scholarly journals Active Vitamin D<sub>3</sub> Protects Against Diabetic Kidney Disease by Regulating the JNK Signaling Pathway in Rats

2021 ◽  
Vol 6 (3) ◽  
pp. 105
Author(s):  
Xiaoju Fan ◽  
Linlin Liu ◽  
Wenzhuo Zhu ◽  
Yumei Zhao ◽  
Haowei Zhang ◽  
...  
Author(s):  
Anne Schön ◽  
Maren Leifheit-Nestler ◽  
Jennifer Deppe ◽  
Dagmar-Christiane Fischer ◽  
Aysun K Bayazit ◽  
...  

Abstract Background Uraemic cardiac remodelling is associated with vitamin D and Klotho deficiency, elevated fibroblast growth factor 23 (FGF23) and activation of the renin–angiotensin system (RAS). The cardioprotective properties of active vitamin D analogues in this setting are unclear. Methods In rats with 5/6 nephrectomy (5/6Nx) treated with calcitriol, the cardiac phenotype and local RAS activation were investigated compared with controls. A nested case–control study was performed within the Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C) study, including children with chronic kidney disease (CKD) Stages 3–5 [estimated glomerular filtration rate (eGFR) 25 mL/min/1.73 m2] treated with and without active vitamin D. Echocardiograms, plasma FGF23 and soluble Klotho (sKlotho) were assessed at baseline and after 9 months. Results In rats with 5/6Nx, left ventricular (LV) hypertrophy, LV fibrosis and upregulated cardiac RAS were dose-dependently attenuated by calcitriol. Calcitriol further stimulated FGF23 synthesis in bone but not in the heart, and normalized suppressed renal Klotho expression. In the 4C study cohort, treatment over a mean period of 9 months with active vitamin D was associated with increased FGF23 and phosphate and decreased sKlotho and eGFR compared with vitamin D naïve controls, whereas LV mass index did not differ between groups. Conclusions Active vitamin D ameliorates cardiac remodelling and normalizes renal Klotho expression in 5/6Nx rats but does not improve the cardiac phenotype in children with CKD Stages 3–5. This discrepancy may be due to further enhancement of circulating FGF23 and faster progression of CKD associated with reduced sKlotho and higher serum phosphate in vitamin D-treated patients.


BMJ Open ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. e025784 ◽  
Author(s):  
Kirsten PJ Smits ◽  
Grigory Sidorenkov ◽  
Frans J van Ittersum ◽  
Femke Waanders ◽  
Henk JG Bilo ◽  
...  

ObjectivesInsight in the prescribing quality for patients with chronic kidney disease (CKD) in secondary care is limited. The aim of this study is to assess the prescribing quality in secondary care patients with CKD stages 3–5 and possible differences in quality between CKD stages.DesignThis was a retrospective cohort study.SettingData were collected at two university (n=569 and n=845) and one non-university nephrology outpatient clinic (n=1718) in the Netherlands.ParticipantsBetween March 2015 and August 2016, data were collected from patients with stages 3a–5 CKD seen at the clinics. Blood pressure measurements, laboratory measurements and prescription data were extracted from medical records. For each prescribing quality indicator, patients with incomplete data required for calculation were excluded.Outcome measuresPotentially appropriate prescribing of antihypertensives, renin-angiotensin-aldosterone system (RAAS) inhibitors, statins, phosphate binders and potentially inappropriate prescribing according to prevailing guidelines was assessed using prescribing quality indicators. Χ2or Fisher’s exact tests were used to test for differences in prescribing quality.ResultsRAAS inhibitors alone or in combination with diuretics (57% or 52%, respectively) and statins (42%) were prescribed less often than phosphate binders (72%) or antihypertensives (94%) when indicated. Active vitamin D was relatively often prescribed when potentially not indicated (19%). Patients with high CKD stages were less likely to receive RAAS inhibitors but more likely to receive statins when indicated than stage 3 CKD patients. They also received more active vitamin D and erythropoietin-stimulating agents when potentially not indicated.ConclusionsPriority areas for improvement of prescribing in CKD outpatients include potential underprescribing of RAAS inhibitors and statins, and potential overprescribing of active vitamin D. CKD stage should be taken into account when assessing prescribing quality.


2015 ◽  
Vol 42 (3) ◽  
pp. 228-236 ◽  
Author(s):  
Mario Cozzolino ◽  
Adrian Covic ◽  
Blanca Martinez-Placencia ◽  
Konstantinos Xynos

Background: In patients with chronic kidney disease (CKD), impaired renal function leads to decreased vitamin D levels, which causes an increase in parathyroid hormone (PTH) production and contributes to the development of secondary hyperparathyroidism (SHPT). This may result in adverse clinical effects such as bone disorders, vascular calcification, cardiovascular disease, and increased mortality. Current treatment practices and associated outcomes with active vitamin D treatment in patients with CKD were reviewed with the objective to assess parameters (such as PTH and serum calcium levels) that may be used to define the failure of vitamin D treatment. Summary: Reports based on observational data have noted improved outcomes with active vitamin D treatment (calcitriol, paricalcitol, alfacalcidol, or doxercalciferol) in patients with CKD. Criteria for the identification of active vitamin D treatment failure are unclear from current guidelines, although up to 50% of patients may experience treatment failure eventually because of development of hypercalcemia or resistant SHPT, characterized by an elevated intact PTH (iPTH) level despite treatment. We propose a definition of vitamin D treatment failure as iPTH >600 pg/ml after 6 months of intravenous active vitamin D treatment and corrected total calcium serum levels >10.2 mg/dl, and review factors that may predict the response to vitamin D treatment. Key Message: Active vitamin D treatment failure is an important challenge in clinical practice. The aim of the proposed definition is to suggest a possible framework for hypothesis generation and to encourage further research into this common problem.


2012 ◽  
Vol 9 (1) ◽  
pp. 6-7 ◽  
Author(s):  
Peter Rossing ◽  
Christel Joergensen

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