台灣自2002年起，洗腎病患的發生率及盛行率為世界第一，在結石疾病方面，大約每10位台灣人中，就有一人為尿路結石的患者，而且以草酸鈣結石病患居多。臨床研究發現草酸鈣結石發生的位置大都在腎乳突處或是集尿管中。因此本研究目的是要利用模擬方式來探討草酸鈣在腎小管的濃度變化和草酸鈣結石的關係並與臨床結石尿液濃度資料比較。本研究使用Merletti所提出的腎臟模型，模擬正常腎小管對水和離子的調節功能及變化；之後再加入草酸還有鈣離子在腎小管的過濾、重吸收、排出及檸檬酸抑制劑等機制，來模擬及觀察草酸鈣在腎小管的濃度變化並以草酸鈣的溶解度積是否超過沈澱閾值來判斷是否有草酸鈣結石的形成。模擬結果發現正常血鈣濃度和血漿草酸因為有檸檬酸的抑制，沒有產生草酸鈣結石沉澱；在高血鈣症和高草酸吸收的草酸鈣濃度模擬結果發現，結石產生的位置發生在集尿管；在原發性結石患者、單水與雙水草酸鈣患者，模擬結果發現腎小管中沒有產生結石沉澱，但其尿液草酸鈣溶解度積值卻意味會產生草酸鈣結石；在飲食與草酸鈣濃度關係模擬中，我們發現高鈣的攝取不會讓草酸鈣在腎小管中產生沉澱。目前此模型若在未來加入其他控制機制如荷爾蒙調空機制，將更能接近草酸鈣結石的實際模擬。

Taiwan has been in the position of the worst dialysis prevalence rate in the world since 2002. It has been reported that one in ten Taiwanese lives with the kidney stone disease in Taiwan and that most of them are with the calcium oxalate kidney stone. Clinical studies indicate the location of the kidney stones happens in the mastoid and collecting duct of the kidney. Therefore, the purpose of this study is to simulate the change of the calcium oxalate concentration in the tubule, to investigate its relationship to the calcium oxalate kidney stones, and to evaluate this simulation with existed clinical data. This study first used the kidney model proposed by Merletti to simulate regulation function of water and ion concentration in the tubule of normal kidney. Then, mechanisms of tubular filtration, reabsorption, and excecretion for calcium and oxalate ions, and inhibitory function of citrate ion were included in the model to simulate and observe the change of calcium oxalate concentration in each portion of the tubule. The threshold of the solubility product (Ksp) of the calcium oxalate was used to judge if there exists the calcium oxalate kidney stone in the tubule. Simulated results show that there is no precipitation of calcium oxalate stones under normal plasma calcium and oxalate ion concentration. And the calcium oxalate kidney stones were found in the collecting duct from the simulated results of hypercalcemia and high-oxalate absorption clinical symptoms. In addition, there is no kidney stones in the tubule but with over-threshold solubility product of the calcium oxalate from our simulated results for the patients of idiopathic calcium stone, calcium oxalate monohydrate and dihydrate. Finally, diet of high calcium was simulated and the results indicate there is no precipitation of calcium oxalate stone in the tubule. Current model will better simulate the formation mechanism of the calcium oxalate kidney stone in the human body if other control mechanisms, such as hormone regulation mechanism, were included in the simulation.

Abrabams, H.M., Meng, M.V., Stoller, M.L,(2007).Urinary stone inhibitors:Citrate and Magnesium.In Stoller,M.L& Meng M.V(Eds.), urinary stone disease: the practical guide to medical and surgical management(pp 157-173),Totowa: New Jersey 07512,Humana Press Inc.
Bauzá, A.C., Ramis, M., Montesinos, V.,• Antonio Conte • Pedro Pizá •Enrique Pieras • Felix Grases. (2007). Type of renal calculi: variation with age and sex. World J Urol , 25,415–421.
Chung, H.J., Abrabams, H. M., Meng, M.V., Stoller, M.L., (2007).Urinary stone inhibitors:Citrate and Magnesium.In Stoller,M.L& Meng M.V(Eds.), urinary stone disease: the practical guide to medical and surgical management(pp 55-58),Totowa: New Jersey 07512,Humana Press Inc.
Cooney, D.O.,(1976). Biomedical engineering principles. NY, Marcel Dekker Inc.
Daudon, M., Lacour, B., Jungers, P.,(2006). Influence of body size on urinary stone composition in men and women. Urol Res,34,193-199.
Dussol,B., Verdier, J.M., Goff, J.M.L., Berthezene, P., Berland, Y., (2006). Artificial neural networks(ANN) for assessing the risk of urinary calcium stone among men. Urol Res,34,17-25
Egan, T.J., Rodgers, A.L., Siele, T.,(2004). Nucleation of calcium oxalate crystals on an imprinted polymer surface from pure aqueous solution and urine. J Biol Chem. 9:195-202.
Fredericus, B.M.,(1991). Fluid volumes: the program “FLUIDS”. Wijk Brievingh, R.P., Möller, D.P.F.,(1991). Biomedical modeling and simulation on a PC.p286-307.
Hesse, A., Siener, R.(1997). Current aspects of epidemiology and nutrition in urinary stone disease. World J Urol,15,165-171.
Hoppe, Hesse,(1999), Metabolic disorders and molecular background of Urolithiasis in Childhood. Scanning Microscopy, 13,267-280.
Holmes, R. P., Assimos, AD.G., (2004) The impact of dietary oxalate on kidney stone formation. Urol Res, 32, 311–316
Hatch, M., (1993). Oxalate status in stone-formers: two distinct hyperoxaluric entities. Urol Res,21,55-59.
