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Review

Emerging therapeutic strategies for minimal change disease and focal and segmental glomerulosclerosis

, , , , , , , & show all
Pages 839-879 | Received 24 Jun 2018, Accepted 22 Oct 2018, Published online: 30 Oct 2018

References

  • Vivarelli M, Massella L, Ruggiero B, et al. Minimal change disease. Clin J Am Soc Nephrol. 2016;12(2):332–345.
  • Rosenberg AZ, Kopp JB. Focal segmental glomerulosclerosis. Clin J Am Soc Nephrol. 2017;12(3):502–517.
  • Kidney disease: improving global outcomes (KDIGO) glomerulonephritis work group. KDIGO clinical practice guideline for glomerulonephritis. Kidney Inter Suppl. 2012;2:177–185.
  • Hodson EM, Wong SC, Willis NS, et al. Interventions for idiopathic steroid-resistant nephrotic syndrome in children. Cochrane Database Syst Rev. 2016 Oct 11;10:CD003594.
  • Santoro D, Pellicanò V, Visconti L, et al. Monoclonal antibodies for renal diseases: current concepts and ongoing treatments. Expert Opin Biol Ther. 2015;15(8):1119–1143.
  • Benz K, Dötsch J, Rascher W, et al. Change of the course of steroid-dependent nephrotic syndrome after rituximab therapy. Pediatr Nephrol. 2004;19:794–797.
  • Ravani P, Bonanni A, Rossi R, et al. Anti-CD20 antibodies for idiopathic nephrotic syndrome in children. Clin J Am Soc Nephrol. 2016;11(4):710–720.
  • Ravani P, Rossi R, Bonanni A, et al. Rituximab in children with steroid-dependent nephrotic syndrome: a multicenter, open-label, noninferiority, randomized controlled trial. J Am Soc Nephrol. 2015;26(9):2259–2266.
  • Ravani P, Magnasco A, Edefonti A, et al. Short-term effects of rituximab in children with steroid- and calcineurin-dependent nephrotic syndrome: A randomized controlled trial. Clin J Am Soc Nephrol. 2011;6:1308–1315.
  • Takei T, Itabashi M, Moriyama T, et al. Effect of single-dose rituximab on steroid-dependent minimal-change nephrotic syndrome in adults. Nephrol Dial Transplant. 2013;28:1225–1232.
  • Ruggenenti P, Ruggiero B, Cravedi P, et al. Rituximab in nephrotic syndrome of steroid-dependent or frequently relapsing minimal change disease or focal segmental glomerulosclerosis (NEMO) study group. Rituximab in steroid-dependent or frequently relapsing idiopathic nephrotic syndrome. J Am Soc Nephrol. 2014;25:850–863.
  • Basu B. Ofatumumab for rituximab-resistant nephrotic syndrome. N Engl J Med. 2014;370:1268–1270.
  • Bonanni A, Rossi R, Murtas C, et al. Low-dose ofatumumab for rituximab-resistant nephrotic syndrome. BMJ Case Rep 2015;2015: bcr2015210208.
  • Ravani P, Bonanni A, Ghiggeri GM. Randomised controlled trial comparing ofatumumab to rituximab in children with steroid-dependent and calcineurin inhibitor-dependent idiopathic nephrotic syndrome: study protocol. BMJ Open. 2017;7(3):e013319.
  • Delville M, Sigdel TK, Wei C, et al. A circulating antibody panel for pretransplant prediction of FSGS recurrence after kidney transplantation. Sci Transl Med. 2014;6(256).
  • Chen Y-M, Chiang W-C, Lin S-L, et al. Therapeutic efficacy of pentoxifylline on proteinuria and renal progression: an update. J Biomed Sci. 2017;24:84.
  • Saito Y, Okamura M, Nakajima S, et al. Suppression of nephrin expression by TNF-alpha via interfering with the cAMP-retinoic acid receptor pathway. Am J Physiol Renal Physiol. 2010;298:F1436–44.
