Hong Kong Journal of Nephrology

Volume 5 Number 2, 2003

Animal Remnant Kidney Model of Chronic Renal Failure Revisited

Kai-Ming Chow, Zun-Chang Liu, Thomas Ming-Swi Chang

Animal models have been the mainstay of experimental means to study chronic renal failure. An ideal experimental animal model provides a stable uremic milieu to allow experimental manipulation. The model should be technically simple to produce and have a reproducible degree of glomerular filtration rate reduction. There should also be close mimicry of human chronic renal failure without additional (unwanted) physiologic changes. This review article outlines the various choices of animal models in relation to the aforementioned criteria, with particular emphasis on their advantages and shortcomings. In principle, reduction of renal mass is undertaken in these models, after which adaptive changes take place in the remaining/remnant kidney. The glomerular changes, in proportion to the number of nephrons resected or damaged, are characterized by growth as well as hyperfunction. To date, the five-sixths nephrectomy model has remained the state-of-the-art prototype, although it must be acknowledged that no single animal model can ever duplicate the original condition of human kidney disease. It is in this context that a thorough understanding of each animal model allows the most effective modeling strategy in biomedical research. Insofar as the ideal animal model does not exist, researchers should use the biologic and biochemical diversity among the models to experimental advantage. It is expected, with good reason, that the differences can tell us as much as the similarities. Attention to selection of appropriate animal models is important to further advance the nephrology research frontier. [Hong Kong J Nephrol 2003;5(2):57-64]

Key words: animal model, five-sixths nephrectomy model, remnant kidney model

動物模型的應用,一直是慢性腎衰竭實驗的主要方式。一個理想的動物模型,在技術上應易於製作,在腎小球過濾速率降幅上具有可再現性,以提供穩定的腎衰竭環境供實驗操作之用。同時,該模型應可準確模擬人類慢性腎衰竭的狀況,且不會產生額外(不必要)的生理變異。根據這些準則,本文對多個可供選擇的動物模型作一回顧,並集中討論各者的利與弊。原則上,這些模型均採用腎組織的減量,令餘下/殘餘的腎臟逐漸出現適應性的變化。其中的腎小球變化 - 肥大及功能過度 - 與被切除或受損的腎元數目呈正比。雖然目前「六分之五腎切除模型 (five-sixths nephrectomy model)」被認為是動物模型的典範,然而須注意的是,在現階段尚未有一個動物模型,能完全模擬人類腎病的真正狀況,因此,研究人員必須對每個動物模型作充分瞭解,並善用各模型間的生物及生化多樣性於生物醫學研究中。我們有理由預期,各模型間的歧異性與相似性對我們有同等的意義。注重動物模型的適當選取,對腎臟科學研究的進一步發展相當重要。

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