Publications by authors named "Pietro Cippa"

Article Synopsis
  • JC-polyomavirus-associated nephropathy (JC-PVAN) is a rare condition impacting kidney transplant functions, with limited documented cases.
  • Two cases were presented involving patients who developed JC-PVAN more than five years after their kidney transplants, showing specific kidney damage during biopsies.
  • Despite initiating immunosuppressive therapy, both cases experienced a continued decline in kidney function, highlighting the need for thorough diagnostics when graft dysfunction occurs long after transplantation.
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Article Synopsis
  • Kidney structural cells actively participate in the rejection process of kidney transplants, alongside infiltrated immune cells, as shown through single-cell RNA sequencing of biopsies.
  • Upregulation of immune-related genes was observed in endothelial and epithelial cells, indicating their involvement in the alloimmune response, with distinct differences based on the kidney compartment.
  • A significant downregulation of energy metabolism in proximal tubular cells during inflammation correlates with reduced kidney function, emphasizing the graft's crucial role in driving and maintaining rejection after transplantation.
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Aims: Diuretic resistance (i.e., insufficient diuretic and natriuretic response to an appropriate dose of intravenously administered loop diuretic) is a major cause of insufficient decongestion in acute heart failure (AHF).

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Background: Taurine is one of the most abundant amino acids in humans. Low taurine levels are associated with cellular senescence, mitochondrial dysfunction, DNA damage, and inflammation in mouse, all of which can be reversed by supplementation. It is unknown whether taurine metabolism is associated with kidney allograft function and survival.

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  • Accumulating senescent cells contribute to aging and diseases, prompting research into botanical extracts for potential therapies that could target these issues.
  • A standardized extract of Salvia haenkei (HK) was found to extend both lifespan and healthspan in aged mice by reducing inflammation and markers of senescence while improving muscle strength and fur quality.
  • The study identified luteolin, a flavonoid in HK, as a compound that disrupts the interaction between the proteins p16 and CDK6, suggesting a mechanism through which HK promotes longevity by modulating cellular senescence.
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Key Points: Glomerular proteinuria induces large-scale changes in gene expression along the nephron. Increased protein uptake in the proximal tubule results in axial remodeling and injury. Increased protein delivery to the distal tubule causes dedifferentiation of the epithelium.

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The application of single-cell technologies in clinical nephrology remains elusive. We generated an atlas of transcriptionally defined cell types and cell states of human kidney disease by integrating single-cell signatures reported in the literature with newly generated signatures obtained from 5 patients with acute kidney injury. We used this information to develop kidney-specific cell-level information ExtractoR (K-CLIER), a transfer learning approach specifically tailored to evaluate the role of cell types/states on bulk RNAseq data.

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Article Synopsis
  • The study investigates the role of SOX9 in the healing process after acute kidney injury (AKI) and how it influences whether healing leads to fibrosis or not.
  • Researchers found that cells successfully regenerating epithelial tissue turn off SOX9, while those struggling to restore normal structure keep it active, leading to chronic issues such as kidney disease.
  • The findings highlight a potential biomarker for assessing the state of kidney repair, indicating that SOX9 activity can predict whether regeneration will occur with or without fibrosis.
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As the global burden of chronic kidney disease continues to increase, the use of peritoneal dialysis is often advocated as the preferred initial dialysis modality. Observational studies suggest a survival advantage for peritoneal dialysis over hemodialysis for the initial 2-3 years of dialysis. Peritoneal dialysis has been associated with better graft survival after kidney transplantation and has a reduced cost burden compared to hemodialysis.

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Article Synopsis
  • * A total of 193 patients were randomized into two groups: one with immune monitoring and the other receiving standard prophylaxis for set periods (180 or 90 days).
  • * Results showed that while immune monitoring significantly reduced the duration of antiviral treatment by about 26 days, it did not demonstrate a clear advantage in preventing clinically significant CMV infections when compared to the control group.
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Currently circulating SARS-CoV-2 variants have acquired convergent mutations at hot spots in the receptor-binding domain (RBD) of the spike protein. The effects of these mutations on viral infection and transmission and the efficacy of vaccines and therapies remains poorly understood. Here we demonstrate that recently emerged BQ.

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Article Synopsis
  • Exposure to high temperatures may increase the risk of acute kidney injury, but it's uncertain if this occurs in normal community settings rather than during extreme weather or in emergency situations.
  • A 9.5-year study analyzed kidney function data from Swiss primary care patients, comparing their estimated glomerular filtration rate (eGFR) with local temperature data across five temperature categories.
  • Results showed that while higher temperatures correlated with lower eGFR in unadjusted analysis, adjusted models revealed no clear link; notable reductions in kidney function were only seen in patients with multiple risk factors, suggesting limited clinical significance.
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Purpose Of Review: Acute kidney injury (AKI) occurs in approximately 10-15% of patients admitted to hospital and is associated with adverse clinical outcomes. Despite recent advances, management of patients with AKI is still mainly supportive, including the avoidance of nephrotoxins, volume and haemodynamic management and renal replacement therapy. A better understanding of the renal response to injury is the prerequisite to overcome current limitations in AKI diagnostics and therapy.

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Hematopoietic stem cell transplantation (HSCT) has many potential applications beyond current standard indications, including treatment of autoimmune disease, gene therapy, and transplant tolerance induction. However, severe myelosuppression and other toxicities after myeloablative conditioning regimens have hampered wider clinical use. To achieve donor hematopoietic stem cell (HSC) engraftment, it appears essential to establish niches for the donor HSCs by depleting the host HSCs.

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Aim: Noninvasive identification of haemodialysis patients at high risk of cardiovascular events and death might improve their outcome. Growth differentiation factor 15 is a prognostic biomarker in multiple disease entities, including cardiovascular disease. The aim of this study was to assess the association between plasma GDF-15 and mortality in a cohort of haemodialysis patients.

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Article Synopsis
  • A validated measure of vascular access (VA) function is essential for effective hemodialysis (HD), but currently, there is no reliable method to assess this outcome in clinical practice.
  • The VALID study aims to evaluate the accuracy and feasibility of measuring VA function using a defined standard over a 6-month period, comparing routine clinical assessments to expert evaluations.
  • The study will include approximately 612 participants from diverse dialysis units across multiple countries, focusing on gathering data on the effectiveness, time, and acceptability of the VA function measurement process.
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Background: Up to 50% of cases of Shiga-toxin-producing Escherichia coli hemolytic uremic syndrome occur in adults, and the clinical presentation is variable. Microbiological analyses must be performed in all patients with thrombotic microangiopathy to identify Shiga-toxin-producing Escherichia coli, even in the absence of diarrhea.

Case Presentation: A 79-year-old Caucasian woman was admitted to hospital because of severe proctitis.

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Energy metabolism failure in proximal tubule cells (PTCs) is a hallmark of chronic kidney injury. We combined transcriptomic, metabolomic, and lipidomic approaches in experimental models and patient cohorts to investigate the molecular basis of the progression to chronic kidney allograft injury initiated by ischemia/reperfusion injury (IRI). The urinary metabolome of kidney transplant recipients with chronic allograft injury and who experienced severe IRI was substantially enriched with long chain fatty acids (FAs).

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Hyperkalaemia (HK) is one of the most common electrolyte disorders and a frequent reason for nephrological consultations. High serum potassium (K) levels are associated with elevated morbidity and mortality, mainly due to life-threatening arrhythmias. In the majority of cases, HK is associated with chronic kidney disease (CKD), or with the use of renin-angiotensin-aldosterone system inhibitors (RAASis) and/or mineral corticoid antagonists (MRAs).

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Cells subjected to treatment with anti-cancer therapies can evade apoptosis through cellular senescence. Persistent senescent tumor cells remain metabolically active, possess a secretory phenotype, and can promote tumor proliferation and metastatic dissemination. Removal of senescent tumor cells (senolytic therapy) has therefore emerged as a promising therapeutic strategy.

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Introduction: CKD is associated with alterations of tubular function. Renal gluconeogenesis is responsible for 40% of systemic gluconeogenesis during fasting, but how and why CKD affects this process and the repercussions of such regulation are unknown.

Methods: We used data on the renal gluconeogenic pathway from more than 200 renal biopsies performed on CKD patients and from 43 kidney allograft patients, and studied three mouse models, of proteinuric CKD (POD-ATTAC), of ischemic CKD, and of unilateral urinary tract obstruction.

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