Search Results (1,532)

Background/Objectives: Diabetes mellitus and hypertension are the first and second most common causes of chronic kidney disease, respectively. Despite improvements in elucidating the pathophysiology behind these diseases and the expansion of the therapeutic armamentarium, the knowledge about the implicated genes, epigenetics, and biological pathways is limited. Methods: We sought to define diabetic nephropathy-specific and hypertensive nephropathy-specific gene signatures in human glomeruli through computational systems biology approaches. Results: Gene expression data of human glomeruli from patients with diabetic kidney disease (DKD) and hypertensive nephropathy (HTN) were collected and compared to gene expression patterns from healthy kidneys. Pathways were identified with functional enrichment analysis of DEGs. Transcription factor enrichment analysis, protein–protein interaction network expansion, and kinase enrichment analysis were also performed. Finally, novel drugs and small-molecule compounds that may reverse the kidney-specific phenotype of these disorders have been identified. Conclusions: These data suggest putative expansion of the therapeutic armamentarium in DKD and HTN, underscoring that understanding the molecular mechanisms occurring within tissue in kidney diseases may guide personalized therapy. Full article

Background/Objectives: Kidney donation remains a critical component of addressing end-stage renal disease. This study examines differences in awareness, willingness to donate, and concerns related to kidney donation among medical and non-medical university students. By comparing these groups within the context of Croatia’s presumed-consent system for organ donation, the study provides insights into how educational backgrounds shape attitudes in a setting with high transplantation rates but limited data on young adults. Methods: A cross-sectional observational study targeted at medical and non-medical university students in Croatia. Data were collected from 640 participants via a self-administered, close-ended, structured questionnaire with 33 items divided across three sections. Responses were analyzed using IBM SPSS Statistics program (v. 30.0), to identify significant differences. Due to the cross-sectional design, causal relationships could not be inferred. Results: Overall, 190 students (28.7%) reported willingness to donate a kidney during their lifetime, which was more common among medical students (N = 59; 39.0%) than non-medical students (N = 131; 26.8%). Collectively, willingness to donate postmortem was high in both groups (N = 527; 82.3%), as was willingness in a brain-dead state (N = 448; 70.0%). Medical and non-medical students mostly cited perceived health risks as a concern and concerns related to surgical complications. Regarding information sources, 33.2% of students reported inadequate knowledge of kidney donation, with social media and internet searches cited more frequently than healthcare professionals. Conclusions: Our findings indicate that medical and non-medical students exhibit distinct gaps in knowledge, risk perception and willingness toward kidney donation. Within Croatia’s presumed-consent framework, these findings highlight the importance of targeted educational strategies to support informed decision-making among future generations. Full article

Chronic kidney disease (CKD) accelerates vascular dysfunction and cardiovascular disease, partly through the accumulation of the uraemic toxin indoxyl sulphate (IS). Thrombospondin-1 (TSP1) and its receptor CD47 have been implicated in vascular pathology, but their role in CKD-associated vascular remodelling is unknown. We investigated the contribution of TSP1–CD47 signalling to vascular smooth muscle cell (VSMC) dysfunction in CKD. Human aortic VSMCs (hVSMCs) were exposed to IS, TSP1, or plasma from patients with CKD. CKD was induced in wild-type (WT) and CD47-deficient (CD47KO) mice using 5/6 nephrectomy. Vascular changes were assessed by histology, immunohistochemistry, and molecular analyses. IS, TSP1, and CKD plasma increased TSP1 expression in hVSMCs, reduced proliferation, elevated β-galactosidase activity, and activated phosphorylated ERK1/2 and cytoplasmic aryl hydrocarbon receptor. These effects were attenuated by CD47 blockade. CKD plasma further enhanced IS- and TSP1-induced senescence. In vivo, 5/6 nephrectomy induced aortic wall thickening in WT but not in CD47KO mice. Aortic pERK1/2 was reduced in CD47KO mice despite persistent TSP1 upregulation. IS and TSP1 promote VSMC senescence through CD47-dependent ERK1/2 and AhR signalling. CD47 deletion protects against CKD-induced vascular remodelling, suggesting that CD47 blockade may represent a novel therapeutic strategy to mitigate vascular complications in CKD. Full article

