Associate editor: M.K. Pugsley Common pathophysiological mechanisms of chronic kidney disease: Therapeutic perspectives José M. López-Novoa b,d , Carlos Martínez-Salgado a,b,d , Ana B. Rodríguez-Peña c , Francisco J. López Hernández a,b,d, ⁎ a Unidad de Investigación, Hospital Universitario de Salamanca, Salamanca, Spain b Unidad de Fisiopatología Renal y Cardiovascular, Departamento de Fisiología y Farmacología, Universidad de Salamanca, Salamanca, Spain c National Institutes of Health, Bethesda MD, USA d Instituto Reina Sofía de Investigación Nefrológica, Fundación Íñigo Álvarez de Toledo, Spain abstract article info Keywords: Chronic renal disease Animal models Hypertension Diabetes Ureteral obstruction Renal mass reduction Therapy It is estimated that over 10% of the adult population in developed countries have some degree of chronic kidney disease (CKD). CKD is a progressive and irreversible deterioration of the renal excretory function that results in implementation of renal replacement therapy in the form of dialysis or renal transplant, which may also lead to death. CKD poses a growing problem to society as the incidence of the disease increases at an annual rate of 8%, and consumes up to 2% of the global health expenditure. CKD is caused by a variety of factors including diabetes, hypertension, infection, reduced blood supply to the kidneys, obstruction of the urinary tract and genetic alterations. The nephropathies associated with some of these conditions have been modeled in animals, this being crucial to understanding their pathophysiological mechanism and assessing prospective treatments at the preclinical level. This article reviews and updates the pathophysiological knowledge acquired primarily from experimental models and human studies of CKD. It also highlights the common mechanism(s) underlying the most relevant chronic nephropathies which lead to the appearance of a progressive, common renal phenotype regardless of aetiology. Based on this knowledge, a therapeutic horizon for the treatment of CKD is described. Present therapy primarily based upon renin–angiotensin inhibition, future diagnostics and therapeutic perspectives based upon anti-inflammatory, anti-fibrotic and hemodynamic approaches, new drugs targeting specific signaling pathways, and advances in gene and cell therapies, are all elaborated. © 2010 Elsevier Inc. All rights reserved. Contents 1. Introduction to chronic renal disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61 2. Hypertensive nephropathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62 3. Diabetic nephropathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62 4. Renal mass reduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62 5. Obstructive nephropathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 6. Common mechanisms of progression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 7. Current treatments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64 8. Therapeutic perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64 9. Final remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65 1. Introduction to chronic renal disease Chronic kidney disease (CKD) is a life-threatening condition characterized by progressive and irreversible loss of renal function. The increasing inability of the kidneys to properly clear the blood of Pharmacology & Therapeutics 128 (2010) 61–81 ⁎ Corresponding author. Unidad de Investigación, Hospital Universitario de Salamanca, Paseo de San Vicente, 58-182, 37007 Salamanca, Spain. Tel.: +34 923 294 472; fax: +34 923 294 669. E-mail address: flopezher@usal.es (F.J.L. Hernández). 64 65 66 70 70 73 75 76 0163-7258/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.pharmthera.2010.05.006 Contents lists available at ScienceDirect Pharmacology & Therapeutics journal homepage: www.elsevier.com/locate/pharmthera