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Acanthamoeba spp. are facultative, opportunistic pathogens that are found in diverse environments. In the hosts, they lead to multi-organ disease. Recent studies reported that they may induce changes in the kidneys of hosts. The aim of the study was to determine the influence of Acanthamoeba sp. on hypoxia and collagen deposition in the kidneys of immunocompetent and immunosuppressed mice infected with Acanthamoeba sp. The results strongly suggest that Acanthamoeba sp. induces hypoxia in mice with normal and reduced immune response by increasing gene and/or protein expression of HIF1α as well as HIF2α. Additionally, the activation of these factors is probably induced via NOX2/ROS. Hypoxia promotes vessel formation, and we found that angiogenesis occurs in the kidneys of mice infected with the parasite regardless of their immunological status. The proangiogenic factors released in hypoxic conditions cause modulation and inflammation in the kidney cells, which in turn leads to collagen deposition via TGF-β. This work reveals mechanisms occurring in the hosts infected with Acanthamoeba sp., highlights as well as supports the relevance of pathophysiology in the kidneys in hosts with systematic acanthamoebiasis. [ABSTRACT FROM AUTHOR]

Uremic Encephalopathy results from the elevation of toxins and blood-brain barrier (BBB) disruption. Renal Ischemia/Reperfusion (I/R) injury is the principal cause of acute kidney injury and brain tissue injury. The present study was crafted to estimate the restorative impact of platelet-rich plasma (PRP) and exosome injection before the reperfusion phase on the kidney following renal I/R injury and its influence on brain tissue by tracking the histopathological, biochemical, and Doppler ultrasonography alternations in both kidney and brain tissue. Forty mature male rats were divided into five groups as follows: control, I/R, PRP, exosome, and Exosome + PRP. Renal Doppler ultrasonography was traced for all rats. Serum kidney functions and acetylcholine esterase enzyme (AchE) were evaluated. Both Gamma-aminobutyric acid (GABA) and glutamate were assessed in brain tissues. The oxidative stress (malondialdehyde), anti-oxidative (glutathione and catalase), and pro-inflammatory (Tumor necrosis factor- α and interleukin-6) markers were estimated in renal tissues. Additionally, morphometric histological examination was performed in both renal and brain tissues. Both PRP and exosome-received rats exhibited a significant improvement in both serum kidney functions and AchE compared to I/R rats. There was a 3.39-fold increase in GABA and a 2.27-fold decrease in glutamate levels in the brain tissue of PRP rats compared to the I/R rats. A significant elevation (P ≤ 0.0001) of glutathione and catalase besides a significant reduction in the expression of TNF-α and IL-6 was observed in renal tissue compared to I/R rats. A significant severe reduction (P < 0.0001) in the number of Purkinje cells, pyramidal cells in the cerebellar cortex, and the CA1 region in the hippocampus was observed in I/R rats which was significantly alleviated by both PRP and exosome. Furthermore, there was a significant improvement in Doppler parameters. PRP exerted a significant superior impact on the restoration of kidney functions and repairing uremic-induced damage in brain tissue. [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]

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]

Dysnatremia is common in donors and recipients of liver transplantation (LT). However, the influence of dysnatremia on LT prognosis remains controversial. This study aimed to investigate effects of donors' and recipients' serum sodium on LT prognosis. We retrospectively reviewed 248 recipients who underwent orthotopic LT at our center between January 2016 and December 2018. Donors and recipients perioperative and 3-year postoperative clinical data were included. Delta serum sodium was defined as the donors' serum sodium minus the paired recipients' serum sodium. Donors with serum sodium > 145 mmol/L had significantly higher preoperative blood urea nitrogen (BUN) (P < 0.01) and creatinine (Cr) (P < 0.01) than others. Preoperative total bilirubin (TBIL) (P < 0.01), direct bilirubin (DBIL) (P < 0.01), BUN (P < 0.01), Cr (P < 0.01) were significantly higher in the hyponatremia group of recipients than the other groups, but both of donors' and recipients' serum sodium had no effect on the LT prognosis. In the delta serum sodium < 0 mmol/L group, TBIL (P < 0.01) and DBIL (P < 0.01) were significantly higher in postoperative 1 week than the other groups, but delta serum sodium had no effect on the postoperative survival rates. Dysnatremia in donors and recipients of LT have no effect on postoperative survival rates, hepatic and renal function, but recipients with higher serum sodium than donors have significantly higher TBIL and DBIL at 1 week postoperatively. [ABSTRACT FROM AUTHOR]

Abstract Acanthamoeba spp. are facultative, opportunistic pathogens that are found in diverse environments. In the hosts, they lead to multi-organ disease. Recent studies reported that they may induce changes in the kidneys of hosts. The aim of the study was to determine the influence of Acanthamoeba sp. on hypoxia and collagen deposition in the kidneys of immunocompetent and immunosuppressed mice infected with Acanthamoeba sp. The results strongly suggest that Acanthamoeba sp. induces hypoxia in mice with normal and reduced immune response by increasing gene and/or protein expression of HIF1α as well as HIF2α. Additionally, the activation of these factors is probably induced via NOX2/ROS. Hypoxia promotes vessel formation, and we found that angiogenesis occurs in the kidneys of mice infected with the parasite regardless of their immunological status. The proangiogenic factors released in hypoxic conditions cause modulation and inflammation in the kidney cells, which in turn leads to collagen deposition via TGF-β. This work reveals mechanisms occurring in the hosts infected with Acanthamoeba sp., highlights as well as supports the relevance of pathophysiology in the kidneys in hosts with systematic acanthamoebiasis.

Acute kidney injury (AKI) is related to adverse clinical outcomes. Therefore, identifying patients at increased risk of postoperative AKI and proactively providing appropriate care is crucial. However, only a limited number of modifiable risk factors have been recognized to mitigate AKI risk. We retrospectively analyzed adult patients who underwent endotracheal intubation and mechanical ventilation of more than 2 h during non-cardiac surgery at Seoul National University Hospital from January 2011 to November 2022. Patients were grouped into low- or high-tidal volume groups based on their intraoperative tidal volume relative to their predicted body weight (PBW) of 8 ml/kg. The association between intraoperative tidal volume and postoperative AKI was evaluated using inverse probability of treatment weighting (IPTW), adjusting for various preoperative confounders. Among the 37,726 patients included, the incidence of postoperative AKI was 4.1%. The odds of postoperative AKI risk were significantly higher in the high-tidal volume group than in the low-tidal volume group before and after IPTW (odds ratio [OR] 1.20, 95% confidence interval [CI] 1.08–1.32, P = 0.001 and OR: 1.10, 95% CI 1.02–1.19, P = 0.010, respectively). In the multivariable logistic regression analysis after IPTW, a high tidal volume was independently associated with an increased risk of postoperative AKI (OR: 1.21, 95% CI 1.12–1.30, P < 0.001). In this propensity score-weighted analysis, an intraoperative high tidal volume of more than 8 ml/kg PBW was significantly associated with an increased risk of postoperative AKI after IPTW in non-cardiac surgical patients. Intraoperative tidal volume showed potential as a modifiable risk factor for preventing postoperative AKI. [ABSTRACT FROM AUTHOR]

Although Akkermansia muciniphila (Am) plays a beneficial role as a probiotic in the treatment of metabolic syndrome, the mechanisms remain elusive. We tested the hypothesis that Am extracellular vesicles (AmEVs) protect against hypertension through modulation of gene expression in the kidneys of spontaneously hypertensive rats (SHRs). Extracellular vesicles purified from anaerobically cultured Am (1.0 × 108 or 1.0 × 109 particles/kg) or vehicles were injected into the tail veins of Wistar-Kyoto rats (WKYs) and SHRs weekly for 4 weeks. Renal cortical tissues isolated from both rat strains were analyzed by trichrome stain and RT-qPCR. AmEVs protect against the development of hypertension in SHRs without a serious adverse reaction. AmEVs increased the expression of vasocontracting Agt and At1ar as well as vasodilating At2r, Mas1 and Nos2 in the kidneys of both strains. These results indicate that AmEVs have a protective effect against hypertension without a serious adverse reaction. Therefore, it is foreseen that AmEVs may be utilized as a novel therapeutic for the treatment of hypertension. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a widespread condition with considerable health and economic impacts globally. However, existing methodologies for serum creatinine assessment often involve prolonged wait times and sophisticated equipment, such as spectrometers, hindering real-time diagnosis and care. Innovative solutions like point-of-care (POC) devices are emerging to address these challenges. In this context, there is a recognized need for remote, regular, automated, and low-cost analysis of serum creatinine levels, given its role as a critical parameter for CKD diagnosis and management. This study introduces a miniaturized system with integrated heater elements designed for precise serum creatinine measurement. The system operates based on the Jaffe method and accurate serum creatinine measurement within a microreservoir chip. Smartphone-based image processing using the hue-saturation-value (HSV) color space was applied to captured images of microreservoirs. The creatinine analyses were conducted in serum with a limit of detection of ~ 0.4 mg/dL and limit of quantification of ~ 1.3 mg/dL. Smartphone-based image processing employing the HSV color space outperformed spectrometric analysis for creatinine measurement conducted in serum. This pioneering technology and smartphone-based processing offer the potential for decentralized renal function testing, which could significantly contribute to improved patient care. The miniaturized system offers a low-cost alternative ($87 per device), potentially reducing healthcare expenditures (~ $0.5 per test) associated with CKD diagnosis and management. This innovation could greatly improve access to diagnosis and monitoring of CKD, especially in regions where access to sophisticated laboratory equipment is limited. [ABSTRACT FROM AUTHOR]

