Medicine and Pharmacology

Sort by

Case Report
Medicine and Pharmacology
Urology and Nephrology

Mario Bonomini

,

Valeria Vezzani

,

Michele Rossini

,

Lorenzo Di Liberato

,

Liborio Stuppia

,

Valentina Gatta

Abstract: Background and Clinical Significance: Autosomal dominant tubulointerstitial kidney disease caused by mutation in uromodulin gene (ADTKD-UMOD) is a rare kidney disorder characterized by progressive tubulointerstitial damage and slowly progressive loss of renal function. ADTKD is often under-recognized in the clinical setting. In fact, diagnosis of ADTKD-UMOD can be challenging due to its nonspecific symptoms, being confirmed by genetic testing only. Case presentation: We report the case of a 42-years-old male patient referred for evaluation of renal dysfunction, incidentally discovered in routine laboratory checks. He had no significant medical history and no known familiarity for kidney disease or gout. Physical examination was unremarkable. Renal dysfunction was confirmed, with serum creatinine 1.44 mg/dl and eGFR 59.5 ml/min/1.73 m2. Urinalysis was within physiological limits, with proteinuria of 75 mg/day. Uric acid was mildly elevated (7.5 mg/dl) without gout history. Other laboratory findings including autoantibodies were in normal range. Patient underwent kidney biopsy, which however was not diagnostic showing mild focal tubular atrophy and interstitial fibrosis without glomeruli involvement. Immunofluorescence staining was negative for complement and immunoglobulins. Based on above nonspecific findings, the patient was suspected of a possible diagnosis of ADTKD. Genetic investigation using a clinical exome next-generation sequencing approach identified a novel heterozygous missense variant in the UMOD gene (c.409T>C; p.Cys137Arg). Patient is in regular clinical-laboratory monitoring. After one year, his overall health is good, renal function stable with no proteinuria, uric acid mildly increased without gout attacks. Conclusions: Increased clinical awareness is crucial for detecting ADTKD-UMOD. Genetic testing can help to solve clinical diagnostic challenges in patients with unexplained decreased kidney function.

Article
Medicine and Pharmacology
Urology and Nephrology

Athina Varemmenou

,

Effimia Michail

,

Electra Kalaitzopoulou

,

Polyxeni Papadea

,

Marianna Skipitari

,

Marios Papasotiriou

,

Evangelos Papachristou

,

Dimitrios Goumenos

,

Christos D. Georgiou

Abstract: Oxidative stress (OS) is elevated in patients with end-stage kidney disease undergoing maintenance dialysis and contributes to increased cardiovascular risk. While kidney dysfunction and dialysis can generate OS, the acute effects of a single dialysis session remain unclear due to variability in study design and biomarkers used. In this observational study, blood samples from 68 hemodialysis patients were collected before and after a single session. Plasma levels of the reactive oxygen species marker superoxide (O2•) and OS-damage markers lipid hydroperoxides (LOOH), protein-bound malondialdehyde (PrMDA), protein-bound thiobarbituric acid reactive substances (PrTBARS), and protein carbonyls (PrCO) were measured. LOOH increased significantly by 50% post-dialysis, whereas PrMDA and PrTBARS decreased modestly by ~10%. No significant changes were observed in O2• or PrCO. Dialysis vintage correlated positively with LOOH, PrMDA, and PrTBARS, but not with O2• or PrCO. Patients undergoing low-flux hemodialysis exhibited a greater post-dialysis increase in LOOH than those treated with high-flux hemodialysis. No significant associations were found between OS markers and comorbidities or medication. The post-dialysis rise in LOOH, an early-formed and least accumulating lipid peroxidation marker, highlights its sensitivity to acute dialysis-related oxidative changes. The rising tendency of PrMDA and PrTBARS with dialysis vintage suggests cumulative OS over time.

Article
Medicine and Pharmacology
Urology and Nephrology

Zachary Corey

,

Aisha Rashid

,

Kreesha Shah

,

Billal Alamarie

,

Joseph Y. Clark

Abstract: Background/Objectives: To test the accuracy of two sound-based voided volume measurement applications compared to voided volume based on the measurement of pre- and post-void weight using a high-resolution scale. Methods: Seven male and four female volunteers participated. Male and female volunteers used the ProudP and Healthy Bladder-Voiding Diary mobile apps, respectively, to measure sound-based voided volume (SVV). The difference between pre- and post-void weight was calculated and converted to mL to be the true-voided volume (TVV) using a high-resolution scale. A Pearson correlation coefficient and paired t-test were completed. Results: Eighty-two voids were recorded (42M/40F). Median male participant age was 25.9 years. Male SVV ranged from 42-790 mL and TVV ranged from 61-880 mL. Mean difference was 39 mL (95% CI, 18-59 mL). SVV and TVV comparison revealed a strong correlation (r = 0.977, p < 0.0001). Equivalence testing indicated a p-value of 0.022. Median female participant age was 25.0 years. Female SVV ranged from 28-440 mL and TVV ranged from 10-682 mL. Mean difference was 53 mL (95% CI, 22-84 mL). Equivalence testing indicated a p-value of 0.330. SVV and TVV comparison revealed a correlation (r = 0.888, p < 0.0001). Conclusions: The male and female app have a strong correlation to true void volume (male > female app) and can be used by patients to track voided volume at home. The male app accurately measures voided volume within 60 mL from the TVV; however, the female app is less accurate.

