Search
Search
Close this search box.

Podocyte-targeted therapies — progress and future directions – Nature Reviews Nephrology

  • Pavenstadt, H., Kriz, W. & Kretzler, M. Cell biology of the glomerular podocyte. Physiol. Rev. 83, 253–307 (2003).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Abrahamson, D. R. Role of the podocyte (and glomerular endothelium) in building the GBM. Semin. Nephrol. 32, 342–349 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Srivastava, T. et al. Mechanotransduction signaling in podocytes from fluid flow shear stress. Am. J. Physiol. Ren. Physiol. 314, F22–F34 (2018).

    Article 

    Google Scholar
     

  • Smoyer, W. E. & Mundel, P. Regulation of podocyte structure during the development of nephrotic syndrome. J. Mol. Med. 76, 172–183 (1998).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ichimura, K., Kurihara, H. & Sakai, T. Actin filament organization of foot processes in rat podocytes. J. Histochem. Cytochem. 51, 1589–1600 (2003).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Schell, C. & Huber, T. B. The evolving complexity of the podocyte cytoskeleton. J. Am. Soc. Nephrol. 28, 3166–3174 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wharram, B. L. et al. Podocyte depletion causes glomerulosclerosis: diphtheria toxin-induced podocyte depletion in rats expressing human diphtheria toxin receptor transgene. J. Am. Soc. Nephrol. 16, 2941–2952 (2005).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Dimke, H., Maezawa, Y. & Quaggin, S. E. Crosstalk in glomerular injury and repair. Curr. Opin. Nephrol. Hypertens. 24, 231–238 (2015).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Xing, C. Y. et al. Direct effects of dexamethasone on human podocytes. Kidney Int. 70, 1038–1045 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Fornoni, A. et al. Rituximab targets podocytes in recurrent focal segmental glomerulosclerosis. Sci. Transl. Med. 3, 85ra46 (2011).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Faul, C. et al. The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A. Nat. Med. 14, 931–938 (2008).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dahl, N. K. et al. The clinical utility of genetic testing in the diagnosis and management of adults with chronic kidney disease. J. Am. Soc. Nephrol. 34, 2039–2050 (2023).

    Article 
    PubMed 

    Google Scholar
     

  • Thompson, A. et al. Proteinuria reduction as a surrogate end point in trials of IgA nephropathy. Clin. J. Am. Soc. Nephrol. 14, 469–481 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yao, T. et al. Integration of genetic testing and pathology for the diagnosis of adults with FSGS. Clin. J. Am. Soc. Nephrol. 14, 213–223 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sampson, M. G. et al. Using population genetics to interrogate the monogenic nephrotic syndrome diagnosis in a case cohort. J. Am. Soc. Nephrol. 27, 1970–1983 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Trautmann, A., Lipska-Zietkiewicz, B. S. & Schaefer, F. Exploring the clinical and genetic spectrum of steroid resistant nephrotic syndrome: the PodoNet registry. Front. Pediatr. 6, 200 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bierzynska, A. et al. Genomic and clinical profiling of a national nephrotic syndrome cohort advocates a precision medicine approach to disease management. Kidney Int. 91, 937–947 (2017).

    Article 
    PubMed 

    Google Scholar
     

  • Buscher, A. K. et al. Immunosuppression and renal outcome in congenital and pediatric steroid-resistant nephrotic syndrome. Clin. J. Am. Soc. Nephrol. 5, 2075–2084 (2010).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Palmer, N. D. & Freedman, B. I. APOL1 and progression of nondiabetic nephropathy. J. Am. Soc. Nephrol. 24, 1344–1346 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Savin, V. J. et al. Circulating factor associated with increased glomerular permeability to albumin in recurrent focal segmental glomerulosclerosis. N. Engl. J. Med. 334, 878–883 (1996).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Gallon, L., Leventhal, J., Skaro, A., Kanwar, Y. & Alvarado, A. Resolution of recurrent focal segmental glomerulosclerosis after retransplantation. N. Engl. J. Med. 366, 1648–1649 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Cara-Fuentes, G. et al. CD80 and suPAR in patients with minimal change disease and focal segmental glomerulosclerosis: diagnostic and pathogenic significance. Pediatr. Nephrol. 29, 1363–1371 (2013).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wei, C. et al. Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis. Nat. Med. 17, 952–960 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Clement, L. C. et al. Podocyte-secreted angiopoietin-like-4 mediates proteinuria in glucocorticoid-sensitive nephrotic syndrome. Nat. Med. 17, 117–122 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Sharma, M. et al. Janus kinase 2/signal transducer and activator of transcription 3 inhibitors attenuate the effect of cardiotrophin-like cytokine factor 1 and human focal segmental glomerulosclerosis serum on glomerular filtration barrier. Transl. Res. 166, 384–398 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Delville, M. et al. A circulating antibody panel for pretransplant prediction of FSGS recurrence after kidney transplantation. Sci. Transl. Med. 6, 256ra136 (2014).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Deegens, J. K. & Wetzels, J. F. Glomerular disease: the search goes on: suPAR is not the elusive FSGS factor. Nat. Rev. Nephrol. 10, 431–432 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kronbichler, A., Saleem, M. A., Meijers, B. & Shin, J. I. Soluble urokinase receptors in focal segmental glomerulosclerosis: a review on the scientific point of view. J. Immunol. Res. 2016, 2068691 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Watts, A. J. B. et al. Discovery of autoantibodies targeting nephrin in minimal change disease supports a novel autoimmune etiology. J. Am. Soc. Nephrol. 33, 238–252 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Shirai, Y. et al. A multi-institutional study found a possible role of anti-nephrin antibodies in post-transplant focal segmental glomerulosclerosis recurrence. Kidney Int. 105, 608–617 (2023).

    Article 
    PubMed 

    Google Scholar
     

  • Zang, N. et al. cGAS-STING activation contributes to podocyte injury in diabetic kidney disease. iScience 25, 105145 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wu, J. et al. The key role of NLRP3 and STING in APOL1-associated podocytopathy. J. Clin. Invest. 131, e136329 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yu, B. C. et al. Minimal change disease is associated with mitochondrial injury and STING pathway activation. J. Clin. Med. 11, 577 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pedigo, C. E. et al. Local TNF causes NFATc1-dependent cholesterol-mediated podocyte injury. J. Clin. Invest. 126, 3336–3350 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Idasiak-Piechocka, I., Oko, A., Pawliczak, E., Kaczmarek, E. & Czekalski, S. Urinary excretion of soluble tumour necrosis factor receptor 1 as a marker of increased risk of progressive kidney function deterioration in patients with primary chronic glomerulonephritis. Nephrol. Dial. Transpl. 25, 3948–3956 (2010).

