Glomerular Diameter Research Articles

Glomerular Diameter Is Associated with Reduction in Urinary Protein during Treatment with Dapagliflozin, a SGLT2 Inhibitor, in Patients with CKD

Glomerular Diameter Is Associated with Reduction in Urinary Protein during Treatment with Dapagliflozin, a SGLT2 Inhibitor, in Patients with CKD

TOXICITY TEST OF Eusideroxylon zwageri BARK EXTRACT ON KIDNEY HISTOPATHOLOGY GLOMERULAR HYPERTROPHY AND HYDROPIC DEGENERATION

Background: Ironwood bark extract (Eusideroxylon zwageri) has antioxidant properties such as tannins, phenolics, flavonoids, saponins and alkonoids. Most compounds in the ironwood bark extract were phenolics (31.28 mg GAE/g), flavonoids (30.48 mg CE/g), and proanthocyanidins (183.30 mg PE/g). These can be used as alternative herbal medicines, but also has toxic effects, so a toxicity test is necessary. Toxicity tests can be seen through histopathological parameters based on glomerular hypertrophy and hydropic degeneration. Purpose: To determine the toxic effect of ironwood bark extract administration at doses of 1,250 mg/kg, 2,750 mg/kg, and 4,750 mg/kg orally on the kidneys of Wistar rats based on histopathological appearance of glomerular hypertrophy and hydropic degeneration. Methods: Pure experimental study with a posttest-only with control design, consisting of 4 groups with 3 treatment groups given ironwood bark extract at doses of 1,250 mg/kg, 2,750 mg/kg, and 4,750 mg/kg, and 1 control group was given distilled water 2x1 ml every 24 hours orally for 14 days. Results: In administration of ironwood bark extract at doses of 2,750 mg/kgBW and 4,750 mg/kgBW, glomerular diameter was found increased. The histopathological hydropic degeneration showed a score of 1 in all dose groups. The research data were analyzed using the One Way Anova and Kruskal Wallis tests. Both tests showed no significant differences between groups. Conclusion: There was no toxic effect of ironwood bark extract at doses of 1,250 mg/kg, 2,750 mg/kg, and 4,750 mg/kg on the kidneys of Wistar rats based on histopathological appearance of glomerular hypertrophy and hydropic degeneration.

Renoprotective effects of empagliflozin in high-fat diet-induced obesity-related glomerulopathy by regulation of gut-kidney axis.

The increasing prevalence of obesity-related glomerulopathy (ORG) poses a significant threat to public health. Sodium-glucose cotransporter-2 (SGLT2) inhibitors effectively reduce body weight and total fat mass in individuals with obesity and halt the progression of ORG. However, the underlying mechanisms of their reno-protective effects in ORG remain unclear. We established a high-fat diet-induced ORG model using C57BL/6J mice, which were divided into three groups: normal chow diet (NCD group), high-fat diet (HFD) mice treated with placebo (ORG group), and HFD mice treated with empagliflozin (EMPA group). We conducted 16S ribosomal RNA gene sequencing of feces and analyzed metabolites from kidney, feces, liver, and serum samples. ORG mice showed increased urinary albumin creatinine ratio, cholesterol, triglyceride levels, and glomerular diameter compared with NCD mice (all P < 0.05). EMPA treatment significantly alleviated these parameters (all P < 0.05). Multitissue metabolomics analysis revealed lipid metabolic reprogramming in ORG mice, which was significantly altered by EMPA treatment. MetOrigin analysis showed a close association between EMPA-related lipid metabolic pathways and gut microbiota alterations, characterized by reduced abundances of Firmicutes and Desulfovibrio and increased abundance of Akkermansia (all P < 0.05). The metabolic homeostasis of ORG mice, especially in lipid metabolism, was disrupted and closely associated with gut microbiota alterations, contributing to the progression of ORG. EMPA treatment improved kidney function and morphology by regulating lipid metabolism through the gut-kidney axis, highlighting a novel therapeutic approach for ORG. NEW & NOTEWORTHY Our study uncovered that empagliflozin (EMPA) potentially protects renal function and morphology in obesity-related glomerulopathy (ORG) mice by regulating the gut-kidney axis. EMPA's reno-protective effects in ORG mice are associated with the lipid metabolism, especially in glycerophospholipid metabolism and the pantothenate/CoA synthesis pathways. EMPA's modulation of gut microbiota appears to be pivotal in suppressing glycerol 3-phosphate and CoA synthesis. The insights into gut microbiota-host metabolic interactions offer a novel therapeutic approach for ORG.