Article
Medicine and Pharmacology
Urology and Nephrology

Yen-Ta Chen

,

Ke-Xin Huang

,

Chun-Yi Wu

,

Yi-Jang Lee

Abstract: Because human prostate cancer (PCa) grows slowly, establishing PCa tumor models is often time-consuming and unpredictable, limiting the efficiency of preclinical theranostic development. To address this, we used a non-viral PiggyBac transposon system to introduce triple reporter genes into PSMA-expressing C4-2 cells, generating orthotopic and subcutaneous xenograft models that allow noninvasive, real-time monitoring of PCa progression and treatment response. Reporter-engineered C4-2 3R cells were produced by co-transfecting constructs encoding the reporter cassette and PB transposase, followed by enrichment using fluorescence microscopy and FACS, and implanted orthotopically or subcutaneously into mice. Tumor growth and response to a single 2 Gy X-ray dose followed by 14.8 MBq 177Lu-PSMA-617, or to each monotherapy, were monitored weekly using IVIS imaging and confirmed by tumor dissection and H&E staining; PSMA expression was assessed by western blot and 18F-PSMA-1007 PET/CT. C4-2 3R cells successfully expressed mRFP, luc2, and HSV1-tk, generating detectable orthotopic bioluminescence within one week and persisting for at least five weeks, whereas subcutaneous implantation produced only transient luc2 signals with no tumor formation. X-ray exposure did not increase total PSMA levels but induced PSMA relocation to the cell membrane. Combined external beam radiotherapy (EBRT) and 177Lu-PSMA-617 treatment produced the highest 18F-PSMA-1007 uptake and strongest tumor suppression, with minimal residual tumor mass compared to single-treatment or control groups. Overall, the C4-2 3R reporter model enables faster, reliable monitoring of slow-growing PCa tumors and provides an effective platform for evaluating PSMA-targeted therapies with or without the combination of EBRT.

Article
Medicine and Pharmacology
Urology and Nephrology

Saed Sayad

,

Mark Hiatt

,

Hazem Mustafa

Abstract: Background. Benign prostatic hyperplasia (BPH) is a common condition in aging men that causes urinary symptoms. Current treatments have limitations, necessitating new approaches. Single-cell RNA sequencing (scRNA-seq) provides detailed insights into cellular activity, while Artificial Intelligence (AI) techniques such as large language models (LLMs) can analyze complex queries to identify natural substances that may downregulate overexpressed genes, providing a novel approach for the treatment of BPH. Method. Single-cell RNA sequencing (scRNA-seq) data (GSE226237) were obtained from the National Institutes of Health (NIH) Gene Expression Omnibus (GEO) repository. Gene expression profiles from three large prostates were compared with those from three small prostates to identify differentially expressed genes associated with larger prostate tissue. These genes were evaluated as potential therapeutic targets. Candidate natural compounds that may modulate the activity of overexpressed genes were generated using a structured prompt submitted to the large language model ChatGPT. Results. Single-cell RNA sequencing analysis comparing three large prostates with three small prostates identified distinct gene expression differences associated with prostate enlargement. Several genes involved in immune regulation and cellular structure were downregulated in large BPH, while genes related to epithelial integrity, protein synthesis, and proliferation such as SLC14A1, KRT5, KRT14, KRT15, PRAC1, CSTA, RPL36A, GABARAP, RPS17, and FXYD3 were upregulated. To explore potential therapeutic interventions, these overexpressed genes were analyzed using ChatGPT 5.4 to identify candidate natural compounds capable of modulating their activity. The resulting gene/compound associations include natural products such as resveratrol, curcumin, epigallocatechin gallate (EGCG), genistein, quercetin, sulforaphane, berberine, ashwagandha, and lycopene, highlighting promising directions for natural product based modulation of BPH-associated gene expression. Conclusions. These findings highlight molecular changes in BPH progression and show how single-cell transcriptomics reveals gene expression linked to epithelial proliferation, immune modulation, and metabolism. Integrating AI with omics data offers a framework for identifying potential natural therapeutics, though these AI-generated recommendations remain hypothesis-generating rather than definitive.

