Management of progressive renal failure: the role of dietary manipulations.

In the majority of patients with chronic renal failure (CRF), the underlying nephropathy continues to progress well after the initiating events have subsided.' As a result, renal function in these patients declines relentlessly with time as functional renal tissue is progressively destroyed. Such progressive decline in renal function occurs in most patients at a constant and predictable rate.2 This should allow for the testing of the efficacy of therapeutic interventions aimed at slowing the progression of CRF. Unfortunately, the development of such therapies has been hampered in the past by our limited knowledge of the pathophysiology of the underlying renal and glomerular scarring processes. Recently, major advances have been achieved in this field which might suggest more rational and successful therapies. The progression ofCRF is known to be affected by factors such as patients' age and sex,3 underlying disease,4 genetic profile and immune environment.5 Similarly, in individual patients the severity ofproteinuria and systemic hypertension4 can influence the rate of progression of their nephropathy. So far the management of CRF has been confined to the symptomatic reliefofuraemic symptoms, treatment ofrenal osteodystrophy and control of hypertension. Recent observations by Brenner and his colleagues in experimental animals suggest that renal haemodynamic factors play a preponderant role in the initiation and progression ofCRF; following an initial reduction in functional renal mass, compensatory haemodynamic changes take place in the remnant glomeruli. These are brought about by changes in glomerular arteriolar resistances. They are characterized by glomerular vasodilatation, hyperperfusion and hyperfiltration when the initial glomerular lesion is mild or absent' and by glomerular vasoconstriction with subsequent ischaemia when the vessels or glomeruli are severely damaged at the onset.7 Both an increase in glomerular blood flow or in glomerular vascular resistances could lead to a compensatory increase in filtration rate secondary to intra-glomerular hydrostatic hypertension (Figure 1). Glomerular hypertension and hyperfiltration would damage the endothelium layer which in turn would stimulate platelet aggregation and glomerular capillary thrombosis. Such glomerular micro-atherosis, combined with subsequent ischaemic tubulo-interstitial atrophy and calcification, would lead to end stage renal failure. The relevance of these experimental observations to CRF in man remains to be determined. However, they shed some light on the mechanisms of action of some dietary interventions aimed at slowing the progression of CRF. Such therapies could be directed at reversing the early compensatory glomerular haemodynamic adjustments and/or the prevention of the late glomerular cellular damage and subsequent glomerular thrombosis. Finally, interventions could also aim at preventing the destruction of the renal tubules and their calcification. Dietary manipulations designed to achieve some of these goals are currently being evaluated.