    Article 
    CAS 

    Google Scholar
     

  • Chung, C. F. et al. Intrinsic tumor necrosis factor-α pathway is activated in a subset of patients with focal segmental glomerulosclerosis. PLoS One 14, e0216426 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Joy, M. S. 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. 55, 50–60 (2010).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Trachtman, H. et al. Efficacy of galactose and adalimumab in patients with resistant focal segmental glomerulosclerosis: report of the font clinical trial group. BMC Nephrol. 16, 111 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhai, S., Zhao, L., Zhang, Y. & Ma, Q. Interleukin-7 stimulation inhibits nephrin activation and induces podocyte injury. Biochem. Biophys. Res. Commun. 507, 100–105 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Xiong, T. et al. Interleukin-9 protects from early podocyte injury and progressive glomerulosclerosis in Adriamycin-induced nephropathy. Kidney Int. 98, 615–629 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lee, E. Y. et al. The monocyte chemoattractant protein-1/CCR2 loop, inducible by TGF-β, increases podocyte motility and albumin permeability. Am. J. Physiol. Ren. Physiol. 297, F85–F94 (2009).

    Article 
    CAS 

    Google Scholar
     

  • Mariani, L. H. et al. Precision nephrology identified tumor necrosis factor activation variability in minimal change disease and focal segmental glomerulosclerosis. Kidney Int. 103, 565–579 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kim, A. H. et al. B cell-derived IL-4 acts on podocytes to induce proteinuria and foot process effacement. JCI Insight 2, e81836 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhao, H. et al. Role of mitochondrial dysfunction in renal fibrosis promoted by hypochlorite-modified albumin in a remnant kidney model and protective effects of antioxidant peptide SS-31. Eur. J. Pharmacol. 804, 57–67 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Agrawal, S., Brier, M. E., Kerlin, B. A., Smoyer, W. E. & Pediatric Nephrology Research Consortium. Plasma cytokine profiling to predict steroid resistance in pediatric nephrotic syndrome. Kidney Int. Rep. 6, 785–795 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Torban, E. et al. From podocyte biology to novel cures for glomerular disease. Kidney Int. 96, 850–861 (2019).

    Article 
    PubMed 

    Google Scholar
     

  • Angeletti, A. et al. Loss of decay-accelerating factor triggers podocyte injury and glomerulosclerosis. J. Exp. Med. 217, e20191699 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Huang, J. et al. Complement activation profile of patients with primary focal segmental glomerulosclerosis. PLoS One 15, e0234934 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Thurman, J. M. et al. Complement activation in patients with focal segmental glomerulosclerosis. PLoS One 10, e0136558 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lu, Q. et al. Complement factor B in high glucose-induced podocyte injury and diabetic kidney disease. JCI Insight 6, e147716 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tonneijck, L. et al. Glomerular hyperfiltration in diabetes: mechanisms, clinical significance, and treatment. J. Am. Soc. Nephrol. 28, 1023–1039 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rossitto, G. et al. High sodium intake, glomerular hyperfiltration, and protein catabolism in patients with essential hypertension. Cardiovasc. Res. 117, 1372–1381 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Srivastava, T. et al. Role of biomechanical forces in hyperfiltration-mediated glomerular injury in congenital anomalies of the kidney and urinary tract. Nephrol. Dial. Transpl. 32, 759–765 (2017).

    Article 
    CAS 

    Google Scholar
     

  • Holscher, D. L. et al. Next-generation morphometry for pathomics-data mining in histopathology. Nat. Commun. 14, 470 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kriz, W. & Lemley, K. V. A potential role for mechanical forces in the detachment of podocytes and the progression of CKD. J. Am. Soc. Nephrol. 26, 258–269 (2015).

    Article 
    PubMed 

    Google Scholar
     

  • Sharma, M., Sharma, R., McCarthy, E. T., Savin, V. J. & Srivastava, T. Hyperfiltration-associated biomechanical forces in glomerular injury and response: potential role for eicosanoids. Prostaglandins Other Lipid Mediat. 132, 59–68 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gyarmati, G. et al. The role of TRPC6 calcium channels and P2 purinergic receptors in podocyte mechanical and metabolic sensing. Physiol. Int. https://doi.org/10.1556/2060.2021.00205 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dupont, S. et al. Role of YAP/TAZ in mechanotransduction. Nature 474, 179–183 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Endlich, K., Kliewe, F. & Endlich, N. Stressed podocytes-mechanical forces, sensors, signaling and response. Pflug. Arch. 469, 937–949 (2017).

    Article 
    CAS 

    Google Scholar
     

  • Sharma, M. et al. Glomerular biomechanical stress and lipid mediators during cellular changes leading to chronic kidney disease. Biomedicines 10, 407 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Srivastava, T. et al. Prostaglandin E(2) is crucial in the response of podocytes to fluid flow shear stress. J. Cell Commun. Signal. 4, 79–90 (2010).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Liu, S. et al. Single-cell transcriptomics reveals a mechanosensitive injury signaling pathway in early diabetic nephropathy. Genome Med. 15, 2 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Vallon, V. & Thomson, S. C. The tubular hypothesis of nephron filtration and diabetic kidney disease. Nat. Rev. Nephrol. 16, 317–336 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Heerspink, H. J., Perkins, B. A., Fitchett, D. H., Husain, M. & Cherney, D. Z. Sodium glucose cotransporter 2 inhibitors in the treatment of diabetes mellitus: cardiovascular and kidney effects, potential mechanisms, and clinical applications. Circulation 134, 752–772 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Sawada, K. et al. Upregulation of α3β1-integrin in podocytes in early-stage diabetic nephropathy. J. Diabetes Res. 2016, 9265074 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Iglesias-de la Cruz, M. C. et al. Effects of high glucose and TGF-β1 on the expression of collagen IV and vascular endothelial growth factor in mouse podocytes. Kidney Int. 62, 901–913 (2002).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Rabbani, N. & Thornalley, P. J. Advanced glycation end products in the pathogenesis of chronic kidney disease. Kidney Int. 93, 803–813 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lay, A. C. & Coward, R. J. M. The evolving importance of insulin signaling in podocyte health and disease. Front. Endocrinol. 9, 693 (2018).

    Article 

    Google Scholar
     

  • Eid, A. A. et al. Mechanisms of podocyte injury in diabetes: role of cytochrome P450 and NADPH oxidases. Diabetes 58, 1201–1211 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Galvan, D. L. et al. Real-time in vivo mitochondrial redox assessment confirms enhanced mitochondrial reactive oxygen species in diabetic nephropathy. Kidney Int. 92, 1282–1287 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jha, J. C. et al. Podocyte-specific Nox4 deletion affords renoprotection in a mouse model of diabetic nephropathy. Diabetologia 59, 379–389 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Jha, J. C. et al. Independent of renox, NOX5 promotes renal inflammation and fibrosis in diabetes by activating ROS-sensitive pathways. Diabetes 71, 1282–1298 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chen, A. et al. Soluble RARRES1 induces podocyte apoptosis to promote glomerular disease progression. J. Clin. Invest. 130, 5523–5535 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ducasa, G. M. et al. ATP-binding cassette A1 deficiency causes cardiolipin-driven mitochondrial dysfunction in podocytes. J. Clin. Invest. 129, 3387–3400 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wright, M. B. et al. Compounds targeting OSBPL7 increase ABCA1-dependent cholesterol efflux preserving kidney function in two models of kidney disease. Nat. Commun. 12, 4662 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Li, Y. et al. Therapeutic potential targeting podocyte mitochondrial dysfunction in focal segmental glomerulosclerosis. Kidney Dis. 9, 254–264 (2023).

    Article 

    Google Scholar
     

  • Kaneko, S. et al. Mitochondrial DNA deletion-dependent podocyte injuries in Mito-miceΔ, a murine model of mitochondrial disease. Exp. Anim. 71, 14–21 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Jiang, L. et al. Calmodulin-dependent protein kinase II/cAMP response element-binding protein/Wnt/β-catenin signaling cascade regulates angiotensin II-induced podocyte injury and albuminuria. J. Biol. Chem. 288, 23368–23379 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tian, D. et al. Antagonistic regulation of actin dynamics and cell motility by TRPC5 and TRPC6 channels. Sci. Signal. 3, ra77 (2010).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Struk, T. et al. Transcriptome analysis of primary podocytes reveals novel calcium regulated regulatory networks. FASEB J. 34, 14490–14506 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Xu, H. et al. IP3R-Grp75-VDAC1-MCU calcium regulation axis antagonists protect podocytes from apoptosis and decrease proteinuria in an Adriamycin nephropathy rat model. BMC Nephrol. 19, 140 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yang, Q. et al. Loss of UCP2 causes mitochondrial fragmentation by OMA1-dependent proteolytic processing of OPA1 in podocytes. FASEB J. 37, e23265 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Yang, Y. Y. et al. Identification of ULK1 as a novel mitophagy-related gene in diabetic nephropathy. Front. Endocrinol. 13, 1079465 (2022).

    Article 

    Google Scholar
     

  • Kawakami, T. et al. Deficient autophagy results in mitochondrial dysfunction and FSGS. J. Am. Soc. Nephrol. 26, 1040–1052 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Yildirim, D. et al. Role of autophagy and evaluation the effects of microRNAs 214, 132, 34c and prorenin receptor in a rat model of focal segmental glomerulosclerosis. Life Sci. 280, 119671 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Liu, B. et al. Zhen-Wu-Tang induced mitophagy to protect mitochondrial function in chronic glomerulonephritis via PI3K/AKT/mTOR and AMPK pathways. Front. Pharmacol. 12, 777670 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Godel, M. et al. Role of mTOR in podocyte function and diabetic nephropathy in humans and mice. J. Clin. Invest. 121, 2197–2209 (2011).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cina, D. P. et al. Inhibition of MTOR disrupts autophagic flux in podocytes. J. Am. Soc. Nephrol. 23, 412–420 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Inoki, K. et al. mTORC1 activation in podocytes is a critical step in the development of diabetic nephropathy in mice. J. Clin. Invest. 121, 2181–2196 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ito, N. et al. mTORC1 activation triggers the unfolded protein response in podocytes and leads to nephrotic syndrome. Lab. Invest. 91, 1584–1595 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Mao, J. et al. Mammalian target of rapamycin complex 1 activation in podocytes promotes cellular crescent formation. Am. J. Physiol. Ren. Physiol. 307, F1023–F1032 (2014).

    Article 
    CAS 

    Google Scholar
     

  • Munivenkatappa, R. et al. Tubular epithelial cell and podocyte apoptosis with de novo sirolimus based immunosuppression in renal allograft recipients with DGF. Histol. Histopathol. 25, 189–196 (2010).

    CAS 
    PubMed 

    Google Scholar
     

  • Cho, M. E., Hurley, J. K. & Kopp, J. B. Sirolimus therapy of focal segmental glomerulosclerosis is associated with nephrotoxicity. Am. J. Kidney Dis. 49, 310–317 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Tumlin, J. A. et al. A prospective, open-label trial of sirolimus in the treatment of focal segmental glomerulosclerosis. Clin. J. Am. Soc. Nephrol. 1, 109–116 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Liern, M., De Reyes, V., Fayad, A. & Vallejo, G. Use of sirolimus in patients with primary steroid-resistant nephrotic syndrome. Nefrologia 32, 321–328 (2012).

    PubMed 

    Google Scholar
     

  • Kato, H. & Susztak, K. Repair problems in podocytes: Wnt, Notch, and glomerulosclerosis. Semin. Nephrol. 32, 350–356 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Teixeira Vde, P. et al. Functional consequences of integrin-linked kinase activation in podocyte damage. Kidney Int. 67, 514–523 (2005).

    Article 
    PubMed 

    Google Scholar
     

  • Dai, C. et al. Wnt/β-catenin signaling promotes podocyte dysfunction and albuminuria. J. Am. Soc. Nephrol. 20, 1997–2008 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kato, H. et al. Wnt/β-catenin pathway in podocytes integrates cell adhesion, differentiation, and survival. J. Biol. Chem. 286, 26003–26015 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lin, C. L. et al. Dickkopf-1 promotes hyperglycemia-induced accumulation of mesangial matrix and renal dysfunction. J. Am. Soc. Nephrol. 21, 124–135 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Niranjan, T. et al. The Notch pathway in podocytes plays a role in the development of glomerular disease. Nat. Med. 14, 290–298 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Waters, A. M. et al. Ectopic notch activation in developing podocytes causes glomerulosclerosis. J. Am. Soc. Nephrol. 19, 1139–1157 (2008).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lai, A. S. & Lai, K. N. Viral nephropathy. Nat. Clin. Pract. Nephrol. 2, 254–262 (2006).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Angeletti, A., Cantarelli, C. & Cravedi, P. HCV-associated nephropathies in the era of direct acting antiviral agents. Front. Med. 6, 20 (2019).

    Article 

    Google Scholar
     

  • Chan, T. M. Hepatitis B and renal disease. Curr. Hepat. Rep. 9, 99–105 (2010).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bruggeman, L. A. et al. Renal epithelium is a previously unrecognized site of HIV-1 infection. J. Am. Soc. Nephrol. 11, 2079–2087 (2000).

    Article 
    PubMed 

    Google Scholar
     

  • Canaud, G. et al. The kidney as a reservoir for HIV-1 after renal transplantation. J. Am. Soc. Nephrol. 25, 407–419 (2014).

    Article 
    PubMed 

    Google Scholar
     

  • Winston, J. A. et al. Nephropathy and establishment of a renal reservoir of HIV type 1 during primary infection. N. Engl. J. Med. 344, 1979–1984 (2001).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Genovese, G. et al. Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science 329, 841–845 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Friedman, D. J. & Pollak, M. R. APOL1 nephropathy: from genetics to clinical applications. Clin. J. Am. Soc. Nephrol. 16, 294–303 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kudose, S. et al. Kidney biopsy findings in patients with COVID-19. J. Am. Soc. Nephrol. 31, 1959–1968 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Shetty, A. A. et al. COVID-19-associated glomerular disease. J. Am. Soc. Nephrol. 32, 33–40 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wu, H. et al. AKI and collapsing glomerulopathy associated with COVID-19 and APOL 1 high-risk genotype. J. Am. Soc. Nephrol. 31, 1688–1695 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Puelles, V. G. et al. Multiorgan and renal tropism of SARS-CoV-2. N. Engl. J. Med. 383, 590–592 (2020).

    Article 
    PubMed 

    Google Scholar
     

  • Roufosse, C. et al. Electron microscopic investigations in COVID-19: not all crowns are coronas. Kidney Int. 98, 505–506 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hassler, L., Reyes, F., Sparks, M. A., Welling, P. & Batlle, D. Evidence for and against direct kidney infection by SARS-CoV-2 in patients with COVID-19. Clin. J. Am. Soc. Nephrol. 16, 1755–1765 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pagtalunan, M. E. et al. Podocyte loss and progressive glomerular injury in type II diabetes. J. Clin. Invest. 99, 342–348 (1997).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lemley, K. V. et al. Podocytopenia and disease severity in IgA nephropathy. Kidney Int. 61, 1475–1485 (2002).

    Article 
    PubMed 

    Google Scholar
     

  • Yin, L., Yu, L., He, J. C. & Chen, A. Controversies in podocyte loss: death or detachment? Front. Cell Dev. Biol. 9, 771931 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Shankland, S. J., Anders, H. J. & Romagnani, P. Glomerular parietal epithelial cells in kidney physiology, pathology, and repair. Curr. Opin. Nephrol. Hypertens. 22, 302–309 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Appel, D. et al. Recruitment of podocytes from glomerular parietal epithelial cells. J. Am. Soc. Nephrol. 20, 333–343 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lazzeri, E. et al. Regenerative potential of embryonic renal multipotent progenitors in acute renal failure. J. Am. Soc. Nephrol. 18, 3128–3138 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Sagrinati, C. et al. Isolation and characterization of multipotent progenitor cells from the Bowman’s capsule of adult human kidneys. J. Am. Soc. Nephrol. 17, 2443–2456 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ronconi, E. et al. The role of podocyte damage in the pathogenesis of glomerulosclerosis and possible repair mechanisms [Italian]. G. Ital. Nefrol. 26, 660–669 (2009).

    PubMed 

    Google Scholar
     

  • Liu, W. B. et al. Single cell landscape of parietal epithelial cells in healthy and diseased states. Kidney Int. 104, 108–123 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kaverina, N. V. et al. Tracking the stochastic fate of cells of the renin lineage after podocyte depletion using multicolor reporters and intravital imaging. PLoS One 12, e0173891 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lichtnekert, J. et al. Renin-angiotensin-aldosterone system inhibition increases podocyte derivation from cells of renin lineage. J. Am. Soc. Nephrol. 27, 3611–3627 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pippin, J. W. et al. Cells of renin lineage are progenitors of podocytes and parietal epithelial cells in experimental glomerular disease. Am. J. Pathol. 183, 542–557 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Macconi, D. et al. Podocyte repopulation contributes to regression of glomerular injury induced by ACE inhibition. Am. J. Pathol. 174, 797–807 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Watanabe, H. et al. Inhibition of the renin-angiotensin system causes concentric hypertrophy of renal arterioles in mice and humans. JCI Insight 6, e154337 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wanner, N. et al. Unraveling the role of podocyte turnover in glomerular aging and injury. J. Am. Soc. Nephrol. 25, 707–716 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dai, Y. et al. Retinoic acid improves nephrotoxic serum-induced glomerulonephritis through activation of podocyte retinoic acid receptor α. Kidney Int. 92, 1444–1457 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Peired, A. et al. Proteinuria impairs podocyte regeneration by sequestering retinoic acid. J. Am. Soc. Nephrol. 24, 1756–1768 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Grahammer, F., Wanner, N. & Huber, T. B. Podocyte regeneration: who can become a podocyte? Am. J. Pathol. 183, 333–335 (2013).

    Article 
    PubMed 

    Google Scholar
     

  • Arendshorst, W. J., Brannstrom, K. & Ruan, X. Actions of angiotensin II on the renal microvasculature. J. Am. Soc. Nephrol. 10, S149–S161 (1999).

    CAS 
    PubMed 

    Google Scholar
     

  • Casare, F. A. et al. Renovascular remodeling and renal injury after extended angiotensin II infusion. Am. J. Physiol. Ren. Physiol. 310, F1295–F1307 (2016).

    Article 
    CAS 

    Google Scholar
     

  • Lewis, E. J., Hunsicker, L. G., Bain, R. P. & Rohde, R. D. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N. Engl. J. Med. 329, 1456–1462 (1993).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lewis, E. J. et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N. Engl. J. Med. 345, 851–860 (2001).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Gansevoort, R. T., Sluiter, W. J., Hemmelder, M. H., de Zeeuw, D. & de Jong, P. E. Antiproteinuric effect of blood-pressure-lowering agents: a meta-analysis of comparative trials. Nephrol. Dial. Transpl. 10, 1963–1974 (1995).

    CAS 

    Google Scholar
     

  • Apperloo, A. J., de Zeeuw, D., Sluiter, H. E. & de Jong, P. E. Differential effects of enalapril and atenolol on proteinuria and renal haemodynamics in non-diabetic renal disease. BMJ 303, 821–824 (1991).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ren, Z. et al. Angiotensin II induces nephrin dephosphorylation and podocyte injury: role of caveolin-1. Cell Signal. 24, 443–450 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wang, S. et al. Angiotensin II induces reorganization of the actin cytoskeleton and myosin light-chain phosphorylation in podocytes through rho/ROCK-signaling pathway. Ren. Fail. 38, 268–275 (2016).

    Article 
    PubMed 

    Google Scholar
     

  • Cardoso, V. G. et al. Angiotensin II-induced podocyte apoptosis is mediated by endoplasmic reticulum stress/PKC-δ/p38 MAPK pathway activation and trough increased Na+/H+ exchanger isoform 1 activity. BMC Nephrol. 19, 179 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tao, Y. et al. Enhanced Orai1-mediated store-operated Ca2+ channel/calpain signaling contributes to high glucose-induced podocyte injury. J. Biol. Chem. 298, 101990 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tu, P., Gibon, J. & Bouron, A. The TRPC6 channel activator hyperforin induces the release of zinc and calcium from mitochondria. J. Neurochem. 112, 204–213 (2010).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Binz-Lotter, J. et al. Injured podocytes are sensitized to angiotensin II-induced calcium signaling. J. Am. Soc. Nephrol. 31, 532–542 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kidney Disease: Improving Global Outcomes Glomerular Diseases Work Group. KDIGO 2021 clinical practice guideline for the management of glomerular diseases. Kidney Int. 100, S1–S276 (2021).

    Article 

    Google Scholar
     

  • Heerspink, H. J., Johnsson, E., Gause-Nilsson, I., Cain, V. A. & Sjostrom, C. D. Dapagliflozin reduces albuminuria in patients with diabetes and hypertension receiving renin-angiotensin blockers. Diabetes Obes. Metab. 18, 590–597 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cherney, D. et al. The effect of sodium glucose cotransporter 2 inhibition with empagliflozin on microalbuminuria and macroalbuminuria in patients with type 2 diabetes. Diabetologia 59, 1860–1870 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Barnett, A. H. et al. Efficacy and safety of empagliflozin added to existing antidiabetes treatment in patients with type 2 diabetes and chronic kidney disease: a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2, 369–384 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Yale, J. F. et al. Initiation of once daily insulin detemir is not associated with weight gain in patients with type 2 diabetes mellitus: results from an observational study. Diabetol. Metab. Syndr. 5, 56 (2013).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • The EMPA-KIDNEY Collaborative Group et al. Empagliflozin in patients with chronic kidney disease. N. Engl. J. Med. 388, 117–127 (2023).

