Search

The harmful effects of PM2.5 on human health, including an increased risk of chronic kidney disease (CKD), have raised a lot of attention, but the underlying mechanisms are unclear. We used the Shanghai Meteorological and Environmental Animal Exposure System (Shanghai-METAS) to simulate the inhalation of PM2.5 in the real environment and established an animal model by exposing C57BL/6 mice to filtered air (FA) and Particulate Matter (PM2.5) for 8 weeks. PM2.5 impaired the renal function of the mice, and the renal tubules underwent destructive changes. Analysis of NHANES data showed a correlation between reduced kidney function and higher blood levels of PM2.5 components, polychlorinated biphenyls (PCBs) and dioxins, which are Aryl hydrocarbon Receptor (AhR) ligands. PM2.5 exposure induced higher levels of AhR and CYP1A1 and oxidative stress as evidenced by the higher levels of ROS, MDA, and GSSG in kidneys of mice. PM2.5 exposure led to AhR overexpression and nuclear translocation in proximal renal tubular epithelial cells. Inhibition of AhR reduced CYP1A1 expression and PM2.5-increased levels of ROS, MDA and GSSG. Our study suggested metformin can mitigate PM2.5-induced oxidative stress by inhibiting the AhR/CYP1A1 pathway. These findings illuminated the role of AhR/CYP1A1 pathway in PM2.5-induced kidney injury and the protective effect of metformin on PM2.5-induced cellular damage, offering new insights for air pollution-related renal diseases. [ABSTRACT FROM AUTHOR]

Fanconi-Bickel syndrome (FBS) is a rare genetic disorder of carbohydrate metabolism due to pathogenic variants in SLC2A2, a gene encoding glucose transporter 2 (GLUT2), which leads to accumulation of glycogen in the kidney and liver. While consequential complex proximal tubular dysfunction is well acknowledged in the literature, long-term trajectories of kidney function in patients with FBS have not been well characterized, and kidney biopsy is performed infrequently. Here, we report on a patient with FBS followed from infancy through young adulthood who presented early on with hypercalciuria, phosphaturia, and hypophosphatemia, complicated by chronic kidney disease development during childhood. Kidney biopsy, in addition to a widespread glycogen accumulation in proximal tubular epithelial cells, demonstrated medullary nephrocalcinosis. Screening for nephrocalcinosis may be warranted in pediatric patients with FBS, along with close surveillance of their kidney function. [ABSTRACT FROM AUTHOR]

• PPE inhibited the development of glomeruli and promoted compensatory growth of renal tubules. • PPE at clinical dose disturbed fetal kidney development with a time-effect difference, manifested as full-term pregnancy exposure > early pregnancy exposure > mid-late pregnancy exposure. • The developmental toxicity of PPE on fetal kidney was more serious to the female fetuses than the males. Prednisone is a synthetic glucocorticoid that is commonly used in both human and veterinary medication. Now, it is also recognized as an emerging environmental contaminant. Pregnant women may be exposed to prednisone actively or passively through multiple pathways and cause developmental toxicity to the fetus. However, the impact of prenatal prednisone exposure (PPE) on fetal kidney development remains unclear. In this study, pregnant mice were administered prednisone intragastrically during full-term pregnancy with different doses (0.25, 0.5, or 1 mg/(kg·day)), or at the dose of 1 mg/(kg·day) in different gestational days (GD) (GD0-9, GD10-18, or GD0-18). The pregnant mice were euthanized on GD18. HE staining revealed fetal kidney dysplasia, with an enlarged glomerular Bowman's capsule space and a reduced capillary network in the PPE groups. The expression of the podocyte and the mesangial cell marker genes was significantly reduced in the PPE groups. However, overall gene expression in renal tubules and collecting ducts were markedly increased. All of the above effects were more pronounced in high-dose, full-term pregnancy, and female fetuses. Studies on the mechanism of the female fetal kidney have revealed that PPE reduced the expression of Six2, increased the expression of Hnf1β, Hnf4α, and Wnt9b, and inhibited the expression of glial cell line-derived neurotrophic factor (GDNF) and Notch signaling pathways. In conclusion, this study demonstrated that there is a sex difference in the developmental toxicity of PPE to the fetal kidney, and the time effect is manifested as full-term pregnancy > early pregnancy > mid-late pregnancy. [Display omitted] [ABSTRACT FROM AUTHOR]

We conduct a lab experiment that shows that current rules regulating transplant centers (TCs) and organ-procurement organizations (OPOs) create perverse incentives that inefficiently reduce both organ recovery and beneficial transplantations. We model the decision environment with a two-player multiround game between an OPO and a TC. In the condition that simulates current rules, OPOs recover only the highest-quality kidneys and forgo valuable recovery opportunities, and TCs decline some beneficial transplants. Alternative regulations that reward TCs and OPOs together for health outcomes in their entire patient pool lead to behaviors that increase organ recovery and appropriate transplants. [ABSTRACT FROM AUTHOR]

Purpose: To reduce the ringing artifacts of the motion‐resolved images in free‐breathing dynamic pulmonary MRI. Methods: A golden‐step based interleaving (GSI) technique was proposed to reduce ringing artifacts induced by diaphragm drifting. The pulmonary MRI data were acquired using a superior–inferior navigated 3D radial UTE sequence in an interleaved manner during free breathing. Successive interleaves were acquired in an incoherent fashion along the polar direction. Four‐dimensional images were reconstructed from the motion‐resolved k‐space data obtained by retrospectively binning. The reconstruction algorithms included standard nonuniform fast Fourier transform (NUFFT), Voronoi‐density‐compensated NUFFT, extra‐dimensional UTE, and motion‐state weighted motion‐compensation reconstruction. The proposed interleaving technique was compared with a conventional sequential interleaving (SeqI) technique on a phantom and eight subjects. Results: The quantified ringing artifacts level in the motion‐resolved image is positively correlated with the quantified nonuniformity level of the corresponding k‐space. The nonuniformity levels of the end‐expiratory and end‐inspiratory k‐space binned from GSI data (0.34 ± 0.07, 0.33 ± 0.05) are significantly lower with statistical significance (p < 0.05) than that binned from SeqI data (0.44 ± 0.11, 0.42 ± 0.12). Ringing artifacts are substantially reduced in the dynamic images of eight subjects acquired using the proposed technique in comparison with that acquired using the conventional SeqI technique. Conclusion: Ringing artifacts in the motion‐resolved images induced by diaphragm drifting can be reduced using the proposed GSI technique for free‐breathing dynamic pulmonary MRI. This technique has the potential to reduce ringing artifacts in free‐breathing liver and kidney MRI based on full‐echo interleaved 3D radial acquisition. [ABSTRACT FROM AUTHOR]

Soluble biochemical agents are being employed to generate kidney organoids from human‐induced pluripotent stem cells. However, this soluble factor approach does not consider the effect of the mechanical environment on lineage commitment. Here, a mechanoresponsive nano‐environment with cell‐adhesive properties composed of supramolecular hydrogelators that co‐assemble into fibrous superstructures to form a transient network is presented, which is used to encapsulate kidney organoids. The delayed sol‐gel transition of the transient network enables fibrous superstructures to diffuse into the densely packed extracellular organoid space during the encapsulation procedure. This allows the mechanoresponsive matrix to induce a biological response beyond the organoid‐hydrogel border, and tune glomerulogenesis inside kidney organoids. In this manner, biomaterials are used as a complementary tool to soluble biochemical agents in tuning lineage commitment and refining organoid maturation. [ABSTRACT FROM AUTHOR]

Backgrounds: Crush syndrome (CS) is the leading cause of death after earthquakes, second only to direct trauma. Acute kidney injury (AKI) is the most severe complication of CS. Research based on the CS-AKI mouse model and kidney function assessment by glomerular filtration rate (GFR) helps to elucidate the pathogenesis of CS-AKI, which contributes to effective treatment measures. Methods: Mice were modeled by the multi-channel small animal crushing platform. We set up different CS-AKI modeling parameters by applying different crushing weights (0.5 kg, 1.0 kg, 1.5 kg), crushing durations (6 h, 12 h, 16 h), and decompression durations (6 h, 12 h, 24 h). The GFR, serum creatinine (SCr), blood urea nitrogen (BUN), kidney tissue Kim-1 mRNA and Ngal mRNA expression levels, and HE staining were examined to evaluate the results of different protocols. Results: The results showed that with the crushing weight increased, the kidney function assessment’s gold standard GFR significantly decreased, and the levels of SCr and BUN increased. Meanwhile, the longer crushing durations found a higher extension of inflammatory cell infiltration in the kidney. The degree of kidney injury continued to worsen with the duration of decompression, indicating severe damage after reperfusion, which was associated with tubular injury and a sustained elevation of the inflammatory state. Conclusion: We successfully constructed CS-AKI mouse models with different severities under the above parameters. Applying 1.5 kg for 16 h and then decompressing for 24 h induced severe AKI. These findings provide clues for further exploration of the mechanism and treatment of traumatic AKI. [ABSTRACT FROM AUTHOR]

