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AA-amyloidosis is frequent in shelter cats, and chronic kidney disease is the foremost cause of death. The aims were to describe kidney laboratory and microscopic findings in shelter cats with AA-amyloidosis. Cats were included if kidney specimens were collected post-mortem and laboratory data were available within 6 months before death. Renal lesions were evaluated with optical and electron microscopy. Mass spectrometry was used to characterize amyloid. Nine domestic short-hair cats were included; 4 females and 5 males with a median age of 8 years (range = 2–13). All cats had blood analyses and urinalyses available. Serum creatinine concentrations were increased in 6 cats and symmetric dimethylarginine was increased in all of the cats. All of the cats had proteinuria. Eight of 9 cats had amyloid in the medulla, and 9 had amyloid in the cortex (glomeruli). All cats had amyloid in the interstitium. Six cats had concurrent interstitial nephritis and 1 had membranoproliferative glomerulonephritis. All cats had extrarenal amyloid deposits. Amyloid was AA in each case. In conclusion, renal deposition of amyloid occurs in both cortex and medulla in shelter cats and is associated with azotemia and proteinuria. Renal involvement of systemic AA-amyloidosis should be considered in shelter cats with chronic kidney disease. The cat represents a natural model of renal AA-amyloidosis. [ABSTRACT FROM AUTHOR]

Background: Patients with cirrhosis are susceptible to development of acute kidney injury (AKI), which leads to poor outcome. We conducted a study to evaluate the spectrum of AKI in patients with cirrhosis. Materials and Methods: This study was conducted in consecutive cirrhotic patients with AKI admitted in a tertiary care center of India from April 2020 to December 2022. Details including history, examination findings, and results of laboratory investigations were recorded. Results: A total of 243 patients were enrolled in this study. The majority (91.3%) of the patients were males. The most common etiology of cirrhosis was alcohol in 58.4% (n = 142) followed by hepatitis B in 10.3% (n = 25) of patients. Pre-renal form of AKI was present in 54.4% (n = 132) of patients and hepatorenal syndrome (HRS) in 21.8% (n = 53) of patients. IgA nephropathy was the commonest (n = 6) glomerular pathology in nonresponders with intrinsic renal disease. Majority of the patients belonged to stage II (46.9%) and stage I AKI (37%), while only 16.1% had stage III AKI. Various stages of AKI showed a significant correlation (P < 0.05) with Child-- Turcotte--Pugh (CTP) score and Model for End-stage Liver Disease (MELD)-Na score. The overall in-hospital mortality rate was found to be 18.5% (n = 45). Conclusion: Renal dysfunction is a frequent complication among cirrhotic patients. Pre-renal factors were the most common cause of AKI in cirrhotics. Stages of AKI showed significant correlation with liver prognostic scores. Renal biopsy should be considered in patients not responding to treatment, to guide further management. [ABSTRACT FROM AUTHOR]

Abstract Background The utility of urine dipsticks for the quantification of proteinuria is limited because of the influence of urine specific gravity (USG). To circumvent the need for urine protein creatinine ratios (UPCR) some have proposed a calculated dipstick urine protein to USG ratio (DUR) for the detection of proteinuria. However, the performance of DUR has not been evaluated in veterinary patients. Objectives Evaluate the correlation between DUR and UPCR, while also assessing the effect of urine characteristics on this relationship and evaluating the performance of DUR in detecting proteinuria. Animals Urine samples from 308 dogs and 70 cats. Methods Retrospective cohort study of urinalyses and UPCRs from dogs and cats collected between 2016 and 2021. Results Both canine and feline urine samples showed a positive moderate correlation between the UPCR and DUR. The correlation was not influenced by the presence of active urine sediment, glucosuria, or urine pH. In detecting canine urine samples with a UPCR >0.5, an optimal DUR of 1.4 had sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 89%, 83%, 96%, and 63%, respectively. In detecting feline urine samples with a UPCR >0.4, an optimal DUR of 2.1 had sensitivity, specificity, PPV, and NPV of 70%, 100%, 100%, and 75%, respectively. Conclusions and Clinical Importance Use of the DUR can be a relatively reliable method for identification of proteinuria. However, given its poor NPV, the DUR cannot be recommended for exclusion of proteinuric patients.