Obstructed urine flow is known to cause structural and functional kidney damage leading to renal fibrosis. However, limited information is available on the change in kidney lipids during urinary tract obstruction. In this study, we investigated the change in lipidome in a mouse model with unilateral ureteral obstruction (UUO). The establishment of the UUO model was confirmed by histopathological examination using transmission electron microscopy. Untargeted liquid chromatography/mass spectrometry was carried out over a time course of 4 and 7 days. Compared to the sham control, the UUO kidney at 7 days showed dilatation of the renal tubule with loss of brush borders and thickening of the capillary endothelium. In the kidney lipidomes obtained from the UUO 7 days group compared to the control, a significant decrease of ceramide, sphingomyelin, phosphatidylcholine, lysophospholipids, and phosphatidylethanolamine was observed, whereas cholesteryl esters, free fatty acids, phosphatidylglycerol, and cardiolipins were significantly increased. The present study revealed the disturbed lipid metabolism in the UUO model, which may provide a clue to potential lipid pathways and therapeutic targets for the early stage of renal fibrosis. [ABSTRACT FROM AUTHOR]

To quantitatively evaluate chronic kidney disease (CKD), a deep convolutional neural network-based segmentation model was applied to renal enhanced computed tomography (CT) images. A retrospective analysis was conducted on a cohort of 100 individuals diagnosed with CKD and 90 individuals with healthy kidneys, who underwent contrast-enhanced CT scans of the kidneys or abdomen. Demographic and clinical data were collected from all participants. The study consisted of two distinct stages: firstly, the development and validation of a three-dimensional (3D) nnU-Net model for segmenting the arterial phase of renal enhanced CT scans; secondly, the utilization of the 3D nnU-Net model for quantitative evaluation of CKD. The 3D nnU-Net model achieved a mean Dice Similarity Coefficient (DSC) of 93.53% for renal parenchyma and 81.48% for renal cortex. Statistically significant differences were observed among different stages of renal function for renal parenchyma volume (VRP), renal cortex volume (VRC), renal medulla volume (VRM), the CT values of renal parenchyma (HuRP), the CT values of renal cortex (HuRC), and the CT values of renal medulla (HuRM) (F = 93.476, 144.918, 9.637, 170.533, 216.616, and 94.283; p < 0.001). Pearson correlation analysis revealed significant positive associations between glomerular filtration rate (eGFR) and VRP, VRC, VRM, HuRP, HuRC, and HuRM (r = 0.749, 0.818, 0.321, 0.819, 0.820, and 0.747, respectively, all p < 0.001). Similarly, a negative correlation was observed between serum creatinine (Scr) levels and VRP, VRC, VRM, HuRP, HuRC, and HuRM (r = − 0.759, − 0.777, − 0.420, − 0.762, − 0.771, and − 0.726, respectively, all p < 0.001). For predicting CKD in males, VRP had an area under the curve (AUC) of 0.726, p < 0.001; VRC, AUC 0.765, p < 0.001; VRM, AUC 0.578, p = 0.018; HuRP, AUC 0.912, p < 0.001; HuRC, AUC 0.952, p < 0.001; and HuRM, AUC 0.772, p < 0.001 in males. In females, VRP had an AUC of 0.813, p < 0.001; VRC, AUC 0.851, p < 0.001; VRM, AUC 0.623, p = 0.060; HuRP, AUC 0.904, p < 0.001; HuRC, AUC 0.934, p < 0.001; and HuRM, AUC 0.840, p < 0.001. The optimal cutoff values for predicting CKD in HuRP are 99.9 Hu for males and 98.4 Hu for females, while in HuRC are 120.1 Hu for males and 111.8 Hu for females. The kidney was effectively segmented by our AI-based 3D nnU-Net model for enhanced renal CT images. In terms of mild kidney injury, the CT values exhibited higher sensitivity compared to kidney volume. The correlation analysis revealed a stronger association between VRC, HuRP, and HuRC with renal function, while the association between VRP and HuRM was weaker, and the association between VRM was the weakest. Particularly, HuRP and HuRC demonstrated significant potential in predicting renal function. For diagnosing CKD, it is recommended to set the threshold values as follows: HuRP < 99.9 Hu and HuRC < 120.1 Hu in males, and HuRP < 98.4 Hu and HuRC < 111.8 Hu in females. [ABSTRACT FROM AUTHOR]

IgA Nephropathy (IgAN) is the most prevalent glomerular disease worldwide. Complement system activation is crucial in its pathogenesis. Few studies correlated serum C3 and C4 with disease activity and prognosis. This retrospective study investigated the prognostic value of serum complement at the time of diagnosis in patients with IgAN. Specifically we evaluated whether adding serum C3 and C4 levels to established predictive models-one based on variables related to chronic kidney disease (CKD) progression and another incorporating variables from the International IgA Prediction Tool (IntIgAPT)-enhances the accuracy of outcome prediction. A composite renal outcome was defined as 50% decline in eGFR or onset of kidney failure. 101 patients were stratified according to baseline C3 levels in three groups (Low, Medium and High). During a median follow-up of 54 months, the Low group exhibited higher incidence of primary outcome (16.3 events vs 2.9 and 1.7 events × 100 pts/year, p = 0.0026). Model-1 (M1), consisting of CKD progression variables, and Model-3 (M3), comprising IntIgANPT variables, were implemented with baseline C3 and C4 to create Model-2 (M2) and Model-4 (M4), respectively. M2 demonstrated better predictive performance over M1, showing higher discrimination (lower AIC and BIC, higher C-index and NR2). Similarly, M4 outperformed M3, showing enhanced outcome prediction when C3 and C4 levels were added. Implementation of serum C3 and C4 can enhance prediction accuracy of already-validated prognostic models in IgAN. Lower C3 and higher C4 levels were associated with poorer prognosis, highlighting a more 'Complement-Pathic' subset of patients. [ABSTRACT FROM AUTHOR]

This study aimed to create and validate a predictive model for renal function following live kidney donation, using pre-donation factors. Accurately predicting remaining renal function post live kidney donation is currently insufficient, necessitating an effective assessment tool. A multicenter retrospective study of 2318 live kidney donors from two independent centers (May 2007–December 2019) was conducted. The primary endpoint was the reduction in eGFR to below 60 mL/min/m2 6 months post-donation. The primary endpoint was achieved in 14.4% of the training cohort and 25.8% of the validation cohort. Sex, age, BMI, hypertension, preoperative eGFR, and remnant kidney proportion (RKP) measured by computerized tomography (CT) volumetry were found significant in the univariable analysis. These variables informed a scoring system based on multivariable analysis: sex (male: 1, female: 0), age at operation (< 30: 0, 30–39: 1, 40–59: 2, ≥ 60: 3), preoperative eGFR (≥ 100: 0, 90–99: 2, 80–89: 4, < 80: 5), and RKP (≥ 52%: 0, < 52%: 1). The total score ranged from 0 to 10. The model showed good discrimination for the primary endpoint in both cohorts. The prediction model provides a useful tool for estimating post-donation renal dysfunction risk, factoring in the side of the donated kidney. It offers potential enhancement to pre-donation evaluations. [ABSTRACT FROM AUTHOR]