Background: Bilateral duplicated kidney and ureter is a rare condition in urology, and it is even rarer for patients to have multiple stones simultaneously. We delineate the diagnostic and therapeutic trajectory of a patient presenting with bilateral duplex kidneys and ureters, characterized by the presence of multiple stones. Notably, the left kidney is a complete duplication, whereas the right kidney exhibits an incomplete duplication. Case presentation: A 47-year-old male patient was diagnosed with bilateral duplex kidney and ureter combined with multiple stones. Ureteral flexible lithotripsy and percutaneous nephrolithotomy were performed successively in our hospital. On the postoperative five day, he was discharged from the hospital without apparent discomfort.The double J tube was pulled out one month later, and no stone recurrence was found after 3 months of follow-up. Conclusions: Bilateral duplicated renal ureteral malformations combined with multiple stones are very rare. Stones can be removed by ureteroscopic lithotripsy or percutaneous nephrolithotripsy and sometimes multiple procedures are required, which should be chosen according to the patient's relevant condition. [ABSTRACT FROM AUTHOR]

Urinary catheterisation is a crucial procedure in healthcare, requiring a thorough understanding of the anatomical and physiological differences between males and females to ensure safe and effective care. This guide explores the anatomy of the urinary system, detailing the kidneys, ureters, bladder, and urethra, and highlights key differences in catheterisation techniques for men and women. Emphasising evidence-based practices, it discusses recent advancements, such as antimicrobial catheters, and underscores the importance of comprehensive training and competency assessments for healthcare providers. Additionally, the guide advocates for patient-centred approaches, multidisciplinary collaboration, and adherence to updated policies to reduce complications such as catheter-associated urinary tract infections (CAUTIs). By integrating these critical evaluations and best practices, health professionals can enhance patient outcomes and maintain high standards of care in urinary catheterisation. [ABSTRACT FROM AUTHOR]

Background: Cachexia a multifactorial syndrome is a common sequala in patients with cancer. It varies from 42 to 80% depending upon the oncological stage and is directly responsible for 30% of deaths in these patients. Previous research from our laboratory demonstrated that peritoneal ovarian cancer generated in NSG mice resulted in skeletal and cardiac muscle atrophy - leading to loss of skeletal muscle mass and strength, and cardiac dysfunction (cachexia). Treatment of mice bearing i.p. tumors with withaferin A (WFA) showed reversal of skeletal muscle and cardiac cachexia. The present study is focused on determining effects of peritoneal ovarian tumors on kidney damage and effects of WFA treatment on ameliorating kidney damage. Methods: We generated intraperitoneal ovarian cancer by injecting female NSG mice with ovarian cancer cell line (A2780). After one week of injecting cancer cells, mice were treated with WFA (4 mg/kg) every third day, for three weeks. After 4 weeks of injection of cancer cells, the mice were sacrificed and various tissues including kidney and blood were collected, snap-frozen in liquid nitrogen, and stored at -800C. The presence of kidney biomarker creatinine, was measured in the plasma by an ELISA. The mRNA was isolated from mouse kidneys and was used to examine the expression levels of signaling proteins, inflammatory cytokines, and genes responsible for inducing cachexia (IL-1β, IL-6, TNF-α, TGF-β, GDF-15, and MYD88). Results: Our results showed a significant increase in levels of expression of inflammatory cytokine IL-1 β (p < 0.01), IL-6 (p < 0.001), TNF-α (p < 0.001), and other related genes including TRAF6 (p < 0.01), MYD88 (p < 0.01), and GDF-15 (p = 0.005) in tumor-bearing mice compared to controls. Treatment of mice bearing tumors with WFA attenuated the increase in expression of each gene. In addition, our results showed a significant increase in creatinine levels in circulation in tumor-bearing mice compared to control mice. Treatment of tumor-bearing mice with WFA resulted in a significant decrease in plasma creatinine levels compared to tumor-bearing mice. Conclusions: Our results conclude that ovarian tumors in NSG mice caused kidney damage and renal dysfunction, which was effectively ameliorated by WFA treatment, suggesting a protective effect of WFA on kidney injury induced by ovarian cancer. [ABSTRACT FROM AUTHOR]

Background: Among various growth parameters, liver and spleen size is an important parameter used for the evaluation of patients with certain disorders and abnormalities in these organs. Aim: To determine the normal dimensions for the liver, spleen, and kidney in Egyptian infants, children, and adolescents from birth to 18 years. Methods: This cross-sectional randomized study was conducted on 1861 Egyptian infants, children, and adolescents from birth to 18 years for the establishment of Z score reference of liver, spleen, and kidney parameters. Results: Egyptian children of both sexes (51.5% boys and 48.5% girls) from birth to 18 years old were studied. Then Z scores reference for liver, spleen, and kidney parameters for both sexes were represented in detailed tables and graphs. There was no statistically significant difference between both sexes, so we used unisex tables and graphs (P > 0.05). Conclusions: Determination of pathologic changes in the size of the liver, spleen, and kidney necessitates knowing the normal range of dimensions for these organs. So, our study established a Z score chart for normal values of liver, spleen, and kidney size for children and adolescents from birth to 18 years. [ABSTRACT FROM AUTHOR]

Background: T2 and T2* mapping are crucial components of quantitative magnetic resonance imaging, offering valuable insights into tissue characteristics and pathology. Single‐shot methods can achieve ultrafast T2 or T2* mapping by acquiring multiple readout echo trains. However, the extended echo trains pose challenges, such as compromised image quality and diminished quantification accuracy. Purpose: In this study, we develop a single‐shot method for ultrafast T2 and T2* mapping with reduced echo train length. Methods: The proposed method is based on ultrafast single‐shot spatiotemporally encoded (SPEN) MRI combined with reduced field of view (FOV) and spiral out‐in‐out‐in (OIOI) trajectory. Specifically, a biaxial SPEN excitation scheme was employed to excite the spin signal into the spatiotemporal encoding domain. The OIOI trajectory with high acquisition efficiency was employed to acquire signals within targeted reduced FOV. Through non‐Cartesian super‐resolved (SR) reconstruction, 12 aliasing‐free images with different echo times were obtained within 150 ms. These images were subsequently fitted to generate T2 or T2* mapping simultaneously using a derived model. Results: Accurate and co‐registered T2 and T2* maps were generated, closely resembling the reference maps. Numerical simulations demonstrated substantial consistency (R2 > 0.99) with the ground truth values. A mean difference of 0.6% and 1.7% was observed in T2 and T2*, respectively, in in vivo rat brain experiments compared to the reference. Moreover, the proposed method successfully obtained T2 and T2* mappings of rat kidney in free‐breathing mode, demonstrating its superiority over multishot methods lacking respiratory navigation. Conclusions: The results suggest that the proposed method can achieve ultrafast and accurate T2 and T2* mapping, potentially facilitating the application of T2 and T2* mapping in scenarios requiring high temporal resolution. [ABSTRACT FROM AUTHOR]

Pharmaceutical drugs and other chemicals can impact organogenesis, either during pregnancy or by postnatal exposure of very preterm infants. Corticosteroids are administered to pregnant women at risk of preterm delivery in order to reduce neonatal morbidity and mortality. In addition, high-dose corticosteroid exposure of very preterm infants regularly serves to maintain blood pressure and to prevent and treat bronchopulmonary dysplasia, a form of chronic lung disease in prematurely born infants. Despite clinical benefits, there is increasing evidence of corticosteroid-mediated short- and long-term detrimental developmental effects, especially in the kidney. Here, we performed a detailed morphological and functional analysis of corticosteroid-mediated effects on pronephros development in larval zebrafish. About 24-h postfertilization (hpf) transgenic Tg(wt1b: EGFP) zebrafish larvae were exposed to a set of natural and synthetic corticosteroids (hydrocortisone, dexamethasone, 6α-methylprednisolone, betamethasone, prednisolone, fludrocortisone, 11-deoxycorticosterone) with varying glucocorticoid and mineralocorticoid potency for 24 h at different concentrations. A semiautomated, multiparametric in vivo workflow enabled simultaneous assessment of kidney morphology, renal FITC-inulin clearance, and heart rate within the same larva. All corticosteroids exerted significant morphological and functional effects on pronephros development, including a significant hypertrophy of the pronephric glomeruli as well as dose-dependent increases in FITC-inulin clearance as a marker of glomerular filtration rate. In conclusion, the present study demonstrates a significant impact of corticosteroid exposure on kidney development and function in larval zebrafish. Hence, these studies underline that corticosteroid exposure of the fetus and the preterm neonate should be carefully considered due to potential short- and long-term harm to the kidney. [ABSTRACT FROM AUTHOR]

Simple Summary: It is vitally important that methods to combat climate change-induced effects on water availability are studied in agriculture. We have previously determined the voluntary water usage of modern broilers and, in this article, further explore the molecular differences between meat-type chickens that consume more or less water than average. We show here that sugar metabolites and the expression of glucose transporter genes in the kidneys are different between these birds. These differences can aid in the selection of birds that drink less water than average for the same feed intake and body weight gain. This could help reduce the use of water in the poultry industry. Molecular differences exist between birds with high residual water intake (HRWI) compared to those with low residual water intake (LRWI). Residual water intake (RWI) is defined as the difference between the water intake of a bird and the expected water intake corrected for metabolic body weight, feed intake, and body weight gain. Tissue metabolomic analysis revealed significantly increased kidney glucose, fructose, and arabitol in the LRWI group compared to the HRWI group. mRNA expression analysis of apical sodium glucose cotransporters SGLT1, SGLT4, SGLT5, and SGLT6 showed decreased expression of SGLTs 1, 5, and 6 in LRWI birds (p < 0.05), whereas SGLT4 expression was increased compared with HRWI birds (p < 0.01). An analysis of basal glucose transporters GLUT1, GLUT2, GLUT5, and GLUT9 showed significantly increased GLUT2 expression in LRWI birds compared with HRWI birds (p < 0.01). We postulate that SGLT4 is the main apical transporter in chicken kidneys and that its increased expression reduces these birds' need for water, resulting in less drinking. This is balanced by the increased expression of the basal transporter GLUT2, indicating better glucose retention, which may partly explain the physiological mechanism behind why these birds drink less water. Innately driven broiler water intake could therefore be influenced by the expression of kidney solute transporters. [ABSTRACT FROM AUTHOR]

Transporters for organic cations (OCs) facilitate exchange of positively charged molecules through the plasma membrane. Substrates for these transporters encompass neurotransmitters, metabolic byproducts, drugs, and xenobiotics. Consequently, these transporters actively contribute to the regulation of neurotransmission, cellular penetration and elimination process for metabolic products, drugs, and xenobiotics. Therefore, these transporters have significant physiological, pharmacological, and toxicological implications. In cells of renal proximal tubules, the vectorial secretion pathways for OCs involve expression of organic cation transporters (OCTs) and multidrug and toxin extrusion proteins (MATEs) on basolateral and apical membrane domains, respectively. This review provides an overview of documented regulatory mechanisms governing OCTs and MATEs. Additionally, regulation of these transporters under various pathological conditions is summarized. The expression and functionality of OCTs and MATEs are subject to diverse pre‐ and post‐translational modifications, providing insights into their regulation in various pathological conditions. Typically, in diseases, downregulation of transporter expression is observed, probably as a protective mechanism to prevent additional damage to kidney tissue. This regulation may be attributed to the intricate network of modifications these transporters undergo, shedding light on their dynamic responses in pathological contexts. [ABSTRACT FROM AUTHOR]

To identify potentially transplantable organs in a pool of marginal kidneys, 33 porcine slaughterhouse kidneys were perfused for 4 h with whole blood. During the normothermic perfusion, plasma, urine, and tissue samples were taken. Several biomarkers for tubule injury, endothelial activation, and inflammatory response were evaluated for a potential correlation with macroscopic appearance, histology, and filtration activity. Generally, biomarker levels increased during perfusion. TLR-4, EDN-1, and NGAL were not associated with any classification. In contrast, a steeper increase in NAG and IL-6 in plasma correlated with a poor macroscopic appearance at 4 h, indicating a higher inflammatory response in the kidneys with worse macroscopy early on, potentially due to more damage at the tubules. Although long-term effects on the graft could not be assessed in this setting, early observation under machine perfusion with whole blood was feasible. It allowed the assessment of kidneys under conditions comparable to reperfusion. This setting could give surgeons further insight into the quality of marginal kidneys and an opportunity to pre-treat them. [ABSTRACT FROM AUTHOR]

Purpose: This case report describes a patient with a pelvic kidney associated with an aortoiliac aneurysm amenable to open repair. Methods: We chose the selective cold renal perfusion to preserve renal function. Results: Other techniques such as transient or permanent extra-anatomic bypass, extracorporeal circulation and proximal aortic double clamping are also described in this report. Conclusions: Choosing the renal perfusion technique depended on the anatomical evaluations of the kidney and the renal artery location during the preoperative period. [ABSTRACT FROM AUTHOR]

The article focuses on a 10-year-old female with a month-long history of intermittent fever, fatigue, joint pain, and rash, whose condition worsened despite outpatient evaluation, prompting a return to the pediatric emergency department. Topics include the patient's medical history including epilepsy and recent COVID-19 vaccination, laboratory findings such as anemia and a positive respiratory pathogen panel for Coronavirus OC43.

To perform endoscopy in patients with urinary diversions requires specific endoscopic skills, which can currently only be gained in clinical practice. We created a 3D-printed ex vivo ileal conduit model (stoma and conduit with ureters and 2 kidneys) to simulate "conduitoscopy" and evaluated the realism and limitations of the model. Accurate anatomical features were represented using an appropriate reusable design, realistic mechanical qualities with several material types, and 3D-printed components. Different models of bowel and ureters were assessed by the subject-matter experts (SME). The final ileal conduit model (Wallace 1 type anastomosis) was evaluated by 18 SMEs. Most experts gave their approval to the view of the stoma, as well as the appearance of the bowel, ureteric, and pelvicalyceal systems. A total of 72.1% of SMEs approved the ureteric endoscopic view compared to about 66% who accepted the endoscopic examination of the bowel. The model's overall appearance was good for 61.1% and excellent for 38.8% of experts. Conduitoscopy simulation training can now be facilitated using our novel and unique cutting-edge 3D-printed model. We created a model that is highly anatomically accurate and workable. In our study, anatomical and visual realism was demonstrated. The next step would be increasing the length of the conduit and conduct a validation study. [ABSTRACT FROM AUTHOR]

Objective: To explore the usefulness of the 'differential renal length index' (iDRL) before and after pyeloplasty, as the anteroposterior diameter is commonly used to quantify hydronephrosis but inaccuracies arise due to interobserver variability, hydration status and pure intra‐renal dilatation. Patients and Methods: Prospectively collected data, from two centres, of all children undergoing pyeloplasty for isolated unilateral pelvi‐ureteric junction obstruction (PUJO) (2015–2021) were analysed. Subgroup analysis was undertaken: Group A – differential renal function (DRF) ≥40%, Group B – subnormal DRF (20–39%), and Group C – symptomatic. Children with structural anomalies of upper and lower urinary tract, bilateral involvement, and subnormal DRF (<20%) were excluded. All the children had a pre‐ and postoperative ultrasound scan and Tc99m mercapto‐acetyltriglycine (MAG3) renograms. The iDRL was calculated as follows: iDRL = ([a – b]/b) × 100, where 'a' is the length of hydronephrotic kidney (cm) and 'b' is the length of contralateral normal kidney (cm). The mean difference and standard error of mean (SEM) between the pre‐ and postoperative iDRL was evaluated using the paired Student's t‐test, with P < 0.05 considered statistically significant. Results: A total of 119 children with 1‐year follow‐up were included. For the entire cohort, the mean (SEM) preoperative iDRL was 27.7 (1.4) and postoperatively was 12.5 (1.1), with a mean (range) DRF improvement of 54% (44–66%) (P < 0.001). In Group A (n = 97), the mean (SEM) preoperative iDRL was 26.6 (1.5) and postoperatively was 13.1 (1.2), with a mean (range) DRF improvement of 50% (38–63%) (P < 0.001). In Group B (n = 22), the mean (SEM) preoperative iDRL was 32.6 (3.5) and postoperatively was 10.0 (2.8), with a mean (range) DRF improvement of 69% (49–89%) (P < 0.001). In Group C (n = 28), the mean (SEM) preoperative iDRL was 19.9 (2.3) and postoperatively was 7.7 (1.9), with a mean (range) DRF improvement of 61% (38–85%) (P < 0.001). Conclusion: Our study identifies the iDRL as a useful measure of improvement following successful pyeloplasty. In the subgroup with DRF of >39% minimum improvement was >37%. Similar minimum DRF improvement was also noted (>37%) in hypo‐functioning kidneys and symptomatic PUJO. [ABSTRACT FROM AUTHOR]

