Search Results (122)

Glomeruli are signal-processing units of the olfactory bulb (OB) that play a key role in many OB computations, including contrast enhancement, gain control, and odorant-selective habituation. In awake mice, we unveil an extremely stable, inhomogeneous map of basal glomerulus-specific activity that serves as the background against which olfactory signal processing occurs. This activity is strongly driven by centrifugal cholinergic inputs; endogenous and airflow-evoked spiking of olfactory sensory neurons; and, to a minor extent, by the odor environment. Moreover, it is brain-state dependent and suppressed under various forms of anesthesia, and is therefore likely attenuated during sleep. These results reveal an important layer in the OB signal-processing network, likely increasing the system’s variance and dynamic range via glomerulus-specific functional inhomogeneity. Full article

Cultured urine-derived cells (UDCs) have been proposed as a source of material for the RNA-based molecular diagnosis of genetic disorders. Previous studies have shown that UDCs can be clonally expanded, passaged, frozen, regrown and have some stem cell characteristics, but their anatomic origin and diagnostic utility remain insufficiently explored. In this study, we cultured UDCs from 40 individuals (aged 4 to 20 years; 21 females) and extracted RNA for sequencing. We compared UDC gene expression to that of marker genes of the kidney and urinary tract segments. UDC gene expression most closely matched marker genes of parietal epithelial cells that line the inner surface of Bowman’s capsule in the kidney glomerulus. UDCs expressed VCAM1 (CD106) and POUF51 (OCT4), consistent with a progenitor cell type. UDCs also expressed 54.4% of 3125 OMIM-listed disease-causing genes. This indicated that UDCs can be used to diagnose a similar number of genetic disorders as skin fibroblasts and a wider range of genetic disorders than can be analysed by RNA extracted from whole blood. In conclusion, UDCs are a non-invasive cell source for RNA sequencing that is suitable for investigating a broad range of conditions. Full article

Kidney organoids, as three-dimensional microstructures derived from human pluripotent stem cells or adult stem cells, precisely simulate the cellular heterogeneity, spatial conformation, and some physiological functions of human kidney units in vitro. Kidney organoids are three-dimensional microstructures derived from human pluripotent stem cells (hPSCs). They precisely simulate the cellular heterogeneity, spatial conformation, and key physiological functions of human kidney units in vitro. This technology, by replicating the interaction network between the glomerulus and renal tubules, provides an unprecedented window for observing the dynamic development and pathological processes of human kidneys. This technology replicates the interaction network between the glomerulus and renal tubules. It thereby provides an unprecedented window into human kidney development and disease. Based on the strong similarity between organoids and native organs, as well as the human genetic information they carry, both iPSC-derived and patient-specific organoids have demonstrated significant value in kidney disease modeling, drug toxicity testing, and the development of regenerative treatment strategies. This review systematically elucidates the key advancements in the field of kidney organoids, including optimized strategies for stem cell-directed differentiation, innovations in culture systems driven by biomaterials engineering, technological breakthroughs in disease model construction, and applications of organoids in drug screening platforms and regenerative medicine. Additionally, it analyzes translational challenges such as the lack of vascularization, insufficient functional maturity, and obstacles in standardized production. These insights will deepen the understanding of kidney pathological mechanisms and propel organoid technology towards substantial clinical therapeutic applications. This review summarizes how convergent technologies in stem cell biology and bioengineering aim to bridge this functional gap. We examine the use of advanced organoids in disease modeling and drug discovery. We also highlight their current limitations. Our focus is on the core translational bottlenecks: vascularization, long-term maturation, and scalable production. Overcoming these hurdles is essential to transform kidney organoids from a research tool into a platform for precision medicine and regenerative therapy. Full article

