Field Of Nephrology Research Articles

Engaging Students in a Dialysis Unit: A Pilot Study.

Seeking to provide early paediatric nephrology exposure to medical students in the United States, we implemented the Kids In Dialysis, Nephrology Exposure and Education (KIDNEE) club. This club served as an educational intervention in which preclinical medical students were paired with paediatric dialysis patients, as patient buddies. Students were recruited for involvement in the club through the medical school Paediatric Interest Group. For the 2022-2023 academic year, seven first-year students were paired with seven paediatric dialysis patients. Students met with their patient match weekly to play games, watch movies and to act as a friend. The evaluation aimed at assessing the feasibility and acceptability of this intervention as well as influence on student interest in paediatric chronic disease and paediatric nephrology. We developed and distributed surveys to patients, unit staff, and students after programme implementation. From October 2022 to April 2023, medical students collectively spent ~173 h in the dialysis unit. Staff and patients/families unanimously reported that they would recommend the KIDNEE club to other families. Students objectively reported an increased interest in paediatric nephrology and chronic disease and subjectively reported an increased understanding of the patient experience. The KIDNEE club pilot was both feasible and acceptable for patients/families, staff and students. It holds the potential to increase student interest in the field of paediatric nephrology. As our results are limited by small sample size given the pilot nature of the programme, future studies are needed to assess programme expansion and longitudinal influence on students' career paths.

Update in Nephrology

Background: This timely update in nephrology is based on the proceedings of The American Society of Nephrology (ASN) Kidney Week that was held in San Diego, California between October 23, and October 27, 2024. The meeting had 4 sessions dedicated to high-impact clinical trials and late-breaking science. Methods: This update will present 12 studies including 10 clinical trials. Each trial was published in a major peer reviewed journal on the day of the presentation. This will provide the reader with the opportunity to refer to the published study in its entirety. IgA nephropathy (IgAN) management was a major theme in the meeting, and 5 clinical Trials on that topic are included. Other topics included in this review cover kidney transplantation, sodium-glucose cotransporter 2 (SGLT2) inhibitors in chronic kidney disease (CKD), acute kidney injury (AKI), the role of APOL1 risk variants, semaglutide in non-diabetic CKD patients, potassium binders in hemodialysis patients, and blood pressure management strategies in non-cardiac surgery patients. Results: For each study a brief background will be provided, followed by the results of each individual study, then a conclusion and a statement about the study limitations. Conclusions: This update is a window into recent progress in renal medicine. Advances in basic science are propelling novel medications in the field of nephrology with the potential of impacting direct patient care. The excitement in the renal community is palpable.

Point-of-care ultrasound in nephrology: A private practice viewpoint.

Point-of-care ultrasound (POCUS) is a limited ultrasound examination performed by the clinician at the bedside, emerging as a complement to physical examination across various medical specialties. In the field of nephrology, its integration has been gradual, primarily limited to guiding procedures like temporary dialysis catheter placement or, in some cases, diagnostic kidney ultrasounds. In reality, the assessment of hemodynamic status at the bedside holds immense value for nephrologists, yet there exists limited awareness among practitioners regarding its implementation. While there is a growing trend towards incorporating multi-organ POCUS training in fellowship programs, private practice nephrologists remain relatively uninformed. This discussion explores the untapped potential of POCUS as a valuable diagnostic tool in everyday nephrology practice, demonstrating its effectiveness in diverse clinical settings, ranging from medical wards to outpatient dialysis units. Additionally, we delve into the challenges hindering its widespread adoption and consider the future trajectory of this innovative approach.

International Nephrology Masterclass in Chronic Kidney Disease: Rationale, Summary, and Future Perspectives.

