Kidney Structure Research Articles

Daytime Variation in Kidney Perfusion, Oxygenation, and Sodium Concentration Assessed by Multiparametric MRI in Healthy Volunteers.

MRI can provide information on kidney structure, perfusion, and oxygenation. Furthermore, it allows for the assessment of kidney sodium concentrations and handling, allowing multiparametric evaluation of kidney physiology. Multiparametric MRI is promising for establishing prognosis and monitoring treatment responses in kidney diseases, but its intraindividual variation during the day is unresolved. To investigate the variation in multiparametric MRI measurements from the morning to the evening. Prospective. Ten healthy volunteers, aged 29 ± 5 without history of kidney disease. 3 T/T1 mapping, blood-oxygen level dependent imaging, arterial spin labeling perfusion imaging, diffusion weighted imaging, and sodium imaging. A multiparametric MRI protocol, yielding T1, R2*, ADC, renal blood flow and renal sodium levels, was acquired in the morning, noon, and evening. The participants were fasting prior to the first examination. Urine biochemical analyses were performed to complement MRI data. The cortex and medulla were analyzed separately in a semi-automatic fashion, and gradients of total sodium concentration (TSC) and R2* gradients were calculated from outer cortex to inner medulla. Analyses of variance and mixed-effects models to estimate differences from time of day. Coefficients of variation to assess variability within and between participants. A P-value <0.05 was considered statistically significant. The coefficients of variation varied from 5% to 18% for proton-based parametric sequences, while it was 38% for TSC over a day. Multiparametric MRI is stable over the day. The coefficients of variation over a day were lower for proton multiparametric MRI, but higher for sodium MRI. 2 TECHNICAL EFFICACY: Stage 2.

Structure and arterial vascularization of the kidney in the European fallow deer (Dama dama) and red deer (Cervus elaphus)

Abstract The red deer (Cervus elaphus) and the European fallow deer (Dama dama) belong to the deer family and are found in Eurasia, North America and South America. In Poland, just after the European roe deer, they are the most common cervids. The present study aimed to describe the morphological structure and vascularization of kidneys in red and fallow deer. For this purpose, 96 kidneys were obtained from 48 individuals, which were measured and weighed. Preparations were made using two methods. The first allowed the renal arteries to be injected with stained latex and the soft tissues fixed in a formalin solution. The second is to obtain a corrosive preparation by injecting a self-curing polymer and leaving it in an enzymatic bath. The kidneys of the red deer are larger and heavier than those of the European fallow deer. The relation of the cortex to the medulla is similar between the two species, with a marked difference between wild and farmed specimens, indicating a correlation between kidney morphology and environmental factors. The renal artery is a strongly marked vessel that bifurcates into the cranial renal artery and the caudal renal artery, with subsequent triple segmentation of each, resulting in efficient vascularisation of a vital organ for survival. The information gathered may prove crucial to the future veterinary care of farmed cervids.

Generation of a humanized mesonephros in pigs from induced pluripotent stem cells via embryo complementation.

Heterologous organ transplantation is an effective way of replacing organ function but is limited by severe organ shortage. Although generating human organs in other large mammals through embryo complementation would be a groundbreaking solution, it faces many challenges, especially the poor integration of human cells into the recipient tissues. To produce human cells with superior intra-niche competitiveness, we combined optimized pluripotent stem cell culture conditions with the inducible overexpression of two pro-survivalgenes (MYCN and BCL2). The resulting cells had substantially enhanced viability in the xeno-environment of interspecies chimeric blastocyst and successfully formed organized human-pig chimeric middle-stage kidney (mesonephros) structures up to embryonic day 28 inside nephric-defective pig embryos lacking SIX1 and SALL1. Our findings demonstrate proof of principle of the possibility of generating a humanized primordial organ in organogenesis-disabled pigs, opening an exciting avenue for regenerative medicine and an artificial window for studying human kidney development.

Congenital anomalies of the kidney and urinary tract: antenatal diagnosis, management and counselling of families.

Congenital anomalies of the kidney and urinary tract are collectively one of the most commonly diagnosed antenatal conditions. Clinicians have several tools available to diagnose anomalies, including imaging, biomarkers, family history and genetic studies. In certain cases, antenatal interventions such as vesico-amniotic shunting may be considered to improve postnatal outcomes.Congenital kidney anomalies detected antenatally can vary in clinical significance from almost no impact postnatally to significant morbidity and perinatal mortality. Prognosis broadly depends on kidney size, structure and amount of amniotic fluid, alongside genetics and family history, and progression on subsequent scans. It is important to counsel parents appropriately using a parent-focused and personalised approach. The use of a multidisciplinary team should always be considered.

