Search Results (6,118)

Chronic kidney disease is a global public health concern, representing a critical global public health challenge with increasing morbidity and mortality rates. The disease is a long-term condition characterized by the progressive loss of renal function. Early detection of declining kidney health and timely intervention are crucial to slow disease progression and improve prognosis, mitigating complications, including cardiovascular events. Current diagnostic standards are unable to detect early stages of kidney disease, reflecting early signs of glomerular and tubular damage. This creates an urgent need to identify reliable biomarkers for early detection, prognosis and therapeutic monitoring of kidney diseases. Novel biomarkers, including urinary microRNA, exosomal components, proteomic signatures and integrated multi-omics profiles, facilitated by up-to-date technologies offer strong promise for enhancing early diagnosis, risk assessment and monitoring of the disease. We focus on the fundamental biological significance and clinical application of these markers, discussing a critical evaluation of novel methodologies and clinical evidence supporting their potential for earlier and more precise diagnosis. This review summarizes innovative urinary biomarkers and advanced analytical technologies that can provide a more comprehensive and accurate assessment of the kidney status towards early diagnosis, better prognosis and better quality of life for patients with chronic kidney disease. Full article

Early diagnosis of chronic kidney disease (CKD) remains a major clinical challenge. Periostin (POST) and kidney injury molecule-1 (KIM-1) have been proposed as biomarkers of tubular injury and fibrosis. This study aimed to evaluate their utility as markers associated with CKD stage and their associations with renal function and proteinuria in children. Twenty-three children with CKD stages I–IV and 23 healthy controls were enrolled. Serum and urinary POST and KIM-1 were measured together with creatinine (CR), cystatin C (CysC), proteinuria, albuminuria, and urinary α1- and β2-microglobulin. Patients were classified as early stage (ES; CKD I–II) or late stage (LS; CKD III–IV). Serum and urinary POST and KIM-1, uPOST/CR, uKIM-1/CR, fractional excretion indices (FePOST, FeKIM-1), and UPCR were higher in CKD patients than in controls. Absolute biomarker concentrations did not differ between ES and LS and were not associated with eGFR, UPCR, UACR, or tubular protein excretion. In contrast, uPOST/CR, uKIM-1/CR, FePOST, and FeKIM-1 increased with CKD stage, were higher in LS than ES, correlated positively with CysC, and inversely with eGFR. FePOST and FeKIM-1 also correlated strongly with tubular protein markers. The FePOST/FeKIM-1 ratio was elevated in ES patients compared with controls and remained stable across CKD stages. Fractional excretion of POST and KIM-1 is associated with CKD stage and reflects ongoing tubular injury in children. The FePOST/FeKIM-1 ratio may represent a sensitive marker of early CKD. Full article

Background/Objectives: X-linked Alport syndrome (XLAS) arises from pathogenic variants in COL4A5. Truncating variants are generally classified as severe, but whether clinically meaningful heterogeneity exists within this group remains unclear. This study aimed to establish a novel Col4a5 knock-in mouse model based on a clinical variant and to determine whether truncating mutation position influences disease severity. Methods: A de novo COL4A5 frameshift variant, c.2440delG, was identified in a patient with severe early-onset XLAS. A Col4a5-G814fs knock-in mouse was generated by CRISPR/Cas9 on the C57BL/6J inbred mouse strain background and compared with the established Col4a5-G5X nonsense model using survival analysis, serial functional measurements, kidney histopathology, transmission electron microscopy, and RNA sequencing. Results: The Col4a5-G814fs knock-in mouse was successfully generated and showed loss of glomerular α5(IV) collagen chain expression. Compared with G5X mice, G814fs mice exhibited shorter survival (median 141 vs. 161.5 days, p = 0.0004), earlier onset of proteinuria, and more severe kidney functional decline. By 16 weeks, G814fs mice also showed more severe glomerular basement membrane abnormalities and more extensive glomerulosclerosis. RNA sequencing revealed a shared inflammatory gene signature in both models, together with selective upregulation of genes related to the PPAR signaling pathway and fatty acid metabolism in G814fs kidneys. Conclusions: This study reports a novel de novo COL4A5 frameshift variant and establishes the first Col4a5-G814fs knock-in mouse model. Direct comparison with the G5X model shows that distinct truncating COL4A5 mutations can be associated with substantially different disease severity, providing a useful platform for future mechanistic and therapeutic studies in XLAS. Full article

The red cusk-eel (Genypterus chilensis) is an endemic Chilean teleost fish of significant importance to fisheries and aquaculture; however, no reference genome is available for this species. In this study, we present the first hybrid genome assembly of G. chilensis using Nanopore long-reads and Illumina short-reads, integrated with structural and functional annotations from RNA-seq data of the intestine and head kidney. The resulting genome assembly was 439.89 Mb in size, with an N50 of 7.96 Mb, containing 35,029 coding genes. Comparative genomics with G. blacodes revealed high similarity in genome size and completeness. Additionally, 14,681 lncRNAs were annotated, with 641 lncRNAs and 7323 coding genes differentially expressed in a tissue-specific expression pattern. These findings provide a high-quality genomic resource that enhances the understanding of lncRNA regulation and genome structure in the Genypterus genus. This study establishes a foundation for future research on commercial traits, conservation, and the evolution of the Ophidiiformes order. Full article

Chronic kidney disease (CKD) represents a growing medical, diagnostic and social challenge, and it is estimated to effect 8.5–9.8% of the global population and requires expensive modes of treatment, such as hemodialysis or renal transplants. Currently, a diagnosis of CKD is set based on the level of creatinine in the blood, which is the gold standard of renal function diagnostics. Unfortunately, decrease in GFR is secondary to damage of the kidney parenchyma and indicates that the best time to start more aggressive treatment has already passed. Therefore, several non-invasive methods have been proposed for predicting increased risk of CKD progression; however, in most of the cases kidney biopsy is essential. Currently, the greatest hopes for a method that can confirm CKD are associated with the development of MRI, the most tissue-specific imaging method, and it is already proven to be capable to detect inflammatory and edematous changes, fibrosis, as well as perfusion and oxygenation disturbances. Therefore, in our manuscript we decided to present up-to-date knowledge about kidney MRI from a clinical point of view. Full article

Background/Objectives: Given the narrow therapeutic range of tacrolimus and substantial inter-individual variability in trough levels, both total daily dose and the trough level-to-dose ratio are commonly used to guide dose optimization. In this study, Life-Cycle Pharma tacrolimus was compared with immediate-release tacrolimus in a real-world setting. Methods: This longitudinal observational study included kidney transplant recipients at two Hungarian university clinics. Sixty-three (63) patients completed the study and were included in the statistical analysis. They received either Life-Cycle Pharma-tacrolimus (n = 40) or immediate-release tacrolimus (n = 23) as maintenance therapy in the two study arms, each combined with everolimus or mycophenolic acid and corticosteroids. Patients were enrolled 4–6 weeks after transplantation and prospectively followed for 48 months. Tacrolimus trough level, total daily dose and their ratio were recorded at each of the seven follow-up visits during the 48-month study period. Epidemiological data, patient characteristics, laboratory parameters (including eGFR, de novo donor-specific antibodies, and CMV and BK virus incidence), and acute rejection episodes were monitored. Results: The mean age at enrolment was 53.35 years, and 41 patients (65.08%) were male. A stable therapeutic maintenance trough level was achieved in both study arms. Life-Cycle Pharma tacrolimus required a 30% lower total daily dose than immediate-release tacrolimus to achieve comparable exposure. A gradual decline in eGFR was observed in the immediate-release tacrolimus arm (a mean decrease of 6.06 mL/min/1.73 m² over 4 years) from a baseline level of 58.52 mL/min/1.73 m² (±16.69), whereas GFR increased in the Life-Cycle Pharma tacrolimus arm (a mean increase of 4.76 mL/min/1.73 m² over the same period) from a significantly lower baseline level of 46.55 mL/min/1.73 m² (±17.04). Conclusions: Both formulations provided effective long-term maintenance immunosuppression in kidney transplant recipients and maintained stable trough levels. Life-Cycle Pharma tacrolimus represents a potential option for dose minimization, and it also helped to stabilize renal function despite the worse baseline condition. Full article

