The pathophysiology underlying proteinuria remains incompletely understood and warrants further research. We currently initiated the investigation of the genetic basis of proteinuria in the Sabra rat, a model of salt-susceptibility which we have previously shown to be also a model of spontaneous proteinuria that is unrelated to salt-loading or the development of hypertension. We applied the total genome scan strategy in 75 F2 male animals derived from a cross between SBH/y which are prone to develop proteinuria and SBN/y which are relatively resistant to the development of proteinuria. Animals were subjected to uninephrectomy (UNx) to accelerate the development of proteinuria and provided chow with a low salt content, thus avoiding the development of hypertension. Urinary protein excretion was monitored prior to UNx and monthly thereafter for 8 months. The genotype of F2 was determined with microsatellite markers. The data were analyzed for co-segregation by ANOVA and for genetic linkage using a novel multi-faceted statistical genetic paradigm. We detected three proteinuria-related QTL that were associated with the H alleles from SBH/y: SUP2, SUP17 and SUP20 on rat chromosomes (Chr) 2, 17 and 20. We detected an additional QTL on Chr 3, SUP3, that was associated with the N alleles from SBN/y. A temporal effect was noted: QTL SUP2 and SUP17 surfaced at months 7-8, QTL SUP20 at months 6-8 and QTL SUP3 at months 5-6. The QTL emerging from this study lead us a step closer to identifying the genes associated with and elucidate the pathophysiology of proteinuria.