Unilateral kidney hypoplasia is a congenital condition characterized by the underdevelopment of one kidney. Although often asymptomatic, it can cause severe renal complications in patients combined with contralateral renal injury, leading to acute renal failure. This case report describes a patient with unilateral kidney hypoplasia who underwent a kidney biopsy on the contralateral normal‐sized kidney and subsequently developed oliguric acute kidney injury. This report discusses the challenges encountered while diagnosing and managing this rare case, highlighting the importance of awareness and recognition to perform timely intervention and optimize the patient's outcome. [ABSTRACT FROM AUTHOR]

Hyperammonemia (HA) can induce oxidative and nitrosative stress in peripheral organs, potentially exacerbating Hepatic Encephalopathy (HE). This study assessed the efficacy of Andrographis paniculata aqueous extract (APAE) in mitigating oxidative and nitrosative stress caused by non-cirrhotic HA in rat livers, spleens, and kidneys. HA was induced via intraperitoneal injection of ammonium acetate, while APAE was administered orally. The study measured malondialdehyde (MDA), superoxide dismutase (SOD), catalase, and glutathione reductase (GR) to gauge oxidative stress, and nitric oxide (NO) levels as a marker of nitrosative stress. Both acute and chronic HA altered the levels of antioxidant enzymes, MDA, and NO in the organs studied. APAE treatment helped restore SOD, catalase, and GR levels, and decreased MDA and NO levels, demonstrating its potential in reducing oxidative stress linked to HA in the liver, spleen, and kidney. [ABSTRACT FROM AUTHOR]

Aim: To elucidate the effects of sleep parameters and renal function on the risk of developing new‐onset severe metabolic dysfunction‐associated steatotic liver disease (MASLD). Materials and Methods: The primary analysis involved a cohort of 305 257 participants. Multivariable Cox models were employed to calculate hazard ratios and 95% confidence intervals. Traditional mediation and two‐step Mendelian randomization (MR) analyses were conducted to assess the associations and mediating roles of renal function indicators between sleep and new‐onset severe MASLD. Results: Poor sleep score and renal function biomarker score (RFS) were associated with an increased risk of new‐onset severe MASLD (all ptrend <0.001). Participants with poor sleep patterns and the highest RFS had a 5.45‐fold higher risk of new‐onset severe MASLD, compared to those with healthy sleep patterns and the lowest RFS (p < 0.001). The RFS could explain 10.08% of the correlations between poor sleep score and risk of new‐onset severe MASLD. Additionally, MR analyses supported a causal link between insomnia and new‐onset severe MASLD and revealed a mediating role of chronic kidney disease in the connection between insomnia and new‐onset severe MASLD risk. Conclusions: This study highlights the independent and combined associations of sleep parameters and renal function indicators with new‐onset severe MASLD, underscoring the bidirectional communication of the liver–kidney axis and providing modifiable strategies for preventing MASLD. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the renal fat deposition on Dixon-based magnetic resonance imaging (MRI) and to explore the predictive value of renal fat biomarkers of magnetic resonance (MR-RFBs) for early kidney damage in obesity. Methods: This prospective study included 56 obese volunteers and 47 non-obese healthy volunteers. All volunteers underwent renal magnetic resonance examinations. The differences in MR-RFBs [including renal proton density fat fraction (PDFF), renal sinus fat volume (RSFV), and perirenal fat thickness (PRFT)] measured on Dixon-based MRI between the obese and non-obese volunteers were analyzed using a general linear model, taking sex, age, diabetes, and hypertension as covariates. The relationship between estimated glomerular filtration rate (eGFR) and demographic, laboratory, and imaging parameters in obese volunteers was examined by correlation analysis. Results: Obese volunteers had higher MR-RFBs than non-obese volunteers after controlling for confounders (all p < 0.001). Renal PDFF (r = − 0.383; p = 0.004), RSFV (r = − 0.368; p = 0.005), and PRFT (r = − 0.451; p < 0.001) were significantly negatively correlated with eGFR in obesity. After adjusting for age, sex, body mass index, diabetes, hypertension, visceral adipose tissue, subcutaneous adipose tissue, renal PDFF, and RSFV, PRFT remained independently negatively associated with eGFR (β = − 0.587; p = 0.003). Conclusions: All MR-RFBs are negatively correlated with eGFR in obesity. The MR-RFBs, especially PRFT, may have predictive value for early kidney damage in obesity. [ABSTRACT FROM AUTHOR]

Background: Craniospinal irradiation (CSI) poses a challenging planning process because of the complex target volume. Traditional 3D conformal CSI does not spare any critical organs, resulting in toxicity in patients. Here the dosimetric advantages of volumetricmodulated arc therapy (VMAT) using partial arc and avoidance sectors are compared with each other in planning in adult patients undergoing CSI to develop a clinically feasible technique that is both effective and efficient. Patient and methods: Eight adult patients treated with CSI were retrospectively identified. In total 16 plans were made. We generated two plans for each patient: 1. VMAT plan using partial arc, namely VMAT&lowbar;pa. 2. VMAT plan using avoidance sectors, namely VMAT&lowbar;as. The dose prescribed was 36 Gy in 20 fractions. The dose-volume histogram for planning target volume (PTV) and organs at risk (OAR) (lens, eye, heart, thyroid, lungs, liver, gonads and kidneys) were analysed and compared. Dose parameters of mean dose, V95%, and V107% for the PTV were evaluated. Results: The median length of PTV is 65.58 cm (45.8-79.5). The volume of PTV receiving 95% of the dose (V95%) in both the plans are 97.51% (VMAT&lowbar;as) and 97.99% (VMAT&lowbar;pa) (p = 0.121) while V107% are 0.733 and 0.742 for VMAT&lowbar;as and VMAT&lowbar;pa, respectively (p = 0.969). The doses of OARs such as lens, eye, liver and gonads were comparable. The mean heart dose was 10.4 and 9.0 Gy in VMAT&lowbar;as and VMAT&lowbar;pa plans, respectively (p = 0.005). Significant lower doses to the thyroid, kidneys and lungs were seen in VMAT plans using avoidance sectors. Conclusion: This study provides a practically useful VMAT planning method for the treatment of CSI and illustrates the ability of VMAT using avoidance sectors to generate highly conformal and homogeneous treatment plans for CSI, while limiting the dose to the relevant OARs. [ABSTRACT FROM AUTHOR]

Background: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and glomerulonephritis is uncommon in children. We sought to characterize the histological and clinical features of the disease and report on risk factors for adverse outcomes in a pediatric cohort. Methods: Retrospective single-center cohort of all pediatric (< 20 years) patients diagnosed with ANCA-associated glomerulonephritis (AAGN) by kidney biopsy between 2002 and 2022 at Johns Hopkins University. Histological and clinical features were extracted from the medical record. Clinical, laboratory, and histological findings were analyzed to determine the association with kidney failure (KF) and/or death. Results: A total of 17 patients were identified (GPA n = 7, MPA = 10) with a median age of 15 years (IQR 12–17) at presentation, a slight female predominance (59%), with seven patients reaching the composite outcome of death (n = 1) or kidney failure (n = 6). There was no difference in presenting clinical symptoms or extra-renal manifestations between the two groups. Univariable Cox regression identified several factors associated with an increased hazard of endpoint including the degree of global or segmental sclerosis, interstitial fibrosis and tubular atrophy (IFTA), C3 and C1q staining, presence of subendothelial deposits, and proteinuria. Multivariable regression was not performed due to the small sample size. We saw a trend towards increased utilization of plasma exchange and a decrease in cyclophosphamide utilization in the more recent era. There was no association between treatment modality and outcome. Conclusions: Pediatric AAGN is a rare disease associated with significant morbidity. We identified glomerulosclerosis and IFTA on histology, and proteinuria on initial presentation as risk factors for KF/death. [ABSTRACT FROM AUTHOR]

Background: Evaluating glomerular filtration rate (GFR) remains challenging in pediatrics; new formulas were developed to increase performance of GFR estimation (eGFR). We aimed to evaluate the recently published formulas as applied to another pediatric population. Methods: A retrospective study was conducted in a cohort of 307 patients with a "kidney risk" (mean age 12.1 ± 4.5 years, sex ratio 1/1) assessed in a tertiary pediatric nephrology center and a mean measured GFR (mGFR) using plasma iohexol clearance of 85.5 ± 25.3 mL/min/1.73 m2; creatinine levels were measured by IDMS-standardized enzymatic method and cystatin C by immunonephelometry. The following eGFRs were calculated: Schwartz2009, Schwartz-Lyon, CKiDU25creat, and EKFC for eGFR using creatinine (eGFR-creat), CKiDU25cys and FAScys for eGFR using cystatin (eGFR-cys) as well as combined SchwartzCreat-Cys, average (CKiDU25creat-CKiDU25cys), and average (EKFC-FAScys) for eGFR using both biomarkers. The performance of the different formulas was evaluated compared to mGFR by absolute bias measurement and accuracy (p10%, p30%). Results are expressed as mean ± SD. Results: Creatinine-based formulas and especially the new CKiDU25 and EKFC overestimate GFR, even in children with normal kidney function. However, the bias is constant with these two formulas whatever the age group or gender, contrary to the previously published formulas. In contrast, cystatin C-based equations and combined formulas showed good performance in all age groups and all medical conditions with an acceptable bias and p30%. Conclusions: In our pediatric population, the performance of all creatinine-based formulas is inadequate with significant GFR overestimation, mainly in subjects with mGFR > 75 mL/min/1.73 m2. Conversely, cystatin C-based or combined formulas have acceptable performance in patients followed in a tertiary pediatric nephrology unit. [ABSTRACT FROM AUTHOR]

