Effect of Vitamin D and Tacrolimus Combination Therapy on IgA Nephropathy

Overview

Journal Med Sci Monit

Specialties General Medicine
Pathology

Date 2017 Jun 30

PMID 28659572

Citations 8

Authors

Dong Yuan

Zhan Fang

Fang Sun

Jing Chang

Jian Teng

Shuhua Lin

Xiaoming Liu

Affiliations

Soon will be listed here.

Abstract

BACKGROUND To explore the effects and the mechanism of vitamin D (VD) and tacrolimus (TAC) combinatorial therapy in the treatment of IgA nephropathy (IgAN) in a rat model. MATERIAL AND METHODS IgAN rat models constructed by oral immunization with bovine serum albumin (BSA) and lipopolysaccharide (LPS) (n=30) and were treated with: saline (model group), TAC (TAC group), or TAC+VD therapy (TAC+VD group) through gavage daily for 14 days. Serum creatinine (Scr), albumin (ALB), blood urea nitrogen (BUN), and urinary protein (UAE) levels were determined. Histopathology of renal tissues was examined after hematoxylin and eosin (H&E) staining. The levels of cytokines TGF-β1, IL-5, IFN-γ, and IL-4 in serum were detected by enzyme-linked immunosorbent assay (ELISA). Changes in TLR4/NF-κB pathway were evaluated by western blot. RESULTS Both TAC and TAC+VD treatment significantly restored the dysregulated Scr, ALB, BUN, and UAE levels in IgAN rats. TAC+VD therapy more prominently restored Scr and UAE levels (p<0.05). TAC+VD therapy demonstrated superior efficacy in reducing glomerular mesangial cells hyperplasia, reducing thickening of the glomerular basement membrane and glomerular infiltration of inflammatory cells. Thymus and spleen indexes were also increased (p<0.05). The levels of TGF-β1, IL-5, and IL-4 of the TAC+VD group were also lower than those of the TAC group (p<0.05). The TAC+VD group also demonstrated increased IFN-γ, and decreased p-P65/P65 and TLR4 compared to the TAC group. CONCLUSIONS TAC+VD combinatorial therapy can effectively alleviate renal tissue damage in IgAN rats by regulating immune response and the NF-κB/TLR4 pathway.

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References

Baeuerle P, Henkel T . Function and activation of NF-kappa B in the immune system. Annu Rev Immunol. 1994; 12:141-79. DOI: 10.1146/annurev.iy.12.040194.001041. View

Li X, Huang X, Pan L, Wang C, Qin J, Nong F . Vitamin D deficiency may predict a poorer outcome of IgA nephropathy. BMC Nephrol. 2016; 17(1):164. PMC: 5094030. DOI: 10.1186/s12882-016-0378-4. View

Nakamura H, Aoki M, Tamai K, Oishi M, Ogihara T, Kaneda Y . Prevention and regression of atopic dermatitis by ointment containing NF-kB decoy oligodeoxynucleotides in NC/Nga atopic mouse model. Gene Ther. 2002; 9(18):1221-9. DOI: 10.1038/sj.gt.3301724. View

Jiang J, Shi D, Zhou X, Yin L, Feng L, Jiang W . Vitamin D inhibits lipopolysaccharide-induced inflammatory response potentially through the Toll-like receptor 4 signalling pathway in the intestine and enterocytes of juvenile Jian carp (Cyprinus carpio var. Jian). Br J Nutr. 2015; 114(10):1560-8. DOI: 10.1017/S0007114515003256. View

Katzir Z, Leibovitch E, Vaknin H, Schreiber L, Berger E, Matas Z . Effect of atorvastatin on IgA nephropathy in the rat. Clin Nephrol. 2012; 79(3):214-20. DOI: 10.5414/CN107621. View

Tang H, Hua F, Wang J, Yousuf S, Atif F, Sayeed I . Progesterone and vitamin D combination therapy modulates inflammatory response after traumatic brain injury. Brain Inj. 2015; 29(10):1165-1174. PMC: 4894830. DOI: 10.3109/02699052.2015.1035330. View

