Sexual dimorphIsM in renal PrOgenitors to explain gender- Specificity In kidney physiOlogy aNd diseases (SIMPOSION)

Sexual dimorphIsM in renal PrOgenitors to explain gender- Specificity In kidney physiOlogy aNd diseases (SIMPOSION)


Chronic kidney disease (CKD) represents a global health burden with a prevalence >10% of the global population [1]. CKD can progress toward end-stage kidney disease, requiring renal replacement therapy, i.e. dialysis and transplantation with high related risk of comorbidities and death for any cause and mostly for cardiovascular diseases [1]. Kidney disease show a consistent sexual dimorphism  [2,3]. CKD progresses more fastly and kidney cancer is more frequent in males in comparison to females [2-5]. By contrast, preeclampsia still represents the most frequent form of kidney disease all over the world, affecting 7% of pregnancies [6]. The consequences of preeclampsia extend far beyond pregnancy, resulting in increased susceptibility to hypertension and CKD for the mother and the offspring [7].

How sex influences kidney biology and cardiovascular risk is still largely unknown. This generates crucial gaps in CKD prevention and treatment. Understanding the reason for these diversities may help unlocking crucial mechanisms for targeting preeclampsia, kidney cancer, CKD, and the related cardiovascular risk.

We first identified renal progenitors as crucial mediators of the kidney response to injury [8-15]. In this project we propose that sexual dimorphism in kidney diseases may result from different response of renal progenitors to sex hormone in males and females. We also propose that targeting the capacity of renal progenitors to respond to injury may help finding new treatments for different kidney diseases.



1.         Romagnani, P.; Remuzzi, G.; Glassock, R.; Levin, A.; Jager, K.J.; Tonelli, M.; Massy, Z.; Wanner, C.; Anders, H.J. Chronic kidney disease. Nat Rev Dis Primers 2017, 3, 17088, doi:10.1038/nrdp.2017.88.

2.         Minutolo, R.; Gabbai, F.B.; Chiodini, P.; Provenzano, M.; Borrelli, S.; Garofalo, C.; Bellizzi, V.; Russo, D.; Conte, G.; De Nicola, L., et al. Sex Differences in the Progression of CKD Among Older Patients: Pooled Analysis of 4 Cohort Studies. Am J Kidney Dis 2020, 75, 30-38, doi:10.1053/j.ajkd.2019.05.019.

3.         Ricardo, A.C.; Yang, W.; Sha, D.; Appel, L.J.; Chen, J.; Krousel-Wood, M.; Manoharan, A.; Steigerwalt, S.; Wright, J.; Rahman, M., et al. Sex-Related Disparities in CKD Progression. J Am Soc Nephrol 2019, 30, 137-146, doi:10.1681/ASN.2018030296.

4.         Peired, A.J.; Campi, R.; Angelotti, M.L.; Antonelli, G.; Conte, C.; Lazzeri, E.; Becherucci, F.; Calistri, L.; Serni, S.; Romagnani, P. Sex and Gender Differences in Kidney Cancer: Clinical and Experimental Evidence. Cancers (Basel) 2021, 13, doi:10.3390/cancers13184588.

5.         Aron, M.; Nguyen, M.M.; Stein, R.J.; Gill, I.S. Impact of gender in renal cell carcinoma: an analysis of the SEER database. Eur Urol 2008, 54, 133-140, doi:10.1016/j.eururo.2007.12.001.

6.         Moghaddas Sani, H.; Zununi Vahed, S.; Ardalan, M. Preeclampsia: A close look at renal dysfunction. Biomed Pharmacother 2019, 109, 408-416, doi:10.1016/j.biopha.2018.10.082.

7.         Turbeville, H.R.; Sasser, J.M. Preeclampsia beyond pregnancy: long-term consequences for mother and child. Am J Physiol Renal Physiol 2020, 318, F1315-F1326, doi:10.1152/ajprenal.00071.2020.

8.         Sagrinati, C.; Netti, G.S.; Mazzinghi, B.; Lazzeri, E.; Liotta, F.; Frosali, F.; Ronconi, E.; Meini, C.; Gacci, M.; Squecco, R., et al. Isolation and characterization of multipotent progenitor cells from the Bowman's capsule of adult human kidneys. J Am Soc Nephrol 2006, 17, 2443-2456, doi:10.1681/ASN.2006010089.

9.         Ronconi, E.; Sagrinati, C.; Angelotti, M.L.; Lazzeri, E.; Mazzinghi, B.; Ballerini, L.; Parente, E.; Becherucci, F.; Gacci, M.; Carini, M., et al. Regeneration of glomerular podocytes by human renal progenitors. J Am Soc Nephrol 2009, 20, 322-332, doi:10.1681/ASN.2008070709.

10.       Angelotti, M.L.; Ronconi, E.; Ballerini, L.; Peired, A.; Mazzinghi, B.; Sagrinati, C.; Parente, E.; Gacci, M.; Carini, M.; Rotondi, M., et al. Characterization of renal progenitors committed toward tubular lineage and their regenerative potential in renal tubular injury. Stem Cells 2012, 30, 1714-1725, doi:10.1002/stem.1130.