Background and Objectives: This study compared the effects of rosuvastatin and chitosan on the kidneys of rabbits fed a high-fat diet. Materials and Methods: In total, 28 New Zealand White rabbits (Oryctolagus cuniculus) were randomly divided into four groups of 7 rabbits: a control group (CG) fed a regular diet; a hyperlipidic group (HG) fed the regular diet and 20 mL of egg yolk daily; and the third (RG) and fourth (ChiG) groups fed the HG diet plus rosuvastatin and chitosan, respectively. Cholesterol, triglyceride, glucose, creatinine, and urea levels were analyzed. After kidney excision, glomerular height and length were analyzed and stereological analysis was conducted. The Kruskal–Wallis and Dunn multiple comparison tests were used for statistical analysis, and a p value of <0.05 was considered significant. Results: The chicken egg yolk diet was successful in inducing a hypercholesterolemic state. Total cholesterol levels showed a significant reduction in rabbits treated with rosuvastatin, and chitosan and rosuvastatin significantly reduced triglyceride, VLDL, creatinine, and glucose levels. The size of the glomerulus was increased significantly in the HG rabbits. Stereological analysis showed a mean glomerular volumetric density of 8.27 ± 3.27, 4.14 ± 2.87, 10.03 ± 3.22, and 6.18 ± 3.50 vV% for CG, HG, RG, and ChiG, respectively. Conclusions: Chitosan reduced triglyceride, VLDL, creatinine, and glucose levels but was less effective than rosuvastatin. Kidney morphology was slightly altered in the animals fed a high-fat diet, and these changes were ameliorated by treatment with chitosan or rosuvastatin. Full article

The circulating renin–angiotensin–aldosterone system (RAAS) plays a key role in regulating blood volume and electrolyte levels. While important for the maintenance of intravascular volume systemically, the local activation of tissue RAAS and the generation of angiotensin II contribute to inflammation and fibrosis. In the kidney, angiotensin II plays a key role in the development and progression of glomerular injury. Angiotensin-converting enzyme 2 (ACE2), an enzyme that degrades angiotensin II, is expressed in the glomerulus, focusing attention not only on the complexity of the RAAS but also identifying a potential new determinant of glomerular injury. Accordingly, we performed a narrative review using the search terms ACE2 and glomerulus in PubMed and Google Scholar to summarize the current understanding of the role of ACE2 in glomerular injury. We also discuss the role of ACE2 as a cellular receptor for SARS-CoV-2 and the potential impact of this function on glomerular injury in the setting of COVID-19. Full article

Background: Radiation-induced tissue degeneration is the most important side effect of radiotherapy. Sitagliptin with its anti-inflammatory and antioxidant capacity was tested in alleviating the radiation-induced cellular degeneration in kidney and testis tissues. Methods: Wistar albino rats were divided into four groups as control, radiation (RT), radiation + sitagliptin (RT + SGT), and sitagliptin + radiation (SGT + RT). The RT group received 8 Gy radiation. Sitagliptin was applied per os at a 10 mg/kg dose for 14 days to the SGT groups either after or before radiation. Results: Radiation induced marked oxidative stress in kidney and testis tissues, whereas sitagliptin partially restored several antioxidant parameters in the kidney and reduced MDA levels in the testis. Histologically, radiation caused degenerative changes in the renal tubules and glomerulus and the testicular seminiferous tubules, while sitagliptin treatment attenuated these changes in both organs. Caspase-3 expression increased significantly after radiation treatment in the kidney without substantial improvement by sitagliptin; however, VEGF expression, which was markedly reduced by radiation in both tissues, was restored in sitagliptin-treated groups. FGF expression suppressed in all irradiated groups as compared to the control with no significant differences among them. Conclusions: Overall, the results indicated that sitagliptin can be used to attenuate the degenerative effects induced by radiation. Sitagliptin use after radiation as compared to the before use showed significantly better results especially in the kidney tissue. Full article

Accurate segmentation of kidney microstructures in whole slide images (WSIs) is essential for the diagnosis and monitoring of renal diseases. In this study, an end-to-end instance segmentation pipeline was developed for the detection of glomeruli and blood vessels in hematoxylin and eosin (H&E) stained kidney tissue. A tiling-based strategy was employed using Slicing Aided Hyper Inference (SAHI) to manage the resolution and scale of WSIs and the performance of two segmentation models, YOLOv11 and YOLOv12, was comparatively evaluated. The influence of tile overlap ratios on segmentation quality and inference efficiency was assessed, with configurations identified that balance object continuity and computational cost. To address object fragmentation at tile boundaries, an Enhanced Syncretic Mask Merging algorithm was introduced, incorporating morphological and spatial constraints. The algorithm’s hyperparameters were optimized using Particle Swarm Optimization (PSO), with vessel and glomerulus-specific performance targets. The optimization process revealed key parameters affecting segmentation quality, particularly for vessel structures with fine, elongated morphology. When compared with a baseline without postprocessing, improvements in segmentation precision were observed, notably a 48% average increase for glomeruli and up to 17% for blood vessels. The proposed framework demonstrates a balance between accuracy and efficiency, supporting scalable histopathology analysis and contributing to the Vasculature Common Coordinate Framework (VCCF) and Human Reference Atlas (HRA). Full article

