Levamisole in steroid-sensitive nephrotic syndrome: Usefulness in adult patients and laboratory insights into mechanisms of action via direct action on the kidney podocyte

Clinical Science

Volumn 128, Issue 12, 2015, Pages 883-893

  Jiang, Lulu ^a   Dasgupta, Ishita ^a,b   Hurcombe, Jenny A ^a   Colyer, Heather F ^a   Mathieson, Peter W ^a,b,c   Welsh, Gavin I ^a  

^a UNIVERSITY OF BRISTOL   (United Kingdom)

^b SOUTHMEAD HOSPITAL   (United Kingdom)

^c UNIVERSITY OF HONG KONG   (Hong Kong)

Author keywords

Levamisole; Minimal change nephropathy; Podocyte; Primary nephrotic syndrome; Steroid sensitive nephrotic syndrome

Indexed keywords

GLUCOCORTICOID RECEPTOR; LEVAMISOLE; MIFEPRISTONE; PREDNISOLONE; PUROMYCIN AMINONUCLEOSIDE; TACROLIMUS; GLUCOCORTICOID;

ADOLESCENT; ADULT; ARTICLE; CELL IMMORTALIZATION; CLINICAL ARTICLE; CONTROLLED STUDY; DRUG EFFECT; DRUG HYPERSENSITIVITY; DRUG MECHANISM; DRUG TOLERABILITY; DRUG WITHDRAWAL; FEMALE; FEVER; GASTROINTESTINAL SYMPTOM; HUMAN; HUMAN CELL; KIDNEY DISEASE; MALE; NEPHROTIC SYNDROME; NEUTROPENIA; PODOCYTE; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; STEROID SENSITIVE NEPHROTIC SYNDROME; ANTAGONISTS AND INHIBITORS; CELL CULTURE; CLINICAL TRIAL; DRUG COMBINATION; DRUG EFFECTS; METABOLISM; MIDDLE AGED; OFF LABEL DRUG USE; PATHOLOGY; YOUNG ADULT;

ADOLESCENT; ADULT; CELLS, CULTURED; DRUG THERAPY, COMBINATION; FEMALE; GLUCOCORTICOIDS; HUMANS; LEVAMISOLE; MALE; MIDDLE AGED; MIFEPRISTONE; NEPHROTIC SYNDROME; OFF-LABEL USE; PODOCYTES; PREDNISOLONE; PUROMYCIN AMINONUCLEOSIDE; RECEPTORS, GLUCOCORTICOID; SIGNAL TRANSDUCTION; YOUNG ADULT;

EID: 84929938519     PISSN: 01435221     EISSN: 14708736     Source Type: Journal    
DOI: 10.1042/CS20140749     Document Type: Article

References (52)