The effect of ginger essential oil (Zingiber officinale) on catalase in rat kidney tissue

We were aimed to investigate the effect of ginger essential oil (Zingiber officinale) on catalase release in rat kidney tissue by histopathological and immunohistochemically method. This study, 21 male Wistar albino rats were used. Rats were divided into three groups: control, 100 mg/kg ginger essential oil (G100), and 500 mg/kg ginger essential oil (G500). Hematoxylin-eosin staining method was used for histopathological evaluations. Immunohistochemically localization of catalase in kidney tissue was determined by streptavidin-biotin peroxidase method. As a result of histopathological evaluations, an increase in glomerulus diameter was observed in kidney tissues of G100 and G500 groups. In addition, vacuolar degeneration was observed in the proximal and distal tubule epithelial cells in the renal cortex of the G100 group. The immunoreactivity of catalase in the renal cortex region; In the control group, it is strong in the proximal tubules and weak in the mesangial cells. While moderate severity in the proximal tubules and weak in the mesangial cells in the G100 group, very weak catalase immunoreactivity was observed in the G500 group. Strong catalase immunoreactivity was detected in the proximal and collecting ducts of the kidney medulla regions of the rats in all groups. We think that ginger essential oil can be used in appropriate doses and times to reduce kidney damage caused by oxidative stress in the kidney.

Glomerular Diameter Measurements on Light Microscopy: A New Parameter Available to Pathologists and its Utility in IgA Nephropathy.

With the availability of whole slide digital scanners, fairly accurate glomerular diameter (GD) measurements are now possible on light microscopy. The value of these measurements in prognosis and diagnosis of immunoglobulin A nephropathy (IgAN) have not been studied widely. IgAN is a major cause of end-stage renal disease (ESRD) worldwide, and its progression is currently assessed using Oxford scores, serum creatinine, and 24-h urinary protein. We aimed to correlate the mean and maximum GDs with serum creatinine, 24-h urinary protein, and Oxford scores in patients with IgAN. One hundred biopsies of IgAN with a minimum of eight viable glomeruli were collected along with data of their 24-h proteinuria, serum creatinine, and Oxford scores. The slides were scanned using the Philips IntelliSite Pathology Solution-Ultra Fast Scanner. Mean GD of each glomerulus was calculated as the mean of two measurements, that is, the maximal diameter of the glomerulus and the maximal chord perpendicular to the maximal diameter. Maximum GD was also recorded for each case. The Spearman rho/Pearson R correlation coefficient was used to make this correlation. P-values <0.05 were considered statistically significant. The mean age of the patients was 34.67 ± 12.03 years, and they showed a male preponderance. The overall mean GD was 151.82 ± 28.69 µm, and maximum GD was 205.40 ± 32.76 µm. No statistically significant correlation was observed between the mean or maximum GD and the 24-h proteinuria, serum creatinine levels, and Oxford scores. GD in IgAN does not correlate with proteinuria, serum creatinine, or Oxford scores.

Novel in vivo optogenetic tools reveal autonomous pacemaker control of renal hemodynamics by macula densa cells