Steroid-resistant nephrotic syndrome (SRNS) is the second most frequent cause of chronic kidney disease before the age of 25 yr. Nephrin, encoded by NPHS1, localizes to the slit diaphragm of glomerular podocytes and is the predominant structural component of the glomerular filtration barrier. Biallelic variants in NPHS1 can cause congenital nephrotic syndrome of the Finnish type, for which, to date, no causative therapy is available. Recently, adeno-associated virus (AAV) vectors targeting the glomerular podocyte have been assessed as a means for gene replacement therapy. Here, we established quantitative and reproducible phenotyping of a published, conditional Nphs1 knockout mouse model (Nphs1tm1.1Pgarg/J and Nphs2-Creþ) in preparation for a gene replacement study using AAV vectors. Nphs1 knockout mice (Nphs1fl/fl Nphs2-Creþ) exhibited 1) a median survival rate of 18 days (range: from 9 to 43 days; males: 16.5 days and females: 20 days); 2) an average foot process (FP) density of 1.0 FP/lm compared with 2.0 FP/lm in controls and a mean filtration slit density of 2.64 lm/lm2 compared with 4.36 lm/lm2 in controls; 3) a high number of proximal tubular microcysts; 4) the development of proteinuria within the first week of life as evidenced by urine albumin-to-creatinine ratios; and 5) significantly reduced levels of serum albumin and elevated blood urea nitrogen and creatinine levels. For none of these phenotypes, significant differences between sexes in Nphs1 knockout mice were observed. We quantitatively characterized five different phenotypic features of congenital nephrotic syndrome in Nphs1fl/fl Nphs2-Creþ mice. Our results will facilitate future gene replacement therapy projects by allowing for sensitive detection of even subtle molecular effects. [ABSTRACT FROM AUTHOR]

Background: The utility of urine dipsticks for the quantification of proteinuria is limited because of the influence of urine specific gravity (USG). To circumvent the need for urine protein creatinine ratios (UPCR) some have proposed a calculated dipstick urine protein to USG ratio (DUR) for the detection of proteinuria. However, the performance of DUR has not been evaluated in veterinary patients. Objectives: Evaluate the correlation between DUR and UPCR, while also assessing the effect of urine characteristics on this relationship and evaluating the performance of DUR in detecting proteinuria. Animals: Urine samples from 308 dogs and 70 cats. Methods: Retrospective cohort study of urinalyses and UPCRs from dogs and cats collected between 2016 and 2021. Results: Both canine and feline urine samples showed a positive moderate correlation between the UPCR and DUR. The correlation was not influenced by the presence of active urine sediment, glucosuria, or urine pH. In detecting canine urine samples with a UPCR >0.5, an optimal DUR of 1.4 had sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 89%, 83%, 96%, and 63%, respectively. In detecting feline urine samples with a UPCR >0.4, an optimal DUR of 2.1 had sensitivity, specificity, PPV, and NPV of 70%, 100%, 100%, and 75%, respectively. Conclusions and Clinical Importance: Use of the DUR can be a relatively reliable method for identification of proteinuria. However, given its poor NPV, the DUR cannot be recommended for exclusion of proteinuric patients. [ABSTRACT FROM AUTHOR]

