Anti-podocin Enzyme-Linked Immunosorbent Assay Guides Immunotherapy in Steroid-Resistant Nephrotic Syndrome Valentina Raglianti, Luigi Cirillo, Maria Lucia Angelotti, Letizia De Chiara, Benedetta Mazzinghi, Giulia Antonelli, Carolina Conte, Maria Elena Melica, Anna Julie Peired, Elena Lazzeri, Laura Lasagni, Viviana Palazzo, Samuela Landini, Anna Maria Buccoliero, Samantha Innocenti, Carmela Errichiello, Elisa Buti, Giulia Sansavini, Andrea La Tessa, Francesca Becherucci, Hans-Joachim Anders, Paola Romagnani Kidney International Reports, 2025 Steroid-resistant nephrotic syndrome (SRNS) has diverse causes, yet treatment often relies on high-dose corticosteroids, calcineurin inhibitors (CNI), mycophenolate mofetil (MMF), cyclophosphamide, or rituximab (RTX) in a trial-and-error fashion, without identifying the underlying etiology1. Recently, autoantibodies against slit diaphragm proteins—nephrin, podocin, and Kirrel1—have been found in patients responsive to second-line immunosuppression, but not in genetic SRNS2-6. However, diagnostic tools for detecting autoimmune podocytopathies (APs) remain limited.
Estrogen-regulated renal progenitors determine pregnancy adaptation and preeclampsia Carolina Conte, Maria Lucia Angelotti, Benedetta Mazzinghi, Maria Elena Melica, Giulia Antonelli, Giulia Carangelo, Samuela Landini, Valentina Raglianti, Fiammetta Ravaglia, Luigi Cirillo, Camilla Fantini, Tommaso Dafichi, Martin Klaus, Ersilia Lucenteforte, Alice Molli, Letizia De Chiara, Anna Julie Peired, Elena Lazzeri, Hans-Joachim Anders, Laura Lasagni, Paola Romagnani Science, 2025 The global burden of kidney disease displays marked sexual dimorphism. Lineage tracing and single-cell RNA-sequencing revealed that starting from puberty, estrogen signaling in female mice supports self-renewal and differentiation of renal progenitors to increase filtration capacity, reducing sensitivity to glomerular injury compared with that of males. This phenomenon accelerated as female kidneys adapted to the workload of pregnancy. Deletion of estrogen receptor α in renal progenitors disrupted this adaptation, leading to preeclampsia, fetal growth restriction, and increased maternal risk of hypertension and chronic kidney disease. Offspring from affected mothers had fewer nephrons, resulting in early-life hypertension and greater susceptibility to kidney disease. These results highlight the fundamental role of kidney fitness and renal progenitors for pregnancy and preeclampsia and as a determinant of sexual dimorphism in kidney disease.
Cover Image Maria Elena Melica, Giulia Antonelli, Roberto Semeraro, Gilda La Regina, Tommaso Dafichi, Camilla Fantini, Giulia Carangelo, Giuseppina Comito, Carolina Conte, Laura Maggi, Samuela Landini, Valentina Raglianti, Maria Lucia Angelotti, Alice Molli, Daniela Buonvicino, Letizia De Chiara, Elena Lazzeri, Benedetta Mazzinghi, Anna Julie Peired, Paola Romagnani, Laura Lasagni Journal of the American Society of Nephrology, 2025 Immunofluorescence image displays coexpression of Piezo1 (green) and nephrin (red) in a human glomerulus of a healthy participant. All nuclei are stained with 4’,6-diamidino-2-phenylindole (white) to visualize the tissue. Figure 1C from “Piezo1, F-actin Remodeling, and Podocyte Survival and Regeneration” by Maria Elena Melica, Giulia Antonelli, Roberto Semeraro, Gilda La Regina, Tommaso Dafichi, Camilla Fantini, Giulia Carangelo, Giuseppina Comito, Carolina Conte, Laura Maggi, Samuela Landini, Valentina Raglianti, Maria Lucia Angelotti, Alice Molli, Daniela Buonvicino, Letizia De Chiara, Elena Lazzeri, Benedetta Mazzinghi, Anna Julie Peired, Paola Romagnani, and Laura Lasagni. J Am Soc Nephrol . 2025;36(9):1749–1763. doi:10.1681/ASN.0000000697.