Blood creatinine content and rat kidney structure after intramuscular injection of pegylated antibiotic enrofloxacin

Background. Polyethylene glycol (PEG) is able to affect the permeability of memb­ra­nes by increasing the entry of antibiotics into the cell of microorganism; therefore, PEGylation may improve the effectiveness of antibiotics due to chemical modification of their molecules. It is important to assess the safety and toxicity of new compounds for drug development activity. The aim of this research was to study the functional state and structure of the kidneys of laboratory rats after intramuscular administration of PEGylated antibiotic enrofloxacin, as well as commercial antibiotic enrofloxacin and polymer PEG-400, which were used for the synthesis of PEGylated antibiotic enrofloxacin. Materials and Methods. PEGylated antibiotic enrofloxacin was obtained via the reaction between enrofloxacin chloride and PEG-400 polymer (polyethylene glycol with a molecular weight of 400 Da). The research was conducted on four groups of rats: control and three experimental ones, 12 animals in each group. Physiological saline solution was intramuscularly injected to the control rats; commercial antibiotic enrofloxacin – to rats of the first experimental group; polymer PEG-400 – to rats of the second experimental group; PEGylated antibiotic enrofloxacin – to rats of the third experimental group. Results. The conducted studies did not show a significant difference between the serum creatinine in control rats and experimental ones on the 7th, 14th and 21st days after the last administration of the drugs. Creatinine levels in the blood of all groups of animals were within physiological ranges. Histological studies of the kidney structure in control rats indicated no changes during the experiment. Histological changes in the structure of the kidneys were observed within the first seven days after the end of the intramuscular administration of polymer PEG-400 and PEGylated antibiotic enrofloxacin. Injections of the commercial form of antibiotic enrofloxacin to experimental rats caused histological changes in the kidney structure for 21 days of the experiment. Conclusions. Quadruple intramuscular administration of PEGylated and commercial antibiotics enrofloxacin to rats showed that PEGylation reduces nephrotoxicity and shortens the duration of adverse effects in the kidneys.

Plasma selenium and zinc alter associations between nephrotoxic metals and chronic kidney disease: Results from NHANES database 2011-2018.

Chronic kidney disease (CKD) is a condition defined as a persistent change in kidney structure or function, or both, that compromises human health. Environmental exposure to heavy metals (e.g. cadmium, lead, arsenic and mercury) is common, and high exposure levels are known to cause nephrotoxicity. Micronutrients such as selenium and zinc are positively associated with better kidney function and renal outcomes. This study determined the associations between CKD and heavy metal exposures measured in blood or urine within a community-dwelling population, and assessed whether and how selenium and zinc modified the associations. Data were extracted from 4 cycles of the US National Health and Nutrition Examination Survey (NHANES) database (2011-2012, 2013-2014, 2015-2016 and 2017-2018). Univariate analysis showed that higher quartiles of plasma lead and cadmium concentration were more likely associated with CKD than the lowest quartile, and along with folate, were linked to greater odds of CKD. Conversely, as plasma selenium and serum zinc increased, the odds of CKD decreased. Multivariate analysis had similar results after adjusting for relevant confounders. Higher plasma cadmium quartiles were associated with higher odds of CKD. Associations between higher quartiles of plasma selenium and serum zinc were significantly associated with lower odds of CKD. Elevated blood levels of heavy metals increase CKD, whereas elevated concentrations of plasma selenium and serum zinc decrease CKD. A high serum zinc concentration appears to interact with low-toxicity heavy metals to reduce CKD risk. This study suggests that increased selenium and zinc in the body along with avoidance of heavy metal exposures could protect against CKD.

"Hi, how can i help you?": embracing artificial intelligence in kidney research.