Chronic kidney disease (CKD) is a progressive condition that affects more than 10% of the population worldwide, accounting for more than 843 million (M) individuals. The prevalence of CKD (844 M patients) is higher than that of diabetes mellitus (422 M patients), cancer (42 M patients), and HIV (37 M patients), but people are often less aware of it. Global expert groups predict reductions in the nephrology workforce in the next decade, with a declining interest in nephrology careers. Over time, KDIGO guidelines have also focused on topics related to the prevention or management of CKD patients in real-life settings. On these premises, a new educational program with international experts in the field of nephrology took place from November 2022 until March 2023 in Milan, Italy. This multinational masterclass provided an educational platform providing unbiased education on diagnosis and treatment by sharing the most recent research data on CKD and comorbidities, therefore creating a snowball effect to increase the implementation of best practices worldwide, using examples from 'real-life' patient outcomes. This paper provides an overview of the International Nephrology Masterclass (INM) concept, summarizing the key lectures and discussions, and giving an outline of future key developments.

Nursing Care and Postgraduate Education of Nephrology and Dialysis Nurses in Italy.

Introduction. Patients with chronic kidney disease undergoing renal replacement therapy have complex care needs. To address this, nephrology and dialysis nurses must possess expertise in advanced specialist and disciplinary skills. The aim of this review is to analyze post-graduate academic training pathways and clinical-care training in the field of nephrology and dialysis nursing in the Italian context. Methodology. A narrative review of the literature was conducted in May 2024, using databases such as CINAHL and Medline-PubMed, with a selection criterion limited to primary and secondary studies published in Italian and English. To supplement the search, particularly within the Italian context, grey literature sources were consulted. Results. Post-graduate nephrology nursing education in Italy is mainly offered through First-Level Masters, as well as Second Level Masters and specialization courses, which are provided at various academic institutions. Analysis of the educational programs revealed the presence of common "core" teachings across all pathways, covering renal disease pathophysiology, hemodialysis, peritoneal dialysis, and dialysis nursing care, alongside significant heterogeneity in other proposed teachings. Clinical-care training emerged as a fundamental aspect in both post-graduate education, professional integration for newcomers, and continuous professional development. Conclusions. The growing healthcare need for specialist skills suggests the necessity of integrating field-based training with standardized post-graduate academic pathways, possibly in collaboration with relevant Nursing Scientific Societies. This synergy would not only promote the enhancement of nursing competencies but also ensure a high quality of care delivery.

The utility of point-of-care ultrasound in critical care nephrology.

Point-of-care ultrasonography (POCUS) is gaining heightened significance in critical care settings as it allows for quick decision-making at the bedside. While computerized tomography is still considered the standard imaging modality for many diseases, the risks and delays associated with transferring a critically ill patient out of the intensive care unit (ICU) have prompted physicians to explore alternative tools. Ultrasound guidance has increased the safety of invasive procedures in the ICU, such as the placement of vascular catheters and drainage of collections. Ultrasonography is now seen as an extension of the clinical examination, providing quick answers for rapidly deteriorating patients in the ICU. The field of nephrology is increasingly acknowledging the value of diagnostic point-of-care ultrasound (POCUS). By employing multi-organ POCUS, nephrologists can address specific queries that arise during the diagnosis and treatment of patients with acute kidney injury. This approach aids in ruling out hydronephrosis and offers immediate information on hemodynamics, thereby consolidating patient data and facilitating the development of personalized treatment strategies.

Risk Stratification in People with Diabetes for Fasting During Ramadan: Consensus from Arabic Association for the Study of Diabetes and Metabolism.

Current international guidelines recommend a pre-Ramadan risk assessment for people with diabetes (PwDM) who plan on fasting during the Holy month. However, a comprehensive risk assessment-based recommendation for the management of PwDM intending to fast is still controversial. Therefore, the Arabic Association for the Study of Diabetes and Metabolism (AASD) developed this consensus to provide further insights into risk stratification in PwDM intending to fast during Ramadan. The present consensus was based on the three-step modified Delphi method. The modified Delphi method is based on a series of voting rounds and in-between meetings of the expert panel to reach agreements on the statements that did not reach the consensus level during voting. The panel group comprised professors and consultants in endocrinology (both adult and pediatric). Other members included experts in the fields of cardiovascular medicine, nephrology, ophthalmology, and vascular surgery, affiliated with academic institutions in Egypt. In PwDM who intend to fast during Ramadan, risk stratification is crucial to optimize patient outcomes and prevent serious complications. The present consensus provides risk assessment of those living with diabetes according to several factors, including the type of diabetes, presence, and severity of complications, number of fasting hours, and other socioeconomic factors. According to their risk factors, patients were classified into four categories (very high, high, moderate, and low risk). Future research is warranted due to the controversial literature regarding the impact of fasting on certain comorbidities.