    Article 

    Google Scholar
     

  • Wheeler, D. C. et al. Effects of dapagliflozin on major adverse kidney and cardiovascular events in patients with diabetic and non-diabetic chronic kidney disease: a prespecified analysis from the DAPA-CKD trial. Lancet Diabetes Endocrinol. 9, 22–31 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wheeler, D. C. et al. A pre-specified analysis of the DAPA-CKD trial demonstrates the effects of dapagliflozin on major adverse kidney events in patients with IgA nephropathy. Kidney Int. 100, 215–224 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wheeler, D. C. et al. Safety and efficacy of dapagliflozin in patients with focal segmental glomerulosclerosis: a prespecified analysis of the dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trial. Nephrol. Dial. Transpl. 37, 1647–1656 (2022).

    Article 
    CAS 

    Google Scholar
     

  • Nuffield Department of Population Health Renal Studies Group; SGLT2 inhibitor Meta-Analysis Cardio-Renal Trialists’ Consortium. Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials. Lancet 400, 1788–1801 (2022).

    Article 

    Google Scholar
     

  • Cassis, P. et al. SGLT2 inhibitor dapagliflozin limits podocyte damage in proteinuric nondiabetic nephropathy. JCI Insight 3, e98720 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ge, M. et al. Empagliflozin reduces podocyte lipotoxicity in experimental Alport syndrome. eLife 12, e83353 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wu, H., Kirita, Y., Donnelly, E. L. & Humphreys, B. D. Advantages of single-nucleus over single-cell RNA sequencing of adult kidney: rare cell types and novel cell states revealed in fibrosis. J. Am. Soc. Nephrol. 30, 23–32 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Tomita, I. et al. SGLT2 inhibition mediates protection from diabetic kidney disease by promoting ketone body-induced mTORC1 inhibition. Cell Metab. 32, 404–419.e6 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wang, X. X. et al. SGLT2 protein expression is increased in human diabetic nephropathy: SGLT2 protein inhibition decreases renal lipid accumulation, inflammation, and the development of nephropathy in diabetic mice. J. Biol. Chem. 292, 5335–5348 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Locatelli, M. et al. Empagliflozin protects glomerular endothelial cell architecture in experimental diabetes through the VEGF-A/caveolin-1/PV-1 signaling pathway. J. Pathol. 256, 468–479 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kim, J. J. et al. Discoidin domain receptor 1 activation links extracellular matrix to podocyte lipotoxicity in Alport syndrome. EBioMedicine 63, 103162 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Jiang, L. et al. RNA sequencing analysis of human podocytes reveals glucocorticoid regulated gene networks targeting non-immune pathways. Sci. Rep. 6, 35671 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhou, H. et al. Loss of the podocyte glucocorticoid receptor exacerbates proteinuria after injury. Sci. Rep. 7, 9833 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lewko, B. et al. Dexamethasone-dependent modulation of cyclic GMP synthesis in podocytes. Mol. Cell Biochem. 409, 243–253 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • McCaffrey, J. C. et al. Glucocorticoid therapy regulates podocyte motility by inhibition of Rac1. Sci. Rep. 7, 6725 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mallipattu, S. K. et al. Kruppel-like factor 15 mediates glucocorticoid-induced restoration of podocyte differentiation markers. J. Am. Soc. Nephrol. 28, 166–184 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Mallipattu, S. K. et al. Kruppel-like factor 15 (KLF15) is a key regulator of podocyte differentiation. J. Biol. Chem. 287, 19122–19135 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Agrawal, S. et al. Pioglitazone enhances the beneficial effects of glucocorticoids in experimental nephrotic syndrome. Sci. Rep. 6, 24392 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yu, M., Ren, Q. & Yu, S. Y. Role of nephrin phosphorylation inducted by dexamethasone and angiotensin II in podocytes. Mol. Biol. Rep. 41, 3591–3595 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ohashi, T., Uchida, K., Uchida, S., Sasaki, S. & Nitta, K. Dexamethasone increases the phosphorylation of nephrin in cultured podocytes. Clin. Exp. Nephrol. 15, 688–693 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wan, X. et al. Loss of epithelial membrane protein 2 aggravates podocyte injury via upregulation of caveolin-1. J. Am. Soc. Nephrol. 27, 1066–1075 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zhou, T. et al. Implication of dysregulation of the canonical wingless-type MMTV integration site (WNT) pathway in diabetic nephropathy. Diabetologia 55, 255–266 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Srivastava, S. P. et al. Loss of endothelial glucocorticoid receptor accelerates diabetic nephropathy. Nat. Commun. 12, 2368 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wu, X. et al. Glucocorticoids inhibit EGFR signaling activation in podocytes in anti-GBM crescentic glomerulonephritis. Front. Med. 9, 697443 (2022).

    Article 

    Google Scholar
     

  • Shi, S. et al. Podocyte-selective deletion of dicer induces proteinuria and glomerulosclerosis. J. Am. Soc. Nephrol. 19, 2159–2169 (2008).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wu, J. et al. Downregulation of microRNA-30 facilitates podocyte injury and is prevented by glucocorticoids. J. Am. Soc. Nephrol. 25, 92–104 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Aramburu, J., Heitman, J. & Crabtree, G. R. Calcineurin: a central controller of signalling in eukaryotes. EMBO Rep. 5, 343–348 (2004).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Massella, L. et al. Cyclosporine A treatment in patients with Alport syndrome: a single-center experience. Pediatr. Nephrol. 25, 1269–1275 (2010).

    Article 
    PubMed 

    Google Scholar
     

  • Wu, J. et al. MicroRNA-30 family members regulate calcium/calcineurin signaling in podocytes. J. Clin. Invest. 125, 4091–4106 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Shen, X. et al. Calcineurin inhibitors cyclosporin A and tacrolimus protect against podocyte injury induced by puromycin aminonucleoside in rodent models. Sci. Rep. 6, 32087 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jeruschke, S., Alex, D., Hoyer, P. F. & Weber, S. Protective effects of rituximab on puromycin-induced apoptosis, loss of adhesion and cytoskeletal alterations in human podocytes. Sci. Rep. 12, 12297 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT04983888 (2021).

  • Aghajan, M. et al. Antisense oligonucleotide treatment ameliorates IFN-γ-induced proteinuria in APOL1-transgenic mice. JCI Insight 4, e126124 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yang, Y. W. et al. Antisense oligonucleotides ameliorate kidney dysfunction in podocyte-specific APOL1 risk variant mice. Mol. Ther. 30, 2491–2504 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Olabisi, O. A. & Heneghan, J. F. APOL1 nephrotoxicity: what does ion transport have to do with it? Semin. Nephrol. 37, 546–551 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Olabisi, O. A. et al. APOL1 kidney disease risk variants cause cytotoxicity by depleting cellular potassium and inducing stress-activated protein kinases. Proc. Natl Acad. Sci. USA 113, 830–837 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Schaub, C. et al. Cation channel conductance and pH gating of the innate immunity factor APOL1 are governed by pore-lining residues within the C-terminal domain. J. Biol. Chem. 295, 13138–13149 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT05312879 (2022).