  • Lin SL, Chen RH, Chen YM, et al. Pentoxifylline attenuates tubulointerstitial fibrosis by blocking Smad3/4-activated transcription and profibrogenic effects of connective tissue growth factor. J Am Soc Nephrol. 2005;16:2702–2713.
  • Chen YM, Chien CT, Hu-Tsai MI, et al. Pentoxifylline attenuates experimental mesangial proliferative glomerulonephritis. Kidney Int. 1999;56:932–943.
  • Lin SL, Chen YM, Chien CT, et al. Pentoxifylline attenuated the renal disease progression in rats with remnant kidney. J Am Soc Nephrol. 2002;13:2916–2929.
  • Ng YY, Chen YM, Tsai TJ, et al. Pentoxifylline inhibits transforming growth factor-beta signaling and renal fibrosis in experimental crescentic glomerulonephritis in rats. Am J Nephrol. 2009;29:43–53.
  • Matousovic K, Grande JP, Chini CCS, et al. Inhibitors of cyclic nucleotide phosphodiesterase isozymes type-lIl and type-IV suppress mitogenesis of rat mesangial cells. J Clin Invest. 1995;96:401–410.
  • Tsuboi Y, Shankland SJ, Grande JP, et al. Suppression of mesangial proliferative glomerulonephritis development in rats by inhibitors of cAMP phosphodiesterase isozymes types III and IV. J Clin Invest. 1996;98:262–270.
  • Chen YM, Lin SL, Chiang WC, et al. Pentoxifylline ameliorates proteinuria through suppression of renal monocyte chemoattractant protein-1 in patients with proteinuric primary glomerular diseases. Kidney Int. 2006;69:1410–1415.
  • Renke M, Tylicki L, Rutkowski P, et al. Effect of pentoxifylline on proteinuria, markers of tubular injury and oxidative stress in non-diabetic patients with chronic kidney disease - placebo controlled, randomized, cross-over study. Acta Biochim Pol. 2010;57:119–123.
  • Badri S, Dashti-Khavidaki S, Ahmadi F, et al. Effect of add-on pentoxifylline on proteinuria in membranous glomerulonephritis: a 6-month placebo-controlled trial. Clin Drug Investig. 2013;33:215–222.
  • Gong R. The renaissance of corticotropin therapy in proteinuric nephropathies. Nat Rev Nephrol. 2012;8:122–128.
  • Tumlin JA, Galphin CM, Rovin BH. Advanced diabetic nephropathy with nephrotic range proteinuria: a pilot study of the long-term efficacy of subcutaneous ACTH gel on proteinuria, progression of CKD, and urinary levels of VEGF and MCP-1. J Diabetes Res. 2013;6:1–8.
  • Lindskog A, Ebefors K, Johansson ME. Melanocortin 1 receptor agonists reduce proteinuria. J Am Soc Nephrol. 2010;1290–1298.
  • Elvin J, Buvall L, Lindskog Jonsson A, et al. Melanocortin 1 receptor agonist protects podocytes through catalase and RhoA activation. Am J Physiol Renal Physiol. 2016;310:F846–F856.
  • 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. 2008;14:931–938.
  • Andersen GN, Hägglund M, Nagaeva O, et al. Quantitative measurement of the levels of melanocortin receptor subtype 1, 2, 3 and 5 and pro-opio-melanocortin peptide gene expression in subsets of human peripheral blood leucocytes. Scand J Immunol. 2005;61:279–284.
  • Olsen NJ, Decker DA, Higgins P, et al. Direct effects of HP ACTHar Gel on human B lymphocyte activation in vitro. Arthritis Res Ther. 2015;17:300–308.
  • Hogan J, Bomback AS, Meht K, et al. Treatment of idiopathic FSGS with adrenocorticotropic hormone gel. Clin J Am Soc Nephrol. 2013;8:2072–2081.