Dr. Manuel Martinez-Maldonado: A Pioneer in Renal Therapeutics and Mentor to a Generation of Minority Physician-Scientists.

Dr. Manuel Martinez-Maldonado is a distinguished Puerto Rican internist, nephrologist, physician-scientist, mentor, and prolific writer whose leadership in academic and clinical settings has significantly advanced the fields of nephrology, renal physiology and pharmacology, fluids and electrolyte metabolism, calcium metabolism, hypertension research, and medical education. His research on electrolyte imbalances has led to innovative hypercalcemia treatments, notably furosemide withIV fluid therapy. This is an approach that, combined with pharmacotherapy using calcitonin and bisphosphonates, became the standard practice for managing hypercalcemia until specific therapies became available. His nephrology research team and laboratory in the San Juan VA (Veterans Affairs) Medical Center and the Medical School of the University of Puerto Rico were internationally renowned. Throughout his career, he fostered a culture of mentorship while spearheading superb clinical teaching and research initiatives. His transformative tenures at several institutions, including Baylor College of Medicine; the University of Puerto Rico-Medical Sciences Campus; the VA medical centers in Atlanta, Houston, and San Juan; Emory University; Oregon Health Sciences University; Ponce School of Medicine; and the University of Louisville School of Medicine demonstrate his lasting contributions to medical science and education. His interdisciplinary approach, advocacy for kidney and clinical research, and contributions to understanding the renin-angiotensin system and the role of sodium-potassium-activated adenosine triphosphatase in renal concentration mechanisms illustrate his enduring impact on renal physiology and human health.

Basal knowledge in the field of pediatric nephrology and its enhancement following specific training of ChatGPT-4 “omni” and Gemini 1.5 Flash

BackgroundWe aimed to evaluate the baseline performance and improvement of ChatGPT-4 “omni” (ChatGPT-4o) and Gemini 1.5 Flash (Gemini 1.5) in answering multiple-choice questions related to pediatric nephrology after specific training.MethodsUsing questions from the “Educational Review” articles published by Pediatric Nephrology between January 2014 and April 2024, the models were tested both before and after specific training with Portable Data Format (PDF) and text (TXT) file formats of the Educational Review articles removing the last page containing the correct answers using a Python script. The number of correct answers was recorded.ResultsBefore training, ChatGPT-4o correctly answered 75.2% of the 1395 questions, outperforming Gemini 1.5, which answered 64.9% correctly (p < 0.001). After training with PDF files, ChatGPT-4o’s accuracy increased to 77.8%, while Gemini 1.5 improved significantly to 84.7% (p < 0.001). Training with TXT files showed similar results, with ChatGPT-4o maintaining 77.8% accuracy and Gemini 1.5 further improving to 87.6% (p < 0.001).ConclusionsThe study highlights that while ChatGPT-4o has strong baseline performance, specific training does not significantly enhance its accuracy. Conversely, Gemini 1.5, despite its lower initial performance, shows substantial improvement with training, particularly with TXT files. These findings suggest Gemini 1.5’s superior ability to store and retrieve information, making it potentially more effective in clinical applications, albeit with a dependency on additional data for optimal performance.Graphical A higher resolution version of the Graphical abstract is available as Supplementary information

Responding to the workforce crisis: consensus recommendations from the Second Workforce Summit of the American Society of Pediatric Nephrology