Background/Objectives: Although essential for oxygen transport and DNA synthesis, excess iron is toxic and can damage organs such as the kidneys. Research has shown that iron overload induces kidney injury, and aging contributes to kidney dysfunction through functional and structural changes. The interaction between iron overload and aging remains poorly understood. Therefore, this study investigated their combined effects on renal microstructure and function using an iron-dextran-injected mouse model. Methods: Young and old mice were divided into control and iron overload groups, renal function was evaluated by serum creatinine and albuminuria, and urinary iron excretion was also measured to assess iron handling. The structural changes were assessed using histological analysis and electron microscopy. Results: Although the iron overload groups had similar blood iron levels, the old iron overload group exhibited significantly higher levels of albuminuria, urinary iron excretion, and serum creatinine compared with the young group. In the iron overload model, histological and ultrastructural analyses demonstrated iron accumulation in mesangial and endothelial cells, glomerular basement membrane thickening, and foot process widening, which were more pronounced in aged mice, suggesting that aging exacerbates iron-induced kidney injury. Conclusions: These findings demonstrate that aging increases susceptibility to iron-induced kidney injury, as shown by the accelerated glomerular injury observed in iron-overloaded aged mice. Therefore, elucidating the effects of aging on iron metabolism may contribute to identifying approaches for reducing age-associated renal injury. Full article

Renal function refers to the combined actions of the glomerulus and tubular system to achieve homeostasis in bodily fluids. While the glomerulus is essential in the first step of urine formation through a coordinated filtration mechanism, the tubular system carries out active mechanisms of secretion and reabsorption of solutes and proteins using specific transporters in the epithelial cells. The assessment of renal function usually focuses on glomerular function, so the tubular function is often underestimated as a fundamental part of daily clinical practice. Therefore, it is essential to properly understand the tubular physiological mechanisms and their clinical association with prevalent human pathologies. This review discusses the primary solutes handled by the kidneys, including glucose, amino acids, sodium, potassium, calcium, phosphate, citrate, magnesium and uric acid. Additionally, it emphasizes the significance of physicochemical characteristics of urine, such as pH and osmolarity. The use of a concise methodology for the comprehensive assessment of urine should be strengthened in the basic training of nephrologists when dealing with problems such as water and electrolyte balance disorders, acid-base disorders, and harmful effects of commonly used drugs such as chemotherapy, antibiotics, or diuretics to avoid isolated replacement of the solute without carrying out comprehensive approaches, which can lead to potentially severe complications. Full article

Kidney injury encompasses a broad spectrum of structural and functional abnormalities, directly associated with stem cell transplantation. Acute kidney injury and chronic kidney disease represent perilous complications of hematopoietic stem cell transplantation (HSCT), with an elevated risk of mortality and progression to end-stage renal disease. The early detection of these complications is, therefore, paramount, and research is increasingly focused on the identification of novel biomarkers of kidney damage. Recently, proenkephalin (PENK), a monomeric peptide that is freely filtered by the glomerulus and thus reflects glomerular filtration very well, has been shown to be an additional useful predictor of the occurrence of acute kidney injury and heart failure. Dickkopf-3 (DKK3) is a glycoprotein secreted by the renal tubular epithelium in response to stress and has been implicated in the development of interstitial fibrosis. It has therefore been evaluated primarily as a marker of fibrosis in chronic kidney disease (CKD), but may also help predict the development of acute kiney injury. Uromodulin is regarded as a renal marker. Previous studies have examined the potential of PENK, DKK-3 and uromodulin as a biomarker in individuals with preserved renal function. However, the urinary levels of PENK, DKK-3 and uromodulin in patients following HSCT have not yet been established. The objective of the present study was to assess urinary PENK, DKK-3, and uromodulin concentrations in patients who had been under ambulatory care of the Hematology, Transplantation and Internal Medicine Department for a minimum of three months following HSCT, and to investigate their correlations with kidney function, as reflected by serum creatinine and eGFR. The study population comprised 80 patients who had undergone allogeneic HSCT for various reasons, primarily hematological malignancies such as acute leukemias and lymphomas. In addition, 32 healthy volunteers were included in order to establish normal ranges for the biomarkers of interest. Urine concentrations of proenkephalin, DKK-3, and uromodulin were evaluated using a commercially available sandwich ELISA immunoassay. Demographic and clinical data were retrieved from the patients’ records. Statistical analyses were conducted using XLSLAT 2022 (Lumivero, Denver, CO, USA) and STATISTICAv13.0 (StatSoft, Tulsa, OH, USA). The results showed that PENK and DKK-3 levels were significantly higher in patients after HSCT compared to healthy volunteers. Furthermore, when patients were divided according to kidney function (below and over 60 mL/min/1.72 m²), it was found that the concentration of PENK and DKK-3 were significantly higher in 23 patients with CKD stage 3 relative to patients with eGFR over 60 mL min 1.72 m². In univariate correlations, PENK demonstrated an inverse relationship with eGFR (r: −0.21, p < 0.05), while DKK-3 exhibited no significant correlation with creatinine or eGFR.Patients following allogeneic HSCT, despite having normal or near-normal kidney function, exhibited evidence of kidney injury. However, further research is necessary to ascertain the clinical utility of the novel biomarker. Full article

