Tubular-derived cytokines and human renal disease progression

We still know remarkably little about why renal function in many chronically-diseased human kidneys continues to decline at a predictable rate over time. If patients whose renal function is likely to decline can be diagnosed early, effective measures to slow the rate of progression could be introduced before irreversible renal scarring occurs. Three such predictive factors have emerged. Firstly, the preservation of the tubulointerstitium rather than the glomerulus appears to be the major histological determinant of renal outcome in a wide variety of classical glomerulopathies [1]. Secondly, the extent of the interstitial infiltrate (which consists largely of T cells and macrophages) correlates well with the degree of functional impairment and is a good predictor of long-term prognosis [2]. Thirdly, the magnitude of proteinuria appears to correlate positively with the rate of progression in patients with impaired glomerular filtration rates according to preliminary results from the large multicentre 'Modification of Renal Disease by Diet' study [3]. No doubt, controversy will continue to rage over the pathogenic potential of filtered plasma proteins since direct in-vivo evidence of this, in the absence of other potentially relevant factors such as changes in glomerular function, has not yet been obtained [4], It seems possible though that, in addition to filtered albumin, larger non-albumin proteins such as lipoproteins [5] might prove to be 'tubulo-toxic' and thus provide a convenient link between primary glomerular injury and secondary tubular injury.