ABSTRACT
Over the next decade, the number of patients with end-stage renal disease (ESRD) treated by dialysis may double, and even developed nations will have difficulty in coping with this alarming increase. This review will outline the proven and unproven strategies that have the potential to retard the progression of chronic kidney disease (CKD). Recently, a number of randomised clinical trials have demonstrated the efficacy of several strategies to slow the progression of CKD. Proven strategies include adequate blood pressure control (with angiotensin blockade), and for diabetic nephropathy good glycaemic control. Other potentially beneficial strategies include smoking cessation, lipid control and aldosterone blockade. The early institution of these strategies has the potential to regress established CKD as well as improve the long-term cardiovascular outcomes of these patients. Proof of the efficacy in humans of promising experimental approaches, such as the administration of growth factors (e.g., recombinant bone morphogenetic protein-7), anti-fibrotic agents (e.g., pirfenidone) and novel anti-proteinuric drugs (e.g., pentosan polysulphate), is awaited. Finally, the primary prevention of CKD, at least in part, by the eradication of type 2 diabetes and obesity (through improvement of lifestyle factors), and adequate treatment of hypertension, have the potential to eliminate up to half of the most common causes of CKD (or ESRD) in developed countries.
By 2010 there will be more than 2 million patients worldwide on maintenance dialysis, a 400% increase in 20 years.1 This increase, occurring predominantly in developing nations, is being driven especially by a worldwide increase in the incidence of diabetes, and is too great to be offset by increased rates of renal transplantation. The societal and financial costs of renal replacement therapy are proving too great for developed nations to cope with, and are an impossible burden for developing nations to meet. The number of patients with end-stage renal disease (ESRD) is but the tip of the iceberg of the total number of patients with progressive chronic kidney disease (CKD). Over the past decade or so, there have been a number of relatively large hard-endpoint trials demonstrating the efficacy of several therapeutic strategies for slowing or even preventing the progression of CKD. These therapies may be effective in patients with even advanced disease yet it appears that cardiovascular outcomes are better and total costs less if the treatments are instituted early in the course of disease. Universal application of these therapies has the potential to greatly reduce the burden of renal failure worldwide. In addition, there are a number of strategies of possible benefit whose efficacy remains to be proven. Proof of efficacy and widespread clinical application of these therapies was preceded and driven by basic research. There has been a rapid expansion of basic research into the pathogenesis of progressive CKD, which has exposed new targets for future therapies. The effectiveness of existing therapies means that much larger clinical trials will be required to prove the usefulness of any new strategies.2
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