Differences on the Natural Course of Chronic Kidney Disease Progression, Induced by 5/6 Renal Ablation Model in Three Different Rat Stains: Wistar, Lewis, and Fischer 344

Almost 10% of the global population suffers from chronic kidney disease (CKD). The inexistence of a therapeutic to restore renal function motivates the scientific community to search for new treatments. The 5/6 nephrectomy (Nx) rat model is widely used to mimic human CKD, but the impact of strain-specific responses on disease progression remains unclear. Here, we aimed to compare CKD development in Wistar, Lewis, and Fischer rats submitted to the Nx model. In summary, even submitted to the same surgical procedure, the three studied rat strains presented distinct patterns of CKD progression: Wistar rats exhibited faster and sustained renal function loss, with exuberant hypertension, proteinuria, and renal inflammation, being considered as excellent models to study rapidly progressive human nephropathy. Lewis animals, in turn, presented mild low-progressive CKD, which make this rat strain especially useful to simulate intermediate degrees of human CKD and to develop long-term tests. Finally, Fischer rats submitted to Nx did not even develop hypertension, proteinuria, or glomerular damage within 30 days. Moreover, compared to Wistar rats, both Lewis and Fischer animals have a relatively higher basal number of nephrons and a lower number of whole blood leukocytes, which may have contributed to the renoprotection exhibited by these rat strains.