Classification of glomerular pathology based on histology sections is the key to diagnose the type and degree of kidney diseases. To address problems in the classification of glomerular lesions in children, a deep learning-based complete glomerular classification framework was designed to detect and classify glomerular pathology. A neural network integrating Resnet and Senet (RS-INet) was proposed and a glomerular classification algorithm implemented to achieve high-precision classification of glomerular pathology. SE-Resnet was applied with improvement by transforming the convolutional layer of the original Resnet residual block into a convolutional block with smaller parameters as well as reduced network parameters on the premise of ensuring network performance. Experimental results showed that our algorithm had the best performance in differentiating mesangial proliferative glomerulonephritis (MsPGN), crescent glomerulonephritis (CGN), and glomerulosclerosis (GS) from normal glomerulus (Normal) compared with other classification algorithms. The accuracy rates were 0.960, 0.940, 0.937, and 0.968, respectively. This suggests that the classification algorithm proposed in the present study is able to identify glomerular lesions with a higher precision, and distinguish similar glomerular pathologies from each other. [ABSTRACT FROM AUTHOR]

Abstract Background Angiotensin‐converting enzyme inhibitors (ACEi) are a recommended treatment for glomerular proteinuria. Frequency of response to ACEi and the association of achieving proposed urine protein‐to‐creatinine ratio (UPC) targets on survival is unknown. Objectives To determine response rates to ACEi therapy and whether a positive response is associated with improved survival. Animals Eighty‐five dogs with proteinuria (UPC > 2.0). Methods Retrospective study including dogs (UPC > 2.0) prescribed an ACEi for treatment of proteinuria. Baseline creatinine, albumin, cholesterol, UPC, and systolic blood pressure were recorded, and cases reviewed to track UPC. Treatment response was defined as achieving a UPC of 2.0, achieving recommended UPC targets within 3 months appears to be associated with a significant survival benefit. Response to treatment is still associated with survival benefit in dogs with less severe disease (no azotemia or hypoalbuminemia).

Thalassemia is one of the most prevalent genetic disorders worldwide and has previously been found to have an association with several physiological and organ complications. Several studies have found both its positive and inverse correlation with the glomerular filtration rate (GFR). Therefore, in this meta-analysis, we tried to assess the accurate correlation of β-thalassemia major (β-TM) with GFR. We searched in Google Scholar, PubMed, and ScienceDirect, and from the initial 96 articles, we finally included 12 studies. The quality and publication bias assessment confirmed that all the studies were of high to moderate quality with no publication bias. The main outcome of the mean difference (MD) was −6.94, 95%CI: −20.69, 6.80 (p < 0.00001), which indicated a negative correlation of the GFR with β-TM. The sensitivity analyses found one study to be a slight outlier, and reanalyzing the data excluding that study, an MD was achieved of −16.46, 95%CI: −26.81, −6.11 (p < 0.00001), which provides even stronger support for our main outcome. Our result determined that the GFR is generally higher in healthy people as compared to β-TM patients.

Background: Angiotensin‐converting enzyme inhibitors (ACEi) are a recommended treatment for glomerular proteinuria. Frequency of response to ACEi and the association of achieving proposed urine protein‐to‐creatinine ratio (UPC) targets on survival is unknown. Objectives: To determine response rates to ACEi therapy and whether a positive response is associated with improved survival. Animals: Eighty‐five dogs with proteinuria (UPC > 2.0). Methods: Retrospective study including dogs (UPC > 2.0) prescribed an ACEi for treatment of proteinuria. Baseline creatinine, albumin, cholesterol, UPC, and systolic blood pressure were recorded, and cases reviewed to track UPC. Treatment response was defined as achieving a UPC of <0.5 or reduction of ≥50% from baseline within 3 months. Outcome data were collected to determine overall and 12‐month survival. Results: Thirty‐five (41%) dogs responded to ACEi treatment. Treatment response was statistically associated with both median survival time (664 days [95% confidence interval (CI): 459‐869] for responders compared to 177 [95% CI: 131‐223] for non‐responders) and 12‐month survival (79% responders alive compared to 28% non‐responders). Baseline azotemia or hypoalbuminemia were also associated with a worse prognosis, with odds ratios of death at 12 months of 5.34 (CI: 1.85‐17.32) and 4.51 (CI: 1.66‐13.14), respectively. In the 25 dogs with normal baseline creatinine and albumin, response to treatment was associated with 12‐month survival (92% responders alive compared to 54% non‐responders, P =.04). Conclusions and Clinical Importance: When the UPC is >2.0, achieving recommended UPC targets within 3 months appears to be associated with a significant survival benefit. Response to treatment is still associated with survival benefit in dogs with less severe disease (no azotemia or hypoalbuminemia). [ABSTRACT FROM AUTHOR]

