The pathogenesis of fibrosis and renal disease in scleroderma: recent insights from glomerulosclerosis

Acute and chronic renal diseases remain common complications of systemic sclerosis. Although treatment for acute scleroderma renal crisis may arrest the rapid progression of renal disease, many patients develop persistent renal dysfunction. Based on recent insights gained from progressive renal diseases of diverse etiologies, novel approaches to understanding the pathobiology of scleroderma renal disease may be applicable. Key factors involved in progression of renal disease include accumulation of extracellular matrix in the glomerular and tubulointerstitial compartments, epithelial to mesenchymal transformation, and vascular changes. The relevant factors mediating these events include the renin-angiotensin system, the profibrotic growth factors, transforming growth factor-beta and connective tissue growth factor, and reactive oxygen species. Much of the molecular details of the role of these factors have been revealed and promise to alter the practice of therapy of progressive renal disease.