Capillary Tuft Research Articles

Mitochondrial-Derived Signaling Mediates Differentiation of Parietal Epithelial Cells into Podocytes.

Aims: Parietal epithelial cells (PECs) are potential stem cells within the glomerulus, migrating into site of podocyte loss to differentiate into podocytes. Little is known about the mechanism mediating differentiation of PECs into podocytes. Results: In vitro differentiation of PECs into podocytes led to upregulation of podocyte markers such as Wilms' tumor gene 1 (WT-1), Forkhead box C1 (FOXC1), synaptopodin and podocin, accompanied by increased mitochondrial abundance. Preincubation with a mitochondrial reactive oxygen species (ROS) inhibitor prevented all these events in PECs. In vivo, adriamycin (ADR)-treated mice exhibited albuminuria, decreased WT1 positive cells, and claudin-1 expressed in glomerular capillary tuft, as well as peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) overproduction in PECs. Expression of the ROS-related molecule nuclear factor erythroid 2-related factor 2 (Nrf2) and its target protein Brahma-related gene 1 (Brg1) increased during differentiation of PECs into podocytes. Suppressing Nrf2 or Brg1 reduced the differentiation of PECs, whereas overexpression had the opposite effect. Brg1 directly regulated WT-1 transcription in PECs. Activation of Nrf2 with bardoxolone-methyl (CDDO-Me) resulted in less proteinuria and more WT1 positive cells in ADR mice. PECs conditional human Nrf2 knock-in mice showed increased WT1 cell numbers. Conclusion: It concluded that mitochondria-derived ROS mediated differentiation of PECs into podocytes via Nrf2 and Brg1 signaling.

Analysis of fetal renal cortex development: Cortical maturation index as a new potential guide in fetal renal cortex assessment

Background/Aim. To date, most of the scientific attention has been aimed at the morphometric analysis of the nephrogenic zone (NZ) of the fetal renal cortex, while the quantification and analysis of the maturation zone (MZ) and other indicators of renal maturity were missing. The aim of the study was to examine the characteristics of fetal kidney cortex maturation, as well as to propose the development of a new cortical maturity index (CMI). Methods. The study included 42 paraffin molds of the fetal kidney, divided into three groups according to gestational age (GA). After hematoxylin and eosin staining, tissue sections were analyzed through the following parameters: the thickness of the NZ and MZ, the renal corpuscles area (RCa) and the glomerular capillary tuft area (GCTa), and the maturation stages of the glomeruli. In addition, a new parameter, CMI, was formed as a ratio of NZ and MZ thickness. The collected data were statistically processed. Results. Changes in NZ and MZ thickness were statistically significant, and they correlated with GA. A value of CMI higher than 0.2 was recorded in the kidney samples of fetuses younger than the 20th gestational week (GW), while a value lower than 0.1 was recorded in the samples older than the 30th GW. With an increase in GA in all zones of the renal cortex, RCa and GCTa decreased. A statistically significant reduction of GCTa was observed in the oldest group in the juxtamedullary and intermediate zones of the cortex (p < 0.01). Glomeruli located in the deeper parts of the cortex were more mature than the superficial ones. Conclusion. The measured parameters can serve as a starting point for future studies that would analyze the histomorphological characteristics of the fetal kidney cortex. In the absence of clinical data, a newly formed parameter CMI can represent assistance with the determination of GA, as it significantly correlates with GA (p < 0.01).

Five-Year study on renal outcomes in biopsy-proven focal segmental glomerulosclerosis patients in Shiraz, Iran.

