrombin gene mutation: a new risk factor for early renal allograft thrombosis.

BACKGROUND: Underlying thrombophilic disorders increase the risk of early allograft loss after renal transplantation. We report three cases of early graft thrombosis in two carriers of a recently discovered prothrombotic variation of the prothrombin gene. CASE REPORTS: The first patient, an adolescent girl, developed multiple thrombotic shunt occlusions after the initiation of hemodialysis until continuous cumarin anticoagulation was instituted. During living-related kidney transplantation, peracute thrombosis of the renal arteries and veins occurred during surgery despite excellent intraoperative conditions and continuous low-dose heparinization. A few hours after reperfusion of the organ by immediate thrombectomy and intrarenal fibrinolysis, an irreversible rethrombosis occurred. A detailed evaluation of the coagulation system showed highly elevated prothrombin protein activity and concentrations. A heterozygous G-->A transition at position 20210 of the prothrombin gene was identified. Hemodialysis was resumed using recombinant hirudin, a direct and selective thrombin inhibitor, as an anticoagulant. The second patient, a girl with end-stage renal failure due to atypical hemolytic uremic syndrome, lost two cadaver kidney allografts, each time by massive thrombosis a few days after transplantation. In this patient also, elevated prothrombin activity and concentrations were present and a heterozygous G-->A transition at position 2210 of the prothrombin gene was detected. CONCLUSIONS: The prothrombin gene mutation is a new risk factor for thrombotic complications both on hemodialysis and after renal transplantation. It may be useful to screen for this disorder in the pretransplant thrombophilia work-up.     

Effects of urinary prothrombin fragment 1 in the formation of calcium oxalate calculus

PURPOSE: We investigated the effects of urinary prothrombin fragment 1 in the formation of calcium oxalate urolithiasis. MATERIALS AND METHODS: Fresh urine and renal parenchyma from patients with calcium oxalate calculus and normal controls were collected. Urinary prothrombin fragment 1 was isolated and purified from urine. It was identified by sodium dodecyl sulfide-polyacrylamide gel electrophoresis and analysis of its first 13 N-amino acids. The inhibitory activity of urinary prothrombin fragment 1 on calcium oxalate crystal growth was tested by the seeded crystallization technique. Meanwhile, the gamma-carboxyglutamic acid composition of urinary prothrombin fragment 1 was analyzed by a previously described method and genetic mutation of the gamma-carboxyglutamic acid domain of urinary prothrombin fragment 1 from renal parenchyma was detected by polymerase chain reaction-single strand conformational polymorphism sequencing. RESULTS: The gamma-carboxyglutamic acid composition of urinary prothrombin fragment 1 was significantly decreased from normal (24.4 to 1.7 mol/1,000 amino acids) in patients with calcium oxalate calculus. The mean growth index +/- SD of urinary prothrombin fragment 1 to calcium oxalate crystals was 42.3 +/- 4.2 compared with the normal index of 19.2 +/- 2.8 (p <0.01). The polymerase chain reaction-single strand conformational polymorphism sequencing technique revealed no genetic mutation of the gamma-carboxyglutamic acid domain of urinary prothrombin fragment 1 in patients with calcium oxalate calculus. CONCLUSIONS: The gamma-carboxyglutamic acid composition of urinary prothrombin fragment 1 as well as its ability to inhibit calcium oxalate crystal growth was significantly decreased in patients with calcium oxalate calculus. This was not caused by genetic mutation of the gamma-carboxyglutamic acid domain of urinary prothrombin fragment 1. It is important to elucidate the mechanisms of calcium oxalate stones in view of urinary prothrombin fragment 1.     

Glycosylation of prothrombin fragment 1 governs calcium oxalate crystal nucleation and aggregation,but not crystal growth

Urinary glycoproteins play an important role in the modulation of calcium oxalate crystallisation. In several cases, this has been attributed to glycosylation of the proteins as evidenced by urinary prothrombin fragment 1 where there is a correlation between sialylation and calcium oxalate kidney stone disease. In the present study, plasma-derived prothrombin fragment 1 (PTF1) was enzymatically modified in order to generate its asialo and aglyco forms. The parent glycoprotein and its two glycoforms were used in calcium oxalate crystallisation studies to assess the role of the carbohydrate moeity in PTF1’s potent inhibitory activity. The glycans inhibited crystal aggregation and promoted crystal nucleation, but had no effect on crystal growth. The terminal sialic acid residues had a small effect on inhibition of crystal aggregation whereas they contributed significantly to promotion of nucleation. These results indicate that glycosylation of PTF1 governs calcium oxalate crystal nucleation and aggregation but it does not affect the protein’s role in inhibiting crystal growth. Since promotion of nucleation and inhibition of aggregation are both regarded as protective mechanisms against calcium oxalate urinary stone formation, the kringle domain on which the glycans are located is implicated in PTF1’s inhibitory activity. It is speculated that modifications in the glycosylation of urinary PTF1 in stone-formers may regulate its capacity to protect against calcium urolithiasis.     

Isolation and partial characterization of crystal matrix protein as a potent inhibitor of calcium oxalate crystal aggregation: evidence of activation peptide of human prothrombin

In order to clarify the characteristics of crystal matrix protein (CMP), which exhibits a remarkable affinity for calcium oxalate crystals and may be important in stone pathogenesis, we have isolated CMP from macromolecular matrix substances of newly-formed calcium oxalate crystals. Purification of CMP consisted of calcium oxalate crystal formation, dissolution of crystals, electrodialysis, anion exchange chromatography and high-performance liquid chromatography. CMP showed the protein band of 31 kDa in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The N-terminal amino acid sequence of CMP was identical to that of human prothrombin. Both anti-CMP polyclonal antibody and antihuman prothrombin antibody cross-reacted well with human prothrombin and CMP in Western blotting. Its amino acid composition and its molecular weight of 31 kDa strongly suggest that CMP is the activation peptide of human prothrombin.     

Changing concepts in the aetiology of renal stones

In the past two decades an increasing number of nephrolithiasis-related urinary proteins have been identified. This paper focuses on two of them, namely prothrombin fragment 1 and bikunin, members of the prothrombin and inter-alpha-trypsin inhibitor families of proteins, respectively. Besides their role as inhibitors of crystallization, these proteins are also involved in inflammation-mediated tissue repair. This is the basis for the concept that the response of renal tissue to injury might play an important role in the aetiology of kidney stones.