Glomerular endothelial cell (GEnC) fenestrations are a critical component of the glomerular filtration barrier. Their unique non-diaphragmed structure is key to their function in glomerular hydraulic permeability, and their aberration in disease can contribute to loss of glomerular filtration function. This review provides a comprehensive update of current understanding of the regulation and biogenesis of fenestrae. We consider diseases in which GEnC fenestration loss is recognized or may play a role and discuss methods with potential to facilitate the study of these critical structures. Literature is drawn from GEnCs as well as other fenestrated cell types such as liver sinusoidal endothelial cells that most closely parallel GEnCs. [ABSTRACT FROM AUTHOR]

Glomeruli are interconnected capillaries in the renal cortex that are responsible for blood filtration. Damage to these glomeruli often signifies the presence of kidney disorders like glomerulonephritis and glomerulosclerosis, which can ultimately lead to chronic kidney disease and kidney failure. The timely detection of such conditions is essential for effective treatment. This paper proposes a modified UNet model to accurately detect glomeruli in whole-slide images of kidney tissue. The UNet model was modified by changing the number of filters and feature map dimensions from the first to the last layer to enhance the model's capacity for feature extraction. Moreover, the depth of the UNet model was also improved by adding one more convolution block to both the encoder and decoder sections. The dataset used in the study comprised 20 large whole-side images. Due to their large size, the images were cropped into 512 × 512-pixel patches, resulting in a dataset comprising 50,486 images. The proposed model performed well, with 95.7% accuracy, 97.2% precision, 96.4% recall, and 96.7% F1-score. These results demonstrate the proposed model's superior performance compared to the original UNet model, the UNet model with EfficientNetb3, and the current state-of-the-art. Based on these experimental findings, it has been determined that the proposed model accurately identifies glomeruli in extracted kidney patches. [ABSTRACT FROM AUTHOR]

Thalassemia is one of the most prevalent genetic disorders worldwide and has previously been found to have an association with several physiological and organ complications. Several studies have found both its positive and inverse correlation with the glomerular filtration rate (GFR). Therefore, in this meta-analysis, we tried to assess the accurate correlation of β-thalassemia major (β-TM) with GFR. We searched in Google Scholar, PubMed, and ScienceDirect, and from the initial 96 articles, we finally included 12 studies. The quality and publication bias assessment confirmed that all the studies were of high to moderate quality with no publication bias. The main outcome of the mean difference (MD) was −6.94, 95%CI: −20.69, 6.80 (p < 0.00001), which indicated a negative correlation of the GFR with β-TM. The sensitivity analyses found one study to be a slight outlier, and reanalyzing the data excluding that study, an MD was achieved of −16.46, 95%CI: −26.81, −6.11 (p < 0.00001), which provides even stronger support for our main outcome. Our result determined that the GFR is generally higher in healthy people as compared to β-TM patients. [ABSTRACT FROM AUTHOR]