Focal segmental glomerulosclerosis (FSGS) is a prevalent glomerular disease that often leads to nephrotic syndrome. It is characterized by consolidating a portion of the glomerular capillary tuft connected to Bowman's capsule. This retrospective cohort study aimed to determine the demographic characteristics, risk factors, and prognostic indicators associated with FSGS in Shiraz, Iran. The study included 53 primary FSGS patients aged over 18 years who were referred to clinics affiliated with Shiraz University of Medical Sciences. Data were collected through a comprehensive data-gathering sheet encompassing demographic information, medical history, laboratory test results, and histopathological findings. Statistical analysis was performed using SPSS 18, considering a significance level of p<0.05. A five-year follow-up was conducted on the 53 patients, with the mean age of 41.0±13.3 years. The most common FSGS variants observed were "not otherwise specified" (NOS, 13.2%) and tip variant (7.5%). Older patients exhibited higher disease activity, whereas remission rates were higher among younger individuals (P=0.012). Patients achieving remission had lower creatinine and Pro/Cr ratios and higher glomerular filtration rates (p<0.05). Treatment involving a combination of corticosteroids and mycophenolate mofetil showed a significant correlation with remission (P=0.036). Older patients with higher creatinine levels, higher Pro/Cr ratios, and lower glomerular filtration rates at disease onset may require more aggressive treatment. Combination therapy with mycophenolate mofetil and corticosteroids yields better outcomes, leading to increased remission rates. These findings provide valuable insights for managing FSGS patients.

A glomerulus chip with spherically twisted cell-laden hollow fibers as glomerular capillary tufts

Glomerulus-on-a-chip, as a promising alternative for drug nephrotoxicity evaluation, is attracting increasing attention. For glomerulus-on-a-chip, the more biomimetic the chip is, the more convincing the application of the chip is. In this study, we proposed a hollow fiber-based biomimetic glomerulus chip that can regulate filtration in response to blood pressure and hormone levels. On the chip developed here, bundles of hollow fibers were spherically twisted and embedded in designed Bowman’s capsules to form spherical glomerular capillary tufts, with podocytes and endotheliocytes cultured on the outer and inner surfaces of the hollow fibers, respectively. We evaluated the morphology of cells, the viability of cells, and the metabolic function of cells in terms of glucose consumption and urea synthesis by comparing the results obtained under fluidic and static conditions, confirmed the barrier function of the endotheliocyte-fiber membrane-podocyte structure by monitoring the diffusion of fluorescein isothiocyanate (FITC)-labeled inulin, albumin and IgG, and, for the first time, achieved on-chip filtration regulation in response to the hormone atrial natriuretic peptide. In addition, the application of the chip in the evaluation of drug nephrotoxicity was also preliminarily demonstrated. This work offers insights into the design of a more physiologically similar glomerulus on a microfluidic chip.

Aqueous extract of Daucus carota exerts a protective effect on the Renal, Hepatic and Duodenal mucosal histology in Diclofenac Induced Tissue Injury

Objective: The use of ethnobiology in treatment of many diseases especially in rural residents with limited access to medical technology, treatment and equipment is beneficial and necessary. Daucus carota (DC) root extract was used as pre-treatment in adult Wistar rats exposed to diclofenac sodium (DF) to investigate a protective effect on the histology of liver, kidney and duodenum. Materials and Method: Twenty-five adult Wistar rats were used for this study and were randomly divided into 5 groups of 5 rats each, which included: Group A - Normal control; Group B – 50mg/kg DF control; Group C – 50mg/kg DC + 50mg/kg DF, Group D – 100mg/kg DC + 50mg/kg DF; and, Group E – 140mg/kg DC + 50mg/kg DC. Results and Discussion: The results showed a reduction in damage to the hepatocytes, maintenance of sinusoidal integrity and reduction in the number of inflammatory cells in the hepatic parenchyma, In the kidney tissue, the extract preserved the glomerular capillary tuft, renal tubular epithelial cells, conserved Bowman’s space and lining epithelium of the capsule in a dose dependent manner. The intestinal mucosa in groups treated with higher doses of the extract were completely preserved and intact with minimal erosion of epithelial lining along with preservation of lamina propria and intestinal glands. Conclusion: Pre-administration of DC, preferably at concentrations of 100mg/kg and 140mg/kg reduced hepatotoxicity, renal tissue and mucosal layer damage in the duodenum following administration of DF. This preservation of tissues improved as concentration of the extract increased verifying that its efficiency was dose dependent.