Piezo1, F-Actin Remodeling, and Podocyte Survival and Regeneration Maria Elena Melica, Giulia Antonelli, Roberto Semeraro, Gilda La Regina, Tommaso Dafichi, Camilla Fantini, Giulia Carangelo, Giuseppina Comito, Carolina Conte, Laura Maggi, Samuela Landini, Valentina Raglianti, Maria Lucia Angelotti, Alice Molli, Daniela Buonvicino, Letizia De Chiara, Elena Lazzeri, Benedetta Mazzinghi, Anna Julie Peired, Paola Romagnani, Laura Lasagni Journal of the American Society of Nephrology, 2025 Background: Podocytes and podocyte progenitors are interdependent components of the kidney's glomerular structure, with podocytes forming the glomerular filtration barrier and progenitors being key players in podocyte regeneration during pathophysiological processes. Both cell types are subjected to constant mechanical forces, whose alterations can initiate podocytopathy and worsen glomerular injury. Despite this, the specific mechanosensors and mechanotransduction pathways involved in their response to mechanical cues remain only partially explored. Methods: We used transcriptomics, immunofluorescence, and silencing experiments on human primary podocyte progenitor cell cultures to demonstrate the expression and function of Piezo1 channels. We generated inducible podocyte- and podocyte progenitor-specific Piezo1 knockout mice to evaluate the effects of Piezo1 loss in the context of Adriamycin nephropathy and over 10 months of aging. Results: Silencing of Piezo1 in progenitors triggered F-actin remodelling, induced cell shape modification and nuclear envelope defects with accumulation of DNA damage that led to mitotic catastrophe in differentiated podocytes. Podocyte-specific knockout of Piezo1 induced higher susceptibility to podocyte injury in Adriamycin nephropathy and led to accumulation of DNA damage and mild albuminuria starting from adult age. Podocyte progenitor-specific knockout of Piezo1 in mouse resulted in severe albuminuria during Adriamycin nephropathy, leading to the generation of defective podocytes. Conclusions: These results demonstrated that Piezo1, thanks to its role in F-actin cytoskeleton maintenance, is essential for the survival of podocytes exposed to mechanical stress conditions and for their correct regeneration.
Tubular Cell Polyploidy and AKI-to-CKD Transition Elena Lazzeri, Paola Romagnani Journal of the American Society of Nephrology, 2025 Episodes of AKI are a major driver of CKD, which is a growing global health challenge that sometimes remains undetected until advanced stages of kidney disease. To compensate for nephron loss, the kidney relies on tubular cell (TC) hypertrophy to maintain function. A crucial adaptive mechanism recently identified in this process is TC polyploidization, which helps mitigate irreversible TC loss during AKI. Polyploid TCs acquire extra genome copies through alternative cell cycles, allowing them to sustain kidney function under stress. However, although polyploidization provides short-term protection, its persistent activation promotes DNA damage, p21 upregulation, and fibrosis, ultimately accelerating CKD progression.
Anti-slit Antibodies against Podocin and Kirrel1 in Pediatric and Adult Podocytopathies Valentina Raglianti, Maria Lucia Angelotti, Letizia De Chiara, Marco Allinovi, Luigi Cirillo, Anna Manonelles Montero, Josep Maria Cruzado, Maria Elena Melica, Giulia Antonelli, Carolina Conte, Anna Julie Peired, Laura Lasagni, Bärbel Lange-Sperandio, Hans-Joachim Anders, Francesca Becherucci, Elena Lazzeri, Benedetta Mazzinghi, Paola Romagnani Journal of the American Society of Nephrology, 2025 No abstract available
Anti-slit diaphragm antibodies on kidney biopsy identify pediatric patients with steroid-resistant nephrotic syndrome responsive to second-line immunosuppressants Valentina Raglianti, Maria Lucia Angelotti, Luigi Cirillo, Fiammetta Ravaglia, Samuela Landini, Viviana Palazzo, Maria Elena Melica, Giulia Antonelli, Carolina Conte, Elisa Buti, Carmela Errichiello, Letizia De Chiara, Anna Julie Peired, Laura Lasagni, Anna Maria Buccoliero, Marco Allinovi, Anna Manonelles Montero, Josep Maria Cruzado, Maurizio Bruschi, Gian Marco Ghiggeri, Andrea Angeletti, Hans-Joachim Anders, Elena Lazzeri, Benedetta Mazzinghi, Francesca Becherucci, Paola Romagnani Kidney International, 2024 Podocytopathies represent a group of glomerular disorders associated with minimal changes (MC) or focal segmental glomerulosclerosis (FSGS) lesion patterns at biopsy and heterogeneous responses to steroids. Anti-nephrin antibodies were previously found in such patients, suggesting an autoimmune form of podocytopathy. High resolution confocal microscopy on kidney biopsies of a cohort of 128 pediatric patients revealed localization of IgG along the slit diaphragm in 30% of