  • Tumlin J, Galphin C, Santos R, et al. Efficacy of combination ACTHar gel and tacrolimus in treatment-resistant focal segmental glomerulosclerosis and membranous glomerulopathy. Kidney Int Rep. 2017;2(5):924–932.
  • Kohan DE, Pollock DM. Endothelin antagonists for diabetic and non-diabetic chronic kidney disease. Br J Clin Pharmacol. 2013;76(4):573–579.
  • Komers R, Gipson DS, Nelson P, et al. Efficacy and safety of sparsentan compared with irbesartan in patients with primary focal segmental glomerulosclerosis: randomized, controlled trial design (DUET). Kidney Int Rep. 2017;2(4):654–664.
  • Dhaun N, MacIntyre IM, Kerr D, et al. Selective endothelin-A receptor antagonism reduces proteinuria, blood pressure, and arterial stiffness in chronic proteinuric kidney disease. Hypertension. 2011 Apr;57(4):772–779.
  • Clement LC, Avila-Casado C, Macé C, et al. Podocyte secreted Angiopoietin-like 4 mediates proteinuria in glucocorticoid sensitive nephrotic syndrome. Nat Med. 2011;17(1):117–122.
  • Rajasekeran H, Reich HN, Hladunewich MA, et al. Dapagliflozin in focal segmental glomerulosclerosis: a combined human-rodent pilot study. Am J Physiol Renal Physiol. 2018 Mar 1;314(3):F412–F422.
  • Neal B, Perkovic V, Mahaffey KW, et al. CANVAS program collaborative group. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377:644–657.
  • Wanner C, Inzucchi SE, Lachin JM, et al. EMPA-REG OUTCOME Investigators. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016;375:323–334.
  • Dekkers CCJ, Gansevoort RT, Heerspink HJL. New diabetes therapies and diabetic kidney disease progression: the role of SGLT-2 inhibitors. Curr Diab Rep. 2018;18(5):27.
  • Wang Q, Usinger W, Nichols B, et al. Cooperative interaction of CTGF and TGF-β in animal models of fibrotic disease. Fibrogenesis Tissue Repair. 2011;4:4.
  • Kok HM, Falke LL, Goldschmeding R, et al. Targeting CTGF, EGF and PDGF pathways to prevent progression of kidney disease. Nat Rev Nephrol. 2014;10(12):700–711.
  • Adler SG, Schwartz S, Williams ME, et al. Phase 1 study of anti-CTGF monoclonal antibody in patients with diabetes and microalbuminuria. Clin J Am Soc Nephrol. 2010;5(8):1420–1428.
  • Ling H, Li X, Jha S, et al. Therapeutic role of TGF-b–neutralizing antibody in mouse cyclosporin A nephropathy: morphologic improvement associated with functional preservation. J Am Soc Nephrol. 2003;14:377–388.
  • Dahly-Vernon AJ, Sharma M, McCarthy ET, et al. Transforming growth factor-b, 20-HETE interaction, and glomerular injury in Dahl salt- sensitive rats. Hypertension. 2005;45:643–648.
  • Benigni A, Zoja C, Campana M, et al. Beneficial effect of TGF b antagonism in treating diabetic nephropathy depends on when treatment is started. Nephron Exp Nephrol. 2006;104:e158–e168.
  • Trachtman H, Fervenza FC, Gipson DS, et al. A phase 1, single-dose study of Fresolimumab, an anti-TGF-β antibody, in treatment-resistant primary focal segmental glomerulosclerosis. Kidney Int. 2011;79(11):1236–1243.
  • Vincenti F, Fervenza FC, Campbell KN, et al. A phase 2, double-blind, placebo-controlled, randomized study of fresolimumab in patients with steroid-resistant primary focal segmental glomerulosclerosis. Kidney Int Rep. 2017;2(5):800–810.
  • Van Beneden K, Geers C, Pauwels M, et al. Valproic acid attenuates proteinuria and kidney injury. J Am Soc Nephrol. 2011;22(10):1863–1875.
  • Cho ME, Kopp JB. Pirfenidone: an anti-fibrotic and cytoprotective agent as therapy for progressive kidney disease. Expert Opin Investig Drugs. 2010;19(2):275–283.
  • Hewitson TD, Kelynack KJ, Tait MG, et al. Pirfenidone reduces in vitro rat renal fibroblast activation and mitogenesis. J Nephrol. 2001;14:453–460.
  • Leh S, Vaagnes O, Margolin SB, et al. Pirfenidone and candesartan ameliorate morphological damage in mild chronic anti-GBM nephritis in rats. Nephrol Dial Transplant. 2005;20:71–82.
  • Cho ME, Smith DC, Branton MH, et al. Pirfenidone slows renal function decline in patients with focal segmental glomerulosclerosis. Clin J Am Soc Nephrol. 2007;2:906–913.
  • Garin EH, Diaz LN, Mu W, et al. Urinary CD80 excretion increases in idiopathic minimal-change disease. J Am Soc Nephrol. 2009;20(2):260–266.
  • Taylor PA, Lees CJ, Fournier S, et al. B7 expression on T cells down-regulates immune responses through CTLA-4 ligation via T-T interactions [corrections]. J Immunol. 2004;172(1):34–39.
  • Finger EB, Bluestone JA. When ligand becomes receptor—tolerance via B7 signaling on DCs. Nat Immunol. 2002;3(11):1056–1057.
  • Le Berre L, Bruneau S, Naulet J, et al. Induction of T regulatory cells attenuates idiopathic nephrotic syndrome. J Am Soc Nephrol. 2009;20(1):57–67.
  • Wang YM, Zhang GY, Hu M, et al. CD8+ regulatory T cells induced by T cell vaccination protect against autoimmune nephritis. J Am Soc Nephrol. 2012;23(6):1058–1067.
  • Saadoun D, Rosenzwajg M, Joly F, et al. Regulatory T-cell responses to low-dose interleukin-2 in HCV-induced vasculitis. N Engl J Med. 2011;365(22):2067–2077.
  • Koreth J, Matsuoka K, Kim HT, et al. Interleukin-2 and regulatory T cells in graft-vs-host disease. N Engl J Med. 2011;365(22):2055–2066.
  • Bonanni A, Bertelli R, Rossi R, et al. A pilot study of IL2 in drug-resistant idiopathic nephrotic syndrome. PLoS ONE. 2015;10(9):e0138343. Cravedi P, ed.
  • Yu CC, Fornoni A, Weins A, et al. Abatacept in B7-1-positive proteinuric kidney disease. N Engl J Med. 2013;369:2416–2423.
  • Delville M, Baye E, Durrbach A, et al. B7–1 blockade does not improve post–transplant nephrotic syndrome caused by recurrent FSGS. J Am Soc Nephrol. 2016;27(8):2520–2527.
  • Jayaraman VK, Thomas M. Abatacept experience in steroid and rituximab-resistant focal segmental glomerulosclerosis. BMJ Case Rep. 2016;2016:bcr2016214396.
  • Sprenger-Mähr H, Zitt E, Soleiman A, et al. Successful treatment of focal segmental glomerulosclerosis after kidney transplantation with plasma exchange and abatacept in a patient with juvenile rheumatoid arthritis. Case Rep Transplant. 2016; 2016: 7137584.
  • Garin EH, Reiser J, Cara-Fuentes G, et al. CTLA4-IgG1 therapy in minimal change disease and focal segmental glomerulosclerosis. Pediatr Nephrol. 2015;30:469–477.
  • Trachtman H, Gipson DS, Somers M, et al. Randomized clinical trial design to assess abatacept in resistant nephrotic syndrome. Kidney Int Rep. 2018;3(1):115–121.
  • Mishra OP, Kumar R, Narayan G, et al. Toll-like receptor 3 (TLR-3), TLR-4 and CD80 expression in peripheral blood mononuclear cells and urinary CD80 levels in children with idiopathic nephrotic syndrome. Pediatr Nephrol. 2017 Aug;32(8):1355–1361.
  • Joy MS, Gipson DS, Powell L, et al. Phase 1 trial of adalimumab in Focal Segmental Glomerulosclerosis (FSGS): II. Report of the FONT (Novel therapies for resistant FSGS) study group. Am J Kidney Dis. 2010 Jan;55(1):50–60.
  • 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. 2010;11:2.
  • Trachtman H, Vento S, Herreshoff E, et al. Efficacy of galactose and adalimumab in patients with resistant focal segmental glomerulosclerosis: report of the font clinical trial group. BMC Nephrol. 2015;16:111.
  • Gibson KL, Glenn D, Ferris ME. Back to the future: therapies for idiopathic nephrotic syndrome. Blood Purif. 2015;39(1–3):105–109.
  • Ma FY, Liu J, Nikolic-Paterson DJ. The role of stress-activated protein kinase signaling in renal pathophysiology. Braz J Med Biol Res. 2009 Jan;42(1):29–37.
  • Olabisi OA, Zhang J-Y, VerPlank L, et al. APOL1 kidney disease risk variants cause cytotoxicity by depleting cellular potassium and inducing stress-activated protein kinases. Proc Natl Acad Sci U S A. 2016;113(4):830–837.
  • Mallipattu SK, He JC. The beneficial role of retinoids in glomerular disease. Front Med. 2015;2:16.
  • Vaughan MR, Pippin JW, Griffin SV, et al. ATRA induces podocyte differentiation and alters nephrin and podocin expression in vitro and in vivo. Kidney Int. 2005;68(1):133–144.
  • Zhang J, Pippin JW, Vaughan MR, et al. Retinoids augment the expression of podocyte proteins by glomerular parietal epithelial cells in experimental glomerular disease. Nephron Exp Nephrol. 2012;121(1–2):e23–37.
  • Lehrke I, Schaier M, Schade K, et al. Retinoid receptor-specific agonists alleviate experimental glomerulonephritis. Am J Physiol Renal Physiol. 2002;282(4):F741–51.10.
  • Zhong Y, Wu Y, Liu R, et al. Roflumilast enhances the renal protective effects of retinoids in an HIV-1 transgenic mouse model of rapidly progressive renal failure. Kidney Int. 2012;81(9):856–864.
  • Wang W, Li C, Yang T. Protection of nitro-fatty acid against kidney diseases. Am J Physiol Ren Physiol. 2016;310(8):F697–F704.
  • Kim HJ, Vaziri ND. Contribution of impaired Nrf2-Keap1 pathway to oxidative stress and inflammation in chronic renal failure. Am J Physiol Renal Physiol. 2010;298:F662–F671.
  • Inoue BH, Arruda-Junior DF, Campos L, et al. Nitro-oleic acid protects against adriamycin-induced nephropathy in mice. Am J Physiol Renal Physiol. 2013;305:F216–26.
  • de Zeeuw D, Akizawa T, Audhya P, et al. Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease. N Engl J Med. 2013;369:2492–2503.
  • Chin MP, Bakris GL, Block GA, et al. Bardoxolone methyl improves kidney function in patients with chronic kidney disease stage 4 and type 2 diabetes: post-hoc analyses from bardoxolone methyl evaluation in patients with chronic kidney disease and type 2 diabetes study. Am J Nephrol. 2018;47(1):40–47.
  • Savin VJ, McCarthy ET, Sharma R, et al. Galactose binds to focal segmental glomerulosclerosis permeability factor and inhibits its activity. Translational Res. 2008;151:288–292.
  • Nakajo A, Khoshnoodi J, Takenaka H, et al. Mizoribine corrects defective nephrin biogenesis by restoring intracellular energy balance. J Am Soc Nephrol. 2007 Sep;18(9):2554–2564.