In recent years, biology and precision medicine have benefited from major advancements in generating large-scale molecular and biomedical datasets and in analyzing those data using advanced machine learning algorithms. Machine learning applications in kidney physiology and pathophysiology include segmenting kidney structures from imaging data and predicting conditions like acute kidney injury or chronic kidney disease using electronic health records. Despite the potential of machine learning to revolutionize nephrology by providing innovative diagnostic and therapeutic tools, its adoption in kidney research has been slower than in other organ systems. Several factors contribute to this underutilization. The complexity of the kidney as an organ, with intricate physiology and specialized cell populations, makes it challenging to extrapolate bulk omics data to specific processes. In addition, kidney diseases often present with overlapping manifestations and morphological changes, making diagnosis and treatment complex. Moreover, kidney diseases receive less funding compared with other pathologies, leading to lower awareness and limited public-private partnerships. To promote the use of machine learning in kidney research, this review provides an introduction to machine learning and reviews its notable applications in renal research, such as morphological analysis, omics data examination, and disease diagnosis and prognosis. Challenges and limitations associated with data-driven predictive techniques are also discussed. The goal of this review is to raise awareness and encourage the kidney research community to embrace machine learning as a powerful tool that can drive advancements in understanding kidney diseases and improving patient care.

Soluble thrombomodulin alleviates Diquat-induced acute kidney injury by inhibiting the HMGB1/IκBα/NF-κB signalling pathway.

Our research aimed to investigate whether soluble thrombomodulin (sTM) relieved Diquat (DQ)-induced acute kidney injury (AKI) via HMGB1/IκBα/NF-κB signaling pathways. An AKI rat model was constructed using DQ. Pathological changes in renal tissue were detected by HE and Masson staining. Gene expression was determined using qRT-PCR, IHC, and western blotting. Cell activity and apoptosis were analysed using CCK-8 and Flow cytometry, respectively. An abnormal kidney structure was observed in DQ rats. The levels of blood urea nitrogen (BUN), creatinine (CRE), uric acid (UA), oxidative stress, and inflammatory responses in the DQ group increased on the 7th day but decreased on the 14th day, compared with the control group. Additionally, HMGB1, sTM, and NF-kappaB (NF-κB) expression had increased in the DQ group compared with the control group, while the IκKα and IκB-α levels had decreased. In addition, sTM relieved the damaging effects of diquat on renal tubular epithelial cell viability, apoptosis, and the inflammatory response. The levels of HMGB1, TM, and NF-κB mRNA and protein were significantly decreased in the DQ+sTM group compared with the DQ group. These findings indicated that sTM could relieve Diquat-induced AKI through HMGB1/IκBα/NF-κB signaling pathways, which provides a treatment strategy for Diquat-induced AKI.

Factors That Influence Behavior of Chronic Kidney Disease Prevention in Medan Citizens

Chronic kidney disease is defined as the abnormality of kidney structure and function., which stays for more than 3 months long, with health implications. Today, chronic kidney disease is giving a great contribution to the world’s burden. Chronic kidney disease also affects 8%-16% of the world’s population. The huge number of chronic kidney disease cases has proven to be caused by the lack of knowledge regarding the signs and risk factors of chronic kidney disease. This is observational analytical research with a cross-sectional design. The data used in this research are primary data, obtained from questionnaire instruments on Medan citizens. The data is analyzed univariately, bivariate, and multivariately. Out of 100 respondents, it is acquired that adult (p&lt;0,001), male gender (p&lt;0,001), and higher education (p&lt;0,001) were the only factors significantly associated with good knowledge, good attitude, and positive behavior. Lastly, respondents with good knowledge (p=0,002) (PR = 8,017 (90% CI: 2,759-23,296)) and, good attitude (p&lt;0,001) (PR= 13,668 (90% CI: 4,269-43,767)) will have a positive behavior

A Comparative Study of Deep Learning Methods for Multi-Class Semantic Segmentation of 2D Kidney Ultrasound Images.

Ultrasound (US) imaging is a widely used medical imaging modality for the diagnosis, monitoring, and surgical planning for kidney conditions. Thus, accurate segmentation of the kidney and internal structures in US images is essential for the assessment of kidney function and the detection of pathological conditions, such as cysts, tumors, and kidney stones. Therefore, there is a need for automated methods that can accurately segment the kidney and internal structures in US images. Over the years, automatic strategies were proposed for such purpose, with deep learning methods achieving the current state-of-the-art results. However, these strategies typically ignore the segmentation of the internal structures of the kidney. Moreover, they were evaluated in different private datasets, hampering the direct comparison of results, and making it difficult to determination the optimal strategy for this task. In this study, we perform a comparative analysis of 7 deep learning networks for the segmentation of the kidney and internal structures (Capsule, Central Echogenic Complex (CEC), Cortex and Medulla) in 2D US images in an open access multi-class kidney US dataset. The dataset includes 514 images, acquired in multiple clinical centers using different US machines and protocols. The dataset contains the annotation of two experts, but 321 images with complete segmentation of all 4 classes were used. Overall, the results demonstrate that the DeepLabV3+ network outperformed the inter-rater variability with a Dice score of 78.0% compared to 75.6% for inter-rater variability. Specifically, DeepLabV3Plus achieved mean Dice scores of 94.2% for the Capsule, 85.8% for the CEC, 62.4% for the Cortex, and 69.6% for the Medulla. These findings suggest the potential of deep learning-based methods in improving the accuracy of kidney segmentation in US images.Clinical Relevance- This study shows the potential of DL for improving accuracy of kidney segmentation in US, leading to increased diagnostic efficiency, and enabling new applications such as computer-aided diagnosis and treatment, ultimately resulting in improved patient outcomes and reduced healthcare costs.1.

