The progression of chronic renal failure: a harmful quartet

Abstract

The progression of chronic renal failure (CRF) remains one of the main challenges in clinical nephrology. Over the last quarter of a century, animal experimentation has identified many of the pathophysiological mechanisms underlying the associated renal scarring process. Consequently, research has implicated a wide range of mediators, including prominent roles for cytokines, chemokines and growth factors.1 This has suggested therapies based on the manipulation of these mediators and aimed at the prevention of progressive renal fibrosis and functional decline.1 Unfortunately, the relevance of these interventions and their applicability to patients with progressive renal insufficiency remain uncertain. Meanwhile, nephrologists continue to be faced with an increasing number of patients with progressive CRF. It is therefore imperative to review available clinical interventions based on the manipulation of known clinical risk factors for the progression of CRF. Hypertension has been linked to the progression of chronic renal failure (CRF) since the pioneering days of Richard Bright in the 19th century and Volhard and Farr early this century. More recently, a large body of evidence has suggested that the progression of CRF is accelerated by raised systemic blood pressure.2,,3 The Multiple Risk Factor Intervention Trial (MRFIT) identified systemic hypertension as a significant risk factor for the development of endstage renal disease (ESRD).4 This study also confirmed the increased susceptibility of hypertensive Black patients to progressive renal failure.4 The Modification of Diet in Renal Disease (MDRD) study showed that the progression of CRF was linked to the level of systemic blood pressure with Black as well as proteinuric patients both at increased risk.5 More recently, the North Italian Cooperative Study Group identified a mean arterial blood pressure (MAP) value of 107 mmHg (around 140/90 mmHg) as discriminatory, with patients with higher values having an accelerated loss of …