1. Palmer, S.C., Nand, K. and Strippoli, G.F. (2008) Interventions for minimal change disease in adults with nephrotic syndrome. Cochrane Database Syst. Rev. CD001537
2. Kidney Disease: Improving Global Outcomes (2012) KDIGO Clinical Practice Guideline for Glomerulonephritis. Kidney Int. Suppl. 2, 139-274
3. Elmas, A.T., Tabel, Y. and Elmas, O.N. (2012) Short- and long-term efficacy of levamisole in children with steroid-sensitive nephrotic syndrome. Int. Urol. Nephrol. 45, 1047-1055
4. Hodson, E.M. and Alexander, S.I. (2008) Evaluation and management of steroid-sensitive nephrotic syndrome. Curr. Opin. Pediatr. 20, 145-150
5. Hodson, E.M., Craig, J.C. and Willis, N.S. (2005) Evidence-based management of steroid-sensitive nephrotic syndrome. Pediatr. Nephrol. 20, 1523-1530
6. Hodson, E.M., Willis, N.S. and Craig, J.C. (2008) Non-corticosteroid treatment for nephrotic syndrome in children. Cochrane Database Syst. Rev. 10, CD002290
7. Pravitsitthikul, N., Willis, N.S., Hodson, E.M. and Craig, J.C. (2013) Non-corticosteroid immunosuppressive medications for steroid-sensitive nephrotic syndrome in children. Cochrane Database Syst. Rev. 10, CD002290
8. Moertel, C.G., Fleming, T.R., Macdonald, J.S., Haller, D.G., Laurie, J.A., Goodman, P.J., Ungerleider, J.S., Emerson, W.A., Tormey, D.C., Glick, J.H. et al. (1990) Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. N. Engl. J. Med. 322, 352-358
9. Anon (1991) Levamisole for childhood nephrotic syndrome. Lancet 337, 1574
10. Davin, J.C. and Merkus, M.P. (2005) Levamisole in steroid-sensitive nephrotic syndrome of childhood: the lost paradise? Pediatr. Nephrol. 20, 10-14
11. Dayal, U., Dayal, A.K., Shastry, J.C. and Raghupathy, P. (1994) Use of levamisole in maintaining remission in steroid-sensitive nephrotic syndrome in children. Nephron 66, 408-412
12. Mathieson, P.W. (2011) The podocyte as a target for therapies-new and old. Nat. Rev. Nephrol. 8, 52-56
13. Xing, C.Y., Saleem, M.A., Coward, R.J., Ni, L., Witherden, I.R. and Mathieson, P.W. (2006) Direct effects of dexamethasone on human podocytes. Kidney Int. 70, 1038-1045
14. Faul, C., Donnelly, M., Merscher-Gomez, S., Chang, Y.H., Franz, S., Delfgaauw, J., Chang, J.M., Choi, H.Y., Campbell, K.N., Kim, K. et al. (2008) The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A. Nat. Med. 14, 931-938
15. Fornoni, A., Sageshima, J., Wei, C., Merscher-Gomez, S., Aguillon-Prada, R., Jauregui, A.N., Li, J., Mattiazzi, A., Ciancio, G., Chen, L. et al. (2011) Rituximab targets podocytes in recurrent focal segmental glomerulosclerosis. Sci. Transl. Med. 3, 85ra46
16. Patrakka, J. and Tryggvason, K. (2009) New insights into the role of podocytes in proteinuria. Nat. Rev. Nephrol. 5, 463-468
17. Awadzi, K., Edwards, G., Opoku, N.O., Ardrey, A.E., Favager, S., Addy, E.T., Attah, S.K., Yamuah, L.K. and Quartey, B.T. (2004) The safety, tolerability and pharmacokinetics of levamisole alone, levamisole plus ivermectin, and levamisole plus albendazole, and their efficacy against Onchocerca volvulus. Ann. Trop. Med. Parasitol. 98, 595-614
18. Saleem, M.A., O'Hare, M.J., Reiser, J., Coward, R.J., Inward, C.D., Farren, T., Xing, C.Y., Ni, L., Mathieson, P.W. and Mundel, P. (2002) A conditionally immortalized human podocyte cell line demonstrating nephrin and podocin expression. J. Am. Soc. Nephrol. 13, 630-638
