Risedronate Attenuates Podocyte Injury in Phosphate Transporter-Overexpressing Rats.
Yohei AsadaTakeshi TakayanagiTsukasa KawakamiEisuke TomatsuAtsushi MasudaYasumasa YoshinoSahoko Sekiguchi-UedaMegumi ShibataTomihiko IdeHajime NiimiEishin YaoitaYusuke SeinoYoshihisa SugimuraAtsushi SuzukiPublished in: International journal of endocrinology (2019)
Osteoporosis patients with chronic kidney disease (CKD) are becoming common in our superaging society. Renal dysfunction causes phosphorus accumulation in the circulating plasma and leads to the development of CKD-mineral bone disorder (MBD). We have previously reported that type III Pi transporter-overexpressing transgenic (Pit-1 TG) rats manifest phosphate (Pi)-dependent podocyte injury. In the present study, we explored the effect of risedronate on Pi-induced podocyte injury in vivo. Pit-1 TG rats and wild-type rats at 5 weeks old were divided into a risedronate-treated group and an untreated group. We subcutaneously administered 5 μg/kg body weight of risedronate or saline twice a week during the experimental period. Risedronate did not alter serum creatinine levels at 5, 8, and 12 weeks of age. However, electron microscopy images showed that thickening of the glomerular basement membrane was improved in the risedronate treatment group. Furthermore, immunostaining for podocyte injury markers revealed that both desmin- and connexin43-positive areas were smaller in the risedronate-treated group than in the untreated group, suggesting that bisphosphonates could rescue Pi-induced podocyte injury. In conclusion, our findings suggest that risedronate could maintain glomerular barrier function by rescuing Pi-induced podocyte injury.
Keyphrases
- high glucose
- endothelial cells
- diabetic nephropathy
- body weight
- chronic kidney disease
- diabetic rats
- electron microscopy
- randomized controlled trial
- bone mineral density
- optical coherence tomography
- newly diagnosed
- convolutional neural network
- heavy metals
- placebo controlled
- combination therapy
- anaerobic digestion