Effects of exogenous advanced glycation end products on oxidative stress and renal injury in healthy mice

AbstractThis study evaluated the biological effects of exogenous advanced glycation end products (AGEs) on the induction of chronic kidney disease and the dose‐effect relationship. Male C57BL/6 mice were placed on four diets, including saline and three other diets differing only in AGEs content (low‐AGEs [LA], medium‐AGEs [MA], and high‐AGEs [HA] ratio, 1:3:5) for 4 weeks. With the increasing intake of AGEs, mice developed a significant increase in blood glucose and lipid levels, the fluorescence intensity of AGEs, Nε‐(carboxymethyl)‐lysine, Nε‐(carboxyethyl)‐lysine, and malondialdehyde levels, whereas their superoxide dismutase activity and glutathione levels were decreased significantly. HA had the highest urinary protein levels and the lowest creatinine clearance compared to the other groups. These suggested that AGEs are an essential contributor to increasing oxidative stress levels and intake of high‐level AGEs induces more severe kidney function impairment. Meanwhile, the AGEs intake damaged the kidney structure in a dose‐dependent manner, as evidenced by granular degeneration of kidney tubular epithelial cells and inflammatory cell infiltration. These findings shed light on the detrimental impacts of AGEs on human kidneys, which also will help reveal a dose‐effect relationship of AGEs.

Effect and Mechanism of CircPTPN4 Expression in Carboxylated Single-Walled Carbon Nanotubes on Renal Fibrosis

This research was aimed to investigate the effect of circPTPN4 overexpression in carboxylated single-walled carbon nanotubes (SWCNT-COOH) on renal fibrosis (RF) in mice. SWCNT was oxidized to SWCNT-COOH by concentrated sulfuric acid and nitric acid (3:1, v/v). After characterization and analysis, the effect of SWCNT-COOH on erythrocyte status was detected. The RF mice (RFM) model was induced by SWCNT-COOH, normal mice as normal control (NC), and 1×108 TU/mL lenti-NC was injected into the tail vein as negative control, and 1×108 TU/mL lenti-circPTPN4 was injected for circPTPN4 overexpression. The expression of circPTPN4 was tested by qRT-PCR. Serum creatinine (Cr), blood urea nitrogen (BUN), interleukin 1β (IL-1β), IL-6, transforming growth factor β1 (TGF-β1), kidney injury molecule 1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) were tested by ELISA. HE, Masson, and immunohistochemistry were used to detect the pathological changes of kidney tissue. The protein expressions of collagen I (COL1), fibronectin (Fn), α-SMA, TGF-β1, Smad3, p-Smad3, and Smad7 were tested by Western blot (WB). It presented SWCNT-COOH was successfully prepared by chemical oxidation method, with an average particle size of 98.1 nm and an average Zeta potential of −38.91 mV. SWCNT-COOH had good hydrophilicity, and did not cause aggregation and morphology changes of red blood cells. As against NC, the expression of circPTPN4 in RFM and lenti-NC groups was decreased; the kidney coefficient was increased, and the normal structure of the kidney was abnormal, accompanied by inflammatory cell infiltration and collagen microformation; serum Cr, BUN, IL-1β, IL-6, and TGF-β1 were increased, and KIM-1 and NGAL in renal cortex were decreased; the protein expressions of COL1, Fn, α-SMA, TGF-β1, and p-Smad3 in the kidney were increased, and the protein expression of Smad7 was decreased (P &lt;0.05). As against RFM, the expression of circPTPN4 in lenti-circPTPN4 group was increased; the kidney coefficient decreased and the kidney structure returned to normal; COL1, Fn, α-SMA, TGF-β1, and p-Smad3 in the kidney were decreased, and that of Smad7 was increased (P &lt;0.05). SWCNT-COOH has good blood compatibility characteristics and can induce RF in mice. The expression of circPTPN4 was down-regulated in the RFM. Overexpression of circPTPN4 can restore the normal renal function of RFM, inhibiting the inflammatory response and RF process.