Angiotensin II (Ang II)-induced hypertension increases afferent (AA) and efferent (EA) arteriole resistances via the actions of Ang II on the AT1 receptor. In addition to the increased interstitial levels of Ang II, the increased arterial pressure increases interstitial ATP concentrations. In turn, ATP acts on the purinergic receptors P2X1 and P2X7 to constrict the AA, preventing increases in plasma flow and single-nephron GFR (SNGFR). While the hemodynamic effects of P2 activation have been characterized, the resulting increases in mechanical stresses (shear stress and circumferential hoop stress) on the glomerular microvasculature have not been quantified. A mathematical microvascular hemodynamic glomerular model was developed to simulate blood flow and plasma filtration in an anatomically accurate rat glomerular capillary network. AA and EA resistances were adjusted to match glomerular hemodynamic data for control, Ang II-induced hypertension, and P2X1-blocked conditions. A blockade of the purinergic receptors reduced both afferent and efferent resistances, maintaining glomerular pressure at hypertensive levels but increasing blood flow and sheer stress significantly. Because glomerular pressure was maintained, hoop stress barely changed. Our results indicate that the activation of the purinergic system protects the glomerular microvasculature from elevated shear stress caused by increased blood flow that would occur in the absence of purinergic stimulation. Full article

As one of the most common air pollutants, fine particulate matter (PM_2.5) increases the risk of diseases in various systems, including the urinary system. In the present study, we exposed male and female C57BL/6J mice to PM_2.5 for 8 weeks. Examination of renal function indices, including creatinine (CRE), blood urea nitrogen (BUN), uric acid (UA), and urinary microalbumin, indicated that the kidneys of female mice, not male mice, underwent early renal injury, exhibiting glomerular hyperfiltration. Meanwhile, pathological staining showed that the kidneys of female mice exhibited enlarged glomerulus that filled the entire Bowman’s capsule in the female mice. Afterward, we explored the potential causes and mechanisms of glomerular hyperfiltration. Variations in mRNA levels of key genes involved in the renin–angiotensin system (RAS) and kallikrein–kinin system (KKS) demonstrated that PM_2.5 led to elevated glomerular capillary hydrostatic pressure in female mice by disturbing the balance between the RAS and KKS, which in turn increased the glomerular filtration rate (GFR). In addition, we found that PM_2.5 increased blood glucose levels in the females, which enhanced tubular reabsorption of glucose, attenuated macular dense sensory signaling, induced renal hypoxia, and affected adenosine triphosphate (ATP) synthesis, thus attenuating tubuloglomerular feedback (TGF)-induced afferent arteriolar constriction and leading to glomerular hyperfiltration. In conclusion, this study indicated that PM_2.5 induced glomerular hyperfiltration in female mice by affecting RAS/KKS imbalances, as well as the regulation of TGF; innovatively unveiled the association between PM_2.5 subchronic exposure and early kidney injury and its gender dependence; enriched the toxicological evidence of PM_2.5 and confirmed the importance of reducing ambient PM_2.5 concentrations. Full article