Review
Medicine and Pharmacology
Urology and Nephrology

Kumar Digvijay

,

Henrik Birn

Abstract: Background and Objectives: Renal transplantation is the optimal treatment for end-stage renal disease, yet long-term allograft survival remains threatened by immune-mediated injury and chronic nephropathy. Conventional monitoring using serum creatinine and protocol biopsy suffers from limited sensitivity for early, subclinical injury. Liquid biopsy-based biomarkers offer a non-invasive alternative. Materials and Methods: We conducted a systematic narrative review of studies published between January 2010 and December 2024, identified through PubMed, Scopus, and Web of Science. Results: Extracellular vesicles carry injury-specific molecular cargo reflecting the biological state of tubular, glomerular, and endothelial cells; urinary EV CXCL9 protein and exosomal CD3ε mRNA have demonstrated AUC values of 0.81–0.88 for detection of T-cell-mediated rejection. Donor-derived cell-free DNA quantifies global graft cell death; the FDA-cleared AlloSure assay achieves AUC 0.74 and NPV 84% at the validated ≥1.0% threshold established in the DART trial. Donor-specific antibodies—particularly complement-fixing C1q-positive DSA—confer markedly inferior 5-year graft survival compared with DSA-negative recipients (54% versus 93%). Multi-biomarker panels integrating all three modalities yield AUC 0.88–0.94 and NPV 91–95%. Conclusions: The integration of EV, ddcfDNA, and DSA monitoring into a unified surveillance framework offers a clinically meaningful advance over creatinine-based monitoring. Prospective randomized trials confirming improvement in long-term allograft survival will be the critical next step.

Article
Medicine and Pharmacology
Urology and Nephrology

Vanessa Talavera-Cobo

,

Jose Enrique Robles-Garcia

,

Francisco Guillen-Grima

,

Andres Calva-Lopez

,

Mario Tapia-Tapia

,

Luis Labairu-Huerta

,

Francisco Javier Ancizu-Marckert

,

Laura Guillen-Aguinaga

,

Daniel Sanchez-Zalabardo

,

Bernardino Miñana-Lopez

Abstract: Background: An accurate D’Amico risk stratification is mandatory for prostate cancer (PCa) management. The purpose of this proof-of-concept study was to establish a methodological framework of integrating validated clinical nomograms with strict data-quality governance in order to generate reliable artificial neural networks (ANN), even when the sample is small. Methods: We performed a retrospective analysis of a curated cohort of 49 patients from one center. A multilayer perceptron (MLP) was trained using 11 variables, including the ISUP biopsy grade and Briganti nomogram. Model development was guided by a proactive data-quality protocol based on FAIR principles, with stringent checks for accuracy, consistency and validity to ensure data were “AI-ready”. A sensitivity analysis was conducted on three data partitioning scenarios (20/80, 34/66 and 39/61). Results: From a starting pool of 76 patients, the FAIR-based data governance architecture was applied to create a highly selected cohort of 49 patients. A multilayer perceptron (MLP) trained on this “AI-ready” dataset achieved a mathematically perfect but clinically uninterpretable discrimination (AUC 1.000) for High vs. Intermediate risk groups on a small internal test set (N=9 for the 20/80 split). However, this complete accuracy is a best-case scenario reflecting the high data quality, not proof of generalizable clinical utility, as the large confidence interval (66.4-100%) and the requirement to exclude instances with unusual attributes for model validation (as described in the methods) highlight. Conclusions: The main contribution of this proof-of-concept study is the effective illustration of a strict, repeatable data governance approach for producing “AI-ready” urological datasets. Although the MLP demonstrated a robust internal signal for risk discrimination, its flawless accuracy is an ideal, non-generalizable situation. The most important deliverable that needs external validation is the framework, not the model’s performance metrics.

Case Report
Medicine and Pharmacology
Urology and Nephrology

Yoshihiro Ono

,

Yoshiyuki Miyazawa

,

Seiji Arai

,

Yoshitaka Sekine

Abstract: Multilocular intratesticular cysts are uncommon benign lesions. We report a case associated with testicular microlithiasis in an 85-year-old man presenting with painless enlargement of the left scrotum. Ultrasonography revealed a multilocular cystic lesion with a 3.0-cm main cyst and several adjacent smaller cysts showing posterior acoustic enhancement without mural irregularity or solid components. Bilateral microlithiasis and small epididymal cysts were also detected, and serum tumor markers were normal. The lesions remained stable during 36 months of follow-up. Recognition of the characteristic ultrasonographic features of benign intratesticular cysts is important to avoid unnecessary surgical intervention.