Introduction: Patients frequently present with renal impairment that does not fit the criteria for acute kidney injury or chronic kidney disease. This condition, known as rapidly progressive renal failure (RPRF), encompasses a diverse range of clinical syndromes characterized by the progressive renal impairment over days to weeks. Case Report: We present a case of a 37-year-old male with a short history of uremic symptoms and decreased urine output with no significant history or examination findings except pallor. The patient had a creatinine of 1.6 mg/dL in April 2022, rising to 4.4 mg/dL, then 11.6 mg/dL during May, 17.6 mg/dL in June, presented to us with a creatinine of 24.6 mg/dL, with normal kidney size and corticomedullary differentiation (CMD). Beta-2-microglobulin was elevated, and renal biopsy showed features suggestive of multiple myeloma (MM). Atypical appearing tubular casts showing 3+ patternless staining for kappa light chains and negativity for lambda light chains were observed. The patient was started on chemotherapy for MM, and renal function was gradually improving. Conclusion: Renal failure as the sole presentation of MM is rare, especially in young adults. This case emphasizes an atypical RPRF, particularly given the patient's young age. [ABSTRACT FROM AUTHOR]

Background: Distal renal tubular acidosis (dRTA) is a condition characterized by the impaired ability to secrete hydrogen ions from the distal tubule. In pediatric patients, common clinical features of dRTA include excessive urine production (polyuria), frequent nighttime urination (nocturia), poor growth and weight gain (failure to thrive), difficulty with bowel movements (constipation), abnormal breathing, and the presence of kidney stones (nephrolithiasis). While urinary tract infections (UTIs) are frequently associated with dRTA, renal failure is uncommon and seldom reported in children. Case Presentation: A 10-year-old girl was referred for the evaluation due to a progressive loss of gross motor milestones over a period of 3 years. She also experienced an acute episode of paralysis and was found to have bilateral medullary nephrocalcinosis (right staghorn calculus) accompanied by moderate renal failure and a UTI. Her development in other areas was appropriate for her age. Importantly, there was a history suggestive of excessive urine production (polyuria), increased thirst (polydipsia), and frequent nighttime urination (nocturia). Physical examination revealed proximal myopathy, characterized by a waddling gait and a positive Gower's sign, as well as diminished reflexes and muscle tone in the lower limbs. Laboratory tests indicated the presence of sepsis (total leukocyte count – 26,660, CRP-174.29) and elevated renal parameters (serum creatinine – 4.27) along with active urinary abnormalities. Urine culture and sensitivity testing showed significant growth of Escherichia coli (>100,000 CFU). A computed tomography scan of the kidneys, ureters, and bladder revealed a staghorn calculus on the right side, as well as bilateral medullary nephrocalcinosis and swollen kidneys. The patient was diagnosed with dRTA based on several factors, including hypokalemic hyperchloremic metabolic acidosis with a normal anion gap, high urine pH, borderline hypercalciuria, presence of medullary nephrocalcinosis, and after ruling out other potential differential diagnoses. Following treatment for the UTI and sepsis, as well as standard treatment for dRTA, the child exhibited symptomatic improvement. Her creatinine levels returned to 0.8 mg/dL, and the septic markers declined to normal levels. To further investigate the cause of the initial decline in renal function in addition to the UTI, a renal biopsy was performed. Conclusion: This case report emphasizes the significance of including medullary nephrocalcinosis and renal tubular acidosis in the list of potential diagnoses for patients presenting with progressive gross motor developmental regression, acute flaccid paralysis, and proximal myopathy. Timely identification of these conditions can help avoid unnecessary and expensive investigations, while also facilitating prompt clinical recovery in affected children. Early diagnosis plays a crucial role in guiding appropriate management strategies and improving patient outcomes. [ABSTRACT FROM AUTHOR]

Objective: Signal regulatory protein α (SIRPα) is found primarily on myeloid cells, including macrophages and neutrophils; binds to CD47; and regulates phagocytosis, antigen presentation, cellular fusion, cell proliferation, and migration. Therefore, SIRPα may be involved in the pathogenesis of autoimmune diseases, including systemic vasculitis. This study aimed to assess SIRPα expression in tissue samples from patients with vasculitis. Methods: Immunohistochemical staining for SIRPα was performed on temporal artery (TA), kidney, and lung biopsy samples from patients with giant cell arteritis (GCA), patients with microscopic polyangiitis (MPA), patients with granulomatosis with polyangiitis (GPA), and patients without vasculitis. A score of SIRPα+ expression was calculated, derived from the percentages of monocytes, macrophages, and dendritic cells and neutrophils with different staining intensities in affected tissues. Results: A total of 46 samples from patients with different vasculitides (GCA, MPA, and GPA) were included in the study. Tissue samples included TA samples from 15 patients with GCA; kidney samples from 11 and 9 patients with GPA and MPA, respectively; and lung samples from 11 patients with GPA. Most tissue samples from patients with active vasculitis (15 of 15 TA samples, 17 of 20 kidney samples, and 9 of 11 lung samples) showed SIRPα staining. SIRPα staining intensity was less in kidney samples compared to TA and lung samples. Conclusion: This study demonstrates high‐level expression of SIRPα in macrophages and monocytes in affected tissue in systemic vasculitis. These findings provide a foundation for further studies exploring the role of the SIRPα–CD47 pathway in the pathogenesis of systemic vasculitis and the potential for the blockade of SIRPα and/or the depletion of SIRPα+ cells as treatment of systemic vasculitis. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to explore the potential role of CYP3A5 (c. 6986A>G) gene polymorphism in predicting kidney function impairment in patients with hypertension who did not have elevated serum cystatin C. Methods: We recruited a group of patients with hypertension who did not have elevated cystatin C and analyzed the CYP3A5 (c. 6986A>G) gene polymorphism. Chi-square tests were used to compare the clinical characteristics and genotypic distribution between the two groups. Logistic regression analysis was used to explore the association between CYP3A5 (c.6986A>G) gene polymorphism and renal function impairment in hypertension with non-elevated cystatin. Results: In patients with hypertension who participated in the study, there was a significant association between CYP3A5 (c. 6986A>G) gene polymorphism and kidney function impairment (p < 0.05). Patients with the CYP3A5 (c. 6986A>G) mutation display a greater risk of kidney function impairment. Conclusion: CYP3A5 (c. 6986A>G) gene AA homozygote polymorphism significantly increases risk of kidney function impairment in patients with hypertension with normal cystatin C. However, further studies are needed to validate this association and to further understand the mechanism of CYP3A5 (c. 6986A>G) gene polymorphism in kidney function impairment in patients with hypertension. The graphical abstract of CYP3A5 (c.6986A>G) gene polymorphism to predicting kidney injury of patients with hypertension complicated with normal cystatin C. [ABSTRACT FROM AUTHOR]

In Egypt, while many studies have focused on the radiometry and mineralogy of black sands, research on their effects on nearby aquatic organisms is rare. This study aimed to assess the combined effects of heat stress (HS) and black sand nanoparticles (BS-NPs) on renal function, antioxidant responses (TAC, SOD, CAT), neuro-stress indicators (AchE, cortisol), and to conduct histopathological investigations in the kidney and spleen tissues of African catfish Clarias gariepinus over a 15-day period to exposure to control, HS (32 °C), BS (6.4 g/kg diet) and HS + BS groups. The outcomes revealed that thermal stress alone showed no significant difference from the control. However, creatinine and uric acid levels were significantly higher in the BS-NPs and HS + BS-NPs groups (p < 0.001). Antioxidant markers (TAC, SOD, and CAT) were substantially reduced across all treated groups (0.05 ≥ p < 0.0001). AchE levels were significantly elevated in BS-NPs and HS + BS-NPs (p < 0.001), while cortisol levels were higher in these groups but not significantly different in HS. Degeneration and necrosis in the white and red pulps, scattered lymphocytes, and increased collagen fiber surrounding blood vessels and the lining of the ellipsoid structure were all evident in the spleen, along with the enlargement of the melanomacrophage centers with big granular, irregular, and brown pigments (hemosiderin). Our study, therefore, provides new insights into how heat stress, an abiotic environmental factor, influences the toxicity of black sand nanoparticles in catfish. [ABSTRACT FROM AUTHOR]

An analytical method was developed for identification and quantification of zilpaterol in bovine liver, meat, heart, and kidney, using liquid chromatography coupled to quadrupole-Orbitrap high-resolution mass spectrometry (LC-Q-Orbitrap HRMS). It was validated in accordance with Commission Implementing Regulation (CIR) EU 2021/808 at six different concentrations, ranging from 0.1 to 5 μg/kg. The mean recoveries ranged from 71% to 99%, while the decision limit (CCα) and detection capability (CCβ) ranges were 0.11–0.12 μg/kg and 0.13–0.15 μg/kg, respectively. The method demonstrated good linearity (R2 > 0.9996) and the limits of detection (LODs) and of quantification (LOQs) were in the range of 0.015–0.061 μg/kg and 0.025–0.091 μg/kg, respectively. Out of 200 samples collected from local markets in Egypt, 17 contained zilpaterol residues. Liver samples revealed the highest detection frequency (26%), followed by meat (6%), at mean concentrations of 2.64 and 1.93 μg/kg, respectively. [ABSTRACT FROM AUTHOR]

Kidney diseases represent a diverse range of conditions that compromise renal function and structure which characterized by a progressive deterioration of kidney function, may ultimately necessitate dialysis or kidney transplantation as end-stage treatment options. This review explores the complex landscape of kidney diseases, highlighting the limitations of existing treatments and the pressing need for innovative strategies. The paper delves into the role of extracellular vesicles (EVs) as emerging biomarkers and therapeutic agents in the context of kidney pathophysiology. Urinary extracellular vesicles (uEVs), in particular, offer a non-invasive means of assessing renal injury and monitoring disease progression. Additionally, mesenchymal stem cell-derived EVs (MSC-EVs) are examined for their immunomodulatory and tissue repair capabilities, presenting a promising avenue for novel therapeutic interventions. And discusses the potential of engineering EVs to enhance their targeting and therapeutic efficacy. This paper systematically integrates the latest research findings and aims to provide a comprehensive overview of the role of EVs in kidney disease, providing cutting-edge insights into their potential as a diagnostic and therapeutic tool. [ABSTRACT FROM AUTHOR]

ABSTRACT The aim of this study was to determine pharmacokinetics of florfenicol and its metabolite florfenicol amine after a single (30 mg/kg) intravenous (IV) and oral administration of florfenicol in chukar partridges. It also aimed to investigate tissue residue and withdrawal time of florfenicol after multiple‐dose (30 mg/kg, every 24 h for 5 days) oral administration. The research was carried out in two stages: pharmacokinetics and residue. Plasma and tissue concentrations of florfenicol and florfenicol amine were determined by HPLC. The elimination half‐life of florfenicol was 5.25 h for IV and 5.44 h for oral. The volume of distribution at a steady state and total body clearance of florfenicol were 0.38 L/kg and 0.07 L/h/kg, respectively, after IV administration. The peak plasma concentration and bioavailability for oral administration were 45.26 ± 4.06 and 51.55%, respectively. After multiple‐dose oral administration, the highest concentration was detected in the liver (9.21 μg/g) for florfenicol and in the kidney (0.67 μg/g) for florfeniol amine. The calculated withdrawal period of florfenicol was determined as 6, 3, 4, and 5 days for muscle, liver, kidney, and skin + fat, respectively. These data indicate that a 6‐day WT after multiple‐dose administration of florfenicol in chukar partridges can be considered safe for human consumption. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigates the influence of various pharmacokinetic parameters on 177Lu-PSMA therapies via physical, biological, and statistical measures. Employing a clinically validated physiologically based pharmacokinetic (PBPK) model, realistic time–activity curves (TACs) in tumors, salivary glands, and kidneys are generated, allowing for the calculation of metrics such as AUC, dose, BED, and fBED. The results demonstrate the significant impact of multiple parameters on the measured outcomes. In addition to the great impact of administered ligand amount, tumor volume, and receptor density, other pharmacokinetic parameters such as rates of radiopharmaceutical association, internalization, and release were identified as key influencers. Notably, alterations in the parameters induced distinct modifications in TAC features, affecting radiobiological, pharmacokinetic, and statistical aspects. These insights contribute to advancing personalized treatment regimens by understanding the key contributions of various parameters towards improving therapeutic efficacy while minimizing radiation-related toxicities. Purpose: To investigate the impact of physiologically based pharmacokinetic (PBPK) parameters on physical, biological, and statistical measures in lutetium-177-labeled radiopharmaceutical therapies (RPTs) targeting the prostate-specific membrane antigen (PSMA). Methods: Using a clinically validated PBPK model, realistic time–activity curves (TACs) for tumors, salivary glands, and kidneys were generated based on various model parameters. These TACs were used to calculate the area-under-the-TAC (AUC), dose, biologically effective dose (BED), and figure-of-merit BED (fBED). The effects of these parameters on radiobiological, pharmacokinetic, time, and statistical features were assessed. Results: Manipulating PBPK parameters significantly influenced AUC, dose, BED, and fBED outcomes across four different BED models. Higher association rates increased AUC, dose, and BED values for tumors, with minimal impact on non-target organs. Increased internalization rates reduced AUC and dose for tumors and kidneys. Higher serum protein-binding rates decreased AUC and dose for all tissues. Elevated tumor receptor density and ligand amounts enhanced uptake and effectiveness in tumors. Larger tumor volumes required dosimetry adjustments to maintain efficacy. Setting the tumor release rate to zero intensified the impact of association and internalization rates, enhancing tumor targeting while minimizing the effects on salivary glands and kidneys. Conclusions: Optimizing PBPK parameters can enhance the efficacy of lutetium-177-labeled RPTs targeting PSMA, providing insights for personalized and effective treatment regimens to minimize toxicity and improve therapeutic outcomes. [ABSTRACT FROM AUTHOR]

Introduction and purpose Contrast enhanced ultrasound (CEUS) is a modern diagnostic method that uses ultrasound waves in combination with intravenous administration of a contrast agent. It enables obtaining high resolution and assessing microcirculation in real time, thanks to which the researcher is able to analyze the enhancement and its features, which may help in diagnosing a specific pathology. Contrast agents, similar to CT and MRI, show specific phases of enhancement after administration - arterial, venous, delayed. Their additional advantage is safety, especially for patients with impaired kidney and thyroid function, and causing fewer allergic reactions. The aim of this review is to present the CEUS examination technique and the latest reports in the field of diagnosis of renal lesions. Material and methods This review was prepared based on the literature available from recent years in the PubMed and Google Scholar scientific databases using the keywords: ultrasonography, contrast enhanced ultrasonography, kidney, renal masses. Results Studies show that CEUS can be an effective method for imaging both cystic and solid lesions in the kidney. When using a contrast agent, the lesions show characteristic features that can guide the investigator to the diagnosis. Moreover, in comparative analyses, CEUS achieved comparable or better results than other diagnostic imaging methods. Conclusions CEUS is a modern and promising diagnostic method that can successfully compete with CT and MRI. Moreover, the metabolism and pharmacokinetics of contrast agents and their safety mean that CEUS can be used for the diagnosis of unclear pathologies in elderly patients, as well as for the control and supervision of changes that require frequent imaging. [ABSTRACT FROM AUTHOR]

Background: Research biopsies have great potential to advance scientific knowledge by helping to establish predictors of favourable or unfavourable outcomes in kidney transplantation. We evaluated punch and core biopsies of different sizes to determine the optimal size for clinical use. Methods: A total of 54 punch biopsies and 18 core needle biopsies were retrieved by three transplant surgeons. Each surgeon obtained three separate 2 mm, 3 mm and 4 mm punch biopsy samples and three 23 mm (length) core needle biopsies from two pig kidneys. Results: 4 mm punch biopsies yielded the greatest amount of protein (2.11 ± 0.41 mg) with good reproducibility between surgeons and biopsy types (Coefficient of Variation ∼ 22.13%). All surgeons found 2 mm biopsies technically challenging to obtain and sample processing was difficult due to the sample size. Shotgun proteomics identified 3853 gene products with no significant difference in the quantitative proteome of 2 mm and 3 mm punch biopsies. However, the expression of 158 Kidney enriched genes, was higher in bigger and deeper 4 mm punch and core needle biopsies compared to 2 mm biopsy. Only 80% of 2 mm biopsies demonstrated the presence of glomeruli, whereas glomeruli were present in 100% of all other biopsy sizes. Conclusions: The 2 mm punch biopsy has been shown to be challenging to use and frequently provides inadequate tissue for histology and proteomics while 3 mm research biopsies were the smallest size that were technically obtainable with adequate tissue for molecular studies. [ABSTRACT FROM AUTHOR]