Justyna, K.J.,(2005). Citrate Kinetics during Regional Citrate Anticoagulation in Extracorporeal Organ Replacement Therapy.
Dissertation, Albert-Ludwigs-Universität.
Karaaslan, F., Denizhan, Y., Kayserilioglu, A., Gulcur, H.O.,(2005)
Long-Term mathematical model involving renal sympathetic nerve activity,arterial pressure,and sodium excretion. Annals of Biomedical Engineering,33,1607-1630.
Khan, S.R., Shevock, P.N., Hackett, R.L.A., (1992), hyperoxaluria renal injury and calcium oxalate urolithiasis. J Urol, 147,226-230.
Khan, S.R.,(1997), Animal model of kidndy stone formation: an analysis. World J, 15,236-243.
Marcano, M., Laytion, A.T., Laytion, H.E.,(2006). An optimization algorithm for a distributed-loop model of an avian urine concentration mechanism. Bulletin of Mathematical Biology,68,1625-1660.
Marumo, F. Yoshikawa, Y. Koshikawa, S. (1967). A Study on the Concentration Mechanism of the Renal Medulla by Mathematical Model. Japanese Circulation Journal ,Vol.3r , September.
Martion, M., Vitale, C., Pertrarulo, M., Bagnis, C., Bruno, M., Ramello, A., (2000). Renal stones: from metabolic to physicochemical abnormalities. How useful are inhibitors.J Nephro ,3, 51-60.
Merletti, R., Weed, R.R., Coraon, S.A., (1993). Analysis and Simulation of Renal Function., 442-449.
Merletti, R., (1972). Computer Simulation and Analysis of the Physiology and Pathology of the Body Fluids and Comparisou of Results with Physiological Data., Dissertation, The Ohio State University.
Okada, A., Nomura, S., Higashibata, Y., Hirose, M., Gao, B., Yoshimura, M., et al.(2007). Successful formation of calcium oxalate crystal deposition in mouse kidney by intraabdominal glyoxylate injection. Urol Res, 35,89-99.
Otnes, B., (1980). Sex differences in the crystalline composition of stones from upper urinary tract. Scand J Urol Nephro,114, 51-56.
Paulo, S., Brazil, Update on dietary recommendations and medical treatment of renal stone disease.(2000), Nephrol Dial Transplant, 15,117-123.
Peak, A.B., Cornelius, J.G., Sidhu, H.,(2000). Oxalosis and calcium oxalate stone disease. National Institute of Diabetes and Digestive and Kidney Diseases, NIH,p10.
Ryall, R.L., (1993). The scientific basis of calcium oxalate urolithiasis.
World J Urol,11,59-65.
Sidhu, H., Chow, J., Luba, J., Peck, A.,(2000). Oxalosis and calcium oxalate stone disease. National Institute of Diabetes and Digestive and Kidney Diseases, NIH,p14.
Siener, R., Ebert, D., Hesse, A.,(2001). Urinary oxalate excretion in female calcium oxalate stone formers with and without a history of recurrent urinary tract infections. Urol Res,29,245-248.
Siener, R., Hesse, A.,(2005). Recent advances in nutritional research on urolithiasis. World J Urol, 23,304-308.
Tiselius, H.G., (2003), Epidemiology and medical management of stone disease. ,BJU International, 91,758-767.
Trinchieri, A., Castelnuovo, C., Lizzano, R., Zanetti, G.,(2005). Calcium stone disease : a multiform reality. Urol Res, 33,194-198.
Zimmermann, D. J., Hesse, A., Unruh, G.E., (2005), Influence of a high-oxalate diet on intestinal oxalate absorption. World J Urol, 23, 324-329.
王中敬, 「細說尿路結石」 ,宏欣文化 , 民85。
劉東昇,「大一化學」,五南,民75。
吳襄、林坤偉, 「生理學大綱」, 藝軒圖書出, 民86。
游祥明、宋晏仁、古宏海、傅毓秀、林光華,「解剖學」,杏華, 民94。
連潔群、楊又才編譯, 「新編實用營養學」,藝軒,民95。
何君坦,「草酸鈣晶體的成長研究」,長庚大學化學工程研究所碩士論文,民87。
林興中,「高血鈣症之處理」,臺灣醫界,37期 pp57-65，民83。
陳汶吉,「尿路結石的生物礦化機制探索」,國立清華大學生命科學系博士論文, 民90。
黃鶴翔,「自由基再實驗性腎結石中的角色」,國立台灣大學醫學院生理研究所博士論文,民91。
行政院衛生署豐原醫院的衛教資訊,民97。
http://www.fyh.doh.gov.tw/main_sec.php?index=hygiene_detail&id=337&no=&mid=26&pid=26&sid=04
Koeslag, J.,( 2007) Countercurrent mechanisms in Physiology.
http://academic.sun.ac.za/medphys/counter.htm
健康生活館，民97。
http://info.goolu.com/column/healthlife.php?ttype=97&id=435
榮總電子報，民92。
http://www7.vghtpe.gov.tw/epaper/article.asp?paperno=0095&serial=1246
北方網，民97。
http://health.big5.enorth.com.cn/system/2008/09/11/003678358.shtml
北京纳諾超微技術研究所，民97。http://www.nanuo.com.cn/list_a_news.php?num=9880
wikipedia(2009)
http://en.wikipedia.org/wiki/Calcium_citrate
eMedicine (2008)
http://emedicine.medscape.com/article/444683-overview