  • He, J. C. et al. Nef stimulates proliferation of glomerular podocytes through activation of Src-dependent Stat3 and MAPK1,2 pathways. J. Clin. Invest. 114, 643–651 (2004).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Meliambro, K. et al. Molecular analysis of the kidney from a patient with COVID-19-associated collapsing glomerulopathy. Kidney Med. 3, 653–658 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nystrom, S. E. et al. JAK inhibitor blocks COVID-19 cytokine-induced JAK/STAT/APOL1 signaling in glomerular cells and podocytopathy in human kidney organoids. JCI Insight 7, e157432 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT05237388 (2023).

  • Kohan, D. E., Rossi, N. F., Inscho, E. W. & Pollock, D. M. Regulation of blood pressure and salt homeostasis by endothelin. Physiol. Rev. 91, 1–77 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Morigi, M. et al. In response to protein load podocytes reorganize cytoskeleton and modulate endothelin-1 gene: implication for permselective dysfunction of chronic nephropathies. Am. J. Pathol. 166, 1309–1320 (2005).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Saleh, M. A., Boesen, E. I., Pollock, J. S., Savin, V. J. & Pollock, D. M. Endothelin-1 increases glomerular permeability and inflammation independent of blood pressure in the rat. Hypertension 56, 942–949 (2010).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lenoir, O. et al. Direct action of endothelin-1 on podocytes promotes diabetic glomerulosclerosis. J. Am. Soc. Nephrol. 25, 1050–1062 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Saleh, M. A., Pollock, J. S. & Pollock, D. M. Distinct actions of endothelin A-selective versus combined endothelin A/B receptor antagonists in early diabetic kidney disease. J. Pharmacol. Exp. Ther. 338, 263–270 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Daehn, I. et al. Endothelial mitochondrial oxidative stress determines podocyte depletion in segmental glomerulosclerosis. J. Clin. Invest. 124, 1608–1621 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ebefors, K. et al. Endothelin receptor-A mediates degradation of the glomerular endothelial surface layer via pathologic crosstalk between activated podocytes and glomerular endothelial cells. Kidney Int. 96, 957–970 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Komers, R. & Plotkin, H. Dual inhibition of renin-angiotensin-aldosterone system and endothelin-1 in treatment of chronic kidney disease. Am. J. Physiol. Regul. Integr. Comp. Physiol. 310, R877–R884 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Trachtman, H. et al. DUET: a phase 2 study evaluating the efficacy and safety of sparsentan in patients with FSGS. J. Am. Soc. Nephrol. 29, 2745–2754 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rheault, M. N. et al. Sparsentan versus irbesartan in focal segmental glomerulosclerosis. N. Engl. J. Med. 389, 2436–2445 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Heerspink, H. J. L. et al. Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial. Lancet 401, 1584–1594 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Syed, Y. Y. Sparsentan: first approval. Drugs 83, 563–568 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Heerspink, H. J. L. et al. Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial. Lancet 393, 1937–1947 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT05213624 (2022).

  • Wieder, N. & Greka, A. Calcium, TRPC channels, and regulation of the actin cytoskeleton in podocytes: towards a future of targeted therapies. Pediatr. Nephrol. 31, 1047–1054 (2016).

    Article 
    PubMed 

    Google Scholar
     

  • Krall, P. et al. Podocyte-specific overexpression of wild type or mutant trpc6 in mice is sufficient to cause glomerular disease. PLoS One 5, e12859 (2010).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Winn, M. P. et al. A mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis. Science 308, 1801–1804 (2005).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Moller, C. C. et al. Induction of TRPC6 channel in acquired forms of proteinuric kidney disease. J. Am. Soc. Nephrol. 18, 29–36 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Shengyou, Y. & Li, Y. The effects of siRNA-silenced TRPC6 on podocyte autophagy and apoptosis induced by AngII. J. Renin Angiotensin Aldosterone Syst. 16, 1266–1273 (2015).

    Article 
    PubMed 

    Google Scholar
     

  • Riehle, M. et al. TRPC6 G757D loss-of-function mutation associates with FSGS. J. Am. Soc. Nephrol. 27, 2771–2783 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Batool, L. et al. An inactivating human TRPC6 channel mutation without focal segmental glomerulosclerosis. Cell Mol. Life Sci. 80, 265 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Walsh, L. et al. Safety and efficacy of GFB-887, a TRPC5 channel inhibitor, in patients with focal segmental glomerulosclerosis, treatment-resistant minimal change disease, or diabetic nephropathy: TRACTION-2 trial design. Kidney Int. Rep. 6, 2575–2584 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Fremeaux-Bacchi, V. et al. Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults. Clin. J. Am. Soc. Nephrol. 8, 554–562 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gou, S. J., Yuan, J., Wang, C., Zhao, M. H. & Chen, M. Alternative complement pathway activation products in urine and kidneys of patients with ANCA-associated GN. Clin. J. Am. Soc. Nephrol. 8, 1884–1891 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Brilland, B. et al. Complement alternative pathway in ANCA-associated vasculitis: two decades from bench to bedside. Autoimmun. Rev. 19, 102424 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Riedl, M., Thorner, P. & Licht, C. C3 glomerulopathy. Pediatr. Nephrol. 32, 43–57 (2017).

    Article 
    PubMed 

    Google Scholar
     

  • Meuleman, M. S. et al. Rare variants in complement gene in C3 glomerulopathy and immunoglobulin-mediated membranoproliferative GN. Clin. J. Am. Soc. Nephrol. 18, 1435–1445 (2023).

    Article 
    PubMed 

    Google Scholar
     

  • Smith, R. J. H. et al. C3 glomerulopathy — understanding a rare complement-driven renal disease. Nat. Rev. Nephrol. 15, 129–143 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rizk, D. V. et al. The emerging role of complement proteins as a target for therapy of IgA nephropathy. Front. Immunol. 10, 504 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Medjeral-Thomas, N. R., Cook, H. T. & Pickering, M. C. Complement activation in IgA nephropathy. Semin. Immunopathol. 43, 679–690 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Donadelli, R. et al. Unraveling the molecular mechanisms underlying complement dysregulation by nephritic factors in C3G and IC-MPGN. Front. Immunol. 9, 2329 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Birmingham, D. J. & Hebert, L. A. The complement system in lupus nephritis. Semin. Nephrol. 35, 444–454 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Weinstein, A., Alexander, R. V. & Zack, D. J. A review of complement activation in SLE. Curr. Rheumatol. Rep. 23, 16 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Seifert, L. et al. The classical pathway triggers pathogenic complement activation in membranous nephropathy. Nat. Commun. 14, 473 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gao, S., Cui, Z. & Zhao, M. H. Complement C3a and C3a receptor activation mediates podocyte injuries in the mechanism of primary membranous nephropathy. J. Am. Soc. Nephrol. 33, 1742–1756 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Anwar, I. J. et al. Complement-targeted therapies in kidney transplantation-insights from preclinical studies. Front. Immunol. 13, 984090 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Filippone, E. J., McCue, P. A. & Farber, J. L. Transplant glomerulopathy. Mod. Pathol. 31, 235–252 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Bonventre, J. V. Complement and renal ischemia-reperfusion injury. Am. J. Kidney Dis. 38, 430–436 (2001).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wang, L. et al. Labile heme aggravates renal inflammation and complement activation after ischemia reperfusion injury. Front. Immunol. 10, 2975 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Legendre, C. M. et al. Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N. Engl. J. Med. 368, 2169–2181 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Bomback, A. S. et al. Eculizumab for dense deposit disease and C3 glomerulonephritis. Clin. J. Am. Soc. Nephrol. 7, 748–756 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lee, A. Avacopan: first approval. Drugs 82, 79–85 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Jayne, D. R. W., Merkel, P. A., Schall, T. J., Bekker, P. & ADVOCATE Study Group. Avacopan for the treatment of ANCA-associated vasculitis. N. Engl. J. Med. 384, 599–609 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Trachtman, H. Emerging drugs for treatment of focal segmental glomerulosclerosis. Expert Opin. Emerg. Drugs 25, 367–375 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT05314231 (2022).

  • Nie, S. et al. Biology drives the discovery of bispecific antibodies as innovative therapeutics. Antib. Ther. 3, 18–62 (2020).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wooden, B., Tarragon, B., Navarro-Torres, M. & Bomback, A. S. Complement inhibitors for kidney disease. Nephrol. Dial. Transpl. 38, ii29–ii39 (2023).

    Article 

    Google Scholar
     

  • Hou, Y. et al. Mitochondria-targeted peptide SS-31 attenuates renal injury via an antioxidant effect in diabetic nephropathy. Am. J. Physiol. Ren. Physiol. 310, F547–F559 (2016).

    Article 
    CAS 

    Google Scholar
     

  • Eirin, A. et al. Mitochondrial protection restores renal function in swine atherosclerotic renovascular disease. Cardiovasc. Res. 103, 461–472 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT02436447 (2015).

  • Zhu, Y. et al. Protective effects of inhibition of mitochondrial fission on organ function after sepsis. Front. Pharmacol. 12, 712489 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Brooks, C., Wei, Q., Cho, S. G. & Dong, Z. Regulation of mitochondrial dynamics in acute kidney injury in cell culture and rodent models. J. Clin. Invest. 119, 1275–1285 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cassina, L., Chiaravalli, M. & Boletta, A. Increased mitochondrial fragmentation in polycystic kidney disease acts as a modifier of disease progression. FASEB J. 34, 6493–6507 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Tanriover, C. et al. The mitochondrion: a promising target for kidney disease. Pharmaceutics 15, 270 (2023).

    Article 

    Google Scholar
     

  • Lindblom, R. S. J. et al. Delineating a role for the mitochondrial permeability transition pore in diabetic kidney disease by targeting cyclophilin D. Clin. Sci. 134, 239–259 (2020).

    Article 
    CAS 

    Google Scholar
     

  • Wang, Z. et al. Pharmacological targeting of GSK3β confers protection against podocytopathy and proteinuria by desensitizing mitochondrial permeability transition. Br. J. Pharmacol. 172, 895–909 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Hong, Q. et al. Increased podocyte Sirtuin-1 function attenuates diabetic kidney injury. Kidney Int. 93, 1330–1343 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wang, X. et al. Role of SIRT1 in HIV-associated kidney disease. Am. J. Physiol. Ren. Physiol. 319, F335–F344 (2020).

    Article 
    CAS 

    Google Scholar
     

  • Sattarinezhad, A., Roozbeh, J., Shirazi Yeganeh, B., Omrani, G. R. & Shams, M. Resveratrol reduces albuminuria in diabetic nephropathy: a randomized double-blind placebo-controlled clinical trial. Diabetes Metab. 45, 53–59 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Xiao, L. et al. The mitochondria-targeted antioxidant MitoQ ameliorated tubular injury mediated by mitophagy in diabetic kidney disease via Nrf2/PINK1. Redox Biol. 11, 297–311 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ahmadi, A. et al. Randomized crossover clinical trial of coenzyme Q10 and nicotinamide riboside in chronic kidney disease. JCI Insight 8, e167274 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Drovandi, S. et al. Oral Coenzyme Q10 supplementation leads to better preservation of kidney function in steroid-resistant nephrotic syndrome due to primary Coenzyme Q10 deficiency. Kidney Int. 102, 604–612 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Bagherniya, M. et al. The use of curcumin for the treatment of renal disorders: a systematic review of randomized controlled trials. Adv. Exp. Med. Biol. 1291, 327–343 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Vanaie, A. et al. Curcumin as a major active component of turmeric attenuates proteinuria in patients with overt diabetic nephropathy. J. Res. Med. Sci. 24, 77 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Weir, M. A. et al. The effect of micro-particle curcumin on chronic kidney disease progression: the MPAC-CKD randomized clinical trial. Nephrol. Dial. Transpl. 38, 2192–2200 (2023).

    Article 
    CAS 

    Google Scholar
     

  • Lindell, E., Zhong, L. & Zhang, X. Quiescent cancer cells — a potential therapeutic target to overcome tumor resistance and relapse. Int. J. Mol. Sci. 24, 3762 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Campbell, K. N. et al. Yes-associated protein (YAP) promotes cell survival by inhibiting proapoptotic dendrin signaling. J. Biol. Chem. 288, 17057–17062 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhong, F. et al. TYRO3 agonist as therapy for glomerular disease. JCI Insight 8, e165207 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Smart, S. K., Vasileiadi, E., Wang, X., DeRyckere, D. & Graham, D. K. The emerging role of TYRO3 as a therapeutic target in cancer. Cancers 10, 474 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lin, B., Ma, Y. Y. & Wang, J. W. Nano-technological approaches for targeting kidney diseases with focus on diabetic nephropathy: recent progress, and future perspectives. Front. Bioeng. Biotechnol. 10, 870049 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sabiu, G. et al. Targeted nanotherapy for kidney diseases: a comprehensive review. Nephrol. Dial. Transpl. 38, 1385–1396 (2023).

    Article 
    CAS 

    Google Scholar
     

  • Wu, L. et al. Albumin-based nanoparticles as methylprednisolone carriers for targeted delivery towards the neonatal Fc receptor in glomerular podocytes. Int. J. Mol. Med. 39, 851–860 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bruni, R. et al. Ultrasmall polymeric nanocarriers for drug delivery to podocytes in kidney glomerulus. J. Control. Rel. 255, 94–107 (2017).