Background: Our study’s objectives were measuring the levels of blood glucose, blood pressure, glomerular filtration rate GFR, body mass index BMI and creatinine in the blood of patients with bladder cancer in order to control the development of a relationship between those hematological parameters in the case of bladder cancer. Methods and Results: Blood samples were collected during the application of this work on 155 participants diagnosed with bladder cancer were admitted to medical –Baghdad city and Al-Kindey teaching hospital. All the participants were with the age ranged (25-70 years).There are many people who have been excluded because of their young age under 20 years old and those who have any type of common cancer, which was outlined as any malignant neoplasm, including those with hematological or lymphoid origin and other tissues associated with them. All the participants wearing light clothing and no shoes in order to measure their height and weight. Blood pressure was recorded using a standard mercury sphygmomanometer after an average of 2 readings taken with a 10 min interval. Creatinine and GFR and DM also were measured meanwhile. It was noticed through the results that there is a high percentage of patients who are of advanced ages about 67(43.2%) with age ≥65 years, and those with high weights BMI ≥ 30 were 64(41.3%). After conducting pathological analyzes of blood samples, it was found that patients were having high levels of sugar, especially those with long duration of diabetics type 2, as well as high blood pressure, creatinine levels, and low GFR levels, and it was clear that males outperformed females in the height of all measurements, which is the dominant characteristic in this research. Conclusion: This study concluded that males are more likely to develop the disease with bladder cancer than female. The disease is directly related with an increase the age and obesity, BP, creatinine, low GFR and long duration of DM. [ABSTRACT FROM AUTHOR]

Hematuria is an important and common symptom of urinary system pathologies in children, and careful evaluation is required for its definitive diagnosis. In this study, we aimed to determine the demographic and clinical characteristics and etiological causes of patients who applied to our pediatric nephrology clinic with hematuria. In this study, the record of 434 patients who were followed up in our clinic for macroscopic and/or microscopic hematuria were evaluated retrospectively. Demographic data, clinical findings, laboratory and imaging examinations and final diagnosis of the patients were recorded. Out of 434 patients with hematuria, 239 (55%) were male and 195 (45%) were female. Of the patients, 291 (67%) had macroscopic hematuria and 83 (19.1%) had glomerular hematuria. Non-glomerular causes were found in 80.9%, with a significantly higher rate. Most of the causes of non-glomerular hematuria were urinary tract infection and renal stones. Acute poststreptococcal glomerulonephritis (APSGN) was found to be responsible for the majority of glomerular diseases. This study shows that most of the pathologies that may cause hematuria can be detected with a detailed history, careful physical examination and simple laboratory tests.

Glomeruli are interconnected capillaries in the renal cortex that are responsible for blood filtration. Damage to these glomeruli often signifies the presence of kidney disorders like glomerulonephritis and glomerulosclerosis, which can ultimately lead to chronic kidney disease and kidney failure. The timely detection of such conditions is essential for effective treatment. This paper proposes a modified UNet model to accurately detect glomeruli in whole-slide images of kidney tissue. The UNet model was modified by changing the number of filters and feature map dimensions from the first to the last layer to enhance the model’s capacity for feature extraction. Moreover, the depth of the UNet model was also improved by adding one more convolution block to both the encoder and decoder sections. The dataset used in the study comprised 20 large whole-side images. Due to their large size, the images were cropped into 512 × 512-pixel patches, resulting in a dataset comprising 50,486 images. The proposed model performed well, with 95.7% accuracy, 97.2% precision, 96.4% recall, and 96.7% F1-score. These results demonstrate the proposed model’s superior performance compared to the original UNet model, the UNet model with EfficientNetb3, and the current state-of-the-art. Based on these experimental findings, it has been determined that the proposed model accurately identifies glomeruli in extracted kidney patches.

Drug induced kidney injury is a frequent adverse event which contributes to morbidity and increased healthcare utilization. Our current knowledge of drug induced kidney disease is limited due to varying definitions of kidney injury, incomplete assessment of concurrent risk factors and lack of long term outcome reporting. Electronic surveillance presents a powerful tool to identify susceptible populations, improve recognition of events and provide decision support on preventative strategies or early intervention in the case of injury. Research in the area of biomarkers for detecting kidney injury and genetic predisposition for this adverse event will enhance detection of injury, identify those susceptible to injury and likely mitigