Membranous nephropathy (MN) is a chronic immune disease of the renal glomeruli, leading to significant proteinuria and thickening of the glomerular basement membrane caused by subepithelial deposits of immune complexes. It can be primary (idiopathic) or secondary, arising from infections, neoplasms, or drug treatment. The disease more often affects men between the ages of 30 and 40 and is the second most common glomerulonephritis in our latitudes, after IgA nephropathy.
Treatment of MN with immunosuppressive drugs is initiated if there are risk factors for disease progression or if complications of nephrotic syndrome develop, such as acute kidney injury or thromboembolism. Tacrolimus inhibits calcineurin and suppresses T-cell activity, thereby reducing the immune response and stopping disease progression.
We present our results in four patients with histologically proven membranous nephropathy, being followed up at the Nephrology Clinic at the University Hospital "St. Marina" in Varna. Tacrolimus was included in their treatment due to an insufficient response to clinical and laboratory symptoms, as well as the appearance of side effects from the initial pathogenetic therapy in some of them.
After six months of observation, a reduction in proteinuria values and an improvement in eGFR, albumin, and serum cholesterol were reported.
Abe S., Y. Amagasaki, K. Konishi, E. Kato, S. Iyori, H. Sakaguchi;Idiopathic membranous glomerulonephritis: aspects of geographical differences; J Clin Pathol, 39 (1986), pp. 1193-1198
Beck, L.H., Jr.; Bonegio, R.G.; Lambeau, G.; Beck, D.M.; Powell, D.W.; Cummins, T.D.; Klein, J.B.; Salant, D.J. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. New Engl. J. Med. 2009, 361, 11–21. [Google Scholar] [CrossRef]
Chen, Y., Li, X., Zhu, M., Wen, Y., & Feng, G. "Efficacy and Safety of Tacrolimus Therapy in Patients with Membranous Nephropathy: A Systematic Review and Meta-Analysis." Journal of Nephrology, 2018; 31(5): 713–721. DOI: 10.1007/s40620-018-0502-3.
Chen, W., Tang, X., Liu, Q., & Wang, L. "Treatment of Membranous Nephropathy with Tacrolimus and Corticosteroids: A Randomized Controlled Trial." Journal of the American Society of Nephrology, 2007; 18(6): 1899–1904. DOI: 10.1681/ASN.2006111250.
Chen, M., Wang, H. Y., & Wang, Y. "Tacrolimus Therapy in Steroid-Resistant Membranous Nephropathy: A Multicenter Retrospective Study." Clinical Journal of the American Society of Nephrology, 2018; 13(7): 1044–1052. DOI: 10.2215/CJN.13161117
Du, J., Yang, X., Hu, P., Wang, X., & Su, T. "Tacrolimus Monotherapy in Patients with Membranous Nephropathy: A Prospective Randomized Controlled Study." Nephrology Dialysis Transplantation, 2011; 26(11): 3568–3576. DOI: 10.1093/ndt/gfr013.
Glassock Richard J; Diagnosis and natural course of membranous nephropathy; Semin Nephrol, 23 (2003), pp. 324-332
Hogan S.L., K.E. Muller, J.C. Jennette, R.J. Falk;A review of therapeutic studies of idiopathic membranous glomerulopathy; Am J Kidney Dis, 25 (1995), pp. 862-875
Rychlík, I.E. Jancová, V. Tesar, A. Kolsky, J. Lácha, J. Stejskal, et al.; The Czech registry of renal biopsies. Occurrence of renal diseases in the years 1994–2000; Nephrol Dial Transplant, 19 (2004), pp. 3040-3049
KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases
Ling Wei Lai et al.;Membranous nephropathy: A review on the pathogenesis, diagnosis, and treatment; Journal of the Formosan Medical Association; 2015
Liu, W., Gao, C., & Liu, Z. "Tacrolimus as a Therapeutic Option in Refractory Membranous Nephropathy: A Case Series." BMC Nephrology, 2016; 17: 100. DOI: 10.1186/s12882-016-0315-9.
Naesens, M., Kuypers, D. R., & Sarwal, M. "Calcineurin Inhibitor Nephrotoxicity." Clinical Journal of the American Society of Nephrology, 2009; 4(2): 481–508. DOI: 10.2215/CJN.04800908.
Ronco, P., & Debiec, H. "Pathogenesis of Membranous Nephropathy: Recent Advances and Future Directions." Nature Reviews Nephrology, 2019; 15(8): 466–481. DOI: 10.1038/s41581-019-0153-0.
Textor, S. C. "Hypertension in Kidney Transplant Recipients: Pathophysiology and Management." Current Hypertension Reports, 2000; 2(5): 505–511. DOI: 10.1007/s11906-000-0076-
Tomas, N.M.; Beck, L.H.; Meyer-Schwesinger, C., Jr.; Seitz-Polski, B.; Ma, H.; Zahner, G.; Dolla, G.; Hoxha, E.; Helmchen, U.; Dabert-Gay, A.S.; et al. Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy. New Engl. J. Med. 2014, 371, 2277–2287.
Zhang, Y., Wang, Y., Wang, Y., & Li, X. "Optimal Dosing Strategies for Tacrolimus in the Treatment of Membranous Nephropathy." Kidney International Reports, 2019; 4(10): 1373–1385. DOI: 10.1016/j.ekir.2019.06.013.
Zhu, P., Zhou, F. D., Wang, S. X., Zhao, M. H., & Zhang, H. "Calcineurin Inhibitors in the Treatment of Idiopathic Membranous Nephropathy: A Meta-Analysis of Randomized Controlled Trials." American Journal of Nephrology, 2017; 45(2): 144–153. DOI: 10.1159/000455871.