Kidney organoids: development and applications

Since the first publication on generating kidney-like cell aggregates from pluripotent stem cells, various modifications have been made to develop more complex and detailed kidney structures. In contrast to earlier models that featured nephron-like structures, these advances have improved the differentiation efficiency and similarity to the human kidney. Presently, kidney organoids contain not only nephrons and ureteric buds but also stromal cells. These organoids mimic the structural similarities and developmental processes of the kidneys, while reflecting their physiological properties. Kidney tubuloids derived from adult stem cells offer the advantage of long-term culture and expansion, but they include only tubular structures and lack glomerular components. In this review, we discuss the induction protocols for kidney organoids and tubuloids, as well as their potential applications in understanding kidney development, renal pathogenesis, and drug screening.

#5453 LIPID NEPHROTOXICITY INDUCED BY HIF-1α ACTIVATION ACCELERATES INTERSTITIAL INJURY IN DIABETIC NEPHROPATHY

Abstract Background and Aims Our previous study demonstrated lipid accumulation contributes to tubulointerstitial injury in diabetic nephropathy. However, the exact mechanism of which accelerate lipid accumulation in tubulointerstitium has not been completely elucidated. Increasing studies suggest that chronic hypoxia plays an important pathophysiologic role in diabetic nephropathy. This study aimed to investigate the effect of hypoxia inducible factor-1α (HIF-1α) activation induced by chronic hypoxia on lipid accumulation in diabetic kidney and to explore its potential mechanism. Method Human proximal tubular cell line HK-2 was incubated with or without cobalt chloride (CoCl2, 100 μM) which stimulates hypoxic condition in the presence or absence of glucose (30 mM) for 24 h. Specific siRNA was transfected in cells to knock down HIF-1α expression. Type 1 diabetic rats model were induced by STZ injection, and Lificiguat (YC-1) was used as HIF-1α inhibitor by intraperitoneal injection. Immunofluorescence staining and Western blot were used to determine the cellular localization and expression of HIF-1α. Periodic Acid-Schiff (PAS) staining was used to observe basic structure and pathological changes of kidney. The expression of carnitine palmitoyl transferase 1A (CPT1A), tissue growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF) were measured by immunohistochemical staining and Western blot. Lipid accumulation was detected by oil red O staining and cellular triglyceride quantification assay. Results In in vitro study, CoCl2 effectively increased the expression of HIF-1α and its translocation from cytoplasm to nucleus. Meanwhile, HIF-1α activation induced by CoCl2 significantly increased lipid accumulation in HK-2 cells. Moreover, CoCl2 treatment increased TGF- β and CTGF expression in HK-2 cells. The presence of glucose (30mM) made no significant difference to HK-2 cells incubated with CoCl2. HIF-1α siRNA treatment significantly reduced lipid deposition in HK-2 cells incubated with CoCl2. In vivo study showed YC-1 treatment decreased the expression of HIF-1α in renal tubules of diabetic rats, which was accompanied by less lipid accumulation compared with the diabetes mellitus (DM) group. PAS staining showed the desquamation and necrosis of tubular epithelial cells in the YC-1 group were alleviated compared with the DM group. YC-1 treatment did not affect the ratio of kidney weight to body weight, whereas decreased the levels of blood glucose, urine albumin creatinine ratio and NAG creatinine ratio in diabetic rats. The expressions of fibrosis factor TGF- β and CTGF were decreased in the YC-1 group compared with the DM group. Furthermore, the protein expression of CPT1A, the key enzyme of fatty acid oxidation, which was decreased in the DM group compared with the controls, was regained by YC-1 treatment. Conclusion Our findings demonstrated that HIF-1α activation contributed to interstitial injury in diabetic nephropathy by inducing lipid accumulation. HIF-1α activation might contribute to lipid nephrotoxicity by downregulating fatty acid oxidation.

Naïve or Engineered Extracellular Vesicles from Different Cell Sources: Therapeutic Tools for Kidney Diseases.