This study was performed to segment the urinary system as the basis for diagnosing urinary system diseases on non-contrast computed tomography (CT). This study was conducted with images obtained between January 2016 and December 2020. During the study period, non-contrast abdominopelvic CT scans of patients and diagnosed and treated with urinary stones at the emergency departments of two institutions were collected. Region of interest extraction was first performed, and urinary system segmentation was performed using a modified U-Net. Thereafter, fivefold cross-validation was performed to evaluate the robustness of the model performance. In fivefold cross-validation results of the segmentation of the urinary system, the average dice coefficient was 0.8673, and the dice coefficients for each class (kidney, ureter, and urinary bladder) were 0.9651, 0.7172, and 0.9196, respectively. In the test dataset, the average dice coefficient of best performing model in fivefold cross validation for whole urinary system was 0.8623, and the dice coefficients for each class (kidney, ureter, and urinary bladder) were 0.9613, 0.7225, and 0.9032, respectively. The segmentation of the urinary system using the modified U-Net proposed in this study could be the basis for the detection of kidney, ureter, and urinary bladder lesions, such as stones and tumours, through machine learning. [ABSTRACT FROM AUTHOR]

Rapamycin slows cystogenesis in murine models of polycystic kidney disease (PKD) but failed in clinical trials, potentially due to insufficient drug dosing. To improve drug efficiency without increasing dose, kidney-specific drug delivery may be used. Mesoscale nanoparticles (MNP) selectively target the proximal tubules in rodents. We explored whether MNPs can target cystic kidney tubules and whether rapamycin-encapsulated-MNPs (RapaMNPs) can slow cyst growth in Pkd1 knockout (KO) mice. MNP was intravenously administered in adult Pkd1KO mice. Serum and organs were harvested after 8, 24, 48 or 72 h to measure MNP localization, mTOR levels, and rapamycin concentration. Pkd1KO mice were then injected bi-weekly for 6 weeks with RapaMNP, rapamycin, or vehicle to determine drug efficacy on kidney cyst growth. Single MNP injections lead to kidney-preferential accumulation over other organs, specifically in tubules and cysts. Likewise, one RapaMNP injection resulted in higher drug delivery to the kidney compared to the liver, and displayed sustained mTOR inhibition. Bi-weekly injections with RapaMNP, rapamycin or vehicle for 6 weeks resulted in inconsistent mTOR inhibition and little change in cyst index, however. MNPs serve as an effective short-term, kidney-specific delivery system, but long-term RapaMNP failed to slow cyst progression in Pkd1KO mice. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a systemic disease that affects energy metabolism in various remote organs in murine models of ischemic AKI. However, AKI-mediated effects in the liver have not been comprehensively assessed. After inducing ischemic AKI in 8–10-week-old, male C57BL/6 mice, mass spectrometry metabolomics revealed that the liver had the most distinct phenotype 24 h after AKI versus 4 h and 7 days. Follow up studies with in vivo [13C6]-glucose tracing on liver and kidney 24 h after AKI revealed 4 major findings: (1) increased flux through glycolysis and the tricarboxylic (TCA) cycle in both kidney and liver; (2) depleted hepatic glutathione levels and its intermediates despite unchanged level of reactive oxygen species, suggesting glutathione consumption exceeds production due to systemic oxidative stress after AKI; (3) hepatic ATP depletion despite unchanged rate of mitochondrial respiration, suggesting increased ATP consumption relative to production; (4) increased hepatic and renal urea cycle intermediates suggesting hypercatabolism and upregulation of the urea cycle independent of impaired renal clearance of nitrogenous waste. Taken together, this is the first study to describe the hepatic metabolome after ischemic AKI in a murine model and demonstrates that there is significant liver-kidney crosstalk after AKI. [ABSTRACT FROM AUTHOR]

Kidney cancer, a type of urogenital cancer, imposes a high burden on patients. Despite this, no recent research has evaluated the burden of this type of cancer in the Middle East and North Africa (MENA) region. This study explored the burden of kidney cancer from 1990 to 2019 according to age, sex and socio-demographic index (SDI). The Global Burden of Disease (GBD) 2019 data was utilized to estimate the incidence, death, and disability-adjusted life-years (DALYs) caused by kidney cancer. These estimates were reported as counts and as age-standardised rates with 95% uncertainty intervals (UIs). The estimated age-standardised incidence, mortality, and DALY rates of kidney cancer in 2019 were 3.2 (2.8–3.6), 1.4 (1.2–1.6), and 37.2 (32.0–42.6) per 100,000, respectively. Over the period from 1990 to 2019, these rates have increased by 98.0%, 48.9%, and 37.7%, respectively. In 2019, the United Arab Emirates, Qatar, and Lebanon had the largest age-standardised incidence, mortality, and DALY rates. The smallest age-standardised incidence rates were seen in Yemen, Afghanistan, and the Syrian Arab Republic. Additionally, the smallest age-standardised mortality and DALY rates were observed in the Syrian Arab Republic, Yemen, and Morocco. The highest incidence rates were found among individuals aged 75–79 in both males and females. In 2019, the MENA/Global DALY ratio exceeded one for females aged 5–19 age and males aged 5–14, compared to 1990age groups in males. The burden of kidney cancer consistently rose with increasing SDI levels from 1990 to 2019. The increasing burden of kidney cancer highlights the urgent need for interventions aimed at improving early diagnosis and treatment in the region. [ABSTRACT FROM AUTHOR]

Mayo Imaging Classification (MIC) for predicting future kidney growth in autosomal dominant polycystic kidney disease (ADPKD) patients is calculated from a single MRI/CT scan assuming exponential kidney volume growth and height-adjusted total kidney volume at birth to be 150 mL/m. However, when multiple scans are available, how this information should be combined to improve prediction accuracy is unclear. Herein, we studied ADPKD subjects ( n = 36 ) with 8+ years imaging follow-up (mean = 11 years) to establish ground truth kidney growth trajectory. MIC annual kidney growth rate predictions were compared to ground truth as well as 1- and 2-parameter least squares fitting. The annualized mean absolute error in MIC for predicting total kidney volume growth rate was 2.1 % ± 2 % compared to 1.1 % ± 1 % ( p = 0.002 ) for a 2-parameter fit to the same exponential growth curve used for MIC when 4 measurements were available or 1.4 % ± 1 % ( p = 0.01 ) with 3 measurements averaging together with MIC. On univariate analysis, male sex ( p = 0.05 ) and PKD2 mutation ( p = 0.04 ) were associated with poorer MIC performance. In ADPKD patients with 3 or more CT/MRI scans, 2-parameter least squares fitting predicted kidney volume growth rate better than MIC, especially in males and with PKD2 mutations where MIC was less accurate. [ABSTRACT FROM AUTHOR]

This study aims to examine whether hypovitaminosis D was associated with cognitive impairment among chronic kidney patients with different level of albuminuria. This population-based cross-sectional study was conducted on elderly (over 60 years old) with urine albumin to creatinine ratio (UACR) ≥ 30 mg/g from 2011 to 2014 in the US National Health and Nutrition Examination Survey (NHANES). Cognitive function was assessed by the Consortium to Establish a Registry for Alzheimer's Disease Word List Learning (CERAD). Subjects were divided into 2 groups according to the absence or presence of cognitive impairment and a propensity score matching (PSM) was further conducted. The association was assessed with Spearman correlation and logistic regression analysis. The positive association of 25-hydroxyvitamin D3 (25(OH)D3) and cognitive score was presented. PSM analysis revealed that a higher level of 25(OH)D3 correlated to a better cognitive function in CKD patients with albuminuria, especially in patients with 30 mg/g ≤ UACR < 300 mg/g. This study indicated that a low 25(OH)D3 level was associated with poor cognitive performance, especially in patients with microalbuminuria. Thus, early diagnosis of vitamin D insufficiency and an effective intervention might be a useful therapeutic strategy to prevent cognitive decline in patients with the progression of renal dysfunction. [ABSTRACT FROM AUTHOR]