Hypertensive nephropathy (HN) is a leading cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD), contributing to significant morbidity, mortality, and rising healthcare costs. In this review article, we explore the role of epigenetic mechanisms in HN progression and their potential therapeutic implications. We begin by examining key epigenetic modifications—DNA methylation, histone modifications, and non-coding RNAs—observed in kidney disease. Next, we discuss the underlying pathophysiology of HN and highlight current in vitro and in vivo models used to study the condition. Finally, we compare various types of HN-induced renal injury and their associated epigenetic mechanisms with those observed in other kidney injury models, drawing inferences on potential epigenetic therapies for HN. The information gathered in this work indicate that epigenetic mechanisms can drive the progression of HN by regulating key molecular signaling pathways involved in renal damage and fibrosis. The limitations of Renin–Angiotensin–Aldosterone System (RAAS) inhibitors underscore the need for alternative treatments targeting epigenetic pathways. This review emphasizes the importance of further research into the epigenetic regulation of HN to develop more effective therapies and preventive strategies. Identifying novel epigenetic markers could provide new therapeutic opportunities for managing CKD and reducing the burden of ESRD. Full article

Background: While dehydration is associated with pediatric renal impairment, the regulation of hydration status can be affected by sleep. However, the interaction of hydration and sleep on kidney health remains unclear. Methods: We conducted a cohort study among 1914 healthy primary school children from October 2018 to November 2019 in Beijing, China. Four-wave urinary β₂-microglobulin and microalbumin excretion were assayed to assess transient renal tubular and glomerular impairment, and specific gravity was measured to determine hydration status with contemporaneous assessment of sleep duration, other anthropometric, and lifestyle covariates. We used generalized linear mixed-effects models to assess longitudinal associations of sleep duration and hydration status with renal impairment. Results: We observed 1378 children with optimal sleep (9–<11 h/d, 72.0%), 472 with short sleep (<9 h/d), and 64 with long sleep (≥11 h/d, 3.3%). Over half (55.4%) of events determined across 6968 person-visits were transient dehydration, 19.4% were tubular, and 4.9% were glomerular impairment events. Taking optimal sleep + euhydration as the reference, the results of generalized linear mixed-effects models showed that children with long sleep + dehydration (odds ratio [OR]: 3.87 for tubular impairment [tubules] and 3.47 for glomerular impairment [glomerulus]), long sleep + euhydration (OR: 2.43 for tubules), optimal sleep + dehydration (OR: 2.35 for tubules and 3.00 for glomerulus), short sleep + dehydration (OR: 2.07 for tubules and 2.69 for glomerulus), or short sleep + euhydration (OR: 1.29 for tubules) were more likely to present transient renal impairment, adjusting for sex, age, body mass index z-score, systolic blood pressure z-score, screen time, physical activity, and Mediterranean diet adherence. Conclusions: Dehydration and suboptimal sleep aggravate transient renal impairment in children, suggesting its role in maintaining pediatric kidney health. Full article

Background/Objectives: Phosphate is a macro-element involved in all cellular energetic processes. As about 90% of the phosphate filtered by the glomerulus is excreted by kidneys, the impairment of renal function and the consequent over-secretion of parathyroid hormone and fibroblast growth factor 23 results in the increase in the serum phosphate levels. The association between phosphate and hemoglobin is controversial, as both direct and indirect relationships have been reported. The present study aims to investigate the relationship between phosphate and hemoglobin in a large prospective, longitudinal cohort including dialysis patients from the Sicilian Registry of Nephrology, Dialysis, and Transplantation. Methods: In this prospective cohort study, we included 6263 hemodialysis patients to achieve a total of 120,462 repeated measurements of serum phosphate and hemoglobin over time. The longitudinal association between phosphate and hemoglobin was analyzed by univariate and multivariate Linear Mixed Models. Results: The mean age was 66 ± 16 years and the median dialysis vintage was 5 months [IQR: 2–16]. Mean and median values of hemoglobin and phosphate were 10.7 g/dL (SD 1.3 g/dL) and 4.6 mg/dL [IQR 3.9–5.5 mg/dL], respectively. The multivariate model, adjusted for potential confounders, confirmed the positive association between serum phosphate and hemoglobin [adjβ = 0.13, 95%CI 0.03–0.23, p = 0.01)]. These results were confirmed in analyses stratified for the use of phosphate binders. Conclusions: In our large cohort of dialysis patients, we found a linear, direct relationship between phosphate and hemoglobin levels. As a reduction in phosphate is associated with a parallel reduction in hemoglobin levels, hypophosphatemia can accentuate anemia in dialysis patients. Our results generate the hypothesis that monitoring serum phosphate in clinical practice might provide a better management of anemia. Full article