PHARMACOLOGICAL EVALUATION OF ANTIUROLITHIATIC ACTIVITY OF DOLICHOS BIFLORUS SEEDEXTRACT IN RAT’S MODEL

Objectives: The main aim of the present study was to investigate the antiurolithiatic activity of Dolichos Biflorus methanolic seed extract in a rat’s model. In the phytochemical screening, it was found that Dolichos Biflorus seed extract showed the presence of tannins steroids, protein, flavonoids, terpenoids, mucilage, saponin, and carbohydrate and the absence of alkaloids fixed oil. Hence, this plant has highly diuretic activity. Methods: Model: Sodium oxalate induced urolithiasis in rats. A total of 30 rats were used for this study and the animals were divided into five groups. Each group contains six rats: Normal control group, disease control group (sodium oxalate 75 mg/kg, IP), standard group (Cystone, 750 mg/kg, PO), treatment group1 (Dolichos Biflorus 150 mg/kg, PO), treatment Group 2 (Dolichos Biflorus 300 mg/kg, PO). Urolithiasis was induced by using sodium oxalate (75 mg/kg, IP) for 28 days. Results: At the end of the experiment, all the animal blood samples were collected to check the various biochemical parameters. Animals were sacrificed by giving a high dose of pentobarbitone and kidneys were collected for antioxidant and histopathological study. From the renal function test, it was found that the drug is showing a potent effect when compared to the disease control group and standard group. Moreover, from the antioxidant and histopathology study, it was found that the drug is showing a potent effect when compared to the disease control and standard group and control group. Conclusion: After all the investigation, it was found that oral administration of Dolichos Biflorus seed extract at the low dose of 150 mg/kg and the high dose of 300 mg/kg against the sodium oxalate-induced urolithiasis and it was found that high is more effective as compared to low dose. Drug was able to suppress oxalate synthesizing enzymes and minerals. Moreover, histopathology study in the treatment group showed recovery and normal architecture of glomerulus with a tuft of capillaries surrounded by Bowman’s capsule. The most of tubules are showing normal architecture and recovery. After seeing all the results, it is confirmed that the test drug Dolichos Biflorus has potent antiurolithiatic activity. (Dolichos Biflorus short form mentioned below as DB)

Ellagic acid ameliorates hexavalent chromium-induced renal toxicity by attenuating oxidative stress, suppressing TNF-α and protecting mitochondria

Nephrotoxicity is an important adverse effect of oxidative stress induced by hexavalent chromium [Cr(VI)]. The effect of ellagic acid, a dietary polyphenolic compound with potent antioxidant activity, was investigated in Cr(VI)-induced kidney injury. Six groups of male Wistar rats were treated intragastrically with vehicle or ellagic acid (15 and 30 mg/kg) for 10 days. On day 10, rats received saline or Cr(VI) (K2Cr2O7 15 mg/kg) subcutaneously. Cr(VI) significantly increased kidney weight, affected kidney function assessed by biomarkers in blood and urine (protein, creatinine and urea nitrogen), caused histological changes (tubular injury and glomerular capillary tuft damage), increased markers of oxidative stress and reduced the activity of antioxidant enzymes. In addition, Cr(VI) altered mitochondrial ultrastructure, impaired mitochondrial respiration, increased lipid peroxidation, and inhibited the function of mitochondrial enzymes. Pretreatment with ellagic acid (30 mg/kg) attenuated all the aforementioned alterations. Furthermore, we explored whether ellagic acid might regulate the tumor necrosis factor-alpha (TNF-α)/receptor-interacting protein kinase 3 (RIPK3) pathway, reducing Cr(VI)-induced tubular necrosis. Cr(VI) upregulated both TNF-α and RIPK3, but ellagic acid only decreased TNF-α levels, having no effect on RIPK3 content. Therefore, understanding the mechanisms through which Cr(VI) promotes necroptosis is crucial for future studies, in order to design strategies to mitigate kidney damage. In conclusion, ellagic acid attenuated Cr(VI)-induced renal alterations by preventing oxidative stress, supporting enzymatic activities, suppressing TNF-α, and preserving mitochondrial ultrastructure and function, most likely due to its antioxidant properties.

