Renoprotective effects of sucroferric oxyhydroxide in a rat model of chronic renal failure

Abstract

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Introduction</jats:title> <jats:p>Sucroferric oxyhydroxide (PA21) is an efficacious, well-tolerated iron-based phosphate binder and a promising alternative to existing compounds. We compared the effects of PA21 with those of a conventional phosphate binder on renal function, mineral homeostasis and vascular calcification in a chronic kidney disease–mineral and bone disorder (CKD-MBD) rat model.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>To induce stable renal failure, rats were administered a 0.25% adenine diet for 8 weeks. Concomitantly, rats were treated with vehicle, 2.5 g/kg/day PA21, 5.0 g/kg/day PA21 or 3.0 g/kg/day calcium carbonate (CaCO3). Renal function and calcium/phosphorus/iron metabolism were evaluated during the study course. Renal fibrosis, inflammation, vascular calcifications and bone histomorphometry were quantified.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Rats treated with 2.5 or 5.0 g/kg/day PA21 showed significantly lower serum creatinine and phosphorus and higher ionized calcium levels after 8 weeks of treatment compared with vehicle-treated rats. The better preserved renal function with PA21 went along with less severe anaemia, which was not observed with CaCO3. Both PA21 doses, in contrast to CaCO3, prevented a dramatic increase in fibroblast growth factor (FGF)-23 and significantly reduced the vascular calcium content while both compounds ameliorated CKD-related hyperparathyroid bone.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>PA21 treatment prevented an increase in serum FGF-23 and had, aside from its phosphate-lowering capacity, a beneficial impact on renal function decline (as assessed by the renal creatinine clearance) and related disorders. The protective effect of this iron-based phosphate binder on the kidney in rats, together with its low pill burden in humans, led us to investigate its use in patients with impaired renal function not yet on dialysis.</jats:p> </jats:sec>

Progression of established non-diabetic chronic kidney disease is halted by metformin treatment in rats

“…Yet, it is of note that the full spectrum of functional and histopathological features of CKD are consistently present in this model and also result in comorbidities relevant to human CKD-MBD. 14,49 Moreover, the fact that metformin is able to attenuate CKD progression in this severe model corroborates its potential as therapeutic renoprotector. A next limitation of this study is the mortality in our metformin-treated groups.…”

Metformin Attenuates Renal Fibrosis in a Mouse Model of Adenine-Induced Renal Injury Through Inhibiting TGF-β1 Signaling Pathways

“…Previous studies have shown that adenine induces renal functional impairment, myofibroblast activation, sterile inflammatory responses and accumulation of cellular matrix proteins (including collagens and fibronectin) in the renal interstitium. Its mechanism of toxicity has been extensively evaluated with many similarities to human tubulointerstitial pathology (Kashioulis et al, 2018 ; Abellán et al, 2019 ; Gong et al, 2019 ; Ichida et al, 2020 ; Neven et al, 2020 ; Sieklucka et al, 2020 ). Hence this model has been widely used as an animal model of tubulointerstitial kidney disease (Jia et al, 2013 ; Mishima et al, 2015 ; Bobeck et al, 2017 ).…”

Towards a better understanding of arterial calcification disease progression in CKD: investigation of early pathological alterations

“…Renal function at each timepoint (2, 4 and 8 weeks) was evaluated by serum creatinine measurement according to the Jaffé method [ 42 ].…”