Nephrol Dial Transplant (2003) 18: 1716-1725
© 2003 European Renal Association-European Dialysis and Transplant Association
Special Feature
The importance of diabetic nephropathy in current nephrological practice
1 Department of Nephrology and Dialysis, Azienda Ospedale di Lecco, Ospedale A. Manzoni, Lecco, Italy, 2 Service de Nephrologie, Hôpital Lapeyronie, Montpellier, France, 3 Department of Nephrology and Medical Intensive Care, Charité, Campus Virchow Klinikum, Berlin, Germany, 4 Division of Renal Medicine, Department of Clinical Science, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden, 5 Division of Nephrology, University Hospital Würzburg, Germany and 6 CNR Centre of Clinical Physiology, Reggio Calabria, Italy
Correspondence and offprint requests to: Professor Francesco Locatelli, Department of Nephrology and Dialysis, Ospedale A. Manzoni, Via Dell’Eremo 11, 23900 Lecco, Italy. Email: nefrologia{at}ospedale.lecco.it
Abstract
Background. Diabetic nephropathy has become the major cause of end-stage renal disease (ESRD) in the western world and is forecast to become the most frequent cause of ESRD in the African continent and in developing countries in other areas.
Methods. A discussion to achieve a consensus on key points relating to diabetic nephropathy.
Results. Given the catastrophic consequences of diabetes not only for renal function but also for the cardiovascular system, major efforts should be aimed at prevention. The cornerstone of primary prevention (development of microalbuminuria) is a tight control of blood pressure and blood glucose. Although ACE inhibitors have proved effective in preventing the development of microalbuminuria in normotensive patients, this is not the case, in comparison with other classes of antihypertensive drugs, in those who are hypertensive but normoalbuminuric. Secondary prevention (transition to overt nephropathy) and tertiary prevention (progression of established nephropathy to ESRD) benefit from the use of inhibitors of the renin-angiotensin system, whilst the role of tight glycaemic control is more controversial at these stages. Therapeutic lifestyle changes are also important. They should include body weight control combined with regular physical exercise, cessation of smoking and reduced salt intake. The pathogenesis of diabetic nephropathy and its association with hypertension, accelerating renal damage, is complex. It involves genetic factors, altered renal sodium handling with sodium retention, metabolic disturbances and oxidative stress with the formation of advanced-glycation end products (AGEs) and reactive oxygen species.
Conclusions. Although the awareness of the importance of normalizing blood pressure levels and tight glycaemic control have allowed improved survival of diabetic patients, the mortality excess remains unacceptably high in patients with diabetic nephropathy. New treatment strategies are under investigation, including inhibitors of AGE formation, protein kinase C inhibitors, antioxidants, glycosaminoglycans, PPAR-
agonists and COX-2 inhibitors.
Keywords: advanced glycation end-products; diabetic nephropathy; glycosaminoglycans; microalbuminuria; oxidative stress; prevention; treatment
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