Hypertensive nephropathy (HN) is a leading cause of chronic kidney disease and end-stage renal disease worldwide and results from the long-term effects of hypertension on renal structure and function. The pathogenesis of HN is complex and involves haemodynamic disturbances, renal vascular injury, oxidative stress, chronic inflammation, and progressive interstitial fibrosis. In recent years, increasing attention has focused on the role of non-coding RNAs (ncRNAs)—including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs)—as key regulators of gene expression involved in these processes. This review summarises the current understanding of the molecular mechanisms underlying HN, with particular emphasis on the roles of oxidative stress, activation of the renin–angiotensin–aldosterone system, transforming growth factor beta signalling, and inflammatory and fibrogenic pathways. The contribution of dysregulated ncRNAs to endothelial dysfunction, inflammatory responses, apoptosis, angiogenesis, and renal remodelling and fibrosis is also discussed. Particular attention is given to miRNAs and lncRNAs as mediators of disease progression and potential biomarkers, as well as to the emerging role of circRNAs in hypertensive kidney injury, including their involvement in the regulation of redox balance and intercellular communication. Collectively, available evidence indicates that ncRNAs represent a critical link between haemodynamic stimuli and persistent molecular alterations in renal tissue, highlighting their potential as diagnostic markers and therapeutic targets in HN. Full article

Background: Organic cation transporter 2 (OCT2) mediates the renal uptake of cisplatin and is a principal contributor to its dose-limiting nephrotoxicity. Despite reports of OCT2 inhibition by various phytochemicals, the structure–activity relationships (SARs) governing inhibition and their functional implications remain poorly understood. Methods: We systematically evaluated OCT2 inhibitory activity across a structurally diverse library of 146 phytochemicals, including anthraquinones, flavanols, stilbenes, and isoflavones, using Madin–Darby canine kidney (MDCK) cells stably overexpressing OCT2. Structure–activity relationships were analyzed using non-parametric statistics and multivariate logistic regression, and functional relevance was assessed via cisplatin-induced cytotoxicity assays. Results: Inhibitory activity varied widely across the library, with potent inhibitors identified across multiple chemical scaffolds. Non-parametric statistical analyses revealed no significant differences in overall activity distributions among scaffold classes. Notably, chemical substituent patterns, rather than core scaffold identity, were the primary drivers of OCT2 inhibitory potency. Methoxylation was consistently associated with enhanced OCT2 inhibition, particularly within isoflavones, although its impact varied across structural scaffolds. The selected OCT2 inhibitors markedly reduced cisplatin-mediated cell death in OCT2-expressing cells but not in mock-transfected controls, confirming an OCT2-dependent mechanism of protection. Conclusions: This study establishes a structure-guided framework linking phytochemical OCT2 inhibition to nephroprotective potential and identifies methoxylation as a major determinant of OCT2-targeted intervention strategies. Full article

Background/Objectives: Growing evidence indicates that melatonin contributes to kidney development and function, while disruptions of fetal circadian signaling have been linked to congenital anomalies of the kidney and urinary tract (CAKUT). This study aimed to characterize the developmental and spatial expression patterns of melatonin receptors MTNR1A and MTNR1B in normal human fetal kidneys and in CAKUT phenotypes. Methods: This study analyzed 40 human fetal kidney specimens, including healthy controls and CAKUT cases (horseshoe kidneys, duplex kidneys, and dysplastic kidneys), obtained from spontaneous abortions and pregnancy terminations. Samples were classified into developmental phases Ph2–Ph4 according to established morphological criteria. Immunofluorescence staining was used to visualize MTNR1A and MTNR1B expression. Quantitative analysis was performed using ImageJ, measuring the fluorescence area percentage. Statistical comparisons were conducted using a two-way ANOVA. Results: In control kidneys, MTNR1A expression was predominantly observed in glomeruli and interstitial cells and showed a descending trend across developmental stages, whereas MTNR1B was localized to glomeruli and strongly to the apical membranes of tubules, particularly distal tubules, without substantial developmental variation. CAKUT phenotypes exhibited higher expression of both receptors compared to controls. Significant phase-dependent differences in MTNR1A expression were observed in horseshoe, duplex, and dysplastic kidneys. MTNR1B expression decreased across developmental stages in dysplastic kidneys and differed significantly between Ph3 and Ph4 in duplex kidneys. At Ph3, duplex kidneys showed the highest MTNR1B expression. Conclusions: Altered developmental expression patterns of MTNR1A and MTNR1B in CAKUT suggest an association between melatonin signaling and abnormal human kidney development. Full article

Introduction: Acquired ureteral stricture is an uncommon but clinically relevant complication, mainly associated with long-standing urolithiasis, chronic inflammatory processes, and repeated endourological procedures. Case presentation: We present the case of a 48-year-old woman with left distal ureteral stricture secondary to urolithiasis and repeated endourological procedures, with a complicated clinical course and progressive renal functional impairment. Despite stepwise management including balloon dilations, endoscopic incision, prolonged urinary diversion, and ultimately ureteral reimplantation with a psoas hitch, the patient developed restenosis of the ureteral neomeatus. Due to persistent obstruction, endoscopic dilation with a paclitaxel-coated balloon (Optilume^®) was performed. Subsequent imaging demonstrated partial improvement in ureteral drainage and relative functional improvement of the left kidney. Conclusion: This case highlights the potential complementary role of drug-coated balloons in complex and refractory benign ureteral strictures, although the currently available evidence remains limited. Full article

Background: Early postoperative changes in creatinine-based estimated glomerular filtration rate (eGFR) after bariatric surgery can be misread as a kidney injury. During rapid weight loss, indexing eGFR to a fixed body surface area (BSA) of 1.73 m² may alter apparent trajectories. We compared absolute (mL/min) and BSA-indexed (mL/min/1.73 m²) eGFR changes after sleeve gastrectomy, stratified by baseline glomerular hyperfiltration (GH). Methods: In this retrospective cohort of 145 adults undergoing laparoscopic sleeve gastrectomy, serum creatinine was obtained at baseline (≤30 days pre-op) and 3 months (post-op days 75–105). Indexed eGFR was calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 creatinine equation; BSA with the Mosteller formula; and absolute eGFR as indexed eGFR × (BSA/1.73). GH was defined as indexed eGFR ≥ 120 mL/min/1.73 m². A REML mixed-effects model (Group, Time, Group × Time) with patient-cluster bootstrap inference was used. An age-adjusted sensitivity model including Age and Age × Time was also fitted. Results: Fifty-four participants (37%) met the GH criteria. Absolute eGFR declined by −26.6 mL/min in GH versus −17.3 mL/min in non-GH (difference-in-differences [DiD] −9.3 mL/min; 95% CI −13.9 to −4.7; p < 0.001). The indexed eGFR changes were smaller (−4.2 vs. −0.5 mL/min/1.73 m²; DiD −3.7; 95% CI −7.3 to −0.03; p = 0.048; bootstrap p_sign = 0.052). In the age-adjusted sensitivity model, the Group × Time interaction for absolute eGFR attenuated but remained statistically significant (−6.57 mL/min; 95% CI, −13.09 to −0.06; p = 0.048), whereas the corresponding interaction for indexed eGFR was attenuated and no longer statistically significant (−3.99 mL/min/1.73 m²; 95% CI −9.15 to 1.16; p = 0.129). Conclusions: Within three months after sleeve gastrectomy, participants with higher baseline indexed filtration showed a larger decline in absolute eGFR but only a small change in indexed eGFR. These results show that early postoperative creatinine-based eGFR trajectories are scale dependent and should be interpreted cautiously during rapid weight loss. Because postoperative acute kidney injury (AKI) was not adjudicated and direct kidney function markers were unavailable, this study does not distinguish physiological hemodynamic change from structural kidney injury. Reporting both absolute and indexed eGFR may improve early postoperative interpretation and help align dosing decisions with rapid changes in body size. Full article

Renal surgery for localized renal cell carcinoma carries substantial risk of acute kidney injury (AKI) regardless of surgical approach. This prospective study evaluated early biohumoral markers for AKI detection after robotic renal surgery and assessed their prognostic value for 12-month functional outcomes. Adults undergoing robotic renal tumor surgery with a healthy contralateral kidney were enrolled; AKI followed KDIGO 2012 criteria. Biomarkers measured at baseline and 2/24/72 h were serum β2-microglobulin (sβ2) serum IL-6, as well as urinary β2-microglobulin (uβ2), cystatin C (uC), and α2-macroglobulin (uα2M). Kidney function at 12 months was staged according to KDOQI criteria. Among 170 patients (35 radical nephrectomy, RN; 135 partial nephrectomy, PN), 33 developed AKI, more frequently after RN (p < 0.001); baseline biomarkers levels were similar. sβ2 was significantly higher at 2/24/72 h, and at 2 h, it achieved an AUC of 0.78 (cut-off 0.17: sensitivity 82%, specificity 60%), remaining the earliest independent predictor of AKI (p = 0.015). IL-6 differed at 24 h (AUC 0.80), uC at 72 h (AUC 0.73) and uβ2 at 72 h (AUC 0.66). Clinical AKI predicted KDOQI stage progression at 12 months (p < 0.001). Bulldog clamps (mean ischemia time 17.2 ± 6.9 min) were not associated with AKI (p = 0.99) or with KDOQI stage progression (p = 0.54). RN confers a higher AKI risk than PN. sβ2 at 2 h is the earliest actionable marker, complemented by IL-6 (24 h) and uC (72 h); short warm ischemia during robotic PN appears safe. Sequential multimarker assessment may improve recognition of AKI and support timely nephroprotective strategies. Full article

Background: Kidney transplantation (KT) improves survival and quality of life in patients with end-stage kidney disease; however, long-term allograft survival remains a major challenge. Brain natriuretic peptide (BNP), a biomarker of cardiorenal stress and volume status, may be associated with early postoperative physiological changes after KT. This study evaluated the association between early postoperative BNP changes and long-term allograft survival, and explored the potential role of BNP-derived parameters in relation to graft outcomes. Methods: This retrospective cohort study included adult recipients of deceased-donor KT between 2009 and 2018. Patients were categorized according to early graft function. Serum BNP levels were measured preoperatively and within postoperative 24 h, and the percentage increase (dBNP ratio) was calculated. Cox regression and receiver operating characteristic analyses were used to identify risk factors for graft failure and evaluate the discriminatory performance of BNP-derived biomarkers, respectively. Results: Among the 179 recipients, postoperative BNP levels and dBNP ratios differed significantly across graft function groups, with higher values in delayed graft function. After multivariate adjustment, the dBNP ratio remained significantly associated with graft failure (hazard ratio, 1.16; 95% confidence interval, 1.10–1.21; p < 0.001). Additionally, the dBNP ratio demonstrated better discriminatory performance for graft failure compared with postoperative BNP alone (area under the curve, 0.815 vs. 0.596; p < 0.001), with an exploratory cutoff of approximately 18%. Recipients with a dBNP ratio ≥ 18% had poorer early graft function, lower longitudinal estimated glomerular filtration rates, and significantly reduced graft survival. Conclusions: An increased early postoperative dBNP ratio was significantly associated with adverse long-term kidney allograft outcomes. However, given the potential for residual confounding, these findings should be interpreted as associative and hypothesis-generating rather than predictive. Full article

Ciliopathies, initially known as fibrocystic liver diseases, encompass a group of inherited disorders characterized by cystic dilatation of intrahepatic bile ducts and portal fibrosis, frequently associated with renal anomalies. These disorders are now recognized as resulting from defects in primary cilia. The hepatic manifestations, such as congenital hepatic fibrosis (CHF), Caroli syndrome, and polycystic liver disease, arise from ductal plate malformation. Recent studies have implicated variants in the TULP3 (Tubby related protein variant 3) gene in a novel monogenic ciliopathy affecting the liver, kidneys, and heart. We report an 8-year-old boy who presented with variceal bleeding and evolved to a progressive phenotype of CHF. Whole exome sequencing revealed a homozygous novel TULP3 mutation. The patient was managed by endotherapy and propranolol prophylaxis. Due to repeated episodes of variceal bleeding and progressive worsening of hepatic synthetic functions, he underwent a living donor liver transplantation at the age of 12 years. Full article