Current and emerging treatments for idiopathic focal and segmental glomerulosclerosis in adults

Expert Review of Clinical Immunology

Volumn 9, Issue 3, 2013, Pages 251-261

  Ponticelli, Claudio ^a   Graziani, Giorgio ^a  

^a HUMANITAS CLINICAL AND RESEARCH CENTER   (Italy)

Author keywords

calcineurin inhibitors; focal glomerulosclerosis; glomerulonephritis; glucocorticoids; mycophenolate; nephrotic syndrome; rituximab

Indexed keywords

ADALIMUMAB; ANISPERIMUS; ANTIFIBROTIC AGENT; CALCINEURIN INHIBITOR; CYCLOPHOSPHAMIDE; CYCLOSPORIN; CYTOTOXIC AGENT; DEXAMETHASONE; GALACTOSE; GLUCOCORTICOID; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; PIRFENIDONE; PLACEBO; PREDNISONE; RAPAMYCIN; RITUXIMAB; ROSIGLITAZONE; TACROLIMUS;

ADULT; APHERESIS; CELL DAMAGE; DISEASE COURSE; DRUG DOSE REDUCTION; DRUG WITHDRAWAL; FOCAL GLOMERULOSCLEROSIS; HUMAN; HYPERTRIGLYCERIDEMIA; IDIOPATHIC DISEASE; KIDNEY DISEASE; KIDNEY FAILURE; LOW DRUG DOSE; MORNING DOSAGE; NEPHROTIC SYNDROME; NONHUMAN; PATHOGENESIS; PHASE 2 CLINICAL TRIAL (TOPIC); PODOCYTE; PROGNOSIS; PROTEINURIA; RANDOMIZED CONTROLLED TRIAL (TOPIC); REMISSION; REVIEW; SINGLE DRUG DOSE;

ADULT; ANTIBODIES, MONOCLONAL, MURINE-DERIVED; CALCINEURIN; GLOMERULOSCLEROSIS, FOCAL SEGMENTAL; GLUCOCORTICOIDS; HUMANS; KIDNEY FAILURE, CHRONIC; MYCOPHENOLIC ACID; NEPHROTIC SYNDROME; PROTEINURIA;

EID: 84874629601     PISSN: 1744666X     EISSN: 17448409     Source Type: Journal    
DOI: 10.1586/eci.12.109     Document Type: Review

References (82)

