Vitamin D Ameliorates Kidney Ischemia Reperfusion Injury via Reduction of Inflammation and Myofibroblast Expansion. Arfian Nur,Budiharjo Santosa,Wibisono Dian Prasetyo,Setyaningsih Wiwit Ananda Wahyu,Romi Muhammad Mansyur,Saputri Ramadhea Laila Afifa An-Nur Willya,Rofiah Edreana Khusnur,Rahmanti Trita,Agustin Maulidina,Sari Dwi Cahyani Ratna The Kobe journal of medical sciences The incidence rate of Acute Kidney Injury (AKI) gets escalated each year. Kidney ischemia/reperfusion injury (IR injury) is the main cause of AKI after major cardiovascular surgery, trauma, or kidney transplantation. Reperfusion is considered essential for ischemic tissue. However, the evidence revealed that reperfusion itself has impact in cellular destruction. Vitamin D is not only known as calcium regulating hormone, but also as renoprotective agent. This study aimed to investigate the effect of vitamin D treatment on kidney IR injury in mice. Kidney IR injury was performed using 30 minutes of bilateral clamping of renal pedicles, then released in male Swiss Webster mice (3 months, 30-40 grams, n=20), which were divided into three groups: sham operation (SO) group, IR injury (IRI) group, and IR injury with 0.25 µg/ kg body weight of vitamin D treatment (IR7+VD). Mice were terminated at day 7 post operation, kidneys were harvested and used for paraffin making, immunostaining and RNA extraction. Tubular injury was quantified based on Periodic Acid-Schiff's (PAS) staining. Immunostaining was done for quantification of macrophage (CD68) and myofibroblast (α-SMA). Reverse Transcriptase PCR (RT-PCR) was done to examine Monocyte Chemoattractant Protein-1 (MCP-1) and Toll-like Receptor 4 (TLR4) mRNA expression. Kidney IR injury induced significant increase of tubular injury, which was associated with higher myofibroblast and macrophage number. Meanwhile, Vitamin D treatment significantly reduced tubular, myofibroblast and macrophage number. RTPCR revealed reduction of TLR4 and MCP-1 mRNA expressions after Vitamin D treatment (p<0.05 vs IR group). Vitamin D ameliorates kidney IR injury through reducing inflammation and myofibroblast formation.

Vitamin D and methylarginines in chronic kidney disease (CKD). Torino Claudia,Pizzini Patrizia,Cutrupi Sebastiano,Tripepi Rocco,Tripepi Giovanni,Mallamaci Francesca,Zoccali Carmine PloS one BACKGROUND:Vitamin D associates with the plasma concentration of the endogenous inhibitor of the nitric oxide system asymmetric dimethyl arginine (ADMA) and cross-sectional studies in CKD patients treated with the vitamin D receptor activator paricalcitol show that plasma ADMA is substantially less than in those not receiving this drug. METHODS:In the frame of a randomized, double-blind, placebo controlled trial, the Paracalcitol and ENdothelial fuNction in chronic kidneY disease (PENNY), we investigated whether vitamin D receptor activation by paricalcitol (2 μg/day x 12 weeks) affects the plasma concentration of ADMA and symmetric dimethyl arginine (SDMA) in 88 patients with stage 3 to 4 CKD. RESULTS:Paricalcitol produced the expected small rise in serum calcium and phosphate and a marked PTH suppression. However, ADMA [Paricalcitol: baseline 0.75 μMol/L (95%CI: 0.70-0.81), 12 week 0.72 μMol/L (95%CI: 0.66-0.78); Placebo: baseline 0.75 μMol/L (95%CI: 0.70-0.90) 12 weeks 0.70 μMol/L (95%CI: 0.66-0.74)] and SDMA [Paricalcitol: baseline 0.91 μMol/L (95%CI: 0.82-1.00), 12 week 0.94 μMol/L (95%CI: 0.82-0.1.06); Placebo: baseline 0.91 μMol/L (95%CI: 0.82-1.06) 12 weeks 0.99 μMol/L (95%CI: 0.88-1.10)] remained unchanged during the trial and 2 weeks after stopping these treatments. CONCLUSIONS:Paricalcitol does not modify plasma ADMA and SDMA in patients with stage 3-4 CKD. The apparent beneficial effects of paricalcitol on ADMA registered in cross-sectional studies is likely attributable to confounding by indication rather than to a true effect of this drug on ADMA metabolism. 10.1371/journal.pone.0185449

Vitamin D analogue therapy, cardiovascular risk and kidney function in people with Type 1 diabetes mellitus and diabetic nephropathy: a randomized trial. Joergensen C,Tarnow L,Goetze J P,Rossing P Diabetic medicine : a journal of the British Diabetic Association AIM:To evaluate the effects of therapy with the vitamin D analogue paricalcitol on markers of cardiovascular risk and kidney function in people with Type 1 diabetes mellitus and diabetic nephropathy. METHODS:In a double-blind, randomized placebo-controlled, crossover trial, 48 participants on stable renin angiotensin aldosterone system blockade and diuretics were assigned, in random order, to 12 weeks of paricalcitol and 12 weeks of placebo therapy, separated by a 4-week washout period. Primary and secondary endpoints were changes in plasma N-terminal probrain natriuretic peptide and urinary albumin excretion rate obtained before and after each intervention. Glomerular filtration rates were estimated and measured ((51) Cr-EDTA plasma clearance glomerular filtration rate) after each intervention. RESULTS:The mean (sd) age of the participants was 57 (9) years, the baseline geometric mean (95% CI) urinary albumin excretion rate was 148 (85-259) mg/24 h, the mean (sd) HbA1c was 70 (9) mmol/mol [8.6 (3)%], the mean (sd) estimated glomerular filtration rate was 47 (15) ml/min/1.73 m(2) and the mean (sd) 24-h blood pressure was 135 (17)/74 (10) mmHg. Compared with placebo therapy, vitamin D analogue therapy had no significant effect on plasma N-terminal probrain natriuretic peptide concentration (P = 0.6), urinary albumin excretion rate was reduced by 18% (P = 0.03 for comparison), estimated glomerular filtration rate was reduced by 5 ml/min/1.73 m(2) (P < 0.001) and measured glomerular filtration rate was reduced by 1.5 ml/min/1.73 m(2) (P = 0.2). CONCLUSIONS:Paricalcitol therapy did not affect plasma N-terminal probrain natriuretic peptide concentration in people with Type 1 diabetes and diabetic nephropathy; however, the urinary albumin excretion rate was significantly lowered. 10.1111/dme.12606