Summary Patients with AL amyloidosis can have persistent organ dysfunction despite achieving a haematological complete response (hemCR). We aimed to identify factors for organ non‐response among 143 patients who achieved hemCR for ≥6 months. Kidney, heart and liver non‐response were observed in 40/117 (34%), 19/68 (28%) and 3/17 (18%) patients respectively. Predisposing factors varied by organ system. Kidney non‐responders had more advanced organ dysfunction at diagnosis, whereas heart non‐responders had disproportionately more lambda‐typic amyloidogenic light chains. Most patients without an apparent reason for organ non‐response had detectable residual clonal disease. The interplay of factors impeding organ recovery in AL amyloidosis is complex. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that Averrhoa carambola L. possesses therapeutic potential for diabetes and related complications. However, the specific beneficial effects and molecular mechanisms of 2-dodecyl-6-meth-oxycyclohexa-2,5-diene-1,4-dione (DMDD) isolated from Averrhoa carambola L. on diabetic nephropathy (DN) require further investigation. Methods: 80 C57BL/6 J male mice were subjected to a 1-week adaptive feeding, followed by a high-fat diet and intraperitoneal injection of 100 mg/kg streptozotocin (STZ) to construct an in vivo DN model. Additionally, human renal proximal tubular epithelial cells (HK-2) induced by high glucose (HG) were used as an in vitro DN model. The expression levels of epithelial-mesenchymal transition (EMT), endoplasmic reticulum stress (ERS), and autophagy-related proteins in renal tubular cells were detected by Western Blot, flow cytometry, immunofluorescence, and enzyme-linked immunosorbent assay (ELISA) staining. Transcriptome analysis revealed was conducted to elucidate the specific mechanism of by which DMDD mitigates DN by inhibiting ERS and autophagy. HK-2 cells were transfected with IRE1α overexpression lentivirus to reveal the role of IRE1α overexpression in HG-induced HK-2. Results: The experimental data showed that DMDD significantly reduced blood glucose levels and improved renal pathological alterations in DN mice. Additionally, DMDD inhibited the calcium (Ca2+) pathway, manifested by decreased autophagosome formation and downregulation of LC3II/I, Beclin-1, and ATG5 expression. Moreover, in HG-induced HK-2 cells, DMDD suppressed the overexpression of GRP78, CHOP, LC3II/I, Beclin1, and ATG5. Notably, IRE1α overexpression significantly increased autophagy incidence; however, DMDD treatment subsequently reduced the expression of LC3II/I, Beclin1, and ATG5. Conclusion: DMDD effectively inhibits excessive ERS and autophagy, thereby reducing renal cell apoptosis through the IRE1α pathway and Ca 2+ pathway. [ABSTRACT FROM AUTHOR]

We performed a series of integrative analyses including transcriptome-wide association studies (TWASs) and proteome-wide association studies (PWASs) of renal cell carcinoma (RCC) to nominate and prioritize molecular targets for laboratory investigation. On the basis of a genome-wide association study (GWAS) of 29,020 affected individuals and 835,670 control individuals and prediction models trained in transcriptomic reference models, our TWAS across four kidney transcriptomes (GTEx kidney cortex, kidney tubules, TCGA-KIRC [The Cancer Genome Atlas kidney renal clear-cell carcinoma], and TCGA-KIRP [TCGA kidney renal papillary cell carcinoma]) identified 38 gene associations (false-discovery rate <5%) in at least two of four transcriptomic panels and identified 12 genes that were independent of GWAS susceptibility regions. Analyses combining TWAS associations across 48 tissues from GTEx identified associations that were replicable in tumor transcriptomes for 23 additional genes. Analyses by the two major histologic types (clear-cell RCC and papillary RCC) revealed subtype-specific associations, although at least three gene associations were common to both subtypes. PWAS identified 13 associated proteins, all mapping to GWAS-significant loci. TWAS-identified genes were enriched for active enhancer or promoter regions in RCC tumors and hypoxia-inducible factor binding sites in relevant cell lines. Using gene expression correlation, common cancers (breast and prostate) and RCC risk factors (e.g., hypertension and BMI) display genetic contributions shared with RCC. Our work identifies potential molecular targets for RCC susceptibility for downstream functional investigation. We conducted a series of integrative analyses, including transcriptome-wide and proteome-wide association studies, to identify and prioritize genes and proteins for renal cell carcinoma (RCC) and its two major histologic subtypes. We establish relevance of the findings in relation to known genomic features, transcription factors, and risk factors for RCC. [ABSTRACT FROM AUTHOR]

Background An adequate workforce is needed to guarantee optimal kidney care. We used the International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA) to provide an assessment of the global kidney care workforce. Methods We conducted a multinational cross-sectional survey to evaluate the global capacity of kidney care and assessed data on the number of adult and paediatric nephrologists, the number of trainees in nephrology and shortages of various cadres of the workforce for kidney care. Data are presented according to the ISN region and World Bank income categories. Results Overall, stakeholders from 167 countries responded to the survey. The median global prevalence of nephrologists was 11.75 per million population (pmp) (interquartile range [IQR] 1.78–24.76). Four regions had median nephrologist prevalences below the global median: Africa (1.12 pmp), South Asia (1.81 pmp), Oceania and Southeast Asia (3.18 pmp) and newly independent states and Russia (9.78 pmp). The overall prevalence of paediatric nephrologists was 0.69 pmp (IQR 0.03–1.78), while overall nephrology trainee prevalence was 1.15 pmp (IQR 0.18–3.81), with significant variations across both regions and World Bank income groups. More than half of the countries reported shortages of transplant surgeons (65%), nephrologists (64%), vascular access coordinators (59%), dialysis nurses (58%) and interventional radiologists (54%), with severe shortages reported in low- and lower-middle-income countries. Conclusions There are significant limitations in the available kidney care workforce in large parts of the world. To ensure the delivery of optimal kidney care worldwide, it is essential to develop national and international strategies and training capacity to address workforce shortages. [ABSTRACT FROM AUTHOR]

Severity of deceased donor kidney fibrosis impacts graft survival in deceased-donor kidney transplantation. Our aim was to identify potential miRNA biomarkers in urinary exosomes that mirror interstitial fibrosis and tubular atrophy (IFTA) severity. Among 109 urine samples from deceased donors, 34 displayed no IFTA in the zero-day biopsy (No IFTA group), while the remaining 75 deceased donor kidneys exhibited an IFTA score ≥ 1 (IFTA group). After analyzing previous reports and electronic databases, six miRNAs (miR-19, miR-21, miR-29c, miR-150, miR-200b, and miR-205) were selected as potential IFTA biomarker candidates. MiR-21, miR-29c, miR-150, and miR-205 levels were significantly higher, while miR-19 expression was significantly lower in the IFTA group. MiR-21 (AUC = 0.762; P < 0.001) and miR-29c (AUC = 0.795; P < 0.001) showed good predictive accuracy for IFTA. In the No IFTA group, the eGFR level at 1 week after transplantation was significantly higher compared to the IFTA group (41.34 mL/min/1.73m2 vs. 28.65 mL/min/1.73m2, P = 0.012). These findings signify the potential of urinary exosomal miRNAs as valuable biomarker candidates for evaluating the severity of IFTA in deceased donor kidneys before they undergo recovery. [ABSTRACT FROM AUTHOR]