  • Sayadi L, Laub D. Levamisole-induced vasculitis. Eplasty. 2018;18:ic5.
  • Szeto C, Gillespie KM, Mathieson PW. Levamisole induces interleukin 18 and shifts TH1/TH2 balance. Immunology. 2000;100:217–222.
  • Chen LY, Lin YL, Chiang BL. Levamisole enhances immune response by affecting the activation and maturation of human monocyte-derived dendritic cells. Clin Exp Immunol. 2007;151:174–181.
  • Jiang L, Dasgupta I, Hurcombe JA, et al. Levamisole in steroid-sensitive nephrotic syndrome: usefulness in adult patients and laboratory insights into mechanisms of action via direct action on the kidney podocyte. Clin Sci (Lond). 2015;128:883–89350.
  • Gruppen MP, Bouts AH, Jansen-van Der Weide MC, et al. A randomized clinical trial indicates that levamisole increases the time to relapse in children with steroid-sensitive idiopathic nephrotic syndrome. Kidney Int. 2018;93:510–518.
  • Tao Y, Kim J, Schrier RW, et al. Rapamycin markedly slows disease progression in a rat model of polycystic kidney disease. J Am Soc Nephrol. 2005;16:46–51.
  • Bonegio RG, Fuhro R, Wang Z, et al. Rapamycin ameliorates proteinuria-associated tubulointerstitial inflammation and fibrosis in experimental membranous nephropathy. J Am Soc Nephrol. 2005;16:2063–2072.
  • Lieberthal W, Fuhro R, Andry CC, et al. Rapamycin impairs recovery from acute renal failure: role of cell-cycle arrest and apoptosis of tubular cells. Am J Physiol Renal Physiol. 2001;281:F693–706.
  • Andoh TF, Burdmann EA, Fransechini N, et al. Comparison of acute rapamycin nephrotoxicity with cyclosporine and FK506. Kidney Int. 1996;50:1110–1117.
  • Cho ME, Hurley JK, Kopp JB. Sirolimus therapy of focal segmental glomerulosclerosis is associated with nephrotoxicity. Am J Kidney Dis. 2007 Feb;49(2):310–317.
  • Tojo K, Sakai S, Miyahara T. Possible therapeutic application of low density lipoprotein apheresis (LDL-A) in conjunction with double filtration plasmapheresis (DFPP) in drug-resistant nephrotic syndrome due to focal glomerular sclerosis (FGS). Nihon Jinzo Gakkai Shi. 1988;30:1153–1160.
  • Muso E, Mune M, Fujii Y, et al. Significantly rapid relief from steroid resistant nephrotic syndrome by LDL-apheresis compared with steroid monotherapy. Nephron. 2001;89(4):408–415.
  • Muso E, Mune M, Hirano T, et al. A prospective observational survey on the long-term effect of LDL apheresis on drug-resistant nephrotic syndrome. Nephron Extra. 2015;5(2):58–66.
  • Peired AJ, Sisti A, Romagnani P. Mesenchymal stem cell-based therapy for kidney disease: a review of clinical evidence. Stem Cells Int. 2016;2016:4798639.
  • Ma H, Wu Y, Xu Y, et al. Human umbilical mesenchymal stem cells attenuate the progression of focal segmental glomerulosclerosis. Am J Med Sci. 2013;346(6):486–493.
  • Belingheri M, Lazzari L, Parazzi V, et al. Allogenic mesenchymal stem cell infusion for the stabilization of focal segmental glomerulosclerosis. Biologicals. 2013;41(6):439–445.
  • Kupchan SM, Court WA, Dailey RG Jr, et al. Triptolide and tripdiolide, novel antileukemic diterpenoid triepoxides from Tripterygium wilfordii. J Am Chem Soc. 1972;94(20):7194–7195.
  • Hong Y, Zhou W, Li K, et al. Triptolide is a potent suppressant of C3, CD40 and B7h expression in activated human proximal tubular epithelial cells. Kidney Int. 2002;62(4):1291–1300.
