scholarly journals Low Bone Turnover in Chronic Kidney Disease Is Associated with Decreased VEGF-A Expression and Osteoblast Differentiation

2015 ◽  
Vol 41 (6) ◽  
pp. 464-473 ◽  
Author(s):  
Neal X. Chen ◽  
Kalisha D. O''Neill ◽  
Matthew R. Allen ◽  
Christopher L. Newman ◽  
Sharon M. Moe

Background: Low turnover bone (low bone formation rates (BFRs)) with decreased osteoblast number is common in patients with chronic kidney disease (CKD) and attributed to ‘over-suppression' of the parathyroid hormone (PTH) despite supra-physiologic levels. An alternative hypothesis is abnormal osteoblast differentiation, resulting in low BFRs due to reduced VEGF-A. Methods: We analyzed the expression of VEGF-A and mesenchymal stem cell (MSC) differentiation factors in freshly isolated bone marrow (BM) cells, and in BM cell-derived MSC in rats with different levels of BFRs and PTH (modulated by calcium and zoledronic acid). The regulators of VEGF in MSC were also determined. Results: VEGF-A expression was reduced in the BM cells from CKD vs. normal animals (p < 0.02). In BM-derived MSC from CKD, there were decreased osteoblast transcription factors and mineralization. In CKD animals, the BM VEGF-A expression was positively correlated with BFR (r = 0.80, p < 0.001). Reducing BFRs in CKD animals led to reductions in VEGF-A expression and osteoblast transcription factors regardless of the PTH level. We therefore examined other regulators of VEGF-A and found decreased expression of hypoxia-inducible factor-1α and the master transcription factor of antioxidants nuclear factor (erythroid-derived 2)-like 2 in CKD animals with low PTH. Conclusion: Low BFRs in CKD are associated with a basal decrease in VEGF-A expression in BM that may be driven by altered hypoxia and oxidative stress.

Toxins ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 472
Author(s):  
Elisabetta Margiotta ◽  
Lara Caldiroli ◽  
Maria Luisa Callegari ◽  
Francesco Miragoli ◽  
Francesca Zanoni ◽  
...  

Background: Sarcopenia is a prevalent condition in chronic kidney disease (CKD). We determined gut microbiota (gMB) composition in CKD patients with or without sarcopenia. Furthermore, we investigated whether in these patients, there was any association between gMB, uremic toxins, inflammation and oxidative stress. Methods: We analyzed gMB composition, uremic toxins (indoxyl sulphate and p-cresyl sulphate), inflammatory cytokines (interleukin 10, tumor necrosis factor α, interleukin 6, interleukin 17, interleukin 12 p70, monocyte chemoattractant protein-1 and fetuin-A) and oxidative stress (malondialdehyde) of 64 elderly CKD patients (10 < eGFR < 45 mL/min/1.73 m2, not on dialysis) categorized as sarcopenic and not-sarcopenic. Sarcopenia was defined according to European Working Group on Sarcopenia in Older People 2 criteria. Results: Sarcopenic patients had a greater abundance of the Micrococcaceae and Verrucomicrobiaceae families and of Megasphaera, Rothia, Veillonella, Akkermansia and Coprobacillus genera. They had a lower abundance of the Gemellaceae and Veillonellaceae families and of Acidaminococcus and Gemella genera. GMB was associated with uremic toxins, inflammatory cytokines and MDA. However, uremic toxins, inflammatory cytokines and MDA were not different in sarcopenic compared with not-sarcopenic individuals, except for interleukin 10, which was higher in not-sarcopenic patients. Conclusions: In older CKD patients, gMB was different in sarcopenic than in not-sarcopenic ones. Several bacterial families and genera were associated with uremic toxins and inflammatory cytokines, although none of these latter substantially different in sarcopenic versus not-sarcopenic patients.


PLoS ONE ◽  
2016 ◽  
Vol 11 (8) ◽  
pp. e0159411 ◽  
Author(s):  
Keith G. Avin ◽  
Neal X. Chen ◽  
Jason M. Organ ◽  
Chad Zarse ◽  
Kalisha O’Neill ◽  
...  

2019 ◽  
Vol 317 (5) ◽  
pp. F1189-F1200 ◽  
Author(s):  
Md Mahbub Ullah ◽  
Connie P. C. Ow ◽  
Lucinda M. Hilliard Krause ◽  
Roger G. Evans

To assess whether renal hypoxia is an early event in adenine-induced chronic kidney disease, adenine (100 mg) or its vehicle was administered to male Sprague-Dawley rats by daily oral gavage for 7 days. Kidney oxygenation was assessed by 1) blood oximetry and Clark electrode in thiobutabarbital-anesthetized rats, 2) radiotelemetry in unanesthetized rats, and 3) expression of hypoxia-inducible factor (HIF)-1α and HIF-2α protein. After 7 days of treatment, under anesthesia, renal O2 delivery was 51% less, whereas renal O2 consumption was 65% less, in adenine-treated rats than in vehicle-treated rats. Tissue Po2 measured by Clark electrode was similar in the renal cortex but 44% less in the medulla of adenine-treated rats than in that of vehicle-treated rats. In contrast, in unanesthetized rats, both cortical and medullary tissue Po2 measured by radiotelemetry remained stable across 7 days of adenine treatment. Notably, anesthesia and laparotomy led to greater reductions in medullary tissue Po2 measured by radiotelemetry in rats treated with adenine (37%) than in vehicle-treated rats (16%), possibly explaining differences between our observations with Clark electrodes and radiotelemetry. Renal expression of HIF-1α was less after 7 days of adenine treatment than after vehicle treatment, whereas expression of HIF-2α did not differ significantly between the two groups. Renal dysfunction was evident after 7 days of adenine treatment, with glomerular filtration rate 65% less and serum creatinine concentration 183% greater in adenine-treated rats than in vehicle-treated rats. Renal cortical tissue hypoxia may not precede renal dysfunction in adenine-induced chronic kidney disease and so may not be an early pathological feature in this model.


Medicine ◽  
2020 ◽  
Vol 99 (31) ◽  
pp. e21492 ◽  
Author(s):  
Chengqian Shi ◽  
Keda Lu ◽  
Hong Xia ◽  
Peipei Zhang ◽  
Bingbing Zhang

2019 ◽  
Vol 133 ◽  
pp. 248-253 ◽  
Author(s):  
Takeshi Nakanishi ◽  
Takahiro Kuragano ◽  
Masayoshi Nanami ◽  
Yasuyuki Nagasawa ◽  
Yukiko Hasuike

Sign in / Sign up

Export Citation Format

Share Document