Macula densa (MD) cells, the tubular component of the juxtaglomerular apparatus (JGA) are generally considered as sensor cells detecting tubular salt (NaCl) concentration and based on this information provide feedback control of glomerular hemodynamics (tubuloglomerular feedback, TGF). However, the neuron-like differentiation and activity as non-traditional MD functions are emerging. This study addressed the paradigm-shifting hypothesis that rather than being simply the sensory arm of TGF, MD cells function as the nephron’s autonomous pacemaker and the primary driver and oscillator of glomerular hemodynamics. Single cell MD Ca2+ signaling was analyzed in vivo using intravital multiphoton microscopy (MPM) of MD-GT mice that selectively express the ratiometric Ca2+ reporter GCaMP6f/tdTomato in MD cells. Optogenetic MD stimulation was induced in vivo by blue light (470nm) exposure of MD-Ai27 mouse kidneys that express the depolarizing channelrhodopsin ChR2 specifically in MD cells. Conversely, MD inhibition was induced by yellow light (560nm) exposure of MD-Ai39 mouse kidneys that selectively express the hyperpolarizing halorhodopsin NpHR in MD cells. Cell membrane expression of ChR2 (in MD-Ai27 mice) and NpHR (in MD-Ai39 mice) only in the MD among all renal cell types was confirmed using immunohistochemistry. Pacemaker-like regular Ca2+ oscillations (4-fold elevations in baseline Ca2+ and average frequency of 0.03 Hz) and their cell-to-cell propagation within the MD plaque via long cell processes were observed in MD-GT mice. These Ca2+ oscillations were MD cell autonomous, as they were preserved in freshly dissected single MD cells and in the in vitro dissected and microperfused JGA, and were exclusively confined to the MD area. Bulk and scRNA seq and MD transcriptome analysis identified the high MD expression of genes related to pacemaker function, cell membrane depolarization, voltage-dependent ion channels, Ca2+ signaling and synaptic transmission that was validated by immunohistochemistry. Blue light exposure of single glomeruli/JGAs using ROI scan in MD-Ai27 mouse kidneys that previously underwent superficial corticotomy (open loop nephrons) acutely and reversibly increased capillary and afferent (AA)/efferent arteriole (EA) blood flow by approx. 50% in the light-exposed glomerulus but not in adjacent glomeruli. In contrast, yellow light exposure of single glomeruli/JGAs in MD-Ai39 mouse kidneys acutely and reversibly decreased blood flow but increased glomerular capillary diameter (suggesting preferential EA vs AA vasoconstriction) in the exposed but not in adjacent single nephrons. In addition, yellow light stimulation of single glomeruli in MD-Ai39 mouse kidneys augmented the spontaneous glomerular blood flow oscillations in these open-loop nephrons (frequency of 0.03 Hz), but not in adjacent control nephrons. Altogether, these studies identified MD cells as the nephron’s central pacemaker and oscillator of single nephron blood flow, and emphasized the importance of MD cell membrane potential and Ca2+-dependent vasodilator release as a major driver of nephron function. DK064234 DK123564 DK135290. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The effect of chlorpyrifos oral exposure on the histomorphometric and kidney function in Wistar rat.

Chlorpyrifos belongs to a broad-spectrum organophosphate insecticide that has high toxicity, is metabolized in the liver by the oxidation reaction, and can inhibit acetylcholinesterase activity. Acetylcholinesterase inhibition generates the reactive oxygen species and induces oxidative stress, which ultimately results in cellular damage like in the kidney. Examining blood urea nitrogen (BUN) levels, creatinine, and kidney histopathology is an appropriate indicator to assess the toxicity of chlorpyrifos to the degree of damage to cells and kidney tissue. This research used to determine the effect of duration of exposure to chlorpyrifos and dose-response relationships is important for early detection of the effects of chlorpyrifos toxicity on health. The research study was a true experimental (completely randomized design) consisting of 30 subjects divided into 5 groups. Controlled Group (K1) given 1 mg/kg BW Tween 20 and NaCl 0, 9% until the 56th day. The chlorpyrifos exposed group (P1, P2, P3, and P4) was given chlorpyrifos 5 mg/kg BW for 7, 14, 28, and 56 days. After the treatment, BUN and creatinine levels were measured, and microscopic changes in the kidney were analyzed. The results of BUN, creatinine, and kidney histopathologic were analyzed using the analysis of variance statistical test. The data result showed that compared to the control group, there were significant increases of BUN and creatinine (P = 0.013 and P = 0.003). Histopathological examinations of kidney glomerulus diameter were also smaller compared to the control group (P = 0.00). All the data measurement indicates significant differences compared to the control group. We concluded that sub-chronic oral exposure to chlorpyrifos at low doses can damage the kidneys and cause kidney failure.

