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Therapies of CKD have greatly improved following the introduction of drugs targeting the renin\u2013angiotensin system (RAAS) but even this refined pharmacological approach has failed to stop progression to end\u2010stage renal disease (ESRD) in many individuals.\n                    <jats:italic>In vitro<\/jats:italic>\n                    historical data and recent new findings have suggested that progression of renal fibrosis might occur as a result of an altered tubulo\u2013interstitial microenvironment and, more specifically, as a result of an altered epithelial\u2010mesenchymal crosstalk. Here we the review biological findings that support the hypothesis of an altered cellular crosstalk in an injured local tubulo\u2010interstitial microenvironment leading to renal disease progression. Copyright \u00a9 2012 Pathological Society of Great Britain and Ireland. 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