19. Hale, L.J., Hurcombe, J., Lay, A., Santamaria, B., Valverde, A.M., Saleem, M.A., Mathieson, P.W., Welsh, G.I. and Coward, R.J. (2013) Insulin directly stimulates VEGF-A production in the glomerular podocyte. Am. J. Physiol. Renal Physiol. 305, F182-F188
20. Harris, J.J., McCarthy, H.J., Ni, L., Wherlock, M., Kang, H., Wetzels, J.F., Welsh, G.I. and Saleem, M.A. (2013) Active proteases in nephrotic plasma lead to a podocin-dependent phosphorylation of VASP in podocytes via protease activated receptor-1. J. Pathol. 229, 660-671
21. Wallace, A.D. and Cidlowski, J.A. (2001) Proteasome-mediated glucocorticoid receptor degradation restricts transcriptional signaling by glucocorticoids. J. Biol. Chem. 276, 42714-42721
22. Dong, Y., Poellinger, L., Gustafsson, J.A. and Okret, S. (1988) Regulation of glucocorticoid receptor expression: evidence for transcriptional and posttranslational mechanisms. Mol. Endocrinol. 2, 1256-1264
23. Clark, A.R. and Lasa, M. (2003) Crosstalk between glucocorticoids and mitogen-activated protein kinase signalling pathways. Curr. Opin. Pharmacol. 3, 404-411
24. Paakinaho, V., Makkonen, H., Jaaskelainen, T. and Palvimo, J.J. (2010) Glucocorticoid receptor activates poised FKBP51 locus through long-distance interactions. Mol. Endocrinol. 24, 511-525
25. Ryan, G.B. and Karnovsky, M.J. (1975) An ultrastructural study of the mechanisms of proteinuria in aminonucleoside nephrosis. Kidney Int. 8, 219-232
26. Lowenborg, E.K., Jaremko, G. and Berg, U.B. (2000) Glomerular function and morphology in puromycin aminonucleoside nephropathy in rats. Nephrol. Dial. Transplant. 15, 1547-1555
27. Whiteside, C.I., Cameron, R., Munk, S. and Levy, J. (1993) Podocytic cytoskeletal disaggregation and basement-membrane detachment in puromycin aminonucleoside nephrosis. Am. J. Pathol. 142, 1641-1653
28. Messina, A., Davies, D.J., Dillane, P.C. and Ryan, G.B. (1987) Glomerular epithelial abnormalities associated with the onset of proteinuria in aminonucleoside nephrosis. Am. J. Pathol. 126, 220-229
29. Inokuchi, S., Shirato, I., Kobayashi, N., Koide, H., Tomino, Y. and Sakai, T. (1996) Re-evaluation of foot process effacement in acute puromycin aminonucleoside nephrosis. Kidney Int. 50, 1278-1287
30. Bertram, J.F., Messina, A. and Ryan, G.B. (1990) In vitro effects of puromycin aminonucleoside on the ultrastructure of rat glomerular podocytes. Cell Tissue Res. 260, 555-563
31. Reiser, J., von Gersdorff, G., Loos, M., Oh, J., Asanuma, K., Giardino, L., Rastaldi, M.P., Calvaresi, N., Watanabe, H., Schwarz, K. et al. (2004) Induction of B7-1 in podocytes is associated with nephrotic syndrome. J. Clin. Invest. 113, 1390-1397
32. Garin, E.H., Diaz, L.N., Mu, W., Wasserfall, C., Araya, C., Segal, M. and Johnson, R.J. (2009) Urinary CD80 excretion increases in idiopathic minimal-change disease. J. Am. Soc. Nephrol. 20, 260-266
33. Garin, E.H., Mu, W., Arthur, J.M., Rivard, C.J., Araya, C.E., Shimada, M. and Johnson, R.J. (2010) Urinary CD80 is elevated in minimal change disease but not in focal segmental glomerulosclerosis. Kidney Int. 78, 296-302
34. Shimada, M., Ishimoto, T., Lee, P.Y., Lanaspa, M.A., Rivard, C.J., Roncal-Jimenez, C.A., Wymer, D.T., Yamabe, H., Mathieson, P.W., Saleem, M.A. et al. (2012) Toll-like receptor 3 ligands induce CD80 expression in human podocytes via an NF-kappaB-dependent pathway. Nephrol. Dial. Transplant. 27, 81-89