1. Kritz W. Glomerular diseases: podocyte hypertrophy mismatch and glomerular disease. Nat. Rev. Nephrol. 8, 618-619 (2012).
2. Scolari F, Ponticelli C. Focal and segmental glomerular sclerosis. In: Treatment of Primary Glomerulonephritis. Ponticelli C, Glassock RJ (Eds). Oxford University Press, Oxford, UK, 215-260 (2009).
3. D'Agati VD, Kaskel FJ, Falk RJ. Focal segmental glomerulosclerosis. N. Engl. J. Med. 365(25), 2398-2411 (2011).
4. Barisoni L, Schnaper HW, Kopp JB. Advances in the biology and genetics of the podocytopathies: implications for diagnosis and therapy. Arch. Pathol. Lab. Med. 133(2), 201-216 (2009).
5. Pavenstädt H, Kriz W, Kretzler M. Cell biology of the glomerular podocyte. Physiol. Rev. 83(1), 253-307 (2003).
6. Kriz W. Podocyte is the major culprit accounting for the progression of chronic renal disease. Microsc. Res. Tech. 57(4), 189-195 (2002).
7. Savin VJ, Sharma R, Sharma M et al. Circulating factor associated with increased glomerular permeability to albumin in recurrent focal segmental glomerulosclerosis. N. Engl. J. Med. 334(14), 878-883 (1996).
8. IJpelaar DH, Farris AB, Goemaere N et al. Fidelity and evolution of recurrent FSGS in renal allografts. J. Am. Soc. Nephrol. 19(11), 2219-2224 (2008).
9. McCarthy ET, Sharma M, Savin VJ. Circulating permeability factors in idiopathic nephrotic syndrome and focal segmental glomerulosclerosis. Clin. J. Am. Soc. Nephrol. 5(11), 2115-2121 (2010).
10. Wei C, El Hindi S, Li J et al. Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis. Nat. Med. 17(8), 952-960 (2011).
11. Reiser J, von Gersdorff G, Loos M et al. Induction of B7-1 in podocytes is associated with nephrotic syndrome. J. Clin. Invest. 113(10), 1390-1397 (2004).
12. Shimada M, Ishimoto T, Lee PY et al. Toll-like receptor 3 ligands induce CD80 expression in human podocytes via an NF-kB-dependent pathway. Nephrol. Dial. Transplant. 27(1), 81-89 (2012).
13. Musante L, Candiano G, Bruschi M et al. Circulating anti-actin and anti-ATP synthase antibodies identify a sub-set of patients with idiopathic nephrotic syndrome. Clin. Exp. Immunol. 141(3), 491-499 (2005).
14. Charba DS, Wiggins RC, Goyal M et al. Antibodies to protein tyrosine phosphatase receptor type O (PTPro) increase glomerular albumin permeability (P[alb]). Am. J. Physiol. Renal Physiol. 297(1), F138-F144 (2009).
15. Mundel P, Reiser J. Proteinuria: an enzymatic disease of the podocyte? Kidney Int. 77(7), 571-580 (2010).
16. Fukuda A, Chowdhury MA, Venkatareddy MP et al. Growth-dependent podocyte failure causes glomerulosclerosis. J. Am. Soc. Nephrol. 23(8), 1351-1363 (2012).
17. Ponticelli C, Villa M, Banfi G et al. Can prolonged treatment improve the prognosis in adults with focal segmental glomerulosclerosis? Am. J. Kidney Dis. 34(4), 618-625 (1999).
18. Korbet SM. Angiotensin antagonists and steroids in the treatment of focal segmental glomerulosclerosis. Semin. Nephrol. 23(2), 219-228 (2003).
19. Beaufils H, Alphonse JC, Guedon J, Legrain M. Focal glomerulosclerosis: natural history and treatment. A report of 70 cases. Nephron 21(2), 75-85 (1978).
20. Cameron JS, Turner DR, Ogg CS, Chantler C, Williams DG. The long-term prognosis of patients with focal segmental glomerulosclerosis. Clin. Nephrol. 10(6), 213-218 (1978).
21. Velosa JA, Holley KE, Torres VE, Offord KP. Significance of proteinuria on the outcome of renal function in patients with focal segmental glomerulosclerosis. Mayo Clin. Proc. 58(9), 568-577 (1983).
22. Korbet SM, Schwartz MM, Lewis EJ. Primary focal segmental glomerulosclerosis: clinical course and response to therapy. Am. J. Kidney Dis. 23(6), 773-783 (1994).
