Adenine Rich Diet Is Not a Surrogate of 5/6 Nephrectomy in Rabbits

Abstract

Background: Animal models are important tools needed to understand the mechanisms underlying the progression of renal disease and to implement new therapeutic approaches. A non-surgical model of chronic kidney disease (CKD) developed by chemical nephrectomy using an adenine-enriched diet has been shown to be a robust model to induce kidney failure in mice and rats. The purpose of this study was to implement an adenine diet to induce CKD in rabbits. Methods: Male New Zealand rabbits were fed for 4 weeks with a diet containing 0.75% (w/w) adenine, and renal function was assessed by measuring plasma urea and creatinine concentrations. The glomerular filtration rate (GFR) was measured using the plasmatic clearance of Iohexol. Kidney histology was performed with haematoxylin erythrosine saffron and Sirius red staining. Results: In contrast to what was observed in rodents, adenine diet failed to induce kidney failure in rabbits as is evident in the plasma concentrations of creatinine and urea and the direct measurement of GFR or histopathological studies. Conclusion: Adenine diet is not a surrogate of subtotal nephrectomy to induce kidney failure in rabbits. Several interspecies differences in metabolism and renal physiology could account for this observation.

Chronic treatment of curcumin improves hepatic lipid metabolism and alleviates the renal damage in adenine-induced chronic kidney disease in Sprague-Dawley rats

“…Nevertheless, Aoyama et al [65] has shown that adenine (0.75% w/w) in the diet produced renal damage resembling CKD but also found 50% mortality. Thus, in the present study, we used adenine at the dose of 0.75% w/w in the diet for 24 days and no mortality was found which is consistent with previous reports [61–64]. Furthermore, biochemical evaluations in our study have shown that distinctive CKD was produced in rats upon feeding with adenine.…”

“…Excess adenine in mammalian metabolism becomes a significant substrate for xanthine dehydrogenase and oxidises into low soluble compounds 2, 8-dihydroxyadenine which further precipitate in renal tubules and damage the kidney tissue accompanied by oxidative stress and subsequently renal dysfunction [60]. The adenine model is reproducible, simpler to conduct and more like human CKD than the 5/6 nephrectomy [61, 62]. Adenine-induced renal damage is time-dependent-the longer the feeding time, the more severe the renal damage [63].…”

“…Adenine-induced renal damage is time-dependent-the longer the feeding time, the more severe the renal damage [63]. Previous studies suggested that 0.75% w/w adenine in the diet for 4 weeks is an optimum duration for damage to the renal tissue to occur without mortality [61, 63]. Furthermore, adenine feeding for more than 7 weeks has caused significant mortality [64].…”

Protective effects of hydrogen sulfide on chronic kidney disease by reducing oxidative stress, inflammation and apoptosis

“…In our study using 5/6 nephrectomy model has remained the developed prototype which closely mimics human CKD and is a useful model for studying drug responses in CKD. In contrast to what was observed in 5/6 nephrectomy, adenine diet failed to induce kidney failure in rabbits as is evident in functional indices in a recent study (Florens et al, 2017[ 18 ]). In the current study, we investigated the effects of H 2 S on CKD induced by 5/6 Nx in different dose, administration method and longer time in rats.…”

Curcumin Ameliorates Kidney Function and Oxidative Stress in Experimental Chronic Kidney Disease

“…Adenine and its metabolite, 2,8‐dihydroxyadenine, have a low solubility and precipitate in the renal tubules leading to their occlusion , resulting in inflammation accompanied by oxidative stress and subsequently renal dysfunction . The adenine model is more reproducible, simpler to conduct and more similar to human CKD than the 5/6 nephrectomy . The beneficial action of curcumin occurred in a dose‐dependent manner and encompassed markers of acute as well as of chronic renal damage.…”