35. Thakur, V., Walker, P.D. and Shah, S.V. (1988) Evidence suggesting a role for hydroxyl radical in puromycin aminonucleoside-induced proteinuria. Kidney Int. 34, 494-499
36. Kinra, S., Rath, B. and Kabi, B.C. (2000) Indirect quantification of lipid peroxidation in steroid responsive nephrotic syndrome. Arch. Dis. Child. 82, 76-78
37. Diamond, J.R., Bonventre, J.V. and Karnovsky, M.J. (1986) A role for oxygen free radicals in aminonucleoside nephrosis. Kidney Int. 29, 478-483
38. Kojima, K., Matsui, K. and Nagase, M. (2000) Protection of alpha(3) integrin-mediated podocyte shape by superoxide dismutase in the puromycin aminonucleoside nephrosis rat. Am. J. Kidney Dis. 35, 1175-1185
39. Wang, J.S., Yang, A.H., Chen, S.M., Young, T.K., Chiang, H. and Liu, H.C. (1993) Amelioration of antioxidant enzyme suppression and proteinuria in cyclosporin-treated puromycin nephrosis. Nephron 65, 418-425
40. Kawamura, T., Yoshioka, T., Bills, T., Fogo, A. and Ichikawa, I. (1991) Glucocorticoid activates glomerular antioxidant enzymes and protects glomeruli from oxidant injuries. Kidney Int. 40, 291-301
41. Gill, P.S. and Wilcox, C.S. (2006) NADPH oxidases in the kidney. Antioxid. Redox Signal. 8, 1597-1607
42. Wada, T., Pippin, J.W., Marshall, C.B., Griffin, S.V. and Shankland, S.J. (2005) Dexamethasone prevents podocyte apoptosis induced by puromycin aminonucleoside: role of p53 and Bcl-2-related family proteins. J. Am. Soc. Nephrol. 16, 2615-2625
43. Wada, T., Pippin, J.W., Nangaku, M. and Shankland, S.J. (2008) Dexamethasone's prosurvival benefits in podocytes require extracellular signal-regulated kinase phosphorylation. Nephron Exp. Nephrol. 109, e8-e19
44. Zhu, J., Sun, N., Aoudjit, L., Li, H., Kawachi, H., Lemay, S. and Takano, T. (2008) Nephrin mediates actin reorganization via phosphoinositide 3-kinase in podocytes. Kidney Int. 73, 556-566
45. Zuo, Y., Yang, H.C., Potthoff, S.A., Najafian, B., Kon, V., Ma, L.J. and Fogo, A.B. (2012) Protective effects of PPARγ agonist in acute nephrotic syndrome. Nephrol. Dial. Transplant. 27, 174-181
46. Bertagna, X., Bertagna, C., Luton, J.P., Husson, J.M. and Girard, F. (1984) The new steroid analog RU 486 inhibits glucocorticoid action in man. J. Clin. Endocrinol. Metab. 59, 25-28
47. Mathieson, P.W. (2003) Immune dysregulation in minimal change nephropathy. Nephrol. Dial. Transplant. 18 (Suppl. 6), vi26-vi29
48. Szeto, C., Gillespie, K.M. and Mathieson, P.W. (2000) Levamisole induces interleukin-18 and shifts type 1/type 2 cytokine balance. Immunology 100, 217-224
49. Ransom, R.F., Lam, N.G., Hallett, M.A., Atkinson, S.J. and Smoyer, W.E. (2005) Glucocorticoids protect and enhance recovery of cultured murine podocytes via actin filament stabilization. Kidney Int. 68, 2473-2483
50. Ransom, R.F., Vega-Warner, V., Smoyer, W.E. and Klein, J. (2005) Differential proteomic analysis of proteins induced by glucocorticoids in cultured murine podocytes. Kidney Int. 67, 1275-1285
51. Liu, H., Gao, X., Xu, H., Feng, C., Kuang, X., Li, Z. and Zha, X. (2012) alpha-Actinin-4 is involved in the process by which dexamethasone protects actin cytoskeleton stabilization from adriamycin-induced podocyte injury. Nephrology 17, 669-675
52. Guess, A., Agrawal, S., Wei, C.C., Ransom, R.F., Benndorf, R. and Smoyer, W.E. (2010) Dose- and time-dependent glucocorticoid receptor signaling in podocytes. Am. J. Physiol. Renal Physiol. 299, F845-F853