IgA nephropathy progresses to kidney failure, making early detection important. However, definitive diagnosis depends on invasive kidney biopsy. This study aimed to develop non-invasive prediction models for IgA nephropathy using machine learning. We collected retrospective data on demographic characteristics, blood tests, and urine tests of the patients who underwent kidney biopsy. The dataset was divided into derivation and validation cohorts, with temporal validation. We employed five machine learning models—eXtreme Gradient Boosting (XGBoost), LightGBM, Random Forest, Artificial Neural Networks, and 1 Dimentional-Convolutional Neural Network (1D-CNN)—and logistic regression, evaluating performance via the area under the receiver operating characteristic curve (AUROC) and explored variable importance through SHapley Additive exPlanations method. The study included 1268 participants, with 353 (28%) diagnosed with IgA nephropathy. In the derivation cohort, LightGBM achieved the highest AUROC of 0.913 (95% CI 0.906–0.919), significantly higher than logistic regression, Artificial Neural Network, and 1D-CNN, not significantly different from XGBoost and Random Forest. In the validation cohort, XGBoost demonstrated the highest AUROC of 0.894 (95% CI 0.850–0.935), maintaining its robust performance. Key predictors identified were age, serum albumin, IgA/C3, and urine red blood cells, aligning with existing clinical insights. Machine learning can be a valuable non-invasive tool for IgA nephropathy. [ABSTRACT FROM AUTHOR]

Cancers of the kidney and renal pelvis are among the most prevalent types of urinary cancers. We aimed to outline the incidence trends of kidney and renal pelvis cancers by age, sex, race/ethnicity, and histology in the United States (US) from 2000 to 2020. The data was obtained from the Surveillance, Epidemiology, and End Results (SEER) 22 database. The identification of patients with kidney and renal pelvis cancers with morphologies of renal cell carcinoma, nephroblastoma, sarcoma, and neuroendocrine tumor was conducted utilizing the International Classification of Diseases for Oncology version 3. The average annual percent change (AAPC) were presented. All estimates were given in the form of counts and delayed age-standardized incidence rates (ASIRs) per 100,000 people. From 2000 to 2019, a total of 490,481 cases of kidney and renal pelvic cancer were recorded across all age groups in the US. The majority of them were among Non-Hispanic Whites (NHWs) (69.75%) and those aged 55–69 years (39.96%). The ASIRs per 100,000 for kidney and pelvis cancers were 22.03 for men and 11.14 for women. Non-Hispanic Black men had the highest ASIR (24.53 [24.24, 24.81]), and increase in ASIR over the 2000–2019 period (AAPC: 2.19% [1.84, 2.84]). There was a noticeable increase in incidence of kidney and renal pelvis cancers. Individuals aged 70–84 years had the highest ASIR for kidney and renal pelvis cancers. The COVID-19 era has resulted in a significant reduction in incidence rates across all demographics. [ABSTRACT FROM AUTHOR]

Health equity and accessing Spanish kidney transplant information continues being a substantial challenge facing the Hispanic community. This study evaluated ChatGPT's capabilities in translating 54 English kidney transplant frequently asked questions (FAQs) into Spanish using two versions of the AI model, GPT-3.5 and GPT-4.0. The FAQs included 19 from Organ Procurement and Transplantation Network (OPTN), 15 from National Health Service (NHS), and 20 from National Kidney Foundation (NKF). Two native Spanish-speaking nephrologists, both of whom are of Mexican heritage, scored the translations for linguistic accuracy and cultural sensitivity tailored to Hispanics using a 1–5 rubric. The inter-rater reliability of the evaluators, measured by Cohen's Kappa, was 0.85. Overall linguistic accuracy was 4.89 ± 0.31 for GPT-3.5 versus 4.94 ± 0.23 for GPT-4.0 (non-significant p = 0.23). Both versions scored 4.96 ± 0.19 in cultural sensitivity (p = 1.00). By source, GPT-3.5 linguistic accuracy was 4.84 ± 0.37 (OPTN), 4.93 ± 0.26 (NHS), 4.90 ± 0.31 (NKF). GPT-4.0 scored 4.95 ± 0.23 (OPTN), 4.93 ± 0.26 (NHS), 4.95 ± 0.22 (NKF). For cultural sensitivity, GPT-3.5 scored 4.95 ± 0.23 (OPTN), 4.93 ± 0.26 (NHS), 5.00 ± 0.00 (NKF), while GPT-4.0 scored 5.00 ± 0.00 (OPTN), 5.00 ± 0.00 (NHS), 4.90 ± 0.31 (NKF). These high linguistic and cultural sensitivity scores demonstrate Chat GPT effectively translated the English FAQs into Spanish across systems. The findings suggest Chat GPT's potential to promote health equity by improving Spanish access to essential kidney transplant information. Additional research should evaluate its medical translation capabilities across diverse contexts/languages. These English-to-Spanish translations may increase access to vital transplant information for underserved Spanish-speaking Hispanic patients. [ABSTRACT FROM AUTHOR]

Serum creatinine levels are insensitive to real-time changes in kidney function or injury. There is a growing interest in assessing kidney injury by measuring biomarkers in body fluid. From our previous studies, we identified and reported three urinary biomarkers namely Uromodulin (UMOD), Osteopontin (OPN), and Interleukin-9 (IL-9) to be associated with kidney health. The availability of a rapid point-of-care test for these urinary biomarkers will potentially accelerate its applicability and accessibility. In this study, we aimed to develop novel lateral flow device (LFD) for UMOD, OPN and IL-9. We tested paired antibodies using Enzyme Linked Immunosorbent Assay wherein we observed functionality only for UMOD and OPN and not for IL-9. A conjugation buffer pH of 7.8 and 8.5 was found suitable at a detection antibody concentration of 15 µg/mL for LFD development. The developed LFDs were found to quantitatively measure UMOD standard (LLOD of 80,000 pg/mL) and OPN standard (LLOD of 8600 pg/mL) respectively. The LFD was also able to measure human urinary UMOD and OPN with a percent CV of 12.12 and 5.23 respectively. [ABSTRACT FROM AUTHOR]

The study presented here aims at assessing the effects of hypobaric hypoxia on RAAS pathway and its components along with mitigation of anomalies with quercetin prophylaxis. One hour prior to hypobaric hypoxia exposure, male SD rats were orally supplemented with quercetin (50 mg/kg BW) and acetazolamide (50 mg/kg BW) and exposed them to 25,000 ft. (7,620 m) in a simulated environmental chamber for 12 h at 25 ± 2 °C. Different biochemical parameters like renin activity, aldosterone, angiotensin I, ACE 2 were determined in plasma. As a conventional response to low oxygen conditions, oxidative stress parameters (ROS and MDA) were elevated along with suppressed antioxidant system (GPx and catalase) in plasma of rats. Quercetin prophylaxis significantly down regulated the hypoxia induced oxidative stress by reducing plasma ROS & MDA levels with efficient enhancement of antioxidants (GPx and Catalase). Further, hypoxia mediated regulation of renin and ACE 2 proves the outstanding efficacy of quercetin in repudiating altercations in RAAS cascade due to hypobaric hypoxia. Furthermore, differential protein expression of HIF-1α, NFκB, IL-18 and endothelin-1 analyzed by western blotting approves the biochemical outcomes and showed that quercetin significantly aids in the reduction of inflammation under hypoxia. Studies conducted with Surface Plasmon Resonance demonstrated a binding among quercetin and ACE 2 that indicates that this flavonoid might regulate RAAS pathway via ACE 2. Henceforth, the study promotes the prophylaxis of quercetin for the better adaptability under hypobaric hypoxic conditions via modulating the RAAS pathway. [ABSTRACT FROM AUTHOR]

Cyclosporine A (CsA) is employed for organ transplantation and autoimmune disorders. Nephrotoxicity is a serious side effect that hampers the therapeutic use of CsA. Hesperidin and sitagliptin were investigated for their antioxidant, anti-inflammatory, and tissue-protective properties. We aimed to investigate and compare the possible nephroprotective effects of hesperidin and sitagliptin. Male Wistar rats were utilized for induction of CsA nephrotoxicity (20 mg/kg/day, intraperitoneally for 7 days). Animals were treated with sitagliptin (10 mg/kg/day, orally for 14 days) or hesperidin (200 mg/kg/day, orally for 14 days). Blood urea, serum creatinine, albumin, cystatin-C (CYS-C), myeloperoxidase (MPO), and glucose were measured. The renal malondialdehyde (MDA), glutathione (GSH), catalase, and SOD were estimated. Renal TNF-α protein expression was evaluated. Histopathological examination and immunostaining study of Bax, Nrf-2, and NF-κB were performed. Sitagliptin or hesperidin attenuated CsA-mediated elevations of blood urea, serum creatinine, CYS-C, glucose, renal MDA, and MPO, and preserved the serum albumin, renal catalase, SOD, and GSH. They reduced the expressions of TNF-α, Bax, NF-κB, and pathological kidney damage. Nrf2 expression in the kidney was raised. Hesperidin or sitagliptin could protect the kidney against CsA through the mitigation of oxidative stress, apoptosis, and inflammation. Sitagliptin proved to be more beneficial than hesperidin. [ABSTRACT FROM AUTHOR]