    Article 
    CAS 

    Google Scholar
     

  • Zhan, X. et al. Celastrol antagonizes high glucose-evoked podocyte injury, inflammation and insulin resistance by restoring the HO-1-mediated autophagy pathway. Mol. Immunol. 104, 61–68 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wu, M. et al. Celastrol aggravates LPS-induced inflammation and injuries of liver and kidney in mice. Am. J. Transl. Res. 10, 2078–2086 (2018).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Alallam, B., Choukaife, H., Seyam, S., Lim, V. & Alfatama, M. Advanced drug delivery systems for renal disorders. Gels 9, 115 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Huang, X., Ma, Y., Li, Y., Han, F. & Lin, W. Targeted drug delivery systems for kidney diseases. Front. Bioeng. Biotechnol. 9, 683247 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Vives, E., Brodin, P. & Lebleu, B. A truncated HIV-1 Tat protein basic domain rapidly translocates through the plasma membrane and accumulates in the cell nucleus. J. Biol. Chem. 272, 16010–16017 (1997).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Arif, E. et al. Slit diaphragm protein Neph1 and its signaling: a novel therapeutic target for protection of podocytes against glomerular injury. J. Biol. Chem. 289, 9502–9518 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Belmadani, S. et al. A thrombospondin-1 antagonist of transforming growth factor-β activation blocks cardiomyopathy in rats with diabetes and elevated angiotensin II. Am. J. Pathol. 171, 777–789 (2007).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Grange, C. & Bussolati, B. Extracellular vesicles in kidney disease. Nat. Rev. Nephrol. 18, 499–513 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mason, W. J. et al. Systemic gene therapy with thymosin β4 alleviates glomerular injury in mice. Sci. Rep. 12, 12172 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Daga, S. et al. New frontiers to cure Alport syndrome: COL4A3 and COL4A5 gene editing in podocyte-lineage cells. Eur. J. Hum. Genet. 28, 480–490 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ding, W. Y. et al. Adeno-associated virus gene therapy prevents progression of kidney disease in genetic models of nephrotic syndrome. Sci. Transl. Med. 15, eabc8226 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • De Vriese, A. S., Wetzels, J. F., Glassock, R. J., Sethi, S. & Fervenza, F. C. Therapeutic trials in adult FSGS: lessons learned and the road forward. Nat. Rev. Nephrol. 17, 619–630 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Musante, L. et al. Circulating anti-actin and anti-ATP synthase antibodies identify a sub-set of patients with idiopathic nephrotic syndrome. Clin. Exp. Immunol. 141, 491–499 (2005).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cara-Fuentes, G. et al. Angiopoietin-like-4 and minimal change disease. PLoS One 12, e0176198 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jacobs-Cacha, C. et al. A misprocessed form of Apolipoprotein A-I is specifically associated with recurrent focal segmental glomerulosclerosis. Sci. Rep. 10, 1159 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lopez-Hellin, J. et al. A form of apolipoprotein a-I is found specifically in relapses of focal segmental glomerulosclerosis following transplantation. Am. J. Transpl. 13, 493–500 (2013).

    Article 
    CAS 

    Google Scholar
     

  • Alachkar, N., Gupta, G. & Montgomery, R. A. Angiotensin antibodies and focal segmental glomerulosclerosis. N. Engl. J. Med. 368, 971–973 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Abuzeineh, M., Aala, A., Alasfar, S. & Alachkar, N. Angiotensin II receptor 1 antibodies associate with post-transplant focal segmental glomerulosclerosis and proteinuria. BMC Nephrol. 21, 253 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Savin, V. J. et al. Renal and hematological effects of CLCF-1, a B-cell-stimulating cytokine of the IL-6 family. J. Immunol. Res. 2015, 714964 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wei, C., Sigdel, T. K., Sarwal, M. M. & Reiser, J. Circulating CD40 autoantibody and suPAR synergy drives glomerular injury. Ann. Transl. Med. 3, 300 (2015).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cara-Fuentes, G., Clapp, W. L., Johnson, R. J. & Garin, E. H. Pathogenesis of proteinuria in idiopathic minimal change disease: molecular mechanisms. Pediatr. Nephrol. 31, 2179–2189 (2016).

    Article 
    PubMed 

    Google Scholar
     

  • Garin, E. H. et al. Urinary CD80 excretion increases in idiopathic minimal-change disease. J. Am. Soc. Nephrol. 20, 260–266 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Garin, E. H. et al. Urinary CD80 is elevated in minimal change disease but not in focal segmental glomerulosclerosis. Kidney Int. 78, 296–302 (2010).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Yu, C. C. et al. Abatacept in B7-1-positive proteinuric kidney disease. N. Engl. J. Med. 369, 2416–2423 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zen, R. C. et al. Urinary CD80 and serum suPAR as biomarkers of glomerular disease among adults in Brazil. Diagnostics 13, 203 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lennon, R. et al. Hemopexin induces nephrin-dependent reorganization of the actin cytoskeleton in podocytes. J. Am. Soc. Nephrol. 19, 2140–2149 (2008).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pukajlo-Marczyk, A. & Zwolinska, D. Involvement of hemopexin in the pathogenesis of proteinuria in children with idiopathic nephrotic syndrome. J. Clin. Med. 10, 3160 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Holt, R. C. et al. Heparanase activity is dysregulated in children with steroid-sensitive nephrotic syndrome. Kidney Int. 67, 122–129 (2005).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Youssef, D. M., Elbehidy, R. M., El-Shal, A. S. & Sherief, L. M. T helper 1 and T helper 2 cytokines in atopic children with steroid-sensitive nephrotic syndrome. Iran. J. Kidney Dis. 9, 298–305 (2015).

    PubMed 

    Google Scholar
     

  • Garin, E. H., Blanchard, D. K., Matsushima, K. & Djeu, J. Y. IL-8 production by peripheral blood mononuclear cells in nephrotic patients. Kidney Int. 45, 1311–1317 (1994).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Garin, E. H., Laflam, P. & Chandler, L. Anti-interleukin 8 antibody abolishes effects of lipoid nephrosis cytokine. Pediatr. Nephrol. 12, 381–385 (1998).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Al-Eisa, A. A., Al Rushood, M. & Al-Attiyah, R. J. Urinary excretion of IL-1β, IL-6 and IL-8 cytokines during relapse and remission of idiopathic nephrotic syndrome. J. Inflamm. Res. 10, 1–5 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tain, Y. L., Chen, T. Y. & Yang, K. D. Implications of serum TNF-β and IL-13 in the treatment response of childhood nephrotic syndrome. Cytokine 21, 155–159 (2003).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Yap, H. K. et al. Th1 and Th2 cytokine mRNA profiles in childhood nephrotic syndrome: evidence for increased IL-13 mRNA expression in relapse. J. Am. Soc. Nephrol. 10, 529–537 (1999).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chebotareva, N. et al. A pilot study of anti-nephrin antibodies in podocytopaties among adults. Nephrology 29, 86–92 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Charba, D. S. et al. Antibodies to protein tyrosine phosphatase receptor type O (PTPro) increase glomerular albumin permeability (Palb). Am. J. Physiol. Ren. Physiol. 297, F138–F144 (2009).

    Article 
    CAS 

    Google Scholar
     

  • Beaudreuil, S. et al. Circulating CASK is associated with recurrent focal segmental glomerulosclerosis after transplantation. PLoS One 14, e0219353 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhang, X. et al. CASK, the soluble glomerular permeability factor, is secreted by macrophages in patients with recurrent focal and segmental glomerulo-sclerosis. Front. Immunol. 11, 875 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wei, C., Spear, R., Hahm, E. & Reiser, J. suPAR, a circulating kidney disease factor. Front. Med. 8, 745838 (2021).

    Article 

    Google Scholar
     

  • US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT05003986 (2021).

  • Egbuna, O. et al. Inaxaplin for proteinuric kidney disease in persons with two APOL1 variants. N. Engl. J. Med. 388, 969–979 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT05267262 (2022).

  • US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT05183646 (2022).

  • US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT05599815 (2023).

  • US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT05383547 (2022).

  • US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT05441826 (2022).

  • US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT04009668 (2019).

  • US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT05588063 (2022).

  • US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT05583942 (2022).

  • US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT04065438 (2020).

  • US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT02235857 (2015).