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Toxine geïnduceerde lysosomale opstapelingsziekte: een nieuw etiologisch, mechanistisch, diagnostisch en prognostisch paradigma voor de wereldwijd toenemende prevalentie van agrochemicaliën-geassocieerde nefropathie.
Chronic kidney disease (CKD) is a clinical condition characterized by the progressive loss of functional renal mass. In the last 20 years, an increase in CKD is reported in agricultural communities, worldwide affecting millions of people. This disease was named Chronic Interstitial Nephritis in Agricultural Communities (CINAC). Whereas chronic dehydration has been proposed as cause, increasing evidence points towards exposure to agrochemicals. Yet, the cause remains disputed and the mechanism unknown. Moreover, CINAC-patients can only be identified by excluding traditional causes of CKD (i.e. diabetes, hypertension and numerous other renal diseases), which is clinically cumbersome. Recently, in human kidney biopsies from CINAC-patients, we discovered a lysosomal lesion in proximal epithelial cells, a renal cell type highly susceptible to toxic insults. Moreover, we observed the exact same lysosomal lesion in transplant patients exposed to nephrotoxic immunosuppression by calcineurin inhibitors. This suggests that CINAC is a toxininduced lysosomal storage disease in which the calcineurin pathway might play a role. By integrating herbicide/pesticide time course exposure studies (in vitro and in vivo) with human renal biopsy analysis and state of the art metabolomic, transcriptomic and proteomic techniques, we aim at identifying the CINAC-inducing herbicides/pesticides as well as evaluate the diagnostic and prognostic value of this new paradigm.
Datum:1 jan 2019 → Heden