11.       Romagnani, P.; Lasagni, L.; Remuzzi, G. Renal progenitors: an evolutionary conserved strategy for kidney regeneration. Nat Rev Nephrol 2013, 9, 137-146, doi:10.1038/nrneph.2012.290.

12.       Lasagni, L.; Angelotti, M.L.; Ronconi, E.; Lombardi, D.; Nardi, S.; Peired, A.; Becherucci, F.; Mazzinghi, B.; Sisti, A.; Romoli, S., et al. Podocyte Regeneration Driven by Renal Progenitors Determines Glomerular Disease Remission and Can Be Pharmacologically Enhanced. Stem Cell Reports 2015, 5, 248-263, doi:10.1016/j.stemcr.2015.07.003.

13.       Lazzeri, E.; Angelotti, M.L.; Peired, A.; Conte, C.; Marschner, J.A.; Maggi, L.; Mazzinghi, B.; Lombardi, D.; Melica, M.E.; Nardi, S., et al. Endocycle-related tubular cell hypertrophy and progenitor proliferation recover renal function after acute kidney injury. Nat Commun 2018, 9, 1344, doi:10.1038/s41467-018-03753-4.

14.       Romoli, S.; Angelotti, M.L.; Antonelli, G.; Kumar Vr, S.; Mulay, S.R.; Desai, J.; Anguiano Gomez, L.; Thomasova, D.; Eulberg, D.; Klussmann, S., et al. CXCL12 blockade preferentially regenerates lost podocytes in cortical nephrons by targeting an intrinsic podocyte-progenitor feedback mechanism. Kidney Int 2018, 94, 1111-1126, doi:10.1016/j.kint.2018.08.013.

15.       Peired, A.J.; Antonelli, G.; Angelotti, M.L.; Allinovi, M.; Guzzi, F.; Sisti, A.; Semeraro, R.; Conte, C.; Mazzinghi, B.; Nardi, S., et al. Acute kidney injury promotes development of papillary renal cell adenoma and carcinoma from renal progenitor cells. Sci Transl Med 2020, 12, doi:10.1126/scitranslmed.aaw6003.


Studies funded by SIMPOSION:



Peired, A.J.; Campi, R.; Angelotti, M.L.; Antonelli, G.; Conte, C.; Lazzeri, E.; Becherucci, F.; Calistri, L.; Serni, S.; Romagnani, P. Sex and Gender Differences in Kidney Cancer: Clinical and Experimental Evidence. Cancers (Basel) 2021, 13, doi:10.3390/cancers13184588.


Ravaglia, F.; Melica, M.E.; Angelotti, M.L.; De Chiara, L.; Romagnani, P.; Lasagni, L. The Pathology Lesion Patterns of Podocytopathies: How and why? Front Cell Dev Biol 2022, 10, 838272, doi:10.3389/fcell.2022.838272. 


Melica, M.E.; Antonelli, G.; Semeraro, R.; Angelotti, M.L.; Lugli, G.; Landini, S.; Ravaglia, F.; Regina, G.; Conte, C.; De Chiara, L., et al. Differentiation of crescent-forming kidney progenitor cells into podocytes attenuates severe glomerulonephritis in mice. Sci Transl Med 2022, 14, eabg3277, doi:10.1126/scitranslmed.abg3277. 


De Chiara, L.; Conte, C.; Semeraro, R.; Diaz-Bulnes, P.; Angelotti, M.L.; Mazzinghi, B.; Molli, A.; Antonelli, G.; Landini, S.; Melica, M.E., et al. Tubular cell polyploidy protects from lethal acute kidney injury but promotes consequent chronic kidney disease. Nat Commun 2022, 13, 5805, doi:10.1038/s41467-022-33110-5. 


Melica ME, Angelotti ML, Antonelli G, Peired AJ, Conte C, De Chiara L, Mazzinghi B, Lazzeri E, Lasagni L and Romagnani P. Preparation of human kidney progenitor cultures and their differentiation into podocytes. Bio-protocol. Bio Protoc. 2023 Aug 20;13(16):e4757. doi: 10.21769/BioProtoc.4757. eCollection 2023 Aug 20. PMID: 37638296.


Cirillo L, De Chiara L, Innocenti S, Errichiello C, Romagnani P, Becherucci F. Chronic kidney disease in children: an update. Clin Kidney J. 2023 Apr 24;16(10):1600-1611. doi: 10.1093/ckj/sfad097. eCollection 2023 Oct. PMID: 37779846 


Romagnani P, Kitching AR, Leung N, Anders HJ. The five types of glomerulonephritis classified by pathogenesis, activity and chronicity (GN-AC). Nephrol Dial Transplant. 2023 Nov 8;38(Supplement_2):ii3-ii10. doi: 10.1093/ndt/gfad067. PMID: 37218714


Melica ME, Cialdai F, La Regina G, Risaliti C, Dafichi T, Peired AJ, Romagnani P, Monici M, Lasagni L. Modeled microgravity unravels the roles of mechanical forces in renal progenitor cell physiology. Stem Cell Res Ther. 2024 Jan 17;15(1):20. doi: 10.1186/s13287-024-03633-3. PMID: 38233961


Ultimo aggiornamento



I cookie di questo sito servono al suo corretto funzionamento e non raccolgono alcuna tua informazione personale. Se navighi su di esso accetti la loro presenza.  Maggiori informazioni