548 Metformin normalizes impaired renal and cardiac function in a rat model of transient undernutrition

OBJECTIVES/GOALS: In the U.S., over 4 million people including children experience transient periods of undernutrition annually. Cardio-metabolic and renal diseases are more prevalent in this population. We are investigating therapeutic strategies to reverse the long-term risk of these diseases in a rat model of transient undernutrition followed by refeeding. METHODS/STUDY POPULATION: Thirty six female Fischer rats (3-months of age) were initially divided into 2 groups. Half were fed regular chow (CT) while the other half were severely food restricted (sFR) by 60% from 0-2 weeks (wks) followed by refeeding from 2-14 wks (sFR-Refed). These 2 groups were then subdivided and treated ± metformin (Met) from wk 7 to wk 12 (n=9/group). High precision ultrasound was conducted on live rats to assess heart and kidney function immediately after the sFR period ended (wk 2) and at the end of the study (wk 14). At the conclusion of the experiment, the rats were sacrificed and the histology of the kidney and heart tissues were analyzed in hematoxylin and eosin-stained sections. The protein to DNA ratio was also calculated in homogenates from these tissues. RESULTS/ANTICIPATED RESULTS: In sFR-Refed rats, cardiac output (CO), heart rate (HR) and renal artery blood flow (RBF) were decreased by 11 ± 1.5%#, 7.0 ± 6.0% and 22 ± 0.6%#, respectively, compared to control (CT) rats; #p&lt;0.05. Mean glomerular diameter was reduced in the kidneys of sFR-refed rats compared to CT and this effect was attenuated by metformin treatment [(µm): CT, 406 ± 31; sFR-Refed, 383 ± 11, p&lt;0.06; CT+Met, 393 ± 18; sFR-Refed+Met, 407 ± 18*]. Furthermore, the mean cardiomyocyte thickness was reduced in sFR-Refed rats compared to controls while metformin treatment prevented this effect [(µm): CT, 16.4 ± 3.6; sFR-Refed, 11.5 ± 2.3#; CT+Met, 16.4 ± 3.6; sFR-Refed+Met, 15.9 ± 3.2*]. #p&lt;0.05 vs. CT, same treatment; *p&lt;0.05 vs. Met, same diet; two-way ANOVA. DISCUSSION/SIGNIFICANCE: These findings have promising implications for metformin use to mitigate long-term impairments in heart and kidney structure and function in individuals who have experienced bouts of undernutrition earlier in life for either voluntarily (e.g., very low calorie dieting) or involuntary (e.g., very low food security) reasons.

Correlation of light and electron microscopic morphometric parameters of glomerular capillaries with serum creatinine and proteinuria

ABSTRACT Waste products in the bloodstream are filtered by the glomerular capillaries in the kidneys and excreted into the urine. When making a differential diagnosis of kidney diseases, structural assessment of glomeruli using histological, ultrastructural, and immunological studies is crucial. This study assessed the microscopic and ultrastructural morphometric parameters of glomerular capillaries and examined their correlation with serum creatinine and proteinuria. A total of 60 kidney biopsy cases received by the transmission electron microscope (TEM) laboratory for diagnosis were included in the study. Toluidine blue stained 300 nm thick sections of TEM tissue blocks were scanned for glomerular morphometry by a whole slide imaging system, and the estimation of Bowman’s capsule (BC) area, glomerular capillary lumen diameter (GCLD), glomerular capillary density (GCD), glomerular capillary surface area density (GCSA), and percentage of glomerular capillary lumen space (%GCLS) was performed with QuPath software. TEM images of 70 nm thick sections were used for the evaluation of endothelial fenestration diameter (EFD), glomerular basement membrane (GBM) thickness, and podocyte foot process (PFP) effacement. Proteinuria and serum creatinine showed positive correlations with GBM thickness and PFP effacement. Negative correlations of serum creatinine were observed with EFD, %GCLS, and GCSA. Hence, glomerular filtration is greatly affected by the total area of the glomerular capillary surface and structural changes of GBM. Reduction of glomerulus filtration due to foot process effacement and thickening of GBM results in damage to the filtration barrier leading to the leakage of plasma protein into urine.

Gut microbiota in the association between obesity and kidney function decline: a metagenomics-based study in a rat model