Review
Medicine and Pharmacology
Urology and Nephrology

Olga Balafa

,

Marianthi Androulaki

Abstract: Chronic kidney disease (CKD) is a major global health burden associated with substantially increased risks of morbidity and mortality. Cardiovascular disease remains the leading cause of death across all stages of CKD. Over the past decades, several pharmacologic therapies—including renin–angiotensin system inhibitors, sodium–glucose cotransporter-2 inhibitors, mineralocorticoid receptor antagonists, glucagon-like peptide-1 receptor agonists, and lipid-lowering agents—have demonstrated substantial cardio-nephroprotective benefits and are recommended in international guidelines. However, real-world implementation of these therapies remains incomplete, and emerging evidence highlights important sex-based disparities in prescribing patterns. Although CKD is more prevalent in women worldwide, women with CKD are consistently less likely than men to receive guideline-directed cardioprotective and nephroprotective medications. This treatment gap spans both traditional therapies, such as angiotensin-converting enzyme inhibitors and statins, and newer agents with proven outcome benefits. Women are less likely to initiate treatment, less likely to receive high-intensity or target doses, and less likely to achieve recommended blood pressure and lipid goals. Importantly, the presence of CKD attenuates the usual female survival advantage, and the relative excess cardiovascular risk associated with CKD may be particularly pronounced in women. The under-prescription of cardio-renal therapies in women with CKD reflects a complex interplay of factors. These include older age at presentation, higher reported rates of adverse drug reactions, concerns regarding tolerability and safety in advanced kidney disease, therapeutic inertia, underestimation of cardiovascular risk, and persistent underrepresentation of women in clinical trials. Biological differences in pharmacokinetics and pharmacodynamics, as well as structural and system-level barriers, further contribute to inequities in care. Addressing these disparities requires improved risk recognition, sex-informed prescribing practices, enhanced representation of women in clinical research, and implementation strategies that incorporate sex-disaggregated performance metrics. Reducing treatment gaps is essential to improving cardiovascular and renal outcomes and to achieving equitable, precision-based care for women with CKD.

Article
Medicine and Pharmacology
Urology and Nephrology

Aaron Huang

,

Wayne C. Waltzer

,

Michael Hung

,

Frank Darras

,

Adam M. Kressel

,

Victor Romanov

Abstract: Background and Objectives: Bladder cancer (BCa) is characterized by high rates of re-currence and progression, underscoring the need for reliable non-invasive biomarkers. Circular RNAs (circRNAs) are covalently closed non-coding RNAs generated by back-splicing and are stable in biological fluids, including urine. Increasing evidence im-plies circRNAs in BCa pathogenesis; however, identification of clinically relevant circRNAs remains labor-intensive. This study aimed to streamline circRNA selection and identify functionally relevant urinary circRNAs in BCa. Methods: Using a database-screening ap-proach, we identified circRNAs with high predicted affinity to miR-101-3p, a tu-mor-suppressive microRNA in BCa. Candidate circRNAs were prioritized based on: (i) strong miR-101-3p binding potential; (ii) derivation from genes involved in BCa tumor-igenesis; and (iii) origination from exonic or long non-coding RNA sequences. The po-tential contribution of Argonaute-2 (Ago2) binding sites to circRNA–miRNA complex sta-bility was also evaluated. Expression levels were assessed in urine samples and BCa cell lines, and functional relevance was examined using molecular and cellular assays. Results: circCIAO1(5) and circMALAT1 fulfilled all prioritization criteria and exhibited distinct Ago2-binding site profiles. Both circRNAs were upregulated in urine from BCa patients and in aggressive BCa cell lines and showed differential expression between remission and recurrent disease. CircCIAO1(5) demonstrated higher-affinity binding to miR-101-3p, while RNA immunoprecipitation confirmed interactions of both circRNAs with miR-101-3p and Ago2. Functional assays revealed enhanced proliferation, motility, and invasion upon circRNA expression, consistent with miR-101-3p sequestration and derepression of miR-101-3p target oncogene-EZH2. Conclusions: circCIAO1(5) and circMALAT1 represent promising urinary biomarkers for BCa, illustrating the value of bioinformatics-guided circRNA discovery and significance of circRNA-mediated regulatory mechanisms in BCa biology.