Renal pathophysiology is a multifactorial process involving different kidney structures. Acute kidney injury (AKI) is a clinical condition characterized by tubular necrosis and glomerular hyperfiltration. The maladaptive repair after AKI predisposes to the onset of chronic kidney diseases (CKD). CKD is a progressive and irreversible loss of kidney function, characterized by fibrosis that could lead to end stage renal disease. In this review we provide a comprehensive overview of the most recent scientific publications analyzing the therapeutic potential of Extracellular Vesicles (EV)-based treatments in different animal models of AKI and CKD. EVs from multiple sources act as paracrine effectors involved in cell-cell communication with pro-generative and low immunogenic properties. They represent innovative and promising natural drug delivery vehicles used to treat experimental acute and chronic kidney diseases. Differently from synthetic systems, EVs can cross biological barriers and deliver biomolecules to the recipient cells inducing a physiological response. Moreover, new methods for improving the EVs as carriers have been introduced, such as the engineering of the cargo, the modification of the proteins on the external membrane, or the pre-conditioning of the cell of origin. The new nano-medicine approaches based on bioengineered EVs are an attempt to enhance their drug delivery capacity for potential clinical applications.

Impact of renal tubular Cpt1a overexpression on the kidney metabolome in the folic acid-induced fibrosis mouse model.

Background: Chronic kidney disease (CKD) is characterized by the progressive and irreversible deterioration of kidney function and structure with the appearance of renal fibrosis. A significant decrease in mitochondrial metabolism, specifically a reduction in fatty acid oxidation (FAO) in tubular cells, is observed in tubulointerstitial fibrosis, whereas FAO enhancement provides protection. Untargeted metabolomics offers the potential to provide a comprehensive analysis of the renal metabolome in the context of kidney injury. Methodology: Renal tissue from a carnitine palmitoyl transferase 1a (Cpt1a) overexpressing mouse model, which displays enhanced FAO in the renal tubule, subjected to folic acid nephropathy (FAN) was studied through a multiplatform untargeted metabolomics approach based on LC-MS, CE-MS and GC-MS analysis to achieve the highest coverage of the metabolome and lipidome affected by fibrosis. The expression of genes related to the biochemical routes showing significant changes was also evaluated. Results: By combining different tools for signal processing, statistical analysis and feature annotation, we were able to identify variations in 194 metabolites and lipids involved in many metabolic routes: TCA cycle, polyamines, one-carbon metabolism, amino acid metabolism, purine metabolism, FAO, glycerolipids and glycerophospholipids synthesis and degradation, glycosphingolipids interconversion, and sterol metabolism. We found several metabolites strongly altered by FAN, with no reversion induced by Cpt1a overexpression (v.g. citric acid), whereas other metabolites were influenced by CPT1A-induced FAO (v.g. glycine-betaine). Conclusion: It was implemented a successful multiplatform metabolomics approach for renal tissue analysis. Profound metabolic changes accompany CKD-associated fibrosis, some associated with tubular FAO failure. These results highlight the importance of addressing the crosstalk between metabolism and fibrosis when undertaking studies attempting to elucidate the mechanism of CKD progression.

The renoprotective effects of hesperidin on kidney injury induced by exposure to severe chronic dust storm particulate matter through inhibiting the Smads/TGF-β1 signaling in rat.

Exposure to dust storm particulate matter (PM) is detrimental to kidney tissue. In this study, the impacts of chronic intake of dusty PM were explored as a major objective in a specified compartment to make a real-like dust storm (DS) model, and the role of hesperidin (HSP) as an antioxidant on kidney tissue was assessed in rats. Thirty-two male Wistar rats (200-220 g) were randomly allocated into 4 groups: CA+NS: (clean air and normal saline as a vehicle of HSP). Dusty PM and NS (DS+NS). HSP+ CA: rats received 200 mg/kg of HSP by gavage for 28 days, once daily in addition to exposure to clean air. HSP+DS: HSP plus DS. In DS groups, the animals were exposed to dust storms at a concentration of 5000-8000 μg/m3 in the chamber for 1 h daily, for 4 consecutive weeks, except Thursdays and Fridays. At the end of the experiment, the animals were sacrificed for biochemical, inflammatory, oxidative stress, molecular parameters, and histological evaluation. DS significantly enhanced blood urea nitrogen and creatinine, inflammatory (tumor necrosis factor-α, and interleukin-1β), and oxidative stress indexes. Likewise, a significant increase was seen in mRNA Smads, collagen-I, and transforming growth factor-β1 (TGF-β1) expressions in the kidney. Histological findings showed contracted glomeruli and kidney structure disorder. In addition, Masson's trichrome staining demonstrated renal fibrosis. Nevertheless, HSP could significantly reverse these changes. Our data confirmed that DS results in kidney fibrosis through enhancing Smads/TGF-β1 signaling. However, HSP was able to inhibit these changes as confirmed by histological findings.

