Differences on the Natural Course of Chronic Kidney Disease Progression, Induced by 5/6 Renal Ablation Model, According to the Rat Strain

Almost 10% of the global population suffers from chronic kidney disease (CKD), a severe, progressive and irreversible condition that usually leads to the necessity of life-sustaining renal replacement therapy. The inexistence of a therapeutic intervention able to restore renal function loss motivates the scientific community to develop experimental and preclinical studies in search for new drugs and treatments. Most of these studies require animal models of CKD in order to resemble human nephropathy and human pathophysiological responses, and one of the main employed animals for this purpose is the rat (Rattus norvegicus). Among the variety of available rat CKD models described in the literature, the sub-total nephrectomy model, achieved through the 5/6 renal ablation, stands out, since it better mimics human CKD development and progression. However, there are still no consensus on the most appropriate rat strain for this purpose. The aim of this study was to compare the development and severity of the nephropathy associated to the 5/6 renal ablation model in Wistar, Lewis and Fischer rats. In summary, we observed that, even submitted to the very same surgical procedure of renal mass reduction, the 3 studies rat strains presented completely distinct patterns of CKD progression: Wistar rats exhibited faster, rapidly-progressive and sustained renal function loss, with exuberant hypertension, proteinuria and renal inflammation, and can be considered as excellent animal models to study rapidly progressive, severe human nephropathy and to develop quick tests on new therapies and drugs. Lewis animals, in turn, presented mild and low-progressive CKD, which make this rat strain especially useful to simulate intermediate degrees of human CKD and to develop long-term drug tests. Finally, Fischer rats submitted to the same 5/6 renal ablation model, not even developed hypertension nor proteinuria or structural glomerular damage. We also demonstrated that, compared to Wistar rats, both Lewis and, especially Fischer control rats have a relative higher basal number of nephrons, which may have consistently contributed to the observer renoprotection exhibited by this last rat strain.