Article
Medicine and Pharmacology
Urology and Nephrology

Kelly Chong

,

Igor Litvinovich

,

Christos Argyropoulos

,

Yiliang Zhu

Abstract: Background: Rising kidney discard rates and uncertainty around accepting higher-risk donor kidneys highlight the need for decision-support tools that integrate donor and recipient factors and communicate risk in ways that are understandable and usable at the time of offer. Conventional indices (e.g., KDPI/KDRI) provide population-level signals but do not deliver individualized, cognitively accessible information aligned with real-time clinical workflows. Objective: To describe how key transplant stakeholders—patients, coordinators, and providers—interpret and evaluate a prototype Kidney Risk Calculator app that generates donor–recipient–specific survival projections, and to identify the content, format and features, and functionality needed for clinically meaningful, patient-centered decision support. Design: Qualitative study using focus groups and individual interviews. Setting: University of New Mexico Hospital (UNMH) Kidney Transplant Center. Participants: Five patients (four transplant candidates and one patient advocate), three transplant coordinators, and five transplant providers (3 attending physicians and 2 advanced practice practitioners). Methods: Semi-structured sessions (45–60 minutes) with 13 stakeholders (patients, coordinators, and providers) included a live app demonstration and explored usability, interpretability, contextual information needs, perceived clinical utility, and anticipated barriers/facilitators. Data were collected via one coordinator focus group, one patient focus group, and five provider interviews; sessions were recorded, transcribed, de-identified, and analyzed using inductive reflexive thematic analysis. Results: Stakeholders affirmed the value of personalized projections as an adjunct to clinical judgment, particularly for higher-risk offers. Participants prioritized: 1) Content—clear education on hepatitis C virus (HCV)-positive donors and Public Health Service (PHS) risk criteria; plain explanations of Calculated Panel Reactive Antibody (CPRA); and framing that makes time on dialysis and trade-offs salient; 2) Format & Features—plain-language narratives, percentages rather than decimals, simple visuals, minimized acronyms, U.S. customary units, and a stepwise (“TurboTax‑like”) input flow preferred by patients; and 3) Functionality—attention to cognitive load and workflow alignment, given phone-based time pressure and digital-access constraints. Stakeholders emphasized that the tool’s value hinges on clarity, context, and workflow fit—not predictive accuracy alone. Limitations: Single‑center, formative prototype study with a modest sample; findings are illustrative and may have limited transferability. Participants reacted to a demonstration rather than using the app during real‑time offer calls; convenience/email recruitment and Zoom‑only English sessions may introduce selection bias; team involvement in app development may contribute residual confirmation bias despite mitigation. Conclusions: Early stakeholder input suggests that a kidney offer decision support tool should integrate individualized predictions with plain language explanations, contextual information that addresses common misconceptions, workflow aligned functionality, and accessible outputs. Tools designed and implemented with these features may support acceptance of medically complex kidneys and may help reduce offer bypass and organ discard. These inferences reflect stakeholder perceptions in a formative qualitative study and warrant prospective evaluation.

Article
Medicine and Pharmacology
Urology and Nephrology

Lorenzo Santodirocco

,

Luca A. Morgantini

,

Marwan Alkassis

,

Jinchun Qi

,

Simone Crivellaro

Abstract: Background/Objectives: Urinary continence recovery after robot-assisted radical prostatectomy (RARP) follows a progressive trajectory that is often simplified into binary outcomes. Modeling continence recovery as an ordered process may better reflect post-operative functional patterns and identify clinically relevant predictors. Methods: We retrospectively analyzed 180 patients undergoing extraperitoneal single-port RARP. At 6 months, continence recovery was classified into three ordered categories: early continence, late continence, and persistent incontinence. Multivariable ordinal logistic regression was used to identify independent predictors of continence recovery. The primary model included nerve-sparing (NS) status, postoperative complications, age, and prostate volume. Sensitivity analyses were performed by sequentially replacing prostate volume with body mass index, surgical case number, or preoperative prostate-specific antigen (PSA). An interaction between NS and age group was also tested. Results: NS surgery was the strongest independent predictor of favorable continence recovery (p < .001), followed by absence of postoperative complications (p = .003). Younger age and larger prostate volume were also independently associated with improved continence recovery. Sensitivity analyses confirmed the robustness of the primary model, as replacement of prostate volume with body mass index, surgical case number, or PSA did not improve model performance and did not alter the effect of NS surgery. No significant interaction between NS and age group was observed. Conclusions: Continence recovery after extraperitoneal RARP is primarily driven by NS surgery and an uncomplicated postoperative course, with age and prostate volume providing additional refinement. Modeling continence as an ordinal outcome offers a clinically meaningful framework for evaluating functional recovery after prostatectomy.