Kim Y, Chin H, Koo H, Kim S . Tacrolimus decreases albuminuria in patients with IgA nephropathy and normal blood pressure: a double-blind randomized controlled trial of efficacy of tacrolimus on IgA nephropathy. PLoS One. 2013; 8(8):e71545. PMC: 3747236. DOI: 10.1371/journal.pone.0071545. View

Silva G, Costa R, Ravinal R, Ramalho L, Dos Reis M, Coimbra T . NF-kB expression in IgA nephropathy outcome. Dis Markers. 2011; 31(1):9-15. PMC: 3826481. DOI: 10.3233/DMA-2011-0795. View

Pludowski P, Holick M, Pilz S, Wagner C, Hollis B, Grant W . Vitamin D effects on musculoskeletal health, immunity, autoimmunity, cardiovascular disease, cancer, fertility, pregnancy, dementia and mortality-a review of recent evidence. Autoimmun Rev. 2013; 12(10):976-89. DOI: 10.1016/j.autrev.2013.02.004. View

10.

Klampfer L . Vitamin D and colon cancer. World J Gastrointest Oncol. 2014; 6(11):430-7. PMC: 4229786. DOI: 10.4251/wjgo.v6.i11.430. View

11.

Liang S, Cai G, Duan Z, Liu S, Wu J, Lv Y . Urinary sediment miRNAs reflect tubulointerstitial damage and therapeutic response in IgA nephropathy. BMC Nephrol. 2017; 18(1):63. PMC: 5312444. DOI: 10.1186/s12882-017-0482-0. View

12.

Wyatt R, Julian B . IgA nephropathy. N Engl J Med. 2013; 368(25):2402-14. DOI: 10.1056/NEJMra1206793. View

13.

Li C, Li L . Tacrolimus in preventing transplant rejection in Chinese patients--optimizing use. Drug Des Devel Ther. 2015; 9:473-85. PMC: 4298305. DOI: 10.2147/DDDT.S41349. View

14.

Ballarin J, Poveda R, Ara J, Perez L, Calero F, Grinyo J . Treatment of idiopathic membranous nephropathy with the combination of steroids, tacrolimus and mycophenolate mofetil: results of a pilot study. Nephrol Dial Transplant. 2007; 22(11):3196-201. DOI: 10.1093/ndt/gfm366. View

15.

Hesketh C, Knoll G, Molnar A, Tsampalieros A, Zimmerman D . Vitamin D and kidney transplant outcomes: a protocol for a systematic review and meta-analysis. Syst Rev. 2014; 3:64. PMC: 4065590. DOI: 10.1186/2046-4053-3-64. View

16.

Hu J, Liu Z, Zhang H . Omega-3 fatty acid supplementation as an adjunctive therapy in the treatment of chronic kidney disease: a meta-analysis. Clinics (Sao Paulo). 2017; 72(1):58-64. PMC: 5251198. DOI: 10.6061/clinics/2017(01)10. View

17.

Okada S, Shikata K . A commentary on the VITAL study: Does vitamin D (receptor activation) protect against nephropathy in type 2 diabetes?. J Diabetes Investig. 2014; 3(1):36-8. PMC: 4014930. DOI: 10.1111/j.2040-1124.2011.00161.x. View

18.

Roberts I . Pathology of IgA nephropathy. Nat Rev Nephrol. 2014; 10(8):445-54. DOI: 10.1038/nrneph.2014.92. View

19.

Mann M, Hemmelgarn B, Exner D, Hanley D, Turin T, Wheeler D . Vitamin D supplementation is associated with stabilization of cardiac autonomic tone in IgA nephropathy. Hypertension. 2015; 66(2):e4-6. DOI: 10.1161/HYPERTENSIONAHA.115.05688. View

20.

Tanaka T, Fujita M, Bottino R, Piganelli J, McGrath K, Li J . Endoscopic biopsy of islet transplants in the gastric submucosal space provides evidence of islet graft rejection in diabetic pigs. Islets. 2016; 8(1):1-12. PMC: 4878262. DOI: 10.1080/19382014.2016.1149283. View