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Urine biomarkers and mechanistic insights into early diabetic nephropathy David Cherney, MD CM, PhD, FRCP(C) Associate Professor of Medicine, University of Toronto Clinician Scientist, Division of Nephrology, UHN Director, Renal Physiology Laboratory, UHN Outline ã Review “pre-clinical” factors that may increase future renal risk ã Effect of clamped hyperglycemia, hyperfiltration on urinary inflammatory biomarkers ã Can urinary cytokine/chemokine excretion be suppressed pharmacologically? ã Da
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   rine biomarkers and mechanistic insights into early diabetic nephropathy David Cherney, MD CM, PhD, FRCP(C)    Associate Professor of Medicine, University of Toronto Clinician Scientist, Division of Nephrology, UHN Director, Renal Physiology Laboratory, UHN  Outline ãReview “pre - clinical” factors that may increase future renal risk ã Effect of clamped hyperglycemia, hyperfiltration on urinary inflammatory biomarkers ã Can urinary cytokine/chemokine excretion be suppressed pharmacologically? ã Data from selected clinical trials ã Summary, future directions  Palatini . Nephro Dial Transplant (2012)   Albuminuria is a Flawed Marker of Diabetic Nephropathy Perkins et al. NEJM (2003)  Statement of the clinical problem ã Traditional diabetic nephropathy risk factors fail to identify high-risk patients ã  Albuminuria is a poor biomarker of renal risk  –“Regression”, non -progression  – GFR loss without proteinuria ã“Rapid progressor  ” GFR decline    – Mechanisms poorly understood ã Identification of novel, early markers of renal risk needed Perkins et al. NEJM 2003;348:2285 Perkins et al. JASN 2005;16:1404 Mauer et al. NEJM 2009;361:40

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