Article
Medicine and Pharmacology
Urology and Nephrology

Antonio Benito Porcaro

,

Maria Angela Cerruto

,

Alberto Bianchi

,

Francesco Artoni

,

Francesca Montanaro

,

Alberto Baielli

,

Filippo Caudana

,

Andrea Franceschini

,

Alessandro Veccia

,

Riccardo Rizzetto

+3 authors

Abstract: Background/Objectives: To evaluate index density (Id) of percentage of biopsy positive cores (BPC), the ratio of BPC on prostate volume (Id-BPC), as a prognostic factor of clinical prostate cancer (PCa) progression after robotic surgery. Methods: The study included 1047 consecutive patients who were treated in a period ranging from January 2013 to December 2021. The risk of disease progression, which was defined as at least the occurrence of biochemical and/or loco-regional and metastases recurrence, was evaluated by Cox’s proportional hazards. Results: Disease progression, which occurred in 237 (22.6%) patients after a mean (95% CI) follow-up of 82.5 (80.1 – 84.9) months, was predicted by Id-BPC which was stronger than BPC itself; accordingly, as biopsy tumor load densities increased, so patients were more likely to experience disease progression not only after adjusting for clinical variables (hazard ratio = 1.55; 95% CI: 1.32 – 1.83; p < 0.0001), but also for un-favorable pathology (hazard ratio = 1.37; 95% CI: 1.21 – 1.56; p < 0.0001), as well. Con-clusions: The risk of clinical PCa progression after robotic surgery was independently predicted by Id-BPC which was stronger than BPC; accordingly, as Id-BPC increased so patients were more likely to experience disease progression; likewise, Id-BPC could be a useful clinical marker of cancer biology.

Article
Medicine and Pharmacology
Urology and Nephrology

Veysel Baran Tomar

,

Omer Faruk Akcay

,

Asil Demirezen

,

Taha Enes Cetin

,

Ayser Seda Hasdemir

,

Cansu Dagasan

,

Ozant Helvacı

,

Kadriye Altok

,

Yasemin Erten

Abstract: Peritoneal membrane–related technical failure remains a major limitation of peritoneal dialysis (PD), yet simple predictive biomarkers are lacking. The uric acid–to–HDL cholesterol ratio (UHR) is an integrative marker of metabolic-inflammatory burden. This retrospective cohort study included 214 adult patients who initiated PD between 1997-2025 at a tertiary center. Baseline UHR was calculated from laboratory measurements obtained within three months after PD initiation. The primary outcome was peritoneal membrane–related technical failure, defined as permanent transfer to hemodialysis due to ultrafiltration failure, inadequate solute clearance, or progressive membrane dysfunction. Among 214 patients, 62 (29%) developed membrane failure during follow-up. A UHR cut-off value of 14 was identified by ROC analysis (AUC 0.644). In multivariable Cox regression, UHR &gt;14 was independently associated with increased risk of membrane failure (HR 1.836, 95% CI 1.040–3.241, p = 0.036). A history of kidney transplantation prior to PD initiation also emerged as a strong independent predictor (HR 3.971, 95% CI 1.668–9.455, p = 0.002). Elevated baseline UHR is independently associated with peritoneal membrane–related technical failure. As a simple, inexpensive, and routinely available biomarker, UHR may support early risk stratification and individualized management in PD patients.

Article
Medicine and Pharmacology
Urology and Nephrology

Miroslava Benkova-Petrova

,

Alexander Petrov

,

Pavel Abushev

,

Plamen Kirilov

,

Simeon Marinov

,

Doroteya Malinova

,

Stanila Stoeva-Grigorova

Abstract: Background: Clear cell renal cell carcinoma (ccRCC) constitutes 75–80% of all renal cell carcinomas and exhibits aggressive behavior with high metastatic potential. Common metastatic sites include lungs, bones, lymph nodes, and liver, while urinary bladder involvement is exceedingly rare. Early detection of atypical metastases is critical for risk stratification, surgical planning, and systemic therapy selection. Methods: We report a 69-year-old male presenting with recurrent, painless gross hematuria and dysuria. Contrast-enhanced computed tomography revealed a left renal mass with bilateral pulmonary nodules, regional lymphadenopathy, and a bladder lesion. The patient underwent transurethral resection (TUR) of the bladder lesion, followed by robot-assisted left nephro-adrenalectomy with para-aortic lymphadenectomy. Histopathology and immunohistochemistry (PAX8+, CD10+, CAIX+, CK7–, GATA3–) confirmed ccRCC with synchronous bladder metastasis. Postoperatively, combined immune checkpoint inhibitor (ICI) therapy and tyrosine kinase inhibitors (TKIs) were initiated. Results: TUR provided symptomatic relief and diagnostic confirmation. Robot-assisted surgery enabled precise, oncologically safe excision of the primary tumor and regional metastases with minimal blood loss and no perioperative complications. Pathological staging was pT3aN1M1, ISUP grade 2, with lymphovascular invasion, confirming advanced disease requiring systemic therapy. Early initiation of ICI plus TKI therapy targeted residual micrometastases to potentially prolong survival. Conclusions: This case highlights the rare occurrence of ccRCC with synchronous bladder metastasis and underscores the importance of comprehensive imaging, detailed morphologic and immunohistochemical evaluation, and a multidisciplinary approach. Robot-assisted cytoreductive surgery combined with modern systemic therapy represents an effective strategy for advanced ccRCC, emphasizing the need for individualized treatment and long-term follow-up in atypical metastatic scenarios.