Emerging Insights into Glomerular Vascular Pole and Microcirculation.

The glomerular vascular pole is the gate for the afferent and efferent arterioles and mesangial cells and a frequent location of peripolar cells with an unclear function. It has been studied in definitive detail for >30 years, and functionally interrogated in the context of signal transduction from the macula densa to the mesangial cells and afferent arteriolar smooth muscle cells from 10 to 20 years ago. Two recent discoveries shed additional light on the vascular pole, with possibly far-reaching implications. One, which uses novel serial section electron microscopy, reveals a shorter capillary pathway between the basins of the afferent and efferent arterioles. Such a pathway, when patent, may short-circuit the multitude of capillaries in the glomerular tuft. Notably, this shorter capillary route is enclosed within the glomerular mesangium. The second study used anti-Thy1.1-induced mesangiolysis and intravital microscopy to unequivocally establish in vivo the long-suspected contractile function of mesangial cells, which have the ability to change the geometry and curvature of glomerular capillaries. These studies led me to hypothesize the existence of a glomerular perfusion rheostat, in which the shorter path periodically fluctuates between being more and less patent. This action reduces or increases blood flow through the entire glomerular capillary tuft. A corollary is that the GFR is a net product of balance between the states of capillary perfusion, and that deviations from the balanced state would increase or decrease GFR. Taken together, these studies may pave the way to a more profound understanding of glomerular microcirculation under basal conditions and in progression of glomerulopathies.

Experimental malaria-associated acute kidney injury is independent of parasite sequestration and resolves upon antimalarial treatment.

Malaria remains a important global disease with more than 200 million cases and 600 000 deaths each year. Malaria-associated acute kidney injury (MAKI) may occur in up to 40% of patients with severe malaria and is associated with increased mortality. Histopathological characteristics of AKI in malaria are acute tubular injury, interstitial nephritis, focal segmental glomerulosclerosis, collapsing glomerulopathy and glomerulonephritis. We observed that C57BL/6 mice infected with Plasmodium berghei NK65 (PbNK65) develop MAKI in parallel with malaria-associated acute respiratory distress syndrome (MA-ARDS). MAKI pathology was associated with proteinuria, acute tubular injury and collapse of glomerular capillary tufts, which resolved rapidly after treatment with antimalarial drugs. Importantly, parasite sequestration was not detected in the kidneys in this model. Furthermore, with the use of skeleton binding protein-1 (SBP-1) KO PbNK65 parasites, we found that parasite sequestration in other organs and its subsequent high parasite load are not required for the development of experimental MAKI. Similar proteinuria, histopathological features, and increases in kidney expression of interferon-γ, TNF-α, kidney injury molecule-1 (KIM-1) and heme oxygenase-1 (HO-1) was observed in both infected groups despite a significant difference in parasite load. Taken together, we introduce a model of experimental AKI in malaria with important similarities to AKI in malaria patients. Therefore, this mouse model might be important to further study the pathogenesis of AKI in malaria.