  • Zheng C-X, Chen Z-H, Zeng C-H, et al. Triptolide protects podocytes from puromycin aminonucleoside induced injury in vivo and in vitro. Kidney Int. 2008;74(5):596–612.
  • Chen Y, Gong Z, Chen X, et al. Tripterygium wilfordii Hook F (a traditional Chinese medicine) for primary nephrotic syndrome. Cochrane Database Syst Rev. 2013;(8). Art. No.: CD008568.
  • Song X, Li Y, Zhang H, et al. The anticancer effect of Huaier (Review). Oncol Rep. 2015;34(1):12–21.
  • Liu H, Sun W, Gu L, et al. Huaiqihuang granules reduce proteinuria by enhancing nephrin expression and regulating necrosis factor κB signaling pathway in adriamycin-induced nephropathy. Chin J Integr Med. 2017;23:279.
  • Pu J, Zhang Y, Zhou J. Effect of Huai Qi Huang on epithelial-mesenchymal transition of renal tubular epithelial cells through miR-200a. Evid Based Complement Alternat Med. 2016;2016:8612190.
  • Reiser J, Altintas MM. Podocytes. F1000Research. Fac Rev-114. 2016;5:F1000.
  • Murea M, Park JK, Sharma S, et al. Expression of Notch pathway proteins correlates with albuminuria, glomerulosclerosis, and renal function. Kidney Int. 2010;78:514–522.
  • Marquez-Exposito L, Cantero-Navarro E, Lavoz C, et al. Could Notch signaling pathway be a potential therapeutic option in renal diseases? Nefrologia. 2018; Sep - Oct;38(5):466-475.
  • Purow B. Notch inhibition as a promising new approach to cancer therapy. Adv Exp Med Biol. 2012;727:305–319.
  • Xiao W, Gao Z, Duan Y, et al. Downregulation of miR-19a exhibits inhibitory effects on metastatic renal cell carcinoma by targeting PIK3CA and inactivating Notch signaling in vitro. Oncol Rep. 2015;34:739–746.
  • Gu C, Yaddanapudi S, Weins A, et al. Direct dynamin–actin interactions regulate the actin cytoskeleton. Embo J. 2010;29(21):3593–3606.
  • Hinshaw JE. Dynamin and its role in membrane fission. Annu Rev Cell Dev Biol. 2000;16:483–519.
  • Ross JA, Chen Y, Müller J, et al. Dimeric endophilin A2 stimulates assembly and GTPase activity of dynamin 2. Biophys J. 2011;100(3):729–737.
  • Soda K, Balkin DM, Ferguson SM, et al. Role of dynamin, synaptojanin, and endophilin in podocyte foot processes. J Clin Invest. 2012;122(12):4401–4411.
  • Schiffer M, Teng B, Gu C, et al. Pharmacological targeting of actin-dependent dynamin oligomerization ameliorates chronic kidney disease in diverse animal models. Nat Med. 2015;21(6):601–609.
  • Ono S, Kume S, Yasuda-Yamahara M, et al. O-linked β-N-acetylglucosamine modification of proteins is essential for foot process maturation and survival in podocytes. Nephrol Dial Transplant. 2017 Sep 1;32(9):1477–1487.
  • Hayek SS, Sever S, Ko Y-A, et al. Soluble urokinase receptor and chronic kidney disease. N Engl J Med. 2015;373(20):1916–1925.
  • Davin J-C. The glomerular permeability factors in idiopathic nephrotic syndrome. Pediatr Nephrol. 2016;31:207–215.
  • Sachs N, Kreft M, van den Bergh Weerman MA, et al. Kidney failure in mice lacking the tetraspanin CD151. J Cell Biol. 2006;175(1):33–39.
  • Ley K, Rivera-Nieves J, Sandborn WJ, et al. Integrin-based therapeutics: biological basis, clinical use and new drugs. Nat Rev Drug Discov. 2016;15(3):173–183.