Article
Medicine and Pharmacology
Urology and Nephrology

Selçuk Yazıcı

,

Gülay Turan

,

Merve Akış Yılmaz

,

Büşra Aslan Akyol

,

Caner Yıldırım

,

Oğuzhan Korkut

Abstract: Background: Cisplatin is a potent chemotherapeutic agent whose clinical application is frequently limited by severe nephrotoxicity. N-acetylserotonin (NAS), a precursor of melatonin and a selective agonist of the TrkB receptor, has demonstrated significant antioxidant and neuroprotective properties. This study aimed to evaluate the potential renoprotective effects of NAS against cisplatin-induced acute kidney injury (AKI) in a rat model. Methods: Thirty-five Wistar Albino rats were divided into five groups: Control, Sham, NAS (5 mg/kg), Cisplatin (CP; 7.5 mg/kg), and CP+NAS. NAS was administered daily for seven days, while cisplatin was given as a single dose on the fourth day. Renal function was assessed via serum urea and creatinine. Oxidative stress markers, including Malondialdehyde (MDA), Superoxide Dismutase (SOD), Total Antioxidant Status (TAS), and Total Oxidant Status (TOS), were measured in kidney tissue. Comprehensive histopathological evaluations were performed to assess tubular and glomerular damage. Results: Cisplatin administration significantly increased serum creatinine levels and induced severe histopathological damage (p< 0.05). While cisplatin reduced SOD and TAS levels, NAS treatment showed a trend toward biochemical recovery without reaching statistical significance in oxidative markers. Notably, NAS administration significantly ameliorated cisplatin-induced histopathological lesions, specifically reducing tubular epithelial loss, glomerular degeneration, interstitial inflammation, and vacuolization (p< 0.05). Conclusions: Our findings indicate that NAS exerts a profound structural protective effect against cisplatin-induced renal injury. The preservation of renal parenchyma, despite modest systemic biochemical shifts, suggests that NAS-mediated protection may involve localized TrkB-dependent pro-survival signaling and stabilization of mitochondrial integrity. NAS represents a promising therapeutic candidate for mitigating chemotherapy-induced nephrotoxicity.

Case Report
Medicine and Pharmacology
Urology and Nephrology

Yuni Guo

,

Fanghui Ye

,

Molu Ban

,

Hong Yuan

,

Qingxin Huang

Abstract: This report details a case of IgA nephropathy (IgAN) with nephrotic syndrome (NS), preceded by symptoms of acute pharyngitis. Despite mild renal pathological lesions, the condition proved refractory to conventional pharmacological interventions, including immunosuppressants and corticosteroids. An empiric tonsillectomy led to clinical remission of the nephrotic syndrome, although hypercholesterolemia persisted for approximately four years. This residual hypercholesterolemia was subsequently resolved through targeted lifestyle modifications involving exercise and dietary adjustments. Based on this diagnostic and therapeutic journey, we emphasize the critical importance of individualized etiological analysis and tailored interventions in managing refractory IgAN. Furthermore, this case serves as a paradigm, highlighting the potential value of a meticulous, etiology-oriented approach in the management of complex chronic diseases beyond nephrology.

Article
Medicine and Pharmacology
Urology and Nephrology

Nikolaos Kostakopoulos

,

Konstantinos Evmorfopoulos

,

Gianluca Maresca

,

Grigorios Athanasiadis

,

Athanasios Kostakopoulos

,

Konstantinos Dimitropoulos

Abstract: Background/ Objectives Simultaneous robotic-assisted radical cystectomy (RARC) and nephroureterectomy (RARNU), offers a minimally invasive alternative to open approach, for patients with synchronous bladder and upper urinary tract cancers, as well as in selected benign conditions. This study presents our single-center experience and includes a review of the relevant literature. Methods All patients undergoing combined RARC and RARNU between 2016 and 2023 were retrospectively identified. Clinical and demographic data—including preoperative pathology, operative and re-docking time, estimated blood loss, complications (Clavien-Dindo system), surgical margins, recurrence, morbidity, and follow-up—were collected. A rapid literature review was also conducted. Results From 2016 to 2023, 10 patients (mean age 67.4 years, range 56–77) underwent combined RARC and RARNU for upper/lower tract urothelial malignancy. Mean re-docking time was 68.2 min (range 51–100), operative time 524.5 min (range 380–690), and blood loss 427 cc (range 75–1170). A Pfannenstiel incision was used for en bloc specimen extraction, with no complications or incisional hernias. One case was converted to open surgery, and two required extracorporeal diversion. Postoperatively, five Grade 2, one Grade 3, and one Grade 5 complications were reported. All surgical margins were negative. Mean hospital stay was 11.5 days (range 5–29). At a mean follow-up of 21.7 months, one patient became dialysis-dependent and one experienced recurrence requiring further surgery. Literature review included 74 patients with comparable outcomes. Conclusions Combined RARC and RARNU is a feasible, minimally invasive option for selected patients. Although technically demanding, it offers acceptable safety and should be performed in high-volume, specialized centers.