MicroRNA-155-5p Aggravates Adriamycin-Induced Focal Segmental Glomerulosclerosis through Targeting Nrf2

Introduction: Focal segmental glomerulosclerosis (FSGS) is characterized by focal and segmental obliteration of glomerular capillary tufts with increased matrix and usually associated with nephrotic range proteinuria. FSGS is a huge burden to society; however, the mechanisms remain unclear and treatment is still lacking. Methods: Adriamycin nephropathy was induced by Adriamycin injection and some mice were also injected with Anti-miR-155-5p LNA or YC-1 (a pharmacological inhibitor of HIF-1). At 6 weeks, the mice were sacrificed, and kidneys, blood and urine samples were collected for further analysis. Results: We demonstrated a significant increase of miR-155-5p in kidney tissues in Adriamycin-induced FSGS mouse models. We also found Adriamycin treatment led to the activation of HIF-1, and inhibition of HIF-1 using YC-1 partly prevented the induction of miR-155-5p. Functionally, anti-miR-155-5p attenuated kidney injury and delayed the progression of renal fibrosis. Further, anti-miR-155-5p also enhanced the expression of Nrf2 following Adriamycin treatment. Further, our luciferase microRNA target reporter assay verified Nrf2 as a direct target of miR-155-5p. Our further results indicated anti-miR-155-5p could suppress kidney oxidative stress and inflammation, also supporting Nrf2 was the direct target of miR-155-5p. Finally, we also found miR-155-5p did not increase in serum but significantly increased in urine, indicating urinary miR-155-5p may be useful for FSGS diagnosis. Conclusion: This study identified a HIF-1/miR-155-5p/Nrf2 axis which can promote kidney oxidative stress and inflammation, finally aggravating kidney injury and accelerating the progression of renal fibrosis in FSGS. Moreover, the increase in urinary miR-155-5p may be useful for the diagnosis of FSGS.

Blood Flow Regulates Glomerular Capillary Formation in Zebrafish Pronephros.

The renal glomerulus is a tuft of capillaries in Bowman's capsule and functions as a blood-filtration unit in the kidney. The unique glomerular capillary tuft structure is relatively conserved through vertebrate species. However, the morphogenetic mechanism governing glomerular capillary tuft formation remains elusive. To clarify how glomerular capillaries develop, we analyzed glomerular capillary formation in the zebrafish pronephros by exploiting fluorescence-based bio-imaging technology. During glomerular capillary formation in the zebrafish pronephros, endothelial cells initially sprouted from the dorsal aorta and formed the capillaries surrounding the bilateral glomerular primordia in response to podocyte progenitor-derived vascular endothelial growth factor-A. After formation, blood flow immediately occurred in the glomerular primordia-associated capillaries, while in the absence of blood flow, they were transformed into sheet-like structures enveloping the glomerular primordia. Subsequently, blood flow induced formation of Bowman's space at the lateral sides of the bilateral glomerular primordia. Concomitantly, podocyte progenitors enveloped their surrounding capillaries while moving toward and coalescing at the midline. These capillaries then underwent extensive expansion and remodeling to establish a functional glomerular capillary tuft. However, stopping blood flow inhibited the remodeling of bilateral glomerular primordia, which therefore remained unvascularized but covered by the vascular sheets. We delineated the morphogenetic processes governing glomerular capillary tuft formation in the zebrafish pronephros and demonstrated crucial roles of blood flow in its formation. Blood flow maintains tubular structures of the capillaries surrounding the glomerular primordia and promotes glomerular incorporation of these vessels by inducing the remodeling of glomerular primordia.

Optical coherence tomography angiography in intermediate uveitis-related cystoid macular edema.