23. Troyanov S, Wall CA, Miller JA, Scholey JW, Cattran DC; Toronto Glomerulonephritis Registry Group. Focal and segmental glomerulosclerosis: definition and relevance of a partial remission. J. Am. Soc. Nephrol. 16(4), 1061-1068 (2005).
24. Schena FP, Cameron JS. Treatment of proteinuric idiopathic glomerulonephritides in adults: a retrospective survey. Am. J. Med. 85(3), 315-326 (1988).
25. Pei Y, Cattran D, Delmore T, Katz A, Lang A, Rance P. Evidence suggesting undertreatment in adults with idiopathic focal segmental glomerulosclerosis. Regional Glomerulonephritis Registry Study. Am. J. Med. 82(5), 938-944 (1987).
26. Agarwal SK, Dash SC, Tiwari SC, Bhuyan UN. Idiopathic adult focal segmental glomerulosclerosis: a clinicopathological study and response to steroid. Nephron 63(2), 168-171 (1993).
27. Chun MJ, Korbet SM, Schwartz MM, Lewis EJ. Focal segmental glomerulosclerosis in nephrotic adults: presentation, prognosis, and response to therapy of the histologic variants. J. Am. Soc. Nephrol. 15(8), 2169-2177 (2004).
28. Ransom RF, Lam NG, Hallett MA, Atkinson SJ, Smoyer WE. Glucocorticoids protect and enhance recovery of cultured murine podocytes via actin filament stabilization. Kidney Int. 68(6), 2473-2483 (2005).
29. Hussain S, Romio L, Saleem M et al. Nephrin deficiency activates NF-kB and promotes glomerular injury. JASN 8, 1733 (2009).
30. KDIGO. Clinical practice guidelines for glomerulonephritis. Kidney Int. Suppl. 2(2), 186-197 (2012).
31. Crook ED, Habeeb D, Gowdy O, Nimmagadda S, Salem M. Effects of steroids in focal segmental glomerulosclerosis in a predominantly African-American population. Am. J. Med. Sci. 330(1), 19-24 (2005).
32. Grossman JM, Gordon R, Ranganath VK et al. American College of Rheumatology 2010 recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Care Res. (Hoboken) 62(11), 1515-1526 (2010).
33. Faul C, Donnelly M, Merscher-Gomez S et al. The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A. Nat. Med. 14(9), 931-938 (2008).
34. Korbet SM. Treatment of primary focal segmental glomerulosclerosis. Kidney Int. 62(6), 2301-2310 (2002).
35. Maher ER, Sweny P, Chappel M, Varghese Z, Moorhead JF. Cyclosporin in the treatment of steroid-responsive and steroid-resistant nephrotic syndrome in adults. Nephrol. Dial. Transplant. 3(6), 728-732 (1988).
36. Zietse R, Wenting GJ, Kramer P, Schalekamp MA, Weimar W. Effects of cyclosporin A on glomerular barrier function in the nephrotic syndrome. Clin. Sci. 82(6), 641-650 (1992).
37. Meyrier A. Nephrotic focal segmental glomerulosclerosis in 2004: an update. Nephrol. Dial. Transplant. 19(10), 2437-2444 (2004).
38. Lee HY, Kim HS, Kang CM, Kim SG, Kim MJ. The efficacy of cyclosporine A in adult nephrotic syndrome with minimal change disease and focal-segmental glomerulosclerosis: a multicenter study in Korea. Clin. Nephrol. 43(6), 375-381 (1995).
39. Heering P, Braun N, Müllejans R et al.; German Collaborative Glomerulonephritis Study Group. Cyclosporine A and chlorambucil in the treatment of idiopathic focal segmental glomerulosclerosis. Am. J. Kidney Dis. 43(1), 10-18 (2004).
40. Alexopoulos E, Stangou M, Papagianni A, Pantzaki A, Papadimitriou M. Factors influencing the course and the response to treatment in primary focal segmental glomerulosclerosis. Nephrol. Dial. Transplant. 15(9), 1348-1356 (2000).
41. Meyrier A, Condamin NC, Brooner D et al Treatment of adult idiopathic nephrotic syndrome with cyclosporine A: minimalchange disease and focal-segmental glomerulosclerosis. Clin. Nephrol. 35(Suppl. 1), S37-S42 (1991).