patients with MC and 25% of those with FSGS, but not in other lesion patterns. Anti-nephrin IgG ELISA assay in the serum and stimulated emission depletion microscopy of kidney biopsies showed IgG-nephrin co-localization only in 77.8% of cases. Similar observations were obtained in a cohort of 48 adult patients with MC or FSGS at kidney biopsy, where IgG-nephrin colocalization was only 44.4%, suggesting the existence of autoantibodies binding to other slit proteins. Patients with anti-slit antibodies showed nephrotic syndrome at onset in 94.4% of cases. Patients with primary steroid-resistance had anti-slit antibodies in 27%, while those with secondary steroid-resistance in 87.5% of cases, irrespective of the histopathological lesion pattern. Steroid-resistant patients with anti-slit antibodies responded to second-line immunosuppressants in 92.3% vs. only 20% of patients that were anti-slit negative. No patient with anti-slit antibodies developed kidney failure vs. 51.7% of those negative for antibodies (66.7% with a genetic cause and 41.2% with a non-genetic cause). Thus, the detection of anti-slit antibodies can identify patients with an autoimmune podocytopathy responsive to treatment with second-line immunosuppressants, irrespective of the histopathological lesion pattern at biopsy.
Presentation and progression of MPO-ANCA interstitial lung disease Lorenzo Salvati, Boaz Palterer, Elena Lazzeri, Emanuele Vivarelli, Marina Amendola, Marco Allinovi, Leonardo Caroti, Alessio Mazzoni, Laura Lasagni, Giacomo Emmi, Edoardo Cavigli, Marco Del Carria, Linda Di Pietro, Mariangela Scavone, Daniele Cammelli, Federico Lavorini, Sara Tomassetti, Elisabetta Rosi, Paola Parronchi Journal of Translational Autoimmunity, 2024 The association between MPO-ANCA-associated vasculitis (AAV) and interstitial lung disease (ILD) has been well established. Pulmonary fibrosis may coexist with, follow, or even precede the diagnosis of AAV, and its presence adversely affects the prognosis. The optimal approach to investigating ANCA in patients with ILD remains a subject of ongoing debate. Here we aim to describe presentation and progression of MPO-ANCA ILD. We conducted a retrospective evaluation of a cohort of individuals diagnosed with MPO-ANCA ILD, with or without accompanying renal impairment, at the Immunology and Cell Therapy Unit, Careggi University Hospital, Florence, Italy, between June 2016 and June 2022. Clinical records, imaging studies, pathologic examinations, and laboratory test results were collected. Among the 14 patients identified with MPO-ANCA ILD, we observed a significant association between MPO-ANCA titers assessed at the time of ILD diagnosis and renal involvement. Renal impairment in these cases often manifested as subclinical or slowly progressive kidney damage. Interestingly, complement C3 deposits were consistently found in all renal biopsy specimens, thereby suggesting the potential for novel therapeutic targets in managing renal complications associated with MPO-ANCA ILD. The presentation of MPO-ANCA vasculitis as ILD can be the first and only clinical manifestation. MPO-ANCA levels at ILD diagnosis could warn on the progression to renal involvement in patients with MPO-ANCA ILD, hence caution is needed because renal disease can be subclinical or smoldering.
Polyploid tubular cells: a shortcut to stress adaptation Letizia De Chiara, Elena Lazzeri, Paola Romagnani Kidney International, 2024 Tubular epithelial cells (TCs) compose the majority of kidney parenchyma and play fundamental roles in maintaining homeostasis. Like other tissues, mostly immature TC with progenitor capabilities are able to replace TC lost during injury via clonal expansion and differentiation. In contrast, differentiated TC lack this capacity. However, as the kidney is frequently exposed to toxic injuries, evolution positively selected a response program that endows differentiated TC to maintain residual kidney function during kidney injury. Recently, we and others have described polyploidization of differentiated TC, a mechanism to augment the function of remnant TC after injury by rapid hypertrophy. Polyploidy is a condition characterized by >2 complete sets of chromosomes. Polyploid cells often display an increased functional capacity and are generally more resilient to stress as evidenced by being conserved across many plants and eukaryote species from flies to mammals. Here, we discuss the occurrence of TC polyploidy in different contexts and conditions and how this integrates into existing concepts of kidney cell responses to injury. Collectively, we aim at stimulating the acquisition of novel knowledge in the kidney field as well as accelerating the translation of this basic response mechanism to the clinical sphere.
