Molecular Biology in Renal Diseases

The architecture and compartmentalization of the kidney has stimulated the development of an array of microtechniques to study the functional differences between the distinct nephron segments. With the vast amounts of genomic sequence data now available, the groundwork has been laid for a comprehensive characterization of the molecular pathways defining the differences in nephron function. With the development of sensitive gene expression techniques the tools for a comprehensive molecular analysis of specific renal microenvironments have been provided: Quantitative RT-PCR technologies now allow the analysis of specific mRNAs from as little as single microdissected renal cells. A more global view of gene expression regulation is a logical development from the application of large scale profiling techniques. In this review, we will discuss the power and pitfalls of these approaches, including their potential for the functional characterization of nephron heterogeneity and diagnostic application in renal disease. Copyright © 2002 S. Karger AG, Basel Introduction Recent developments in molecular biology offer new opportunities for experimental and clinical medicine. With the completion of the draft sequence of the human genome the entire human genetic code is being deciphered [1, 2]. In addition, the genomes of laboratory animals such as mice and rats will be available in the near future. The integration of genomic information into biological function will be a major challenge for the biomedical community. A comprehensive analysis of the mRNA and protein expression in health and disease is considered to be an essential next step in this process. Current technical advances now allow a global analysis of the regulatory pathways active in a tissue or disease process [3]. The most promising immediate clinical application for patient care is the identification of mRNA expression patterns that help to characterize pathophysioloical phenomenon in diseased organs and their correlation with the diagnosis, prognosis and responsiveness to the different available treatments [4–6]. To date the most conclusive information available for diagnostic and therapeutic decisions in clinical nephrology is the analysis of the affected organ by fine needle biopsy. Biopsy material is analyzed primarily by histology [7]. The quantitative measurement of mRNA levels encoding functionally relevant molecules will add important information to this powerful diagnostic procedure in nephrology [8, 9].