Cystoid macular edema (CME) is the leading cause of permanent visual impairment in patients with uveitis, particularly in patients with intermediate uveitis (IU). This study was aimed at comparing the changes in the macular microvasculature in patients with IU with uveitic non-responsive CME and without macular edema. In this case-control study, 55 eyes of patients with IU were assessed for macular microvascular structures, including vascular density, foveal avascular zone (FAZ) measurement, and vascular morphological changes, using spectral-domain optical coherence tomography angiography (OCT-A) with the AngioVue OCT-A system. We divided patients into the following two groups: the case group, including 30 eyes with IU-related non-responsive CME, and the control group, including 25 eyes with IU without macular edema. Participants in the case and control groups had comparable age (P = 0.753) and sex (P = 0.124) distributions. Superficial capillary plexus vessel density in the case group was significantly decreased in the whole image (P = 0.027) and the parafoveal area (P = 0.001) compared to the control group. However, there were no statistically significant differences between the two groups in terms of foveal superficial vessel density, deep capillary plexus vessel density, FAZ area, FAZ perimeter, FAZ acircularity index, or foveal vessel density in a 300-µm-wide annulus around the FAZ (all P > 0.05). Vascular morphological changes, such as the capillary tuft, telangiectatic vessels, or micro-aneurism, were not different in the overview images of the OCT-A printout between the two groups. The mean superficial capillary plexus vessel density was lower in eyes with IU-related nonresponsive CME than in those without macular edema. We observed more cystoid spaces in SCP than in DCP. Microcystic changes in the inner retina and ischemia may be the underlying cause in eyes with nonresponsive CME. Future prospective longitudinal studies with healthy, matched controls are warranted to confirm our findings.

Diverse Alterations of Glomerular Capillary Networks in Focal Segmental Glomerular Sclerosis

IntroductionFocal segmental glomerular sclerosis (FSGS) is caused by podocyte injury. It is characterized by obliteration of glomerular capillary tufts with increased extracellular matrix (ECM). Altered communication between podocytes and glomerular endothelial cells (ECs) contributes to sclerosis progression. We focused on EC injury in the FSGS.MethodsA total of 29 FSGS and 18 control biopsy specimens were assessed for clinicopathologic characteristics. CD34 (a marker for EC)-positive capillaries and ECM accumulation were evaluated quantitatively for each variant using computer-assisted image analysis.ResultsThe estimated glomerular filtration rate (eGFR) in the FSGS group was significantly lower than that in the control group. The frequency of FSGS variants was 51.7% for cellular; 13.8% for perihilar (PH), tip, and not otherwise specified (NOS); and 6.9% for collapsing. Regarding sclerotic lesions in all FSGS, narrowing or loss of CD34-positive capillaries was observed. Electron microscopy results showed loss of fenestrae, subendothelial space enlargement, and cytoplasmic swelling, indicating EC injury. Computer-assisted image analysis revealed significantly smaller areas of glomerular capillaries in FSGS with or without sclerotic lesions, with increased ECM. Moreover, in comparison with each variant, narrowed capillaries and ECM accumulation were most prominent in the collapsing variant, whereas the tip variant had the least change.ConclusionEC injury was observed in all FSGS cases, not only in sclerotic lesions but also in nonsclerotic lesions. Severity of EC injury may vary in each variant due to diverse alterations of glomerular capillary networks.

Acute Kidney Injury and Proteinuria in a Man With Hemoptysis

Acute Kidney Injury and Proteinuria in a Man With Hemoptysis

Morphologic Analysis of Urinary Podocytes in Focal Segmental Glomerulosclerosis.

The development of glomerulosclerosis in FSGS is associated with a reduction in podocyte number in the glomerular capillary tufts. Although it has been reported that the number of urinary podocytes in FSGS exceeds that of minimal-change nephrotic syndrome, the nature of events that promote podocyte detachment in FSGS remains elusive. In this study, we provide detailed, morphologic analysis of the urinary podocytes found in FSGS by examining the size of the urinary podocytes from patients with FSGS, minimal-change nephrotic syndrome, and GN. In addition, in urinary podocytes from patients with FSGS and minimal-change nephrotic syndrome, we analyzed podocyte hypertrophy and mitotic catastrophe using immunostaining of p21 and phospho-ribosomal protein S6. The size of the urinary podocytes was strikingly larger in samples obtained from patients with FSGS compared with those with minimal-change nephrotic syndrome and GN (P=0.008). Urinary podocytes from patients with FSGS had a higher frequency of positive immunostaining for p21 (P<0.001) and phospho-ribosomal protein S6 (P=0.02) than those from patients with minimal-change nephrotic syndrome. Characteristic features of mitotic catastrophe were more commonly observed in FSGS than in minimal-change nephrotic syndrome urinary samples (P=0.001). We posit that the significant increase in the size of urinary podocytes in FSGS, compared with those in minimal-change nephrotic syndrome, may be explained by hypertrophy and mitotic catastrophe.