Renal Progenitors Derived from Urine for Personalized Diagnosis of Kidney Diseases Benedetta Mazzinghi, Maria Elena Melica, Laura Lasagni, Paola Romagnani, Elena Lazzeri Kidney and Blood Pressure Research, 2024 Background: Chronic kidney disease affects 10% of the world population and it is associated with progression to end stage kidney disease and increased morbidity and mortality. The advent of multi-omics technologies has expanded our knowledge on the complexity of kidney diseases, revealing their frequent genetic etiology, particularly in young subjects. Genetic heterogeneity and drug screening require patient-derived disease models to establish a correct diagnosis and evaluate new potential treatments and outcome. Summary: Patient-derived renal progenitors can be isolated from urines to set up proper disease modeling. This strategy allows to make diagnosis of genetic kidney disease in patients carrying unknown significance variants or uncover variants missed from peripheral blood analysis. Furthermore, urinary-derived tubuloids obtained from renal progenitors of patients appear to be potentially valuable for modeling kidney diseases to test ex vivo treatment efficacy or to develop new therapeutic approaches. Finally, renal progenitors derived from urine can provide insights into acute kidney injury and predict kidney function recovery and outcome. Key messages: Renal progenitors derived from urine are a promising new non-invasive and easy-to-handle tool, which improves the rate of diagnosis and the therapeutic choice, paving the way toward a personalized healthcare.
A Clinical Workflow for Cost-Saving High-Rate Diagnosis of Genetic Kidney Diseases Francesca Becherucci, Samuela Landini, Viviana Palazzo, Luigi Cirillo, Valentina Raglianti, Gianmarco Lugli, Lucia Tiberi, Elia Dirupo, Stefania Bellelli, Tommaso Mazzierli, Jacopo Lomi, Fiammetta Ravaglia, Giulia Sansavini, Marco Allinovi, Domenico Giannese, Chiara Somma, Giuseppe Spatoliatore, Debora Vergani, Rosangela Artuso, Alberto Rosati, Calogero Cirami, Pietro Claudio Dattolo, Gesualdo Campolo, Letizia De Chiara, Laura Papi, Augusto Vaglio, Elena Lazzeri, Hans-Joachim Anders, Benedetta Mazzinghi, Paola Romagnani Journal of the American Society of Nephrology, 2023
Tubular cell polyploidy protects from lethal acute kidney injury but promotes consequent chronic kidney disease Letizia De Chiara, Carolina Conte, Roberto Semeraro, Paula Diaz-Bulnes, Maria Lucia Angelotti, Benedetta Mazzinghi, Alice Molli, Giulia Antonelli, Samuela Landini, Maria Elena Melica, Anna Julie Peired, Laura Maggi, Marta Donati, Gilda La Regina, Marco Allinovi, Fiammetta Ravaglia, Daniele Guasti, Daniele Bani, Luigi Cirillo, Francesca Becherucci, Francesco Guzzi, Alberto Magi, Francesco Annunziato, Laura Lasagni, Hans-Joachim Anders, Elena Lazzeri, Paola Romagnani Nature Communications, 2022
Differentiation of crescent-forming kidney progenitor cells into podocytes attenuates severe glomerulonephritis in mice Maria Elena Melica, Giulia Antonelli, Roberto Semeraro, Maria Lucia Angelotti, Gianmarco Lugli, Samuela Landini, Fiammetta Ravaglia, Gilda La Regina, Carolina Conte, Letizia De Chiara, Anna Julie Peired, Benedetta Mazzinghi, Marta Donati, Alice Molli, Stefanie Steiger, Alberto Magi, Niccolò Bartalucci, Valentina Raglianti, Francesco Guzzi, Laura Maggi, Francesco Annunziato, Alexa Burger, Elena Lazzeri, Hans-Joachim Anders, Laura Lasagni, Paola Romagnani Science Translational Medicine, 2022
Acute kidney injury promotes development of papillary renal cell adenoma and carcinoma from renal progenitor cells Anna Julie Peired, Giulia Antonelli, Maria Lucia Angelotti, Marco Allinovi, Francesco Guzzi, Alessandro Sisti, Roberto Semeraro, Carolina Conte, Benedetta Mazzinghi, Sara Nardi, Maria Elena Melica, Letizia De Chiara, Elena Lazzeri, Laura Lasagni, Tiziano Lottini, Samuela Landini, Sabrina Giglio, Andrea Mari, Fabrizio Di Maida, Alessandro Antonelli, Francesco Porpiglia, Riccardo Schiavina, Vincenzo Ficarra, Davide Facchiano, Mauro Gacci, Sergio Serni, Marco Carini, George J. Netto, Rosa Maria Roperto, Alberto Magi, Christian Fynbo Christiansen, Mario Rotondi, Helen Liapis, Hans-Joachim Anders, Andrea Minervini, Maria Rosaria Raspollini, Paola Romagnani Science Translational Medicine, 2020
Endocycle-related tubular cell hypertrophy and progenitor proliferation recover renal function after acute kidney injury Elena Lazzeri, Maria Lucia Angelotti, Anna Peired, Carolina Conte, Julian A. Marschner, Laura Maggi, Benedetta Mazzinghi, Duccio Lombardi, Maria Elena Melica, Sara Nardi, Elisa Ronconi, Alessandro Sisti, Giulia Antonelli, Francesca Becherucci, Letizia De Chiara, Ricardo Romero Guevara, Alexa Burger, Beat Schaefer, Francesco Annunziato, Hans-Joachim Anders, Laura Lasagni, Paola Romagnani Nature Communications, 2018
Human urine-derived renal progenitors for personalized modeling of genetic kidney disorders Elena Lazzeri, Elisa Ronconi, Maria Lucia Angelotti, Anna Peired, Benedetta Mazzinghi, Francesca Becherucci, Sara Conti, Giulia Sansavini, Alessandro Sisti, Fiammetta Ravaglia, Duccio Lombardi, Aldesia Provenzano, Anna Manonelles, Josep M. Cruzado, Sabrina Giglio, Rosa Maria Roperto, Marco Materassi, Laura Lasagni, Paola Romagnani Journal of the American Society of Nephrology, 2015
Proteinuria impairs podocyte regeneration by sequestering retinoic acid Anna Peired, Maria Lucia Angelotti, Elisa Ronconi, Giancarlo la Marca, Benedetta Mazzinghi, Alessandro Sisti, Duccio Lombardi, Elisa Giocaliere, Marialuisa Della Bona, Fabio Villanelli, Eliana Parente, Lara Ballerini, Costanza Sagrinati, Nicola Wanner, Tobias B. Huber, Helen Liapis, Elena Lazzeri, Laura Lasagni, Paola Romagnani Journal of the American Society of Nephrology, 2013
Podocyte loss involves MDM2-driven mitotic catastrophe Shrikant R Mulay, Dana Thomasova, Mi Ryu, Onkar P Kulkarni, Adriana Migliorini, Hauke Bruns, Regina Gröbmayr, Elena Lazzeri, Laura Lasagni, Helen Liapis, Paola Romagnani, Hans-Joachim Anders Journal of Pathology, 2013
Podocyte mitosis – A catastrophe L. Lasagni, E. Lazzeri, S. J. Shankland, H.-J. Anders, P. Romagnani Current Molecular Medicine, 2013
[Tubular progenitor cells: new protagonists of tubular regeneration]. Giornale Italiano Di Nefrologia Organo Ufficiale Della Societa Italiana Di Nefrologia, 2012
MicroRNA-324-3p promotes renal fibrosis and is a target of ACE inhibition Daniela Macconi, Susanna Tomasoni, Paola Romagnani, Piera Trionfini, Fabio Sangalli, Benedetta Mazzinghi, Paola Rizzo, Elena Lazzeri, Mauro Abbate, Giuseppe Remuzzi, Ariela Benigni Journal of the American Society of Nephrology, 2012
The role of podocyte damage in the pathogenesis of glomerulosclerosis and possible repair mechanisms Giornale Italiano Di Nefrologia Organo Ufficiale Della Societa Italiana Di Nefrologia, 2009
Chemokines: possible therapeutic targets and useful clinical parameters in renal transplantation Giornale Italiano Di Nefrologia Organo Ufficiale Della Societa Italiana Di Nefrologia, 2007
A young woman with oedema Elena Lazzeri, Giuseppe Stefano Netti, Benedetta Mazzinghi, Calogero Cirami, Maurizio Salvadori, et al. Internal and Emergency Medicine, 2006
High Pre-Transplant Serum Levels of CXCL10 Predict Early Renal Allograft Failure Transplantationsmedizin Organ Der Deutschen Transplantationsgesellschaft, 2003
Cytokines and chemokines in nephropathies and renal transplant Giornale Italiano Di Nefrologia Organo Ufficiale Della Societa Italiana Di Nefrologia, 2002