Article
Medicine and Pharmacology
Urology and Nephrology

Alfred Josef Gagel

,

Gerhard Wiesen

,

Stefano Stuard

,

Bernard Canaud

Abstract: Background: Online hemodiafiltration (HDF) is currently the most advanced kidney replacement therapy that combines diffusive and convective solute removal to clear uremic toxins, particularly larger molecular compounds. Effective HDF therapy is contingent on achieving a high total convective volume, impacting patient survival. Objectives: To explore advancements in dialysis membrane materials, dialyzer design and related monitoring technology that enhance HDF performance, particularly in removing middle and larger uremic toxins, and to examine the challenges related to membrane hemocompatibility, permeability, and optimizing clinical performances. Methods: This review synthesizes findings on materials used in dialysis membranes, advanced technology to spin fibers and dialyzer design, and related monitoring technology emphasizing their effects on hydraulic permeability, solute clearance and hemocompatibility. It also links them to clinical studies that have proved the beneficial impact of convective volume on patient outcomes. Results: Synthetic polymer membranes, such as polysulfone and polyethersulfone together with advances in hollow-fiber spinning technology, have improved the middle molecules clearance through optimized pore sizes and higher ultrafiltration coefficients. When combined with advanced hemodiafiltration machines designed to optimize convective volume and dialysate use, that maximizes convection efficiency while maintaining patient safety comparable to conventional hemodialysis. The development of super-high-flux membranes in a revisited internal filtration approach, known as expanded hemodialysis enhances toxin removal but can lead to albumin loss and inflammatory responses if ultrapure dialysate is not provided. Achieving the right balance in membrane design is essential to delivering efficient and high-volume HDF while minimizing potential adverse effects. Conclusion: Advanced dialysis membranes and HDF monitoring technologies significantly enhance the efficacy of HDF by enabling efficient removal of middle and large uremic toxins. Continued innovation in materials science and dialyzer membrane architecture is essential to further optimize patient outcomes and to consolidate HDF as a mainstream renal replacement therapy.

Review
Medicine and Pharmacology
Urology and Nephrology

Andrei Andreșanu

,

Constantin Gîngu

,

Mihaela Roxana Oliță

,

Mihai Adrian Dobra

,

Bogdan Marian Sorohan

,

Bogdan Obrișcă

,

Dragoș Eugen Georgescu

,

Mihai Adrian Eftimie

,

Ioanel Sinescu

Abstract: Background and Objectives: Paraneoplastic hypercalcemia represents a rare but clinically significant complication of penile squamous cell carcinoma (PSCC), with limited evidence available. This systematic review aimed to comprehensively evaluate the pathophysiological mechanisms, clinical presentation, therapeutic strategies and prognostic outcomes of tumor-induced hypercalcemia in PSCC. Methods: A comprehensive literature search was conducted across PubMed/MEDLINE and Scopus databases from inception to December 2024. Cases were included if they documented histopathologically confirmed PSCC with biochemically verified hypercalcemia and objective evidence of paraneoplastic etiology. Data extraction encompassed tumor characteristics, hypercalcemia severity, mechanistic classification, therapeutic interventions and survival outcomes. Analysis followed PRISMA 2020 guidelines adapted for descriptive synthesis. Results: Twelve published cases spanning six decades (1965-2024) met inclusion criteria. The median age at presentation was 56 years, with 91.6% of patients presenting with advanced disease. Severe hypercalcemia (≥14 mg/dL) occurred in 66.7% of cases, with a median calcium level of 15.45 mg/dL. Three distinct pathophysiological mechanisms were identified: PTHrP-mediated humoral hypercalcemia, bone metastasis-associated hypercalcemia and tumor burden-mediated hypercalcemia. Despite biochemical correction, median overall survival was 9 weeks following hypercalcemia diagnosis. Conclusions: Paraneoplastic hypercalcemia in PSCC represents a rare metabolic emergency. While aggressive management can achieve biochemical correction, the occurrence of hypercalcemia uniformly indicates advanced tumor biology with limited survival benefit. Early recognition and prompt multidisciplinary intervention remain essential for symptomatic relief and quality of life preservation. Future prospective studies are needed to better characterize optimal management strategies and refine prognostic models.

of 22

Prerpints.org logo

Preprints.org is a free preprint server supported by MDPI in Basel, Switzerland.

Subscribe

Disclaimer

Terms of Use

Privacy Policy

Privacy Settings

© 2026 MDPI (Basel, Switzerland) unless otherwise stated