Background/Objectives: Cyclosporine A (CsA) is a key immunosuppressant in post-transplantation therapy protocol characterized by large interindividual and intraindividual pharmacokinetic (PK) variability and a narrow therapeutic range necessitating therapeutic drug monitoring (TDM) to prevent graft rejection and minimize side effects. TDM data can be used for developing PK models with the objective of identification and quantification of variability factors that contribute to the differences in CsA concentrations. Methods: Retrospectively collected data from medical records of 58 patients (children and young adults) regarding CsA blood concentrations, concomitant medications, and laboratory findings of significance were used for the population PK model development in NONMEM^® (version 7.5) with first-order conditional estimation method with interaction (FOCE-I). Simulation of the concentrations and area under the curve (AUC) was performed in the web application e-campsis^®. RStudio (version 4.5.0) was used for the purpose of descriptive statistics analysis and graphs plotting. Results: A one-compartment model with first-order absorption and elimination best described the data. Value of clearance (CL/F) was estimated to be 15 L/h, and volume of distribution (V/F) was 71.1 L for a typical patient weighing 40 kg. Interindividual variability (IIV) on CL/F and V/F was 34.91% and 43.05%, respectively. Interoccasional variability (IOV) was 12.25%. Body weight (WT) was introduced allometrically on CL/F and V/F, with the estimated exponent of 0.89 for CL/F and 1 (fixed) for V/F. According to the final model, CL/F decreases with increasing haemoglobin (HGB) value. A difference of almost 22.5% in CL/F was observed among patients’ HGB values reported in the study. Conclusions: Our findings indicate that HGB levels significantly influence CsA PK, particularly minimum concentration (C_min), highlighting the importance of regular HGB levels monitoring together with CsA levels. Full article

Protein-bound uremic toxins (PBUT), particularly indoxyl sulphate (IS) and p-cresyl sulphate (pCS), are poorly removed by conventional haemodialysis because of their strong albumin binding. These toxins are associated with cardiovascular morbidity and mortality in haemodialysis patients. Displacer molecules such as ibuprofen enhance PBUT clearance by competing for albumin-binding sites, but the optimal dose and route of administration remain unclear. The aim of this study was to evaluate the effect of different ibuprofen doses, infusion durations, and routes of administration on the removal of IS and pCS during on-line hemodiafiltration (OL-HDF). In this prospective, single-centre, crossover study, 21 chronic haemodialysis patients receiving intradialytic analgesia underwent nine OL-HDF sessions. Ibuprofen was administered at two doses (400 or 800 mg) either in the arterial pre-filter line (infusion over 1 h, 2 h, or 3 h) or in the venous post-filter line (30 min). Reduction ratios (RR) of total IS and pCS were determined by LC-MS and corrected for haemoconcentration. Statistical analysis included repeated-measures ANOVA with post-hoc testing. Baseline RR for IS and pCS were 53.7 ± 9.9% and 47.1 ± 10.9%, respectively. The highest RR was achieved with 800 mg ibuprofen infused via the arterial line over 2 h (IS: 60.8 ± 8.6%; pCS: 57.8 ± 9.7%). All arterial-line 800 mg regimens and the 3-h 400 mg infusion significantly improved pCS clearance versus baseline; IS clearance improved significantly only with arterial-line 800 mg regimens and with the 400 mg 3-h infusion. Infusion rate (1–3 h) had no significant effect on RR within the same dose group. Pain scores decreased significantly after dialysis regardless of ibuprofen regimen. Arterial-line administration of ibuprofen enhances total IS and pCS removal during OL-HDF, with higher doses yielding greater clearance. Prolonged low-dose infusion appears similarly effective for pCS and may reduce systemic exposure, potentially lowering toxicity risk. These findings support the arterial line as the preferred route for displacer administration in clinical practice. Full article

Motor disorders are increasingly recognized as a significant complication of chronic kidney disease (CKD), yet they remain underdiagnosed, undertreated, and often overlooked in clinical practice. Patients with CKD experience a broad spectrum of motor disturbances, including restless legs syndrome, myoclonus, flapping tremor, periodic limb movements in sleep, Parkinsonism, and peripheral neuropathy. These disorders arise from complex and often overlapping mechanisms such as uremic neurotoxicity, vascular injury, electrolyte and hormonal imbalances, or inflammatory processes, reflecting the systemic impact of impaired renal function on the central and peripheral nervous systems. The presence of motor disorders in CKD is associated with substantial clinical consequences for quality of life, contributing to impaired mobility, persistent insomnia, daytime fatigue, higher fall risk, and diminished independence. Moreover, these disturbances have been linked to increased cardiovascular morbidity and mortality, further exacerbating the already high burden of disease in this population. Current management approaches focus on optimizing kidney function through dialysis or transplantation, pharmacological therapies such as dopaminergic agents, gabapentinoids, and iron supplementation, as well as non-pharmacological interventions including structured exercise programs and sleep hygiene measures. Despite these strategies, robust evidence on long-term outcomes, comparative effectiveness, and optimal treatment algorithms remains limited. Greater recognition of the clinical impact of motor disorders in CKD, combined with targeted research efforts, is urgently needed to improve patient-centered outcomes and guide evidence-based care. Full article

Metabolic acidosis is common after kidney transplantation and has been linked to adverse renal outcomes. However, its relationship with histological injury in kidney allografts remains poorly characterized. We aimed to explore the association between metabolic acidosis and histopathological features in kidney allograft biopsies. This single-center, cross-sectional observational study included 63 adult kidney transplant recipients who underwent clinically indicated allograft biopsies. Metabolic acidosis was defined as a serum bicarbonate level < 22 mmol/L at the time of biopsy. Histological lesions were assessed according to the Banff classification. Lesion severity was evaluated using descriptive statistics, nonparametric comparisons, ordinal logistic regression, and multivariable logistic regression models adjusted for renal function, proteinuria, and time from transplantation. Sensitivity analyses additionally adjusted for hemoglobin and donor-related variables. Patients with metabolic acidosis exhibited numerically higher severity scores for both acute inflammatory lesions and chronic histological changes, including total inflammation and interstitial fibrosis/tubular atrophy (IFTA). Across ordinal analyses and multivariable regression models, consistent directional trends toward a greater histological injury burden were observed among acidotic patients; however, none of these associations reached statistical significance, and confidence intervals were wide. Sensitivity analyses yielded directionally consistent effect estimates. In this biopsy-based analysis, metabolic acidosis showed consistent directional trends toward a higher burden of inflammatory and chronic histological lesions, although these findings did not reach statistical significance. Full article

Background/Objectives: Frailty, a syndrome characterized by diminished physiological reserves and increased vulnerability to stressors, is a strong predictor of adverse outcomes in heart failure. The MECKI (Metabolic Exercise Cardiac Kidney Index) score, derived from cardiopulmonary exercise testing and renal function parameters, has demonstrated prognostic value in HF patients. This study aimed to evaluate the prognostic value of physical frailty on mortality in patients with advanced heart failure and to compare it directly with the MECKI score. Methods: A total of 104 patients with advanced HF receiving optimized guideline-directed medical therapy were prospectively enrolled. At baseline, all patients underwent clinical, echocardiographic, and laboratory assessment and CPET for MECKI score calculation. Physical frailty was assessed using a modified Fried phenotype tailored for HF. The composite endpoint comprised all-cause mortality, urgent heart transplantation, or LVAD implantation. Results: Over a mean follow-up of 30.0 ± 15.3 months, there were 25 deaths, 5 urgent heart transplants, and 1 LVAD implantation. Patients who experienced the composite outcome had significantly worse NYHA class, higher NT-proBNP, lower VO₂max, higher VE/VCO₂ slope, higher frailty, and higher MECKI score (all p < 0.001). Frailty was significantly correlated with all MECKI score components, as demonstrated by Spearman’s rank correlation analysis. Both frailty (HR = 1.89; 95% CI 1.22–2.93; p = 0.005) and MECKI score (HR = 1.04; 95% CI 1.00–1.08; p = 0.037) independently predicted outcomes. ROC analysis showed high and comparable discriminative performance (AUC = 0.86 for frailty; AUC = 0.88 for MECKI). Conclusions: Physical frailty and MECKI scores independently predict mortality and adverse events in advanced HF. Physical frailty, despite its simplicity and low cost, provides prognostic insight comparable to the MECKI score and may represent a practical alternative when CPET is unavailable. Full article

Chronic kidney disease (CKD), which affects over 850 million individuals globally, is increasingly regarded as a systemic condition in which the gut microbiota represents a key pathogenic node. This review provides an integrated overview of mechanistic, translational and clinical data implicating the gut–kidney axis in CKD. The CKD-associated microbiota displays a characteristic dysbiosis, marked by depletion of short-chain fatty acid–producing commensals, overgrowth of proteolytic and urease-expressing taxa and disruption of epithelial barrier integrity. These disturbances favor the generation and systemic accumulation of gut-derived uremic toxins, most notably indoxyl sulfate, p-cresyl sulfate, indole-3-acetic acid and trimethylamine-N-oxide, which promote endothelial dysfunction, vascular calcification, fibrosis and chronic inflammation, thereby hastening renal function loss and heightening cardiovascular risk. Microbiome-directed interventions, including dietary modification, prebiotics, probiotics, synbiotics, intestinal dialysis, fecal microbiota transplantation, gut-acting sorbents and nephroprotective phytochemicals, are summarized with emphasis on their effects on uremic toxin burden and clinical surrogates. System-level implications of the gut–kidney axis for cardiovascular disease, immunosenescence and sarcopenia are discussed, together with future priorities for integrating multi-omics profiling and precision microbiome-based strategies into nephrology practice. Full article

This article explores the multifaceted role of micro-ribonucleic acids (RNAs) (miRNAs) as critical posttranscriptional regulators in renal physiology and disease, with a focus on their emerging significance in glomerulopathies. miRNAs, small endogenous noncoding RNAs, modulate gene expression by promoting messenger RNA degradation or inhibiting translation, thereby orchestrating essential cellular processes such as proliferation, differentiation, apoptosis, and stress responses. Recent advances have revealed that aberrant miRNA expression profiles are intricately linked to the pathogenesis and progression of various renal diseases, including acute kidney injury, chronic kidney disease, alloimmune injury in solid organ transplantation and glomerulonephritis. This review summarizes the pathogenic and protective roles of miRNAs in major glomerulopathies, discusses their potential as diagnostic and prognostic biomarkers, and outlines future directions for their integration into personalized therapeutic strategies. At the moment, it is not fully established whether some of these mechanisms are the primary pathogenic driver or a secondary response. Combining miRNAs with other molecular markers may further enhance diagnostic and predictive accuracy, facilitating clinical translation, while selective targeting of specific miRNAs at different stages of disease progression could offer promising therapeutic opportunities. Full article

Erectile dysfunction (ED) is a frequent and significant complication of radical prostatectomy that impacts patients’ quality of life. Intracavernous injection treatment has become an important approach to post-prostatectomy ED, providing an immediate and proven means of regaining erectile function in men who are unresponsive to oral phosphodiesterase type 5 inhibitors. The scope of this article is to discuss the mechanisms, efficacy, and safety of ICI treatments using vasoactive compounds as a second-line treatment for ED after radical prostatectomy. We consider clinical results, satisfaction, and compliance, as well as predictors of success, like nerve-sparing procedures. Through our interpretation of evidence and clinical experience, ICI therapy is a cornerstone of penile rehabilitation and ED management following radical prostatectomy. Also, the prospects for further treatment optimization and patient outcomes are discussed. Full article

Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disorder that causes progressive renal failure, nephrolithiasis, and nephrocalcinosis in children. It is characterized by hepatic overproduction of oxalate. Conventional management, which involves combined liver–kidney transplantation, vitamin B6 supplementation, and intense hydration, does not address the underlying metabolic defect for most patients and it generally provides only supportive care. The first approved disease-modifying treatment for pediatric PH1 is Lumasiran, a small interfering RNA (siRNA) therapeutic. By specifically inhibiting the hepatic glycolate oxidase mRNA, Lumasiran lowers the production of oxalate at its origin. Along with fewer kidney stone events and stabilization of nephrocalcinosis, clinical trials (ILLUMINATE-A/B/C) showed significant decreases in urinary oxalate excretion. The most frequently reported adverse event is mild injection-site reactions, which are generally well tolerated. The molecular mechanism, pharmacokinetics, and clinical effectiveness of Lumasiran in children with PH1 are compiled in this review. We go over possible long-term safety concerns, the impact of early intervention on renal outcomes, and the function of siRNA therapies in pediatric precision medicine. Furthermore, we highlight Lumasiran’s importance as a model for targeted treatment in uncommon pediatric kidney diseases by considering it in the larger context of RNAi-based therapies. A paradigm shift in pediatric nephrology is signaled by Lumasiran, which changes the therapeutic approach from supportive care to precision, targeted medicine. Further research and empirical data will clarify its long-term advantages, the best ways to treat it, and the possible use of siRNA technologies for other genetic renal disorders. Full article

Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome encompasses a range of Müllerian duct anomalies characterized by congenital absence of the uterus and the upper two-thirds of the vagina in young women who otherwise exhibit normal endocrine function and a 46,XX karyotype. MRKH syndrome can occur in an isolated form (type I) or in association with other congenital anomalies (type II or MURCS association), which may include renal, vertebral, auditory, and cardiac defects. It represents one of the most frequent causes of primary amenorrhea, affecting approximately 1 in every 4000–5000 women. MRKH syndrome often remains undiagnosed until a patient presents with primary amenorrhea, despite normal development of secondary sexual characteristics. Both genetic and non-genetic factors have been proposed as contributing to abnormal embryonic development, although the exact etiopathogenesis remains unclear. Imaging plays a key role in the evaluation of genital tract anomalies, allowing non-invasive and comprehensive assessment. Alongside physical examination and pelvic ultrasound, pelvic MRI is essential for identifying the presence of rudimentary uterine tissue. MRKH syndrome can have profound and lasting psychological impacts, making it essential for patients and their families to receive counseling both before and throughout treatment. A range of therapeutic options—both surgical and non-surgical—have been proposed for managing MRKH syndrome. Vaginal dilation remains the first-line treatment, as it offers high success rates with minimal risk of complications. Vaginoplasty is considered a second-line option for patients who do not respond to dilation therapy. Additionally, uterine transplantation and gestational surrogacy provide opportunities for women with MRKH syndrome to achieve biological motherhood. This review provides an updated overview of Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome, encompassing its etiological, clinical, diagnostic, psychological, therapeutic, and reproductive aspects. We also present a case involving a 19-year-old woman with MRKH syndrome who presented with primary amenorrhea, highlighting the crucial role and advantages of MRI in diagnosis, differential assessment, and treatment planning. Full article

Cutaneous infections caused by dematiaceous fungi are rare in the general population but are increasingly recognized in solid organ transplant recipients as a consequence of prolonged immunosuppression. When Alternaria species are confirmed as the causative agents of a skin infection, the condition is referred to as alternariosis. These infections may clinically resemble bacterial or neoplastic lesions and require accurate diagnosis and individualized therapy. We report one case of cutaneous alternariosis in a kidney transplant recipient receiving tacrolimus-based immunosuppression. The patient was a 47-year-old woman who sustained minor trauma to her knee three months after transplantation. She developed an ulcerated, crusted lesion, which coincided with severe neutropenia. Histology, culture and molecular identification confirmed A. infectoria. Treatment included systemic azole therapy (voriconazole followed by isavuconazole) and surgical excision, resulting in resolution without recurrence. This case highlights the importance of early recognition of alternariosis in transplant recipients. Successful management typically requires combined surgical and systemic antifungal therapy, with careful monitoring of drug interactions and immunosuppressive levels to prevent toxicity or rejection. Full article

Vitamin C is a small water-soluble molecule primarily cleared by the kidneys. Therefore, its plasma concentration would be expected to increase as kidney function declines. However, studies in patients with chronic kidney disease (CKD) and kidney transplant recipients have shown the opposite: a positive correlation between kidney function and plasma vitamin C levels. In this review, we discuss potential explanations for this counterintuitive finding and suggest alternative mechanisms influencing vitamin C bioavailability in this population. We also explore the hypothesis that this phenomenon may be linked to benzoic acid (benzoate) exposure. Benzoic acid is a widely used food preservative that, like vitamin C, is water-soluble and renally excreted. In individuals with impaired kidney function, reduced clearance may lead to elevated circulating benzoic acid levels, which could increase the likelihood of an in vivo chemical reaction between benzoic acid and vitamin C, resulting in the formation of benzene, which is a known toxic and carcinogenic compound. We summarize experimental evidence demonstrating the vitamin C–benzoic acid reaction in vitro, along with preliminary animal studies suggesting it may also occur in vivo. We also discuss the potential clinical consequences of benzene exposure in the context of patients with kidney function impairment. Given the widespread use of benzoic acid as a food preservative and the ongoing discussion around vitamin C supplementation in patients with kidney disease, this review invites further investigation to evaluate whether this reaction represents a health hazard for this population. Full article