Renal clearable nanoparticles have been drawing much attention as they can avoid prolonged accumulation in the body by efficiently clearing through the kidneys. While much effort has been made to understand their interactions within the kidneys, it remains unclear whether their transport could be influenced by other organs, such as the liver, which plays a crucial role in metabolizing and eliminating both endogenous and exogenous substances through various biotransformation processes. Here, by utilizing renal clearable IRDye800CW conjugated gold nanocluster (800CW4‐GS18‐Au25) as a model, we found that although 800CW4‐GS18‐Au25 strongly resisted serum‐protein binding and exhibited minimal accumulation in the liver, its surface was still gradually modified by hepatic glutathione‐mediated biotransformation when passing through the liver, resulting in the dissociation of IRDye800CW from Au25 and biotransformation‐generated fingerprint message of 800CW4‐GS18‐Au25 in urine, which allowed us to facilely quantify its urinary biotransformation index (UBI) via urine chromatography analysis. Moreover, we observed the linear correlation between UBI and hepatic glutathione concentration, offering us a noninvasive method for quantitative detection of liver glutathione level through a simple urine test. Our discoveries would broaden the fundamental understanding of in vivo transport of nanoparticles and advance the development of urinary probes for noninvasive biodetection. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is one of the most common diseases globally that may have side effects on liver and renal function. Pharmacological treatments to reduce adverse liver and renal effects are still limited. It has been proposed that silymarin may possess hepatoprotective and anti-inflammatory properties. The present trial aims to assess the hepatorenal protective efficacy of silymarin supplementation in cancer patients receiving chemotherapy in an outpatient setting. Method: This is a randomized, placebo-controlled clinical trial that recruited female breast cancer patients. Participants were randomly assigned to one placebo group and two intervention groups. The control group received 140 mg of placebo daily, while the two intervention groups received 140 mg silymarin daily. Follow-up assessments were conducted at baseline, 3 weeks, and 6 weeks. At the beginning of the study, the patients were subjected to a computed tomography (CT) scan, and the liver and renal parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), bilirubin, Blood urea nitrogen (BUN) and Creatinine (Cr) were examined through laboratory tests. Results: Despite two deaths and three dropouts, 100 patients completed the study. Silymarin showed significant effects on liver enzymes in the levels of ALP and bilirubin (P < 0.05), with no significant impact on renal function in the levels of Blood urea nitrogen (BUN) and Creatinine (Cr) (P > 0.05). The medication was well-tolerated, with minimal reported side effects (P > 0.05). Discussion: The study suggests that silymarin may have hepato-renal protective potential in breast cancer patients and improve patient tolerance to chemotherapy. The data presented on the efficacy and safety of silymarin may provide stronger foundation for further trials and for a possible use in clinical practice. Trial registration information: Registration Number: IRCT20201123049474N2, First Trial Registration: 16/08/2021, Access: https://www.irct.behdasht.gov.ir/trial/57641 [ABSTRACT FROM AUTHOR]

Renal anisotropy is a complex property of the kidney and often poses a challenge in obtaining consistent measurements when using shear wave elastography to detect chronic kidney disease. To circumvent the challenge posed by renal anisotropy in clinical settings, a dimensionless biomarker termed the 'anisotropic ratio' was introduced to establish a correlation between changes in degree of renal anisotropy and progression of chronic kidney disease through an in silico perspective. To achieve this, an efficient model reduction approach was developed to model the anisotropic property of kidneys. Good agreement between the numerical and experimental data were obtained, as percentage errors of less than 5.5% were reported when compared against experimental phantom measurement from the literature. To demonstrate the applicability of the model to clinical measurements, the anisotropic ratio of sheep kidneys was quantified, with both numerical and derived experimental results reporting a value of.667. Analysis of the anisotropic ratio with progression of chronic kidney disease demonstrated that patients with normal kidneys would have a lower anisotropic ratio of.872 as opposed to patients suffering from renal impairment, in which the anisotropic ratio may increase to.904, as determined from this study. The findings demonstrate the potential of the anisotropic ratio in improving the detection of chronic kidney disease using shear wave elastography. [ABSTRACT FROM AUTHOR]

The widespread use of pesticides in veterinary medicine, agriculture, public health, and aquatic environments has increasingly threatened aquatic life in recent years. This study aimed to evaluate the acute toxicity, behavioral changes, and histological alterations caused by pymetrozine (PY) in the Nile tilapia (Oreochromis niloticus). The 96-hour LC50 value for PY was found to be 0.28g/ L, indicating the concentration at which half of the test population succumbed within 96 hours. Behavioral changes such as hyperexcitation, irregular swimming, dark coloration, loss of balance, and lethargy were observed and varied with the concentration of PY. The study also demonstrated that the mortality rate, clinical lesions, behavioral changes, and histological alterations in the gills, liver, and kidneys were all influenced by both the dosage of PY and the duration of exposure, highlighting the toxicological impact of PY on the Nile tilapia. [ABSTRACT FROM AUTHOR]

Aging and obesity are associated with a decrease in plasma 25‐hydroxyvitamin D (25(OH)D) levels. In the context of a growing aging population and the rising incidence of obesity, we hypothesized that aging process, either independently or in combination with obesity, could influence vitamin D (VD) metabolism, consequently resulting in the reduced 25(OH)D plasma concentrations. C57BL/6JRJ young (6 months) and old (23 months) mice fed with control (CD) or high fat diet (HF) were compared. Plasma and adipose concentration of cholecalciferol and 25(OH)D and mRNA expression of genes coding for the main VD actors were analyzed. Aging was associated with a decrease in plasma 25(OH)D levels, whereas combined effect of obesity and aging did not generate a cumulative effect on plasma 25(OH)D levels. The mRNA expression of Cyp27a1, Cyp3a11, and Cyp2j6 were decreased in the liver during aging. Together, these regulations could explain the reduced 25‐hydroxylation. Interestingly, the lack of cumulative reduction of 25(OH)D in aged and obese mice could be related to the strong induction of Cyp2j6. In kidneys, a complex modulation of Cyp27b1 and Cyp24a1 could contribute to the reduced 25‐hydroxylation in the liver. In white adipose tissue, an induction of Cyp2r1 was observed during aging and obesity, together with an increase of 25(OH)D quantity, suggesting an exacerbated storage that may participated to the reduced plasma 25(OH)D levels. These findings support the notion that aging alone or combined with obesity, induces regulation of VD metabolism in the organs, beyond the classical reduction of epidermal VD precursor, which may contribute to the decrease in 25(OH)D levels. [ABSTRACT FROM AUTHOR]

Chronic exposure to the nephrotoxic metal pollutant, cadmium (Cd), has been associated with hypertension, but the mechanism by which it raises blood pressure is not understood. We hypothesize that exposure to Cd reduces the glomerular filtration rate (GFR), which in turn causes a rise in blood pressure. Data were collected from 447 Thai subjects with a mean age of 51.1 years, of which 48.8% had hypertension, 15.4% had diabetes, and 6.9% had an estimated GFR (eGFR) below 60 mL/min/1.73 m2 (low eGFR). More than half (58.8%) and 23.9% had moderate and severe tubular proteinuria, respectively. The mean blood and urinary Cd concentrations were 2.75 and 4.23 µg/L, respectively. Doubling of body burden of Cd increased the prevalence odds ratios (POR) for low eGFR and severe tubular proteinuria 41% and 48%, respectively. The POR for hypertension rose twofold in those with blood Cd levels of 0.61–1.69 µg/L or urinary Cd excretion levels ≥ 0.98 µg/g creatinine. In the hypertensive group, the eGFR was inversely associated with age (β = −0.517), the Cd excretion rate (β = −0.177), and diabetes (β = −0.175). By mediation analysis, an increase in SBP was attributable totally to the effect of Cd on GFR. Thus, blood pressure appeared to rise as GFR fell. This finding is consistent with the well-known role of the kidney in long-term blood pressure regulation, and explains a universally high prevalence of hypertension among patients with low eGFR. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) play important roles in the regulation of cellular function and fate via post-transcriptional regulation of gene expression. Although several miRNAs are associated with physiological processes and kidney diseases, not much is known about changes in miRNAs in aging kidneys. We previously demonstrated that sodium hydrogen exchanger 1 (NHERF1) expression regulates cellular responses to cisplatin, age-dependent salt-sensitive hypertension, and sodium-phosphate cotransporter trafficking. However, the mechanisms driving these regulatory effects of NHERF1 on cellular processes are unknown. Here, we hypothesize that dysregulation of miRNA-mediated gene regulatory networks that induce fibrosis and cytokines may depend on NHERF1 expression. To address this hypothesis, we compared miRNA expression in kidneys from both male and female old (12–18-month-old) and young (4–7-month-old) wild-type (WT) and NHERF1 knockout (NHERF1−/−) mice. Our results identified that miRNAs significantly decreased in NHERF1−/− mice included miR-669m, miR-590-3p, miR-153, miR-673-3p, and miR-127. Only miR-702 significantly decreased in aged WT mice, while miR-678 decreased in both WT and NHERF1−/− old versus young mice. miR-153 was shown to downregulate transcription factors NFATc2 and NFATc3 which regulate the transcription of several cytokines. Immunohistochemistry and western blotting revealed a significant increase in nuclear NFATc2 and NFATc3 in old NHERF1−/− mice compared to old WT mice. Our data further show that expression of the cytokines IL-1β, IL-6, IL-17A, MCP1, and TNF-α significantly increased in the old NHERF1−/− mice compared to the WT mice. We conclude that loss of NHERF1 expression induces cytokine expression in the kidney through interactive regulation between miR-153 and NFATc2/NFATc3 expression. [ABSTRACT FROM AUTHOR]