Renal Alterations Induced by Chronic Exposure to Therapeutic Doses of Antihypercholestremic Atorvastatin.

Atorvastatin (ATOR) is widely used for the treatment and prevention of hypercholesterolemia and various diseases, such as cardiovascular complications, with little data about the histopathological and ultrastructural renal alterations that might be induced by this drug. The present study was undertaken to investigate the potential toxicity of therapeutic doses of atorvastatin on the microanatomy and ultrastructure of renal tissues from Wistar albino rats. Adult male Wistar albino rats received an oral daily dose of 5 mg/kg bodyweight for 90 consecutive days. Biopsies from both kidneys of each study rat were taken for histopathological and ultrastructural examination. ATOR-treated rats exhibited glomerular, tubular, and interstitial histological alterations, including degeneration, necrosis, hyaline droplets, edema, cortical hemorrhages, mesangial hypercellularity, and blood capillary dilation and congestion. In addition, ATOR exposure increased the activity of glucose-6-phosphate dehydrogenase and alkaline phosphatase with a concurrent reduction in proteins and neutral mucosubstances content of the glomeruli and renal cells. Moreover, ATOR-treated animals demonstrated glomerular ultrastructural alterations, consisting mainly of capillary tuft dilatation, glomerular basement membrane thickening, and mesangial cell proliferation. The renal cells of the proximal tubules demonstrated damaged mitochondria, degenerative cellular changes, endoplasmic reticulum dilatation, lysosomal and autophagosome activation, nuclear alteration, myelin figure formation, and microvilli disorganization. The findings of the present work may indicate that ATOR can induce renal histological, histochemical, and ultrastructural alterations that may affect kidney and other vital organ functions.

Utility of glomerular morphometry in diagnosing pediatric renal disease

BackgroundMorphometry has now become a useful adjunct to the diagnostic armamentarium of light, immunofluorescence, and electron microscopy, as it provides a deep insight into quantitative parameters of nephropathies. There has been a limited study on its utility especially in diagnosing pediatric renal diseases. This study is probably the first in India to assess the contribution of this diagnostic modality in pediatric renal disease to the best of authors’ knowledge. MethodsIt's a retrospective cross-sectional study covering a period of 05 years at a tertiary care hospital. The study includes 28 cases of pediatric (age till 14 years) nephropathies. The diseases were divided into two groups—nephrotic presentation and nephritic presentation. Glomerular morphometry was performed and mean was calculated for Bowman's capsule area, glomerular capillary tuft area, and Bowman's space area; for the three groups, respectively. Renal parameters serum creatinine, blood urea, 24 h urine protein were studied along with hemoglobin and serum cholesterol for the cases. Data were analyzed using SPSS software, version 25, for one-way ANOVA comparing mean in the three groups. ResultsWe found a positive and significant correlation between Bowman's capsule area with proteinuria, blood urea, and serum creatinine. There was positive and significant correlation between glomerular capillary tuft area and serum creatinine and Bowman's space area and proteinuria in both the groups. ConclusionGlomerular morphometry may contribute to the diagnosis of some glomerulopathies and the association between glomerular morphometric parameters and laboratory data may promote better understanding of the prognosis of these patients.