Inhibiting tubular urate reabsorption may protect the kidney from urate-induced tubular injury. However, this approach may promote intratubular uric acid crystallization, especially in acidified urine, which could be toxic to the kidney. To assess how tubular urate handling affects kidney outcomes, we conducted a retrospective cohort study including 1042 patients with estimated glomerular filtration rates (eGFR) of 15–60 mL/min/1.73 m2. The exposures were fractional excretion of uric acid (FEUA) and urinary uric acid-to-creatinine ratio (UUCR). The kidney outcome was defined as a halving of eGFR from baseline or initiating kidney replacement therapy. The median FEUA and UUCR were 7.2% and 0.33 g/gCre, respectively. During a median follow-up of 1.9 years, 314 kidney outcomes occurred. In a multivariate Cox model, the lowest FEUA quartile exhibited a 1.68-fold higher rate of kidney outcome than the highest FEUA quartile (95% confidence interval, 1.13–2.50; P = 0.01). Similarly, lower UUCR was associated with a higher rate of kidney outcome. Notably, patients in the highest quartile of FEUA and UUCR were at the lowest risk of kidney outcome even among those with aciduria. In conclusion, lower FEUA and UUCR were associated with a higher risk of kidney failure, suggesting that increased urate reabsorption is harmful to the kidney. [ABSTRACT FROM AUTHOR]

Any kidney dimension and volume variation can be a remarkable indicator of kidney disorders. Precise kidney segmentation in standard planes plays an undeniable role in predicting kidney size and volume. On the other hand, ultrasound is the modality of choice in diagnostic procedures. This paper proposes a convolutional neural network with nested layers, namely Fast-Unet++, promoting the Fast and accurate Unet model. First, the model was trained and evaluated for segmenting sagittal and axial images of the kidney. Then, the predicted masks were used to estimate the kidney image biomarkers, including its volume and dimensions (length, width, thickness, and parenchymal thickness). Finally, the proposed model was tested on a publicly available dataset with various shapes and compared with the related networks. Moreover, the network was evaluated using a set of patients who had undergone ultrasound and computed tomography. The dice metric, Jaccard coefficient, and mean absolute distance were used to evaluate the segmentation step. 0.97, 0.94, and 3.23 mm for the sagittal frame, and 0.95, 0.9, and 3.87 mm for the axial frame were achieved. The kidney dimensions and volume were evaluated using accuracy, the area under the curve, sensitivity, specificity, precision, and F1. [ABSTRACT FROM AUTHOR]

Multiple types of T cells have been described and assigned pathophysiologic functions in the kidneys. However, the existence and functions of TCR+CD4+CD8+ (double positive; DP) T cells are understudied in normal and diseased murine and human kidneys. We studied kidney DPT cells in mice at baseline and after ischemia reperfusion (IR) and cisplatin injury. Additionally, effects of viral infection and gut microbiota were studied. Human kidneys from patients with renal cell carcinoma were evaluated. Our results demonstrate that DPT cells expressing CD4 and CD8 co-receptors constitute a minor T cell population in mouse kidneys. DPT cells had significant Ki67 and PD1 expression, effector/central memory phenotype, proinflammatory cytokine (IFNγ, TNFα and IL-17) and metabolic marker (GLUT1, HKII, CPT1a and pS6) expression at baseline. IR, cisplatin and viral infection elevated DPT cell proportions, and induced distinct functional and metabolic changes. scRNA-seq analysis showed increased expression of Klf2 and Ccr7 and enrichment of TNFα and oxidative phosphorylation related genes in DPT cells. DPT cells constituted a minor population in both normal and cancer portion of human kidneys. In conclusion, DPT cells constitute a small population of mouse and human kidney T cells with distinct inflammatory and metabolic profile at baseline and following kidney injury. [ABSTRACT FROM AUTHOR]

A for-cause biopsy is performed to diagnose the cause of allograft dysfunction in kidney transplantation. We occasionally encounter ambiguous biopsy results in symptomatic kidney transplant recipients. Yet, the allograft survival outcome in symptomatic recipients with nonspecific allograft biopsy findings remains unclear. The purpose of this study was to analyze the impact of nonspecific for-cause biopsy findings in symptomatic kidney transplant recipients. We retrospectively collected records from 773 kidney transplant recipients between January 2008 and October 2021. The characteristics of transplant recipients with nonspecific findings in the first for-cause biopsy were analyzed. Nonspecific allograft biopsy findings were defined as other biopsy findings excluding rejection, borderline rejection, calcineurin inhibitor toxicity, infection, glomerulonephritis, and diabetic nephropathy. The graft outcome was compared between recipients who had never undergone a for-cause biopsy and those who had a first for-cause biopsy with nonspecific findings. The graft survival in recipients with nonspecific for-cause biopsy findings was comparable to that in recipients who did not require the for-cause biopsy before and after propensity score matching. Even in symptomatic kidney transplant recipients, nonspecific allograft biopsy findings might not be a poor prognostic factor for allograft survival compared to recipients who did not require the for-cause biopsy. [ABSTRACT FROM AUTHOR]

Increased water intake is recommended for kidney transplant recipients; however, its efficacy remains controversial. We hypothesized that pre-existing histological findings of the allograft might modulate the impact of water intake. We retrospectively analyzed 167 adults with living-donor kidney transplants (April 2011–May 2020; median observation period, 77 months) whose baseline biopsy data were available. We compared the chronic-change group (n = 38) with the control group (n = 129) to assess the impact of self-reported daily water intake on the estimated glomerular filtration rate (eGFR). The range distribution of water intake was as follows: − 1000 ml (n = 4), 1000–1500 ml (n = 23), 1500–2000 ml (n = 64), 2000–2500 ml (n = 57), 2500–3000 ml (n = 16), and 3000 − ml (n = 3). Donor age was significantly higher in the chronic-change group. In the control group, the ΔeGFR/year increase was correlated with water intake. However, the increase in the water intake of the chronic-change group significantly decreased ΔeGFR/year (1000–1500 ml: + 1.95 ml/min/1.73 m2 and > 2000 ml: − 1.92 ml/min/1.73 m2, p = 0.014). This study suggested a potential influence of increased water intake on recipients with marginal grafts in living donor kidney transplantation. [ABSTRACT FROM AUTHOR]

Mesangial proliferation is a diagnostic feature and a prognostic predictor of immunoglobulin A nephropathy (IgAN). We aimed to investigate the gene expression profiles of IgAN glomerulus according to the presence of mesangial proliferation. We performed spatial-specific transcriptomic profiling on kidney biopsy tissues using the GeoMx Digital Spatial Profiler. Twelve cases with three glomeruli for each case were profiled using direct pathologic classification (4 M1-IgAN, 4 M0-IgAN, and 4 donor controls). The results of enriched glom-specific genes demonstrated that M1-IgAN could be distinguished from controls (77 upregulated and 55 downregulated DEGs), while some DEGs were identified between M1-IgAN and M0-IgAN cases (24 upregulated and 8 downregulated DEGs) or between M0 and controls (1 upregulated and 16 downregulated DEGs). TCF21, an early podocyte damage marker, was the only differentially expressed gene (DEG) consistently upregulated in both M1-IgAN and M0-IgAN patients, whereas ATF3, EGR1, DUSP1, FOS, JUNB, KLF2, NR4A1, RHOB, and ZFP36 were consistently downregulated in IgAN cases. Glomeruli from M1-IgAN cases were significantly enriched for cell surface/adhesion molecules and gene expressions associated with vascular development or the extracellular matrix. Spatial transcriptomic analysis may contribute to dissecting structure-specific pathophysiology and molecular changes in IgAN. [ABSTRACT FROM AUTHOR]

Metformin is the primary treatment for type 2 diabetes mellitus (T2DM) due to its effectiveness in improving clinical outcomes in patients with preserved renal function, however, the evidence on the effectiveness of metformin in various renal functions is lacking. We performed a retrospective, multicenter, observational study used data of patients with T2DM obtained from three tertiary hospitals' databases. Patients given metformin within run-in periods and with at least one additional prescription formed the metformin cohort. A control cohort comprised those prescribed oral hypoglycemic agents other than metformin and never subsequently received a metformin prescription within observation period. For patients without diabetic nephropathy (DN), the outcomes included events of DN, major adverse cardiovascular events (MACE), and major adverse kidney events (MAKE). After 1:1 propensity matching, 1994 individuals each were selected for the metformin and control cohorts among T2DM patients without baseline DN. The incidence rate ratios (IRR) for DN, MACEs, and MAKEs between cohorts were 1.06 (95% CI 0.96–1.17), 0.76 (0.64–0.92), and 0.45 (0.33–0.62), respectively. In cohorts with renal function of CKD 3A, 3B, and 4, summarized IRRs of MACEs and MAKEs were 0.70 (0.57–0.87) and 0.39 (0.35–0.43) in CKD 3A, 0.83 (0.74–0.93) and 0.44 (0.40–0.48) in CKD 3B, and 0.71 (0.60–0.85) and 0.45 (0.39–0.51) in CKD 4. Our research indicates that metformin use in T2DM patients across various renal functions consistently correlates with a decreased risk of overt DN, MACE, and MAKE. [ABSTRACT FROM AUTHOR]

Death with a functioning graft is important cause of graft loss after kidney transplantation. However, little is known about factors predicting death with a functioning graft among kidney transplant recipients. In this study, we evaluated the association between post-transplant creatinine-cystatin C ratio and death with a functioning graft in 1592 kidney transplant recipients. We divided the patients into tertiles based on sex-specific creatinine-cystatin C ratio. Among the 1592 recipients, 39.5% were female, and 86.1% underwent living-donor kidney transplantation. The cut-off value for the lowest creatinine-cystatin C ratio tertile was 0.86 in males and 0.73 in females. The lowest tertile had a significantly lower 5-year patient survival rate and was independently associated with death with a functioning graft (adjusted hazard ratio 2.574, 95% confidence interval 1.339–4.950, P < 0.001). Infection was the most common cause of death in the lowest tertile group, accounting for 62% of deaths. A low creatinine-cystatin C ratio was significantly associated with an increased risk of death with a functioning graft after kidney transplantation. [ABSTRACT FROM AUTHOR]

Social trust is a heritable trait that has been linked with physical health and longevity. In this study, we performed genome-wide association studies of self-reported social trust in n = 33,882 Danish blood donors. We observed genome-wide and local evidence of genetic similarity with other brain-related phenotypes and estimated the single nucleotide polymorphism-based heritability of trust to be 6% (95% confidence interval = (2.1, 9.9)). In our discovery cohort (n = 25,819), we identified one significantly associated locus (lead variant: rs12776883) in an intronic enhancer region of PLPP4, a gene highly expressed in brain, kidneys, and testes. However, we could not replicate the signal in an independent set of donors who were phenotyped a year later (n = 8063). In the subsequent meta-analysis, we found a second significantly associated variant (rs71543507) in an intergenic enhancer region. Overall, our work confirms that social trust is heritable, and provides an initial look into the genetic factors that influence it. [ABSTRACT FROM AUTHOR]

Neuropsychiatric and neurodegenerative disorders are correlated with cellular stress. Macroautophagy (autophagy) may represent an important protective pathway to maintain cellular homeostasis and functionality, as it targets cytoplasmic components to lysosomes for degradation and recycling. Given recent evidence that some novel psychiatric treatments, such as the neuroactive steroid (NAS) allopregnanolone (AlloP, brexanolone), may induce autophagy, we stably transfected human embryonic kidney 293 (HEK) cells with a ratiometric fluorescent probe to assay NAS effects on autophagy. We hypothesized that NAS may modulate autophagy in part by the ability of uncharged NAS to readily permeate membranes. Microscopy revealed a weak effect of AlloP on autophagic flux compared with the positive control treatment of Torin1. In high-throughput microplate experiments, we found that autophagy induction was more robust in early passages of HEK cells. Despite limiting studies to early passages for maximum sensitivity, a range of NAS structures failed to reliably induce autophagy or interact with Torin1 or starvation effects. To probe NAS in a system where AlloP effects have been shown previously, we surveyed astrocytes and again saw minimal autophagy induction by AlloP. Combined with other published results, our results suggest that NAS may modulate autophagy in a cell-specific or context-specific manner. Although there is merit to cell lines as a screening tool, future studies may require assaying NAS in cells from brain regions involved in neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

Examining kidney fibrosis is crucial for mechanistic understanding and developing targeted strategies against chronic kidney disease (CKD). Persistent fibroblast activation and tubular epithelial cell (TEC) injury are key CKD contributors. However, cellular and transcriptional landscapes of CKD and specific activated kidney fibroblast clusters remain elusive. Here, we analyzed single cell transcriptomic profiles of two clinically relevant kidney fibrosis models which induced robust kidney parenchymal remodeling. We dissected the molecular and cellular landscapes of kidney stroma and newly identified three distinctive fibroblast clusters with "secretory", "contractile" and "vascular" transcriptional enrichments. Also, both injuries generated failed repair TECs (frTECs) characterized by decline of mature epithelial markers and elevation of stromal and injury markers. Notably, frTECs shared transcriptional identity with distal nephron segments of the embryonic kidney. Moreover, we identified that both models exhibited robust and previously unrecognized distal spatial pattern of TEC injury, outlined by persistent elevation of renal TEC injury markers including Krt8 and Vcam1, while the surviving proximal tubules (PTs) showed restored transcriptional signature. We also found that long-term kidney injuries activated a prominent nephrogenic signature, including Sox4 and Hox gene elevation, which prevailed in the distal tubular segments. Our findings might advance understanding of and targeted intervention in fibrotic kidney disease. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the outcomes of laparoscopic pyelolithotomy, including its efficacy and feasibility in treatment of large renal stones. All patients who underwent laparoscopic pyelolithotomy operations in a referral center were enrolled from 2003 to 2020. The final analysis included 436 patients. The total stone free rate was 88.3% and the stone-free rate for staghorn/multiple stones versus other types of stones was 81% vs. 91% (P = 0.002). Likewise, the total operation duration was 158 ± 50 and the operation duration for staghorn/multiple stones versus other types of stones was 171 ± 51 min vs. 153 ± 49 min (P < 0.001). The operation duration (169 ± 51 vs. 155 ± 58 vs. 155 ± 42 min) and hospitalization (4.5 ± 2.3 vs. 4.0 ± 2.2 vs. 3.6 ± 1.8) decreased with increasing the surgeons' experience over time. The outcomes of laparoscopic pyelolithotomy for children versus adults versus geriatric patients and in patients with normal versus abnormal kidney anatomy did not reveal statistically significant differences. Laparoscopic pyelolithotomy could be employed as an alternative surgical approach for patients with large kidney stones of any age or with kidney abnormalities provided that appropriate expertise is available to carry out the procedure. [ABSTRACT FROM AUTHOR]

To explore whether ferroptosis is involved in focal segmental glomerulosclerosis (FSGS) and its mechanism. The FSGS rat model was constructed by single nephrectomy combined with fractional tail vein injection of doxorubicin. 24-hour urine protein, serum biochemistry, HE, PAS and Masson pathological staining were measured to assess renal injury. Glomerular and morphological changes of ferroptosis were observed by transmission electron microscopy. Iron content in renal tissue was assessed by Prussian blue staining and iron detection. GSH/GSSG kit was used to detect the content and proportion of reduced/oxidized glutathione. Lipid peroxidation related proteins including MDA expression was assessed by colorimetry. The iron metabolism biomarkers such as hepcidin, ferroportin and TFR, ferroptosis biomarkers such as GPX4, ACSL4, and ferritinophagy biomarkers such as LC3II/LC3I, NCOA4, and FTH1 were detected by Western blot. Significant urinary protein, hyperlipidemia, azotemia, increased serum creatinine and hypoproteinemia were observed in FSGS rats. Histology and electron microscopy showed segmental sclerosis of glomeruli, compensatory enlargement of some glomeruli, occlusion of capillary lumen, balloon adhesion, increased mesangial matrix, atrophy of some tubules, and renal interstitial fibrosis in renal tissue of FSGS rats. The morphology of glomerular foot processes disappeared; the foot processes were extensively fused and some foot processes detached. Mitochondria became smaller, membrane density increased, and mitochondrial cristae decreased or disappeared. In addition, iron deposition was observed in renal tissue of FSGS rats. Compared with the control group, the levels of GSH, GSH/GSSG, GPX4, and ferroportin were reduced and the expression of GSSG, MDA, ACSL4, hepcidin, and TFR was increased in the renal tissue of FSGS rats; meanwhile, the expression of LC3II/LC3I and NCOA4 was increased and the expression of FTH1 was decreased. Ferroptosis is involved in the pathological progression of FSGS, which is probably associated with activation of ferritinophagy. This represents a potential therapeutic target for FSGS. [ABSTRACT FROM AUTHOR]

T cells are important in the pathogenesis of acute kidney injury (AKI), and TCR+CD4-CD8- (double negative-DN) are T cells that have regulatory properties. However, there is limited information on DN T cells compared to traditional CD4+ and CD8+ cells. To elucidate the molecular signature and spatial dynamics of DN T cells during AKI, we performed single-cell RNA sequencing (scRNA-seq) on sorted murine DN, CD4+, and CD8+ cells combined with spatial transcriptomic profiling of normal and post AKI mouse kidneys. scRNA-seq revealed distinct transcriptional profiles for DN, CD4+, and CD8+ T cells of mouse kidneys with enrichment of Kcnq5, Klrb1c, Fcer1g, and Klre1 expression in DN T cells compared to CD4+ and CD8+ T cells in normal kidney tissue. We validated the expression of these four genes in mouse kidney DN, CD4+ and CD8+ T cells using RT-PCR and Kcnq5, Klrb1, and Fcer1g genes with the NIH human kidney precision medicine project (KPMP). Spatial transcriptomics in normal and ischemic mouse kidney tissue showed a localized cluster of T cells in the outer medulla expressing DN T cell genes including Fcer1g. These results provide a template for future studies in DN T as well as CD4+ and CD8+ cells in normal and diseased kidneys. [ABSTRACT FROM AUTHOR]

The influence of acute kidney injury (AKI) and renal recovery in deceased donor (DD) on long-term kidney transplant (KT) outcome has not previously been elucidated in large registry study. Our retrospective cohort study included all DDKT performed in Thailand between 2001 and 2018. Donor data was reviewed case by case. AKI was diagnosed according to the KDIGO criteria. Renal recovery was defined if DD had an improvement in AKI to the normal or lower stage. All outcomes were determined until the end of 2020. This study enrolled 4234 KT recipients from 2198 DD. The KDIGO staging of AKI was as follows: stage 1 for 710 donors (32.3%), stage 2 for 490 donors (22.3%) and stage 3 for 342 donors (15.6%). AKI was partial and complete recovery in 265 (17.2%) and 287 (18.6%) before procurement, respectively. Persistent AKI was revealed in 1906 KT of 990 (45%) DD. The ongoing AKI in DD significantly increases the risk of DGF development in the adjusted model (HR 1.69; 95% CI 1.44–1.99; p < 0.001). KT from DD with AKI and partial/complete recovery was associated with a lower risk of transplant loss (log-rank P = 0.04) and recipient mortality (log-rank P = 0.042) than ongoing AKI. KT from a donor with ongoing stage 3 AKI was associated with a higher risk of all-cause graft loss (HR 1.8; 95% CI 1.12–2.88; p = 0.02) and mortality (HR 2.19; 95% CI 1.09–4.41; p = 0.03) than stage 3 AKI with renal recovery. Persistent AKI, but not recovered AKI, significantly increases the risk of DGF. Utilizing kidneys from donors with improving AKI is generally safe. KT from donors with persistent AKI stage 3 results in a higher risk of transplant failure and recipient mortality. Therefore, meticulous pretransplant evaluation of such kidneys and intensive surveillance after KT is recommended. [ABSTRACT FROM AUTHOR]

The results of randomized controlled trials are unclear about the long-term effect of blood pressure (BP) on kidney function assessed as the glomerular filtration rate (GFR) in persons without chronic kidney disease or diabetes. The limited duration of follow-up and use of imprecise methods for assessing BP and GFR are important reasons why this issue has not been settled. Since a long-term randomized trial is unlikely, we investigated the association between 24-h ambulatory BP (ABP) and measured GFR in a cohort study with a median follow-up of 11 years. The Renal Iohexol Clearance Survey (RENIS) cohort is a representative sample of persons aged 50 to 62 years without baseline cardiovascular disease, diabetes, or kidney disease from the general population of Tromsø in northern Norway. ABP was measured at baseline, and iohexol clearance at baseline and twice during follow-up. The study population comprised 1589 persons with 4127 GFR measurements. Baseline ABP or office BP components were not associated with the GFR change rate in multivariable adjusted conventional regression models. In generalized additive models for location, scale, and shape (GAMLSS), higher daytime systolic, diastolic, and mean arterial ABP were associated with a slight shift of the central part of the GFR distribution toward lower GFR and with higher probability of GFR < 60 mL/min/1.73 m2 during follow-up (p < 0.05). The use of a distributional regression method and precise methods for measuring exposure and outcome were necessary to detect an unfavorable association between BP and GFR in this study of the general population. [ABSTRACT FROM AUTHOR]

Several studies conducted in patients with various stages of chronic kidney disease (CKD) have investigated the association of iron status markers, such as transferrin saturation (TSAT) and serum ferritin, with kidney outcomes. However, the associations were inconsistent and remain strongly debated. Therefore, we aimed to investigate whether TSAT and serum ferritin levels were associated with kidney outcome in such a population. In this study, 890 patients who were admitted for the evaluation of and education for CKD were prospectively followed. Primary kidney outcome was a composite of doubling of serum creatinine, end-stage kidney disease, or death due to kidney failure. Participants were divided into quartiles (Q1–Q4) according to TSAT or serum ferritin levels. During a median follow-up period of 2.8 years, kidney events occurred in 358 patients. In the multivariable Cox analyses, compared with Q3 of TSAT, the hazard ratios (95% confidence intervals) for Q1, Q2, and Q4 were 1.20 (0.87, 1.66), 1.38 (1.01, 1.87), and 1.14 (0.82, 1.59), respectively. Compared with Q2 of serum ferritin, lower and higher quartiles had a significantly increased risk for kidney outcome; hazard ratios (95% confidence intervals) for Q1, Q3, and Q4 were 1.64 (1.18, 2.27), 1.71 (1.24, 2.37), and 1.52 (1.10, 2.10), respectively. A Fine-Gray model with death before kidney events as a competing risk showed results similar to the above. In CKD, lower and higher ferritin levels were independent risk factors for kidney disease progression. [ABSTRACT FROM AUTHOR]

We developed a 3D convolutional neural network (CNN)-based automatic kidney segmentation method for patients with chronic kidney disease (CKD) using MRI Dixon-based T1-weighted in-phase (IP)/opposed-phase (OP)/water-only (WO) images. The dataset comprised 100 participants with renal dysfunction (RD; eGFR < 45 mL/min/1.73 m2) and 70 without (non-RD; eGFR ≥ 45 mL/min/1.73 m2). The model was applied to the right, left, and both kidneys; it was first evaluated on the non-RD group data and subsequently on the combined data of the RD and non-RD groups. For bilateral kidney segmentation of the non-RD group, the best performance was obtained when using IP image, with a Dice score of 0.902 ± 0.034, average surface distance of 1.46 ± 0.75 mm, and a difference of − 27 ± 21 mL between ground-truth and automatically computed volume. Slightly worse results were obtained for the combined data of the RD and non-RD groups and for unilateral kidney segmentation, particularly when segmenting the right kidney from the OP images. Our 3D CNN-assisted automatic segmentation tools can be utilized in future studies on total kidney volume measurements and various image analyses of a large number of patients with CKD. [ABSTRACT FROM AUTHOR]

Renal vein thrombosis (RVT) is a rare vascular complication that occurs after renal transplantation and usually results in irreversible kidney damage and graft loss. We report the case of a patient who underwent right iliac fossa allogeneic kidney transplantation and developed RVT combined with ipsilateral thrombosis from the popliteal to the femoral veins, with extension to the common iliac veins, 4 months after transplantation. Under unfractionated heparin anticoagulation, an Aegisy (Life Tech Scientific Co., Ltd., Shenzhen, China) vena cava filter was placed to prevent pulmonary embolism. Percutaneous mechanical thrombectomy combined with balloon angioplasty was performed to aspirate the thrombus and successfully dilate the narrow venous lumen. The patient's renal function was restored postoperatively. Ultrasonography showed the allograft and ipsilateral lower extremity deep veins to be fluent and patent. To conclude, in patients with RVT after renal transplantation, percutaneous mechanical thrombectomy in conjunction with balloon angioplasty can be performed with desirable outcomes and no severe adverse effects. This method reduces the risk of bleeding from exposure to systemic intravenous thrombolysis and avoids surgery-associated trauma. [ABSTRACT FROM AUTHOR]

The milk urea concentration (MUC) serves as indicator of urinary nitrogen emissions, but at comparable crude protein (CP) intake, cows with high (HMU) and low (LMU) MUC excrete equal urea amounts. We hypothesized that urea and uric acid transporters and sizes of the kidney, mammary gland, and rumen account for these phenotypes. Eighteen HMU and 18 LMU Holstein dairy cows fed a low (LP) and normal (NP) CP diet were studied. Milk, plasma and urinary urea concentrations were greater with NP feeding, while plasma and urinary urea concentrations were comparable between phenotypes. Milk and plasma uric acid concentrations were higher with LP feeding but not affected by phenotype. The milk-urine uric acid ratio was greater in HMU cows. The mRNA expressions of the ruminal urea transporter SLC14A1 and AQP10, the mammary gland and rumen AQP3, and the mammary gland uric acid transporter ABCG2 were not affected by group or diet. Renal AQP10, but not AQP3, AQP7, and SLC14A2 expressions, and the kidney weights were lower in HMU cows. These data indicate that renal size and AQP10 limit the urea transfer from blood to urine, and that MUC determines if uric acid is more released with milk or urine. [ABSTRACT FROM AUTHOR]

Cattle Egret (Bubulcus ibis) is one of the most well-known herons in Egypt. It is called the friend of the farmer because it benefits farmers and helps them get rid of insects and worms. It acts as a reservoir for many diseases. Few researchers have discussed the significance of parasitic diseases that affect this wild bird and may lead to mortalities among the population especially the importance of vital organs such as kidneys. Therefore, this study aimed to spotlight parasitic infection-affected herons in Egypt and consider the risks to this beneficial bird. During this study, 23 Bubulcus ibis were captured after their death from Abou Rewash Giza Governorate, Egypt, during the period from February to September (2022). Renicola species (spp.) and Apharyngostrigea spp. are two important digenean parasites that were recovered from the kidneys, and small intestine of the heron Cattle Egret (Bubulcus ibis) with an infection rate of (17.2%) and (11.8%) respectively. Histopathological techniques were used to assess tissue alterations while light microscopy and molecular assays were used to assess the parasites. The parasites' morphological and morphometrical characteristics, as well as polymerase chain reaction and sequencing assays (mitochondrial sections), were investigated for the first time in Egypt. These parasites were given in-depth illustrations and drawings. The distinctive qualities of the two species were discussed. As the first record from Egypt, the nucleotide sequences discovered in this work have been uploaded into the GenBank database (accession numbers: OR021986 and OQ955829). Microscopically, the renal blood vessels had vasculitis, necrosis, and other degenerative alterations. Further research analyzing the health of various heron spp. and environmental deterioration can help to close information gaps about the interactions between parasites, their hosts, and environmental health. [ABSTRACT FROM AUTHOR]

This work proposed KidneyRegNet, a novel deep registration pipeline for 3D CT and 2D U/S kidney scans of free breathing, which comprises a feature network, and a 3D–2D CNN-based registration network. The feature network has handcrafted texture feature layers to reduce the semantic gap. The registration network is an encoder-decoder structure with loss of feature-image-motion (FIM), which enables hierarchical regression at decoder layers and avoids multiple network concatenation. It was first pretrained with a retrospective dataset cum training data generation strategy and then adapted to specific patient data under unsupervised one-cycle transfer learning in onsite applications. The experiment was performed on 132 U/S sequences, 39 multiple-phase CT and 210 public single-phase CT images, and 25 pairs of CT and U/S sequences. This resulted in a mean contour distance (MCD) of 0.94 mm between kidneys on CT and U/S images and MCD of 1.15 mm on CT and reference CT images. Datasets with small transformations resulted in MCDs of 0.82 and 1.02 mm, respectively. Large transformations resulted in MCDs of 1.10 and 1.28 mm, respectively. This work addressed difficulties in 3DCT-2DUS kidney registration during free breathing via novel network structures and training strategies. [ABSTRACT FROM AUTHOR]

Chronic hypoxia may have a huge impact on the cardiovascular and renal systems. Advancements in microscopy, metabolomics, and bioinformatics provide opportunities to identify new biomarkers. In this study, we aimed at elucidating the metabolic alterations in kidney tissues induced by chronic hypoxia using untargeted metabolomic analyses. Reverse phase ultrahigh performance liquid chromatography-mass spectroscopy/mass spectroscopy (RP–UPLC–MS/MS) and hydrophilic interaction liquid chromatography (HILIC)–UPLC–MS/MS methods with positive and negative ion mode electrospray ionization were used for metabolic profiling. The metabolomic profiling revealed an increase in metabolites related to carnitine synthesis and purine metabolism. Additionally, there was a notable increase in bilirubin. Heme, N-acetyl-l-aspartic acid, thyroxine, and 3-beta-Hydroxy-5-cholestenoate were found to be significantly downregulated. 3-beta-Hydroxy-5-cholestenoate was downregulated more significantly in male than female kidneys. Trichome Staining also showed remarkable kidney fibrosis in mice subjected to chronic hypoxia. Our study offers potential intracellular metabolite signatures for hypoxic kidneys. [ABSTRACT FROM AUTHOR]

CLIC5 belongs to a family of ion channels with six members reported so far. In vertebrates, the CLIC5 gene encodes two different isoforms, CLIC5A and CLIC5B. In addition to its ion channel activity, there is evidence for further functions of CLIC5A, such as the remodeling of the actin cytoskeleton during the formation of a functional glomerulus in the vertebrate kidney. However, its specific role is still incompletely understood and a specific functional role for CLIC5B has not been described yet. Here we report our findings on the differential expression and functions of Clic5a and Clic5b during zebrafish kidney development. Whole-mount in situ hybridization studies revealed specific expression of clic5a in the eye and pronephric glomerulus, and clic5b is expressed in the gut, liver and the pronephric tubules. Clic5 immunostainings revealed that Clic5b is localized in the cilia. Whereas knockdown of Clic5a resulted in leakiness of the glomerular filtration barrier, Clic5b deficient embryos displayed defective ciliogenesis, leading to ciliopathy-associated phenotypes such as ventral body curvature, otolith deposition defects, altered left–right asymmetry and formation of hydrocephalus and pronephric cysts. In addition, Clic5 deficiency resulted in dysregulation of cilia-dependent Wnt signalling pathway components. Mechanistically, we identified a Clic5-dependent activation of the membrane-cytoskeletal linker proteins Ezrin/Radixin/Moesin (ERM) in the pronephric tubules of zebrafish. In conclusion, our in vivo data demonstrates a novel role for Clic5 in regulating essential ciliary functions and identified Clic5 as a positive regulator of ERM phosphorylation. [ABSTRACT FROM AUTHOR]

This study evaluated the impact of obesity on abdominal ultrasound diagnostics and assessed effect of high-performance ultrasound probes increased imaging quality. Lean and obese subjects (n = 40; 58% female) were categorized according to body mass index (BMI, 21 to 48 kg/m2). A highly standardized ultrasound examination of the abdomen was performed by trained examiners using three different probes in randomized order (standard probe versus two high-performance probes). Quality of B-mode and duplex ultrasound were assessed using a custom scoring approach for depiction of liver and kidney anatomy and vascularization. Across probes, imaging quality of hepatic and kidney anatomy was inversely related with BMI (P < 0.03, r < − 0.35). Age, sex, and BMI explained 51% of the variance within the ultrasound quality score, with β = − 0.35, P < 0.0001 for BMI. Compared to the standard probe, high-performance probes allowed for a better depiction of kidney and liver anatomy in subjects above BMI 35 kg/m2 (n = 20, all P < 0.05), resulting in a less pronounced deterioration of imaging quality with increased BMI (all P < 0.05). In conclusion the study shows that obesity impairs ultrasound imaging quality of abdominal anatomy. The application of high-performance probes can increase anatomic depiction in obese patients. Registration number of the German Registry of Clinical Studies: DRKS00023498. [ABSTRACT FROM AUTHOR]