ImportancePediatric patients with complex medical problems benefit from pediatric sub-specialty care; however, a significant proportion of children live greater than 80 mi. away from pediatric sub-specialty care.ObjectiveTo identify current knowledge gaps and outline concrete next steps to make progress on issues that have persistently challenged the pediatric nephrology workforce.Evidence reviewWorkforce Summit 2.0 employed the round table format and methodology for consensus building using adapted Delphi principles. Content domains were identified via input from the ASPN Workforce Committee, the ASPN’s 2023 Strategic Plan survey, the ASPN’s Pediatric Nephrology Division Directors survey, and ongoing feedback from ASPN members. Working groups met prior to the Summit to conduct an organized literature review and establish key questions to be addressed. The Summit was held in-person in November 2023. During the Summit, work groups presented their preliminary findings, and the at-large group developed the key action statements and future directions.FindingsA holistic appraisal of the effort required to cover inpatient and outpatient sub-specialty care will help define faculty effort and time distribution. Most pediatric nephrologists practice in academic settings, so work beyond clinical care including education, research, advocacy, and administrative/service tasks may form a substantial amount of a faculty member’s time and effort. An academic relative value unit (RVU) may assist in creating a more inclusive assessment of their contributions to their academic practice. Pediatric sub-specialties, such as nephrology, contribute to the clinical mission and care of their institutions beyond their direct billable RVUs. Advocacy throughout the field of pediatrics is necessary in order for reimbursement of pediatric sub-specialist care to accurately reflect the time and effort required to address complex care needs. Flexible, individualized training pathways may improve recruitment into sub-specialty fields such as nephrology.Conclusions and relevanceThe workforce crisis facing the pediatric nephrology field is echoed throughout many pediatric sub-specialties. Efforts to improve recruitment, retention, and reimbursement are necessary to improve the care delivered to pediatric patients.Graphical A higher resolution version of the Graphical abstract is available as Supplementary information.

In silico medicine and -omics strategies in nephrology: contributions and relevance to the diagnosis and prevention of chronic kidney disease.

Chronic kidney disease (CKD) has been increasing over the last years, with a rate between 0.49% to 0.87% new cases per year. Currently, the number of affected people is around 850 million worldwide. CKD is a slowly progressive disease that leads to irreversible loss of kidney function, end-stage kidney disease, and premature death. Therefore, CKD is considered a global health problem, and this sets the alarm for necessary efficient prediction, management, and disease prevention. At present, modern computer analysis, such as in silico medicine (ISM), denotes an emergent data science that offers interesting promise in the nephrology field. ISM offers reliable computer predictions to suggest optimal treatments in a case-specific manner. In addition, ISM offers the potential to gain a better understanding of the kidney physiology and/or pathophysiology of many complex diseases, together with a multiscale disease modeling. Similarly, -omics platforms (including genomics, transcriptomics, metabolomics, and proteomics), can generate biological data to obtain information on gene expression and regulation, protein turnover, and biological pathway connections in renal diseases. In this sense, the novel patient-centered approach in CKD research is built upon the combination of ISM analysis of human data, the use of in vitro models, and in vivo validation. Thus, one of the main objectives of CKD research is to manage the disease by the identification of new disease drivers, which could be prevented and monitored. This review explores the wide-ranging application of computational medicine and the application of -omics strategies in evaluating and managing kidney diseases.

Green Nephrology - What does this mean for dialysis procedures?

In times in which climate change is becoming increasingly noticeable in the everyday lives of the global population, a rethinking towards an environmentally friendly and climate-neutral way of life is essential in all areas of human activity (including medicine). In the field of nephrology, a reorientation of resource-intensive renal replacement therapy is therefore absolutely necessary, keyword "green nephrology". To this end, awareness of the CO2 emissions caused in the field of nephrology must first be raised so that CO2 savings can then be implemented efficiently. Initially using the current conventional dialysis procedures. In addition, further technical developments such as portable and wearable haemodialysis and peritoneal dialysis machines will enable significant savings in energy and water consumption in the future. Furthermore, innovative research approaches are introducing new alternatives to organ transplantation, such as xenotransplantation, stem cell research and "artificial" organ replacement.A wide variety of promising approaches is therefore available for the renal replacement therapy of the future. The aim of nephrology must now be to drive forward further development and implement it in such a way that environmentally friendly patient care in nephrology is possible in the near future in order to make our contribution to climate protection while at the same time ensuring the treatment and its quality.

Targeting polo-like kinase 1 to treat kidney diseases.

Globally, ∼850 million individuals suffer from some form of kidney disease. This staggering figure underscores the importance of continued research and innovation in the field of nephrology to develop effective treatments and improve overall global kidney health. In current research, the polo-like kinase (Plk) family has emerged as a group of highly conserved enzyme kinases vital for proper cell cycle regulation. Plks are defined by their N-terminal kinase domain and C-terminal polo-box domain, which regulate their catalytic activity, subcellular localization, and substrate recognition. Among the Plk family members, Plk1 has garnered significant attention due to its pivotal role in regulating multiple mitotic processes, particularly in the kidneys. It is a crucial serine-threonine (Ser-Thr) kinase involved in cell division and genomic stability. In this review, we delve into the types and functions of Plks, focusing on Plk1's significance in processes such as cell proliferation, spindle assembly, and DNA damage repair. The review also underscores Plk1's vital contributions to maintaining kidney homeostasis, elucidating its involvement in nuclear envelope breakdown, anaphase-promoting complex/cyclosome activation, and the regulation of mRNA translation machinery. Furthermore, the review discusses how Plk1 contributes to the development and progression of kidney diseases, emphasizing its overexpression in conditions such as acute kidney injury, chronic kidney disease, and so forth. It also highlights the importance of exploring Plk1 modulators as targeted therapies for kidney diseases in future. This review will help in understanding the role of Plk1 in kidney disease development, paving the way for the discovery and development of novel therapeutic approaches to manage kidney diseases effectively.

The potential of ChatGPT in medicine: an example analysis of nephrology specialty exams in Poland.

In November 2022, OpenAI released a chatbot named ChatGPT, a product capable of processing natural language to create human-like conversational dialogue. It has generated a lot of interest, including from the scientific community and the medical science community. Recent publications have shown that ChatGPT can correctly answer questions from medical exams such as the United States Medical Licensing Examination and other specialty exams. To date, there have been no studies in which ChatGPT has been tested on specialty questions in the field of nephrology anywhere in the world. Using the ChatGPT-3.5 and -4.0 algorithms in this comparative cross-sectional study, we analysed 1560 single-answer questions from the national specialty exam in nephrology from 2017 to 2023 that were available in the Polish Medical Examination Center's question database along with answer keys. Of the 1556 questions posed to ChatGPT-4.0, correct answers were obtained with an accuracy of 69.84%, compared with ChatGPT-3.5 (45.70%, P=.0001) and with the top results of medical doctors (85.73%, P=.0001). Of the 13 tests, ChatGPT-4.0 exceeded the required ≥60% pass rate in 11 tests passed, and scored higher than the average of the human exam results. ChatGPT-3.5 was not spectacularly successful in nephrology exams. The ChatGPT-4.0 algorithm was able to pass most of the analysed nephrology specialty exams. New generations of ChatGPT achieve similar results to humans. The best results of humans are better than those of ChatGPT-4.0.

A cross-sectional analysis of reporting guideline and clinical trial registration policies in nephrology journals.

To determine the extent to which nephrology journals recommend and require reporting guideline adherence and clinical trial registration. Despite a rising disease burden, research published on chronic kidney disease (CKD) and the field of nephrology has failed to keep pace and is limited. To improve the quality of research in the field of nephrology, reporting guidelines have been developed to minimize such deficits in research quality. However, the extent to which nephrology journals require and use reporting guidelines in addition to clinical trial registration is unknown. Sixty-two Nephrology journals were selected through the 2021 Scopus CiteScore tool. Each journal's Instructions for Authors was assessed to determine endorsement of study design-specific reporting guidelines or clinical trial registration. Researchers used R (version 4.2.1) and RStudio to create data summaries of descriptive statistics for nephrology journal reporting guidelines. Clinical trial registration was required by 52% (32/62) of nephrology journals within our sample. The reporting guideline for clinical trials, CONSORT, was required by 17.74% (11/62) of journals. The EQUATOR Network was mentioned by 46.77% (29/62) of journals, while 9.67% (6/62) failed to mention the ICMJE. The reporting guideline for systematic review, PRISMA, was only required by 12.90% (8/62) of journals. When contacting journal editors, 9.67% (6/62) responded and 4.83% (3/62) provided clarifying information. Reporting guidelines and clinical trial registration are suboptimally required and recommended by nephrology journals. Their adoption may decrease bias and increase research quality. Thus, nephrology journals should consider a more complete endorsement of these safeguards.

Obesity and kidney disease

The obesity epidemic has led to an increased prevalence of obesity-related glomerulopathy (ORG). This disease is characte-rized by proteinuria, glomerulomegaly, progressive glomerulosclerosis and a decline in renal function. Individuals with obesity frequently display arterial hypertension and diabetes mellitus, exacerbating renal damage. The pathogenesis involves overactivation of the RAAS (Renin-Angiotensin-Aldosterone System), glomerular hyperfiltration, an inflammatory state with oxidative stress, hyperinsulinemia-induced hemodynamic alterations and lipotoxicity. Additionally, obesity represents a significant risk factor for kidney stone formation, further contributing to renal damage. The management of obesity-induced nephropathy primarily involves weight reduction strategies and optimized control of blood pressure and metabolic factors. Early detection is crucial to counteract the progression of kidney disease. Noteworthy, obesity significantly complicates the implementation of renal replacement procedures, including kidney transplantation, and increases the rate of complications. In summary, there are many reasons why obesity should gain attention in the field of nephrology.

#1469 Predicting mortality risk in incident dialysis patients using clinical predictors and patient-reported predictors

Abstract Background and Aims Prognostic prediction models can be used to identify dialysis patients that are at high risk of dying. By doing so, vulnerable patients can be monitored more closely and treatment can be intensified where needed. In addition, individualized predictions can help inform patients about their prognosis. Traditionally, prognostic models primarily rely on known clinical predictors such as age, comorbidities and laboratory markers. Although it is still unchartered territory in the field of nephrology, studies in other fields have shown that patient-reported predictors, like pain and fatigue, can be of use as predictors of survival. Predictive performance of current prognostic models for mortality risk amongst dialysis patients is subpar and we hypothesized that the addition of patient-reported predictors may improve predictions. Therefore, we aimed to develop a novel prognostic model for the prediction of two-year mortality in patients starting dialysis using both clinical predictors and patient-reported predictors. Method Data from the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD) were used to develop two prognostic models for the prediction of 2-year all-cause mortality in incident dialysis patients: a base model consisting of clinical predictors and an updated model containing additional patient-reported predictors. Missing data were handled using a tenfold multiple imputation with fully conditional specification. The imputation model included all candidate predictors as well as the outcome variable of 2-year mortality. Predictors for the base model were selected based on existing mortality models and clinical expertise. Patient-reported predictors to add to the base model were chosen based on availability in NECOSAD, clinical expertise and literature describing patient-reported predictors. The models were developed using multivariate logistic regression and their discriminative abilities were assessed by calculating the area under the curve (AUC). Results A total of 1956 patients from NECOSAD were used for the analyses. Of these, 447 (22.9%) died within two years after baseline (3 months after dialysis initiation). The base model contained the following predictors: age, sex, serum albumin, C-reactive protein, diabetes mellitus, hemoglobin, residual kidney function (GFR at 3 months), body mass index, cardiovascular disease, dialysis modality, malignancy and primary kidney disease. The discriminative abilities of the base model were moderate with a AUC of 0.79 (95% CI: 0.77-0.82). The base model was updated using the following patient-reported predictors: mental component score, physical component score, general health perception, number of symptoms, symptom burden (measured with the KDQOL instrument) depressive symptoms, fatigue and pain. The addition of the patient-reported predictors marginally improved the predictive performance of the model achieving an AUC of 0.81 (95% CI: 0.79-0.84). Conclusion The base model including clinical predictors was enhanced slightly by the addition of patient-reported predictors.

#2170 BET inhibitor nanotherapy reduces chronic kidney disease progression after ischemia-reperfusion injury

Abstract Background and Aims Targeting epigenetic mechanisms offer a potential breakthrough in addressing kidney diseases. Thus, inhibition of the bromodomain and extra-terminal (BET) domain proteins using the small molecule inhibitor JQ1, has shown promise in preclinical models of acute kidney injury (AKI) and chronic kidney disease (CKD). However, clinical translation faces hurdles like poor pharmacokinetics and side effects. To tackle this, we engineered liposomes loaded with JQ1 to enhance kidney drug delivery and minimize side effects. By optimizing the encapsulation of JQ1, our aim was to improve its efficacy compared to freely delivered JQ1 and reduce its cytotoxicity. Moreover, the therapeutic potential of this new nanoformulation to halt the acute renal ischemic injury and its transition to CKD will be explored. Method JQ1 was encapsulated in different types of lipid nanoparticles (NPs), and its effect was analyzed in vitro on the HK2 tubular epithelial line. Additionally, in vivo administration was carried out 1 hour after the induction of 45 minutes bilateral renal ischemia, and its effect was further analyzed at 24 h in the AKI setting or at 21 days for CKD. Non-encapsulated JQ1 was used as a control, and in vivo biodistribution studies were conducted using IVIS and fluorescent Cy5.5-labelled NPs. Damage markers, inflammatory burden and fibrosis development were analyzed through conventional techniques (Western blot, RT-PCR, IHC, flow cytometry), and functional parameters (BUN, Creatinine) were assessed through colorimetric assays. Results Three types of liposomal NPs were assayed to optimize JQ1 encapsulation, being the combined encapsulation of JQ1 in both the core and lipid layer the ones proving the best effectiveness. With an average hydrodynamic diameter of 78 nm, these NPs effectively reached the kidneys as assayed by in vivo biodistribution assays. In vitro assays performed on the HK2 cell line reveal their potential to inhibit TNF-α-induced inflammation. Importantly, in vivo dose-dependent studies determined that a 40 mg/kg dose was effective in post-ischemic acute kidney injury, showing a reduction in inflammatory (Il6, Csf2, Ccl2, Ccl5) and renal damage markers (Ngal), as well as reduced immune cell infiltration into the renal tissue of monocytes (CD45+CD11b+Ly6G−Ly6ChiF4/80low) and neutrophils (CD45+CD11b+Ly6GhiLy6Clow) quantified by flow cytometry. In accordance, decreased levels of serum BUN and Creatinine were detected in the group of mice treated with NPs-JQ1, indicating a better renal function. Of note, none of these effects were observed when the same dose of the unencapsulated inhibitor was used, demonstrating no effectiveness whatsoever. In the long term, by establishing an AKI to CKD transition model analysing fibrosis at 21 days post-ischemia induction, mice receiving a single dose of NPs-JQ1 early after damage displayed reduced fibrosis markers expression (α-SMA and Fibronectin), decreased collagen deposits quantified by Masson's Trichrome tissue staining and a partial recovery of the renal function. Conclusion The encapsulation of JQ1 in lipid nanoparticles is an effective strategy that allows for a decrease in the minimum effective dose of the drug. Due to its higher concentration and stability in the kidney, this therapy could be relevant in the treatment of renal pathologies and represents a significant step forward in the development of an innovative therapy for AKI-to-CKD transition. Our pioneering liposomal formulation not only expands the therapeutic potential of JQ1 but also addresses a significant barrier to its clinical translation in the nephrology field.

Hippocrate’s Contribution Exploring the Tashrih-Al-Nizam-E-Baul (Anatomy of Urinary System): A Comprehensive Review

Hippocrates' early contributions to the understanding of urinary physiology continue to inform contemporary research and medical practice, emphasizing the enduring relevance of his observations in the history of anatomical studies. Hippocrates significantly contributed to understanding the kidneys and urinary system, including the urethra. Furthermore, he recognized the tubes carrying urine from the kidneys to the bladder and the bladder's role in storing and expelling urine. However, his knowledge of blood vessels and the urethra remains limited. Hippocrates, a key figure in the development of clinical nephrology, outlined four renal diseases, including kidney colic, renal tuberculosis, renal vein thrombosis, bilateral papillary necrosis, and chronic suppurative renal infection. In addition, he also described bladder stones, urinary conditions like painful, difficult urination, incontinence, urinary retention, renal colic, and renal tuberculosis. Treatment for urinary disorders included warm applications, baths, plant-derived diuretics, diet, and incision over the kidneys. Urine symptoms included bubbles on the surface, colorless urine, and sudden increases of blood in urine. The Corpus Hippocraticum, a study of the urinary tract, has significantly contributed to urology, particularly in uroscopy and renal stone formation. The study of the urinary tract provides valuable insights into anatomy, physiology, etiology, and treatment of urological diseases. Hippocrates introduced the concept of high-risk operations, advising specialists to perform them and avoiding untrained healers. He differentiated between upper and lower urinary tract infections, identifying blood clots in urine as kidney discharge and bladder infections as bladder stones. This article highlights the fundamental contributions of Hippocrates to the field of nephrology and to the understanding of renal anatomy and shows how his teachings influenced later medical practices and advances in the understanding of renal function and pathology. This review aims to uncover the significance they hold in the historical literature, showcasing the historical impact of his pioneering work on the Tashrih-al-Nizam-e-Baul (Anatomy of Urinary System).

Analysis of thioredoxin 1 levels in a mouse model of unilateral renal ischemia-reperfusion injury

Kidney disease, acute and chronic, is associated with high morbidity and mortality. Currently, a major obstacle in the field of nephrology is the lack of novel and more sensitive biomarkers that would allow an early diagnose and a proper monitoring of disease progression. Oxidative stress and the increased production of reactive oxygen species (ROS) have been implicated in the pathophysiology of a variety of renal diseases. Proteins of the thioredoxin (Trx) family, among others thioredoxins (Trxs) and glutaredoxins (Grxs), represent one of the most important protective systems in the defense against ROS as well as in the repair of their intracellular effects. Thioredoxin 1 (Trx1) is a cytosolic redox protein that catalyzes the reduction of protein disulfides using the thiol groups of two cysteine residues on its CGPC active site. Trx1 is abundantly expressed in different segments of the nephron and has been shown to be released from cells under conditions of oxidative stress in vitro and in vivo. We hypothesized that renal IRI induces the release of Trx1 from cells into extracellular fluids such as serum and tubular fluid/urine and that Trx1 increase may correlate with the degree of damage in the kidney. We established an effective mouse model of unilateral renal ischemia-reperfusion injury (IRI) and studied Trx1 levels in the serum, urine, as well as in various nephron segments of mice following IRI or sham surgery. We compared different reperfusion times (4h, 8h, 16h, 24h, 48h, 96h, and 168h) to track Trx1 levels fluctuation over time. Serum levels of Trx1 increased 4h after renal IRI, while other markers such as blood urea nitrogen and creatinine remained low. Serum Trx1 showed a positive correlation with tubular injury score helping predict intrarenal damage over time. Additionally, immunohistochemistry studies revealed an increase in Trx1 signals in the proximal tubules and collecting ducts as well as a strong nuclear localization in the same nephron segments that became more intense by 96h, a time point characterized by an intense mitotic activity in the tubules. Between 16 and 24h, Trx1 appeared in the lumen of proximal tubules, however urinary levels of Trx1 did not significantly increase. Based on these findings we conclude that serum Trx1 may represent a novel biomarker for assessing renal damage. In addition to this, we hypothesize that intrarenal changes in Trx1 expression and localization might be related to the activation of regeneration mechanisms in the renal tubular epithelium. Further studies are needed to understand the role of Trx1 in the regeneration process after renal IRI. This work was funded by the Center of Integrative Mammalian Research of Ross University School of Veterinary Medicine and by a Startup funding from Long Island University. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.