scholarly journals Regulated necrosis and failed repair in cisplatin-induced chronic kidney disease

2019 ◽  
Vol 95 (4) ◽  
pp. 797-814 ◽  
Author(s):  
Sarah I. Landau ◽  
Xiaojia Guo ◽  
Heino Velazquez ◽  
Richard Torres ◽  
Eben Olson ◽  
...  
2021 ◽  
pp. ASN.2021040439
Author(s):  
Xiaojia Guo ◽  
Leyuan Xu ◽  
Heino Velazquez ◽  
Tian-Min Chen ◽  
Ryan Williams ◽  
...  

Background Repeated administration of cisplatin causes chronic kidney disease (CKD). In previous studies, we reported that the kidney-secreted survival protein renalase and an agonist peptide protected mice from cisplatin-induced acute kidney injury. Methods To investigate whether kidney-targeted delivery of renalase might prevent cisplatin-induced CKD in a mouse model, we achieved specific delivery of a renalase agonist peptide (RP81) to the renal proximal tubule by encapsulating the peptide in mesoscale nanoparticles (MNPs). We used genetic deletion of renalase, single-cell RNA sequencing (RNA-seq) analysis, and Western blotting to determine efficacy and to explore underlying mechanisms. We also measured plasma renalase in patients with advanced head and neck squamous cell carcinoma receiving their first dose of cisplatin chemotherapy. Results In mice with CKD induced by cisplatin, we observed an approximate 60% reduction of kidney renalase; genetic deletion of renalase was associated with significantly more severe cisplatin-induced CKD. In this severe model of cisplatin-induced CKD, systemic administration of MNP-encapsulated RP81 (RP81-MNP) significantly reduced CKD as assessed by plasma creatinine and histology. It also decreased inflammatory cytokines in plasma and inhibited regulated necrosis in kidney. Single-cell RNA seq analyses revealed that RP81-MNP preserved epithelial components of the nephron and the vasculature, as well as suppressed inflammatory macrophages and myofibroblasts. In patients receiving their first dose of cisplatin chemotherapy, plasma renalase levels trended lower at day 14 post-treatment. Conclusions Kidney-targeted delivery of renalase agonist RP81MNP protects against cisplatin-induced CKD by decreasing cell death and improving the viability of the renal proximal tubule. These findings suggest that such an approach might mitigate the development of CKD in patients receiving cisplatin cancer chemotherapy.


Author(s):  
Jiwoon Kim ◽  
Ji Sun Nam ◽  
Heejung Kim ◽  
Hye Sun Lee ◽  
Jung Eun Lee

Abstract. Background/Aims: Trials on the effects of cholecalciferol supplementation in type 2 diabetes with chronic kidney disease patients were underexplored. Therefore, the aim of this study was to investigate the effects of two different doses of vitamin D supplementation on serum 25-hydroxyvitamin D [25(OH)D] concentrations and metabolic parameters in vitamin D-deficient Korean diabetes patients with chronic kidney disease. Methods: 92 patients completed this study: the placebo group (A, n = 33), the oral cholecalciferol 1,000 IU/day group (B, n = 34), or the single 200,000 IU injection group (C, n = 25, equivalent to 2,000 IU/day). 52% of the patients had less than 60 mL/min/1.73m2 of glomerular filtration rates. Laboratory test and pulse wave velocity were performed before and after supplementation. Results: After 12 weeks, serum 25(OH)D concentrations of the patients who received vitamin D supplementation were significantly increased (A, -2.4 ± 1.2 ng/mL vs. B, 10.7 ± 1.2 ng/mL vs. C, 14.6 ± 1.7 ng/mL; p < 0.001). In addition, the lipid profiles in the vitamin D injection group (C) showed a significant decrease in triglyceride and a rise in HDL cholesterol. However, the other parameters showed no differences. Conclusions: Our data indicated that two different doses and routes of vitamin D administration significantly and safely increased serum 25(OH)D concentrations in vitamin D-deficient diabetes patients with comorbid chronic kidney disease. In the group that received the higher vitamin D dose, the lipid profiles showed significant improvement, but there were no beneficial effects on other metabolic parameters.


VASA ◽  
2012 ◽  
Vol 41 (3) ◽  
pp. 159-160
Author(s):  
Espinola-Klein ◽  
F. Dopheide ◽  
Gori

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