  • Wei C, Möller CC, Altintas MM, et al. Modification of kidney barrier function by the urokinase receptor. Nat Med. 2008;14(1):55–63.
  • Hayek SS, Koh KH, Grams ME, et al. A tripartite complex of suPAR, APOL1 risk variants and αvβ3 integrin on podocytes mediates chronic kidney disease. Nat Med. 2017;23(8):945–953.
  • Fornoni A, Merscher S, Kopp JB. Lipid biology of the podocyte–new perspectives offer new opportunities. Nat Rev Nephrol. 2014;10:379–388.
  • Merscher-Gomez S, Guzman J, Pedigo CE, et al. Cyclodextrin protects podocytes in diabetic kidney disease. Diabetes. 2013;62(11):3817–3827.
  • Winn MP, Conlon PJ, Lynn KL, et al. A mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis. Science. 2005;308:1801–1804.
  • Moller CC, Wei C, Altintas MM, et al. Induction of TRPC6 channel in acquired forms of proteinuric kidney disease. J Am Soc Nephrol. 2007;18:29–36.
  • Krall P, Canales CP, Kairath P, et al. Podocyte-specific overexpression of wild type or mutant trpc6 in mice is sufficient to cause glomerular disease. PLoS One. 2010;5:e12859.
  • Hofstra JM, Lainez S, van Kuijk WHM, et al. New TRPC6 gain-of-function mutation in a non-consanguineous Dutch family with late-onset focal segmental glomerulosclerosis. Nephrol Dial Transplant. 2013 July;28(7):1830–1838.
  • Nijenhuis T, Sloan AJ, Hoenderop JG, et al. Angiotensin II contributes to podocyte injury by increasing TRPC6 expression via an NFAT-mediated positive feedback signaling pathway. Am J Pathol. 2011;179:pg. 1719–1732.
  • Kim EY, Hassanzadeh Khayyat N, Dryer SE. Mechanisms underlying modulation of podocyte TRPC6 channels by suPAR: role of NADPH oxidases and Src family tyrosine kinases. Biochim Biophys Acta Mol Basis Dis. 2018 Oct;1864(10):3527–3536.
  • Wu J, Zheng C, Wang X, et al. MicroRNA-30 family members regulate calcium/calcineurin signaling in podocytes. J Clin Invest. 2015;125(11):4091–4106.
  • Singh I, Knezevic N, Ahmmed GU, et al. Galphaq-TRPC6-mediated Ca2+ entry induces RhoA activation and resultant endothelial cell shape change in response to thrombin. J Biol Chem. 2007;282:7833–7843.
  • Tian D, Jacobo SMP, Billing D, et al. Antagonistic regulation of actin dynamics and cell motility by TRPC5 and TRPC6 channels. Sci Signal. 2010;3(145):ra77.
  • Schaldecker T, Kim S, Tarabanis C, et al. Inhibition of the TRPC5 ion channel protects the kidney filter. J Clin Invest. 2013;123:5298–5309.
  • Zhou Y, Castonguay P, Sidhom E-H, et al. A small-molecule inhibitor of TRPC5 ion channels suppresses progressive kidney disease in animal models. Science (New York, NY). 2017;358(6368):1332–1336.
  • Wang X, Dande RR, Yu H, et al. TRPC5 does not cause or aggravate glomerular disease. J Am Soc Nephrol. 2018 Feb;29(2):409–415.
  • Levey AS, Inker LA, Matsushita K, et al. GFR decline as an end point for clinical trials in CKD: a scientific workshop sponsored by the national kidney foundation and the US food and drug administration. Am J Kidney Dis. 2014;64:821–835.
  • Perkovic V, Craig JC, Chailimpamontree W, et al. Action plan for optimizing the design of clinical trials in chronic kidney disease. Kidney Int Supp. 2017;7(2):138–144.

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