Mechanisms of progression of chronic renal damage.

The amount of protein in the urine is a strong predictor of subsequent loss of renal function. Proteinuria and tubular atrophy have been linked with progressive renal insufficiency. In the last few years several studies have indicated that smoking is also a risk factor in the progression of renal disease. In addition, a number of studies have suggested that higher levels of blood pressure are associated with a faster decline in renal function. A number of cytokines, vasoactive compounds, chemoattractant molecules and growth factors are upregulated during the course of progressive renal disease in experimental animals. Recent data indicate that vasoconstrictor substances have a key role in the initial phases of this process. In particular, angiotensin II is increased following the development of renal injury. Angiotensin in turn upregulates the expression of other factors including: transforming growth factor beta, tumor necrosis alpha, nuclear factor kappaB and several chemoattractant compounds. Other vasoactive compounds (endothelin, thromboxane A2 and prostaglandins) may also be upregulated during the course of progressive renal disease