Evaluation of antiproteinuric effect of monocyte chemotactic protein-1 blocking drug in patients with chronicglomerulonephritis


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Aim of the study. To evaluate the efficacy, safety and tolerability of the domestic drug that inhibits the action of MCP-і in patients with protein-uretic forms of chronic glomerulonephritis.
Material & Methods. The study included 7 patients with various morphological variants of CGN. All patients had active forms of CGN: 3 of them had marked nephrotic syndrome with preserved renal function and moderate hypertension, 4 had significant urinary syndrome with persistent proteinuria and hematuria, and 3 - an initially decreased GFR (62-74 ml/min, stage 2 CKD). The treatment course consisted of six weekly injections. Injections were given at different time intervals: 6 hours between injections 1 and 2, 24 hours between injections 3 and 4, and 48 hours between injections 5 and 6. For 6 patients the treatment course was repeated 4 weeks later. Urinary excretion of MCP-1 and TGF-ßl was analyzed using Elisa (MCP-і Bioscience, Austria, TGF-beta1 Invitrogen, usa), IL-8 in serum levels were measured with an Immulite.
Results. Decrease in proteinuria was noted in 4 of 7 CGN patients on days 7-14 of treatment, but antiproteinuretic effect lasted for a month. In contrast, 3 other CGN patients over the same period of observation were found to have the rise of proteinuria with the sharp increase of urinary levels of MCP-1 and IL-8 serum levels («cytokine» rebound) and decrease the urinary TGF-ß index. Further study of the medication was discontinued due to its low efficiency and lack of persistent effect.
Conclusion. The study medication has a quick antiproteinuric action, but absence of consistent effect limits its use in patients with active forms of CGN. The development of long-acting forms of MCP-і inhibitors and evaluation of their effectiveness in combination with standard immunosuppressive therapy is a promising direction of further research.

参考

  1. Panzer U., Thaiss F., Zahner G., Barth P., Reszka M., Reinking R.R., Wolf G., Heimchen U., Stahl R.A. Monocyte chemoattractant protein-1 and osteopontin differentially regulate monocytes recruitment in experimental glomerulonephritis. Kidney Int. 2001; 59: 1762-1769.
  2. Wada T.,Furuichi K.,Sakai N.,Iwata Y., Yoshimoto K.,Shimizu M., Takeda S.I., Takasawa K., Yoshimura M., Kida H., Kobayashi K.I., Mukaida N., Naito T., Matsushima K., Yokoyama H. Up-regulation of monocyte chemoattractant protein-1 in tubulointerstitial lesions of human diabetic nephropathy. Kidney Int 2000; 58: 1492-1499.
  3. Taal M.W., Zandi-Nejad K., Weening B., Shahsafaei A., Kato S., Lee K.W., Ziai F., Jiang T., Brenner B.M., MacKenzie H.S. Proinflammatory gene expression and macrophage recruitment in the rat remnant kudney. Kidney Int. 2000; 58: 1664-1676.
  4. Wada T., Yokoyama H., Kobayashi K. Chemokines: new target molecules in renal diseases. Clin. Exp. Nephrol. 2000; 4: 273-280.
  5. Чеботарева Н.В., Бобкова И.Н., Козловская Л.В. Определение экскреции с мочой моноцитарного хемотаксического протеина-1 (МСР-1) и трансформирующего фактора роста-ß1 (TGF-ß1) у больных ХГН как метод оценки процессов фиброгенеза в почке. Клиническая нефрология. 2010; 4: 45-51.
  6. Wang Y., Rangan G.K., Tay Y.C., Wang Y., Harris D.C. Induction of monocyte chemoattractant protein-1 by albumin is mediated by nuclear factor kB in proximal tubule cells. J. Am. Soc. Nephrol. 1999; 10: 1204-1213.
  7. Viedt C., Orth S. Monocyte chemoattractant protein-1 (MCP-1) in the kidney: does it more than simply attract monocytes? Nephrol. Dial. Transplant. 2002; 17: 204-207.
  8. Tesch G.H., Maifert S., Schwarting A., Rollins B.J., Kelley V.R. Monocyte chemoattractant protein -1-dependent leukocytic infiltrates are responsible for autoimmunune disease in MRL-faslpr mice. J. Exp. Med. 1999; 190: 1813.
  9. Wada T., Yokoyama H., Su S., Mukaida N., Iwano M., Dohi K., Takahashi Y.,Sasaki T., Furuichi K.,Segawa C., Hisada Y., Ohta S., Takasawa K., Kobayashi K., Matsushima K. Monitoring urinary levels of Monocyte chemotactic and activating factor reflects disease activity of lupus nephritis. Kidney Int.1996; 49: 761-767.
  10. Wada T., Yokoyama H., Furuichi K., Kobayashi K.I., Harada K., Naruto M., Su S.B., Akiyama M., Mukaida N., Matsushima K. Intervention of crescentic glomerulonephritis by antibodies to monocyte chemotactic and activatingfactor (MCAF/MCP-1). FASEB J. 1996; 10: 1418-1425.
  11. Burt D., Salvidio G., Tarabra E., Barutta F., Pinach S., Dentelli P., Camussi G., Perin P.C., Gruden G. The monocyte chemoattractant protein-1 / Cognate CC Chemokine receptor 2 system affect cell motility in cultured human podocytes. Am. J. Pathol. 2007; 171: 1789-1799.
  12. Tarabra E., Giunti S., Barutta F., Salvidio G., Burt D., Deferrari G., Gambino R., Vergola D., Pinach S., Perin P.C., Camussi G., Gruden G. Effect of the monocyte chemoattractant protein-1 / СС Chemokine receptor on nephrin expression in streptozoticin-treated mice and human cultured podocytes. Diabetes. 2009; 58: 2109-2118.
  13. Красникова Т.Л., Сидорова М.В., Арефьева Т.И., Кухтина Н.Б., Азьмуко А.А., Беспалова Ж.Д. Разработка нового пептидного противовоспалительного пептидного препарата - ингибитора моноцитарного хемотаксического белка-1 (МСР-1). Российский физиологический журнал им. И.М. Сеченова. 2009; 95(5): 494-506.
  14. Arefieva T.I., Krasnikova T.L., Potekhina A.V., Ruleva N.U., Nikitin P.I., Ksenevich T.I., Gorshkov B.G., Sidorova M.V., Bespalova Z.D., Kukhtina N.B., Provatorov S.I., Noeva E.A., Chazov E.I. Synthetic peptide fragment (65- 76) of monocyte chemotactic protein-1 (MCP-1) inhibits MCP-1 binding to heparin and possesses anti-inflammatory activity in stable angina patients after coronary stenting. Inflamm. Res. 2011; 60(10): 955-964.
  15. Lee E.Y., Chung C.H., Khoury C.C., Yeo T.K., Pyagay P.E., Wang A., Chen S. The monocyte chemoattractant protein-1/CCR2 loop, inducible by TGF-ß, increases podocyte motility and albumin permeability. Am. J. Physiol. Renal. Physiol. 2009; 297: 85-94.
  16. Ble A., Mosca M., Loreto G.D., Guglielmotti A., Biondi G., Bombardieri S., Remuzzi G., Ruggenenti P. Antiproteinuric effect of chemokine C-Cmotif ligand 2 inhibition in subjects with acute proliferative lupus nephritis. Am. J. Nephrol. 2011; 34: 367-372.

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