Objectives Obesity can induce dysbiosis in the gut microbiota and is considered a separate risk factor for kidney function decline. Nonetheless, the precise function of intestinal microorganisms in facilitating the connection between obesity and kidney function decline remains uncertain. Hence, the objective of this study was to investigate the alterations in the gut microbiota composition that take place during obesity and their correlations with renal function utilizing a rat model. Methods For 20 weeks, 25 Sprague–Dawley rats were fed either a high-fat diet (HFD) or a normal-fat normal diet (ND). Physiological indices, peripheral plasma, kidney tissue, and colon contents were collected for comparison between groups. Metagenomic analysis of intestinal flora was performed. Results The HFD group demonstrated significantly increased levels of creatinine and urea nitrogen in the peripheral blood. Additionally, the HFD rats exhibited a significantly larger glomerular diameter compared to the ND group, accompanied by the presence of glomerulosclerosis, tubular vacuolar transformation, and other pathological changes in certain glomeruli. Metagenomics analysis revealed a notable rise in the prevalence of the Firmicutes phylum within the HFD group, primarily comprising the Rumenococcus genus. Functional analysis indicated that the gut microbiota in the HFD group primarily correlated with infectious diseases, signal transduction, and signaling molecules and interactions. Conclusions This study provides evidence that the consumption of a HFD induces modifications in the composition and functionality of the gut microbiome in rats, which may serve as a potential mechanism underlying the relationship between obesity and the progression of kidney function decline.

Cumin Extract Alters The Histology of Kidney and Duodenum in Adult Rabbit

Background: The current study determined the histological alterations of the kidney and duodenum due to the administration of the cumin plant. The objective of the study was how consuming cumin affects the histological structure of the kidney and duodenum. Methods: Ten healthy male rabbits were divided into two groups of five each. They were housed in the animal facility at the College of Veterinary Medicine, Kerbala University. The treatment group received an oral dose of cumin extract at 250 mg/kg body weight once daily for six weeks, while the control group was given a standard diet and water. Hematoxylin and eosin staining was used to examine tissue samples from the kidneys and duodenum. Results: The histological analysis revealed significant changes in the kidney and duodenum tissues of the rabbits treated with cumin extract. In the kidneys, there was an increase in the diameter of glomeruli and a narrower lumen of the proximal tubules, indicating increased activity. Similarly, the duodenum of the treated group exhibited taller villi and deeper crypts, suggesting enhanced absorption activity. Moreover, the arrangement of tall columnar epithelial cells in the duodenal villi was altered. Conclusion: In conclusion, high intake of cumin extract showed various histological alterations in the urinary and digestive systems, particularly in the kidney and duodenum. These findings provided insights into the potential effects of cumin consumption on organ structure and function, highlighting the need for further research to understand its implications for human health better.

A new, deep learning-based method for the analysis of autopsy kidney samples used to study sex differences in glomerular density and size in a forensic population.

Artificial intelligence (AI) is increasingly used in forensic anthropology and genetics to identify the victim and the cause of death. The large autopsy samples from persons with traumatic causes of death but without comorbidities also offer possibilities to analyze normal histology with AI. We propose a new deep learning-based method to rapidly count glomerular number and measure glomerular density (GD) and volume in post-mortem kidney samples obtained in a forensic population. We assessed whether this new method detects glomerular differences between men and women without known kidney disease. Autopsies performed between 2009 and 2015 were analyzed if subjects were aged ≥ 18years and had no known kidney disease, diabetes mellitus, or hypertension. A large biopsy was taken from each kidney, stained with hematoxylin and eosin, and scanned. An in-house developed deep learning-based algorithm counted the glomerular density (GD), number, and size. Out of 1165 forensic autopsies, 86 met all inclusion criteria (54 men). Mean (± SD) age was 43.5 ± 14.6; 786 ± 277 glomeruli were analyzed per individual. There was no significant difference in GD between men and women (2.18 ± 0.49 vs. 2.30 ± 0.57 glomeruli/mm2, p = 0.71); glomerular diameter, area, and volume also did not differ. GD correlated inversely with age, kidney weight, and glomerular area. Glomerular area and volume increased significantly with age. In this study, there were no sex differences in glomerular density or size. Considering the size of the kidney samples, the use of the presented deep learning method can help to analyze large renal autopsy biopsies and opens perspectives for the histological study of other organs.

Bambara groundnut ameliorates kidney histology in female mice with protein deficiency

BACKGROUND Protein deficiency (PD) can lead to kidney damage. Consuming plant-based proteins may improve this condition. Bambara groundnut (Vigna subterranea)has an essential amino acid score of 80%, which is higher than other legumes; thus, it is potent in overcoming malnutrition. This study aimed to determine the effect of Bambara groundnut supplementation on kidney histology in adult female mice with PD.&#x0D; METHODS The study was conducted for 2 months in randomly selected female mice. These mice were grouped into the control, PD, and PD supplemented with Bambara groundnuts at 100, 200, and 300 g/kg of feed. 1 day after the last treatment, the kidneys of the mice were collected and processed histologically using the paraffin method (stained with hematoxylin and eosin and Masson’s trichrome). Parameters for observation included histopathological scoring (glomerular and interstitial space fibrosis and tubular damage), kidney histomorphometry, and organ index. Semi-quantitative data were analyzed using the Kruskal–Wallis test, while quantitative data were analyzed using one-way ANOVA (followed by Tukey’s test) and nested t-test. Statistical analysis was performed using SPSS software version 20 (IBM Corp., USA) (p≤0.05).&#x0D; RESULTS PD caused cell sloughing (moderate level) and dilatation (severe level) of the kidney tubules. It also reduced glomerular diameter and area by approximately 17.66% and 29%, respectively. PD and Bambara groundnut administration had no significant effects on the glomerular number, cortex and medulla thickness, distal and proximal tubule diameter, and kidney organ index (p&gt;0.05).&#x0D; CONCLUSIONS Bambara groundnut (V. subterranea) administration prevented damage to the kidney’s histological structure of protein-deficient mice.

Involvement of Autophagy and Oxidative Stress-Mediated DNA Hypomethylation in Transgenerational Nephrotoxicity Induced in Rats by the Mycotoxin Fumonisin B1.

Fumonisin B1 (FB1), a mycotoxin produced by Fusarium verticillioides, is one of the most common pollutants in natural foods and agricultural crops. It can cause chronic and severe health issues in humans and animals. The aim of this study was to evaluate the transgenerational effects of FB1 exposure on the structure and function of the kidneys in offspring. Virgin female Wistar rats were randomly divided into three groups: group one (control) received sterile water, and groups two and three were intragastrically administered low (20 mg/kg) and high (50 mg/kg) doses of FB1, respectively, from day 6 of pregnancy until delivery. Our results showed that exposure to either dose of FB1 caused histopathological changes, such as atrophy, hypercellularity, hemorrhage, calcification, and a decrease in the glomerular diameter, in both the first and second generations. The levels of the antioxidant markers glutathione, glutathione S-transferase, and catalase significantly decreased, while malondialdehyde levels increased. Moreover, autophagy was induced, as immunofluorescence analysis revealed that LC-3 protein expression was significantly increased in both generations after exposure to either dose of FB1. However, a significant decrease in methyltransferase (DNMT3) protein expression was observed in the first generation in both treatment groups (20 mg/kg and 50 mg/kg), indicating a decrease in DNA methylation as a result of early-life exposure to FB1. Interestingly, global hypomethylation was also observed in the second generation in both treatment groups despite the fact that the mothers of these rats were not exposed to FB1. Thus, early-life exposure to FB1 induced nephrotoxicity in offspring of the first and second generations. The mechanisms of action underlying this transgenerational effect may include oxidative stress, autophagy, and DNA hypomethylation.

Safety Test for Ethanolic Neem Leaf (Azadirachta indica A. Juss.) Extract on Male Mice (Mus musculus L) Renal Structure

Neem leaves (Azadirachta indica A. Juss.) are often used as traditional medicine because they contain bioactive compounds such as azadirachtin, nimbidin and nimbolides. Consumption of traditional medicines for long periods can cause side effect on kidney. This study aims to find out the histological structure of glomerular and proximal tubular in the male mice (Mus musculus L.) kidneys after exposure to the ethanolic of neem leaves extract. Completely Randomized Design (CRD) consists of 2 treatment groups with 15 replications was used in this study. The first group is K (only treated with aquadest) and P group (treated by ethanolic neem leaves extrcat at the dosage 14 mg/ kg body weight). The treatment were given orally with a volume of 0.2 mL for 21 days. Feeding and drinking were carried out ad-libitum. At the 22 days, kidney was isolated, weighted and made for histological processed with 5 μm in thickness using paraffin method with Hematoxylin and Eosin staining. The variables observed in this study were kidney weight, water consumption, glomerular diameter, thick of Bowman capsule, diameter of proximal tubule and lumen diameter. Data were analyzed using the t test with a confidence level of 95%. The results of the analysis showed that the treatment has no significant effect (p&gt; 0.05) to kidney weight, water consumption, glomerular diameter, thick of Bowman capsule, diameter of proximal tubules and lumen diameter. The study showed that the use of ethanolic neem leaves extract for 21 days still safe to be use as a traditional medicine.

Glomerular hyperfiltration and hypertrophy: an evaluation of maximum values in pathological indicators to discriminate "diseased" from "normal".

The success of sodium-glucose cotransporter 2 inhibitors and bariatric surgery in patients with chronic kidney disease has highlighted the importance of glomerular hyperfiltration and hypertrophy in the progression of kidney disease. Sustained glomerular hyperfiltration and hypertrophy can lead to glomerular injury and progressive kidney damage. This article explores the relationship between obesity and chronic kidney disease, focusing on the roles of glomerular hyperfiltration and hypertrophy as hallmarks of obesity-related kidney disease. The pathological mechanisms underlying this association include adipose tissue inflammation, dyslipidemia, insulin resistance, chronic systemic inflammation, oxidative stress, and overactivation of the sympathetic nervous system, as well as the renin-angiotensin aldosterone system. This article explains how glomerular hyperfiltration results from increased renal blood flow and intraglomerular hypertension, inducing mechanical stress on the filtration barrier and post-filtration structures. Injured glomeruli increase in size before sclerosing and collapsing. Therefore, using extreme values, such as the maximal glomerular diameter, could improve the understanding of the data distribution and allow for better kidney failure predictions. This review provides important insights into the mechanisms underlying glomerular hyperfiltration and hypertrophy and highlights the need for further research using glomerular size, including maximum glomerular profile, calculated using needle biopsy specimens.

Uji In Vivo Elaeocarpus sphaericus Schum terhadap Kadar Gula Darah dan Struktur Jaringan Testis, Pankreas, dan Ginjal

Genitri plant (Elaeocarpus sphaericus Schum) has a complex chemical compound that has the potential to lower blood sugar levels. The purpose of this study was to analyze in vivo blood sugar levels and changes in tissue structure of the pancreas, testes seminiferous tubules, and sucrose-induced kidneys. The study used an experimental approach, 24 male Mus musculus mice were grouped into 4 treatment groups. Negative control (P0), positive control giving sucrose at a dose of 1.125 mg/g (P1); Sucrose induction treatment was at a dose of 1.125 mg/g and Gintri seed simplicia was at a dose of 1.300 mg/g (P2). Experimental animals before being induced by sucrose were fasted for 2 hours. Sucrose induction was carried out for 5 days, the experimental animals were given food and drink ad libitum. Checking blood sugar levels every 4 hours through the tail vein. Blood sugar levels of experimental animals P2 and P3 were 126 mg/ each followed by administration of a solution of genitri seeds and fruit for 36 days, every 6 days data was collected on blood sugar levels. On the 37th day, dislocation, surgery and organ harvesting of the testes, pancreas and kidneys were carried out, and preparation of HE staining tissue was made. Data analysis using One Way Anova. The results showed that sucrose induction reduced the diameter of the islets of Langerhans, increased the diameter of the seminiferous tubules of the testes, and reduced the diameter of the glomerulus of the kidney. Giving genitri seeds and fruit lowers blood sugar levels, affects the tissue structure of the pancreas, testes, and glomerulus. The F value of the diameter of the pancreatic islets of Langerhans 16,662; testicular seminiferous tubule diameter 13,433; Glomerular diameter 28,958.

Deficiency for scavenger receptors Stabilin-1 and Stabilin-2 leads to age-dependent renal and hepatic depositions of fasciclin domain proteins TGFBI and Periostin in mice.

Stabilin-1 (Stab1) and Stabilin-2 (Stab2) are two major scavenger receptors of liver sinusoidal endothelial cells that mediate removal of diverse molecules from the plasma. Double-knockout mice (Stab-DKO) develop impaired kidney function and a decreased lifespan, while single Stabilin deficiency or therapeutic inhibition ameliorates atherosclerosis and Stab1-inhibition is subject of clinical trials in immuno-oncology. Although POSTN and TFGBI have recently been described as novel Stabilin ligands, the dynamics and functional implications of these ligands have not been comprehensively studied. Immunofluorescence, Western Blotting and Simple Western™ as well as in situ hybridization (RNAScope™) and qRT-PCR were used to analyze transcription levels and tissue distribution of POSTN and TGFBI in Stab-KO mice. Stab-POSTN-Triple deficient mice were generated to assess kidney and liver fibrosis and function in young and aged mice. TGFBI and POSTN protein accumulated in liver tissue in Stab-DKO mice and age-dependent in glomeruli of Stabilin-deficient mice despite unchanged transcriptional levels. Stab-POSTN-Triple KO mice showed glomerulofibrosis and a reduced lifespan comparable to Stab-DKO mice. However, alterations of the glomerular diameter and vascular density were partially normalized in Stab-POSTN-Triple KO. TGFBI and POSTN are Stabilin-ligands that are deposited in an age-dependent manner in the kidneys and liver due to insufficient scavenging in the liver. Functionally, POSTN might partially contribute to the observed renal phenotype in Stab-DKO mice. This study provides details on downstream effects how Stabilin dysfunction affects organ function on a molecular and functional level.

Prognostic impact of renal sinus fat accumulation in patients with chronic kidney disease.

Obesity is associated with the development and progression of chronic kidney disease (CKD). In the general population, the amount of renal sinus fat was associated with hypertension and renal impairment. However, its impact upon those with CKD remains uncertain. We prospectively included CKD patients who underwent renal biopsy and simultaneously measured their renal sinus fat volume. The association between the percentage of renal sinus fat volume, which was adjusted by kidney volume, and renal outcomes was investigated. A total of 56 patients (median 55years old, 35 men) were included. Among baseline characteristics, age and visceral fat volume were positively correlated with the percentage of renal sinus fat volume (p < 0.05). The percentage of renal sinus fat volume was associated with hypertension (p < 0.01) and tended to be associated with max glomerular diameter (p = 0.078) and urine angiotensinogen creatinine ratio (p = 0.064) after adjustment with several clinical factors. The percentage of renal sinus fat volume was significantly associated with a future > 50% decline in estimated glomerular filtration rate (p < 0.05). Among those with CKD who required renal biopsy, the amount of renal sinus fat was associated with poor renal outcomes accompanied by systemic hypertension.

Pathological and clinical characteristics of late-onset oligomeganephronia based on a histomorphometric study

BackgroundLate-onset oligomeganephronia (OMN) is a rare chronic kidney disease and has no quantitative criteria for diagnosis yet. The current study aimed to explore its clinicopathological features by histomorphometric analysis.MethodsWe retrospectively re-reviewed all patients with enlarged and sparse glomeruli by light microscopy at Peking University First Hospital from 2012 to 2021, excluding those with any factor known to contribute to similar changes. Age- and sex-matched patients with thin basement membrane nephropathy were selected as control to establish the cut-off values for glomerulomegaly and rarity. Late-onset OMN cases were then confirmed and the clinicopathological characteristics were summarized.ResultsMean diameter and density of cortical glomeruli in control was 156.53 ± 27.50 μm and 4.07 ± 0.63 /mm2, giving a lower limit of 211.53 μm for glomerulomegaly and an upper of 2.81 /mm2 for rarity. Seven adults of three females and four males were finally diagnosed as late-onset OMN with a mean age of 26.57 years. They showed mild to moderate proteinuria and/or renal dysfunction at biopsy with the mean proteinuria, serum creatinine (Scr) level, and estimated glomerular filtration rate of 0.50 g/d (0.10–0.95 g/d), 140.9 µmol/L (95.1–227.1 µmol/L), and 58.7 mL/min/1.73m2 (21.3–98.0 mL/min/1.73m2), respectively. Four patients (57.1%) had normal Scr at diagnosis. Six patients with available data showed renal tubular injury with increased urinary microalbumin in all, elevated N-acetyl-β-glucosaminidase in two, and elevated α1 microglobulin in five. Kidney size was normal or slightly reduced. The mean density and glomerular diameter of the seven cases was 0.86 mm2 (0.55–1.41 /mm2) and 229.73 μm (211.88–260.66 μm). Segmental glomerular sclerosis was observed in six (85.7%) with four (66.7%) of perihilar type. Proximal tubule dilation was observed in all, focal to diffuse, lining with enlarged epithelial cells. The mean foot process width was 634.02 nm, wider than 472.54 nm of the control (P = 0.0002).ConclusionLate-onset OMN should be considered a special entity with relatively slow clinical progress characterized by hypertrophy of the sparsely distributed nephron.