Proteineria and Progression in Glomerular Diseases.

Abstract

Contains fulltext : 27029.pdf (publisher's version ) (Open Access)Proteinuria is a strong predictor of progressive renal insufficiency. The precise mechanisms to explain this relationship are still unknown, although many experimental studies have shown that proteinuria may induce tubulo-interstitial injury. Many investigators have observed that tubulo-interstitial injury better reflects renal insufficiency than glomerular injury. Indeed, in pilot-studies we demonstrated that the urinary excretion of the low molecular weight protein 2-microglobulin, a marker of tubulo-interstitial injury, predicted the development of chronic renal insufficiency in patients with idiopathic membranous nephropathy. It remains unknown which components in proteinuric urine are responsible for the induction of tubulo-interstitial injury. Identification of these components should enable to develop more specific therapeutic interventions and to identify patients at risk for chronic renal insufficiency with higher specificity and at an earlier stage. Therefore, we have initiated studies in patients with proteinuria to evaluate tubulo-toxic injury and possible mediators. We specifically have focussed on patients with membranous nephropathy, the most common cause of the nephrotic syndrome in adults. In these patients we also have evaluated the efficacy of immunosuppressive therapy. Our studies demonstrated that urinary albumin per se is not the cause of renal damage. Other components must be more important. In patients with proteinuria serum creatinine proved not a good marker of glomerular filtration rate. We have validated the accuracy of urinary 2-microglobulin excretion in predicting outcome in patients with idiopathic membranous nephropathy. Sensitivity and specificity were 88% and 91% respectively. Use of this urinary marker allows tailor-made treatment in individual patients. In patients with iMN cyclophosphamide is more effective and less toxic than chlorambucil.RU Radboud Universiteit Nijmegen, 29 november 2005Promotor : Wetzels, J.F.M.156 p