Kidney Organoid Derived from Human Pluripotent and Adult Stem Cells for Disease Modeling.

Kidney disease affects a significant portion of the global population, yet effective therapies are lacking despite advancements in identifying genetic causes. This limitation can be attributed to the absence of adequate in vitro models that accurately mimic human kidney disease, hindering targeted therapeutic development. However, the emergence of human induced pluripotent stem cells (PSCs) and the development of organoids using them have opened up a way to model kidney development and disease in humans, as well as validate the effects of new drugs. To fully leverage their capabilities in these fields, it is crucial for kidney organoids to closely resemble the structure and functionality of adult human kidneys. In this review, we aim to discuss the potential of using human PSCs or adult kidney stem cell-derived kidney organoids to model genetic kidney disease and renal cancer.

RENAL12: Can Renal Autologous Cell Therapy (REACT) Delay Dialysis and Renal Transplantation in Chronic Kidney Disease with Type 2 Diabetes? The proact 1 and 2 Phase 3 Trial Design

Introduction: REACT is being developed to preserve renal function and delay or prevent ESRD. REACT is composed of bioactive selected renal cells (SRCs), isolated from a participant’s kidney, which participate in kidney repair and regeneration. Preclinical studies have demonstrated that SRCs injected directly into the kidney cortex produced a regenerative response improving kidney function and structure. Description of therapy REACT is derived from a standard kidney biopsy in an outpatient setting. SRCs are expanded ex vivo, cryopreserved, and shipped to the clinical site approximately 12 weeks later. REACT is percutaneously injected into the kidney cortex utilizing CT guidance in each kidney, 3 months apart. Participants proact 1 and proact will enroll 1200 pts from ~150 sites in the US and ~25 other countries with up to 60 months of follow-up, aged 30-80 years with type 2 diabetes who have an eGFR of 20-50 mL/min/1.73 m2, and UACR 300-5000 mg/g. Eligible participants will be randomized 1:1 to REACT or sham biopsy/injection in a single blind manner. Standard-of-care therapies including RAASi, SGLT2i, and MRAs are given per local guidance. Study Endpoints Time-to-event primary composite endpoint from first injection to the earliest of >≥40% eGFR decline, eGFR < 15 mL/min/1.73m2 sustained for 30 days, initiation of chronic dialysis, kidney transplantation, cardiovascular or renal death. Conclusion:proact 1 and 2 are global phase 3 randomized controlled trials evaluating the safety and efficacy of REACT on major kidney disease endpoints, among participants with type 2 diabetes and Stage 3a/4 CKD. REACT, a novel cell therapy comprised of SRCs, has the potential to directly preserve kidney function with a goal to prevent kidney failure.

Effects of Aqueous Extract of Cumin Seed (Cuminum cyminum) on the Structure and Function of Albino Rat Kidneys Treated with Dibutyl Phthalate

This study was aimed to investigate the effects of Cuminum cyminum seed aqueous extract on the function and histological structure of rat kidney treated with dibutyl phthalate (DBP). Eighteen albino rats weighing 190-240g and aged 10-12 weeks were used for this study which went on for 28 days. The rats were divided into three groups (each with six animals): 1st group: control rats were given food and tap water, 2nd group was given DBP (420mg/Kg. B.W.) with tap water and diet, 3rd group were fed cumin plant orally at a daily dose of (200 mg/kg B.W.) and DBP (420mg/kg. B.W.) was given with drinking water and fed with diet daily. Kidney and liver function parameters were measured and histological structure of kidney was examined. Results showed that DBP significantly increased creatinine, urea as well as liver parameters AST and ALT, while decreased ALP level, destruction, hemorrhage and inflammation in kidney. Cumin decreased AST and ALT level but increased ALP level and elevated kidney hemorrhage which concluded that DBP may cause oxidative stress for rat liver and kidney. Despite hepatoprotective role of cumin, it interacts with DPB and increases bleeding in kidney.