A Histological Study of the Renal Corpusclenephron Distribution in Iraqi Camels (Camelusdromedaries)

Aims: The present histological study was carried out to map the renal corpuscle nephron distribution and their histological properties in Iraqi camels(Camelusdromedaries).Materials and methods: Both kidneys from each of 10 (5 males and 5 females) adult camels were collected as soon as possible after the camels were sacrificed for human consumption purposes in a slaughterhouse. Following the preparation of tissues(cortex and medulla), the sections were slide-stained using alum hematoxylin and eosin (H&amp;E) stain and Periodic Acid Schiff (PAS) stain. The renal corpuscle diameters (numbers and percentages) in the subcapsular area, the cortical area, andthe juxtamedullary area were measured using an ocular micrometer.Results:The findings demonstrated that the renal capsule in camels is thick.The numbers of the renal corpuscles were low in numbers in the subscapular region which keep increasing towards the midcorticaland the Juxtamedullary regions. Moreover, the camel kidney has high numbers of long-loops of Henle nephrons and low numbers of short-loop nephrons. No significant (p?0.05) differences in the renal corpuscle diameters were noticed between midcorticaland juxtamedullaryareas. However, a significant (p?0.05) decrease in diameters of the renal corpuscles was seen in the subcapsular region. In addition, two layers consist the renal corpuscleswith a tuft of capillaries. The proximal convoluted tubules (PCTs)showed wide lumens with the presence of cuboidal epithelial cells (CuECs)and spherical nuclei. The distal convoluted tubules(DCTs) displayedthe presence of CuECs (smaller and lighter than those in the PCTs with apical spherical nuclei(ASN).Large lumens and simple columnar epithelial cells (CoECs). Furthermore, PAS staining showed high positive results in the basement membrane of the renal corpuscles.Conclusion: The current histological study provides insight about the renal corpuscle nephron distribution and their histological properties in Iraqi camels(Camelusdromedaries).

IL-1β Drives Production of FGF-23 at the Onset of Chronic Kidney Disease in Mice.

FGF-23 has arisen as an early biomarker of renal dysfunction, but at the onset of chronic kidney disease (CKD), data suggest that FGF-23 may be produced independently of the parathyroid hormone (PTH), 1,25(OH)2 -vitamin D3 signaling axis. Iron status is inversely correlated to the level of circulating FGF-23, and improvement in iron bioavailability within patients correlates with a decrease in FGF-23. Alternately, recent evidence also supports a regulatory role of inflammatory cytokines in the modulation of FGF-23 expression. To determine the identity of the signal from the kidney-inducing upregulation of osteocytic FGF-23 at the onset of CKD, we utilized a mouse model of congenital CKD that fails to properly mature the glomerular capillary tuft. We profiled the sequential presentation of indicators of renal dysfunction, phosphate imbalance, and iron bioavailability and transport to identify the events that initiate osteocytic production of FGF-23 during the onset of CKD. We report here that elevations in circulating intact-FGF-23 coincide with the earliest indicators of renal dysfunction (P14), and precede changes in serum phosphate or iron homeostasis. Serum PTH was also not changed within the first month. Instead, production of the inflammatory protein IL-1β from the kidney and systemic elevation of it in the circulation matched the induction of FGF-23. IL-1β's ability to induce FGF-23 was confirmed on bone chips in culture and within mice in vivo. Furthermore, neutralizing antibody to IL-1β blocked FGF-23 expression in both our congenital model of CKD and a second nephrotoxic serum-mediated model. We conclude that early CKD resembles a situation of primary FGF-23 excess mediated by inflammation. These findings do not preclude that altered mineral availability or anemia can later modulate FGF-23 levels but find that in early CKD they are not the driving stimulus for the initial upregulation of FGF-23. © 2020 American Society for Bone and Mineral Research.

A practical guide to the stereological assessment of glomerular number, size, and cellular composition.

The evaluation of a range of measures in the kidneys, such as developmental stage, rate and success, injury, and disease processes, relies on obtaining information on the three-dimensional structure of the renal corpuscles, and in particular the glomerular capillary tufts. To do this in the most accurate, comprehensive, and unbiased manner depends on a knowledge of stereological methods. In this article, we provide a practical guide for researchers on how to quantitate a number of structures in the kidneys, including the estimation of total glomerular number, glomerular capillary length and filtration surface area, and the cellular composition of individual glomeruli. Guidance is also provided on how to apply these methods to kidneys at different sizes and levels of maturity.