42. Ponticelli C, Rizzoni G, Edefonti A et al. A randomized trial of cyclosporine in steroid-resistant idiopathic nephrotic syndrome. Kidney Int. 43(6), 1377-1384 (1993).
43. Cattran DC, Appel GB, Hebert LA et al. A randomized trial of cyclosporine in patients with steroid-resistant focal segmental glomerulosclerosis. North America Nephrotic Syndrome Study Group. Kidney Int. 56(6), 2220-2226 (1999).
44. McCauley J, Shapiro R, Ellis D, Igdal H, Tzakis A, Starzl TE. Pilot trial of FK 506 in the management of steroid-resistant nephrotic syndrome. Nephrol. Dial. Transplant. 8(11), 1286-1290 (1993).
45. Segarra A, Vila J, Pou L et al. Combined therapy of tacrolimus and corticosteroids in cyclosporin-resistant or -dependent idiopathic focal glomerulosclerosis: a preliminary uncontrolled study with prospective follow-up. Nephrol. Dial. Transplant. 17(4), 655-662 (2002).
46. Duncan N, Dhaygude A, Owen J et al. Treatment of focal and segmental glomerulosclerosis in adults with tacrolimus monotherapy. Nephrol. Dial. Transplant. 19(12), 3062-3067 (2004).
47. Li X, Li H, Ye H et al. Tacrolimus therapy in adults with steroid- and cyclophosphamide- resistant nephrotic syndrome and normal or mildly reduced GFR. Am. J. Kidney Dis. 54(1), 51-58 (2009).
48. Meyrier A, Noël LH, Auriche P, Callard P. Long-term renal tolerance of cyclosporin A treatment in adult idiopathic nephrotic syndrome. Collaborative Group of the Société de Néphrologie. Kidney Int. 45(5), 1446-1456 (1994).
49. Cattran DC, Alexopoulos E, Heering P et al. Cyclosporin in idiopathic glomerular disease associated with the nephrotic syndrome: workshop recommendations. Kidney Int. 72(12), 1429-1447 (2007).
50. Meyrier A. Treatment of primary focal segmental glomerulosclerosis. Nephrol. Dial. Transplant. 14(Suppl. 3), 74-78 (1999).
51. Braun N, Schmutzler F, Lange C et al. Immunosuppressive treatment for focal segmental glomerulosclerosis in adults. Cochrane Database Syst. Rev. 16(3), CD003233 (2008).
52. Chapman RM. Gonadal injury resulting from chemotherapy. Am. J. Ind. Med. 4(1-2), 149-161 (1983).
53. Faurschou M, Sorensen IJ, Mellemkjaer L et al. Malignancies in Wegener's granulomatosis: incidence and relation to cyclophosphamide therapy in a cohort of 293 patients. J. Rheumatol. 35(1), 100-105 (2008).
54. Choi MJ, Eustace JA, Gimenez LF et al. Mycophenolate mofetil treatment for primary glomerular diseases. Kidney Int. 61(3), 1098-1114 (2002).
55. Cattran DC, Wang MM, Appel G, Matalon A, Briggs W. Mycophenolate mofetil in the treatment of focal segmental glomerulosclerosis. Clin. Nephrol. 62(6), 405-411 (2004).
56. Tang S, Ho YW, Leung CY, Lai KN. Mycophenolate mofetil in the treatment of steroid-resistant primary focal segmental glomerulosclerosis. J. Nephrol. 18(4), 429-432 (2005).
57. Senthil Nayagam L, Ganguli A, Rathi M et al. Mycophenolate mofetil or standard therapy for membranous nephropathy and focal segmental glomerulosclerosis: a pilot study. Nephrol. Dial. Transplant. 23(6), 1926-1930 (2008).
58. Segarra Medrano A, Vila Presas J, Pou Clavé L, Majó Masferrer J, Camps Doménech J. Efficacy and safety of combined cyclosporin A and mycophenolate mofetil therapy in patients with cyclosporin-resistant focal segmental glomerulosclerosis. Nefrologia 31(3), 286-291 (2011).
59. Gipson DS, Trachtman H, Kaskel FJ et al. Clinical trial of focal segmental glomerulosclerosis in children and young adults. Kidney Int. 80(8), 868-878 (2011).
60. Tsagalis G, Psimenou E, Iliadis A, Nakopoulou L, Laggouranis A. Rapamycin for focal segmental glomerulosclerosis: a report of 3 cases. Am. J. Kidney Dis. 54(2), 340-344 (2009).
61. Letavernier E, Bruneval P, Vandermeersch S et al. Sirolimus interacts with pathways essential for podocyte integrity. Nephrol. Dial. Transplant. 24(2), 630-638 (2009).
62. Cho ME, Hurley JK, Kopp JB. Sirolimus therapy of focal segmental glomerulosclerosis is associated with nephrotoxicity. Am. J. Kidney Dis. 49(2), 310-317 (2007).
63. Letavernier E, Bruneval P, Mandet C et al. High sirolimus levels may induce focal segmental glomerulosclerosis de novo. Clin. J. Am. Soc. Nephrol. 2(2), 326-333 (2007).
64. Ponticelli C. Recurrence of focal segmental glomerular sclerosis (FSGS) after renal transplantation. Nephrol. Dial. Transplant. 25(1), 25-31 (2010).
65. Mitwalli AH. Adding plasmapheresis to corticosteroids and alkylating agents: does it benefit patients with focal segmental glomerulosclerosis? Nephrol. Dial. Transplant. 13(6), 1524-1528 (1998).
66. Maloney DG, Smith B, Rose A. Rituximab: mechanism of action and resistance. Semin. Oncol. 29(1 Suppl. 2), 2-9 (2002).
67. Fornoni A, Sageshima J, Wei C et al. Rituximab targets podocytes in recurrent focal segmental glomerulosclerosis. Sci. Transl. Med. 3(85), 85ra46 (2011).
68. Fernandez-Fresnedo G, Segarra A, González E et al.; Trabajo de Enfermedades Glomerulares de la Sociedad Española de Nefrología (GLOSEN). Rituximab treatment of adult patients with steroidresistant focal segmental glomerulosclerosis. Clin. J. Am. Soc. Nephrol. 4(8), 1317-1323 (2009).
69. Ochi A, Takei T, Nakayama K et al. Rituximab treatment for adult patients with focal segmental glomerulosclerosis. Intern. Med. 51(7), 759-762 (2012).
70. Kisner T, Burst V, Teschner S, Benzing T, Kurschat CE. Rituximab treatment for adults with refractory nephrotic syndrome: a single-center experience and review of the literature. Nephron. Clin. Pract. 120(2), c79-c85 (2012).
71. Savin VJ, McCarthy ET, Sharma R, Charba D, Sharma M. Galactose binds to focal segmental glomerulosclerosis permeability factor and inhibits its activity. Transl. Res. 151(6), 288-292 (2008).
72. De Smet E, Rioux JP, Ammann H, Déziel C, Quérin S. FSGS permeability factorassociated nephrotic syndrome: remission after oral galactose therapy. Nephrol. Dial. Transplant. 24(9), 2938-2940 (2009).
73. Kopac M, Meglic A, Rus RR. Partial remission of resistant nephrotic syndrome after oral galactose therapy. Ther. Apher. Dial. 15(3), 269-272 (2011).
74. Cho ME, Smith DC, Branton MH, Penzak SR, Kopp JB. Pirfenidone slows renal function decline in patients with focal segmental glomerulosclerosis. Clin. J. Am. Soc. Nephrol. 2(5), 906-913 (2007).
75. Peyser A, Machardy N, Tarapore F et al. Follow-up of Phase I trial of adalimumab and rosiglitazone in FSGS: III. Report of the FONT study group. BMC Nephrol. 11, 2 (2010).
76. Barton M, Kohan DE. Endothelin antagonists in clinical trials: lessons learned. Contrib. Nephrol. 172, 255-260 (2011).
77. Kohan DE, Cleland JG, Rubin LJ, Theodorescu D, Barton M. Clinical trials with endothelin receptor antagonists: what went wrong and where can we improve? Life Sci. 91(13-14), 528-539 (2012).
78. Le Berre L, Bruneau S, Naulet J et al. Induction of T regulatory cells attenuates idiopathic nephrotic syndrome. J. Am. Soc. Nephrol. 20(1), 57-67 (2009).
79. ClinicalTrials.gov. NCT00550342. http://clinicaltrials.gov/ct2/show/ NCT00550342
80. ClinicalTrials.gov. NCT00816478. http://clinicaltrials.gov/ct2/show/ NCT00816478
81. ClinicalTrials.gov. NCT01113385. http://clinicaltrials.gov/ct2/show/ NCT01113385
82. ClinicalTrials.gov. NCT00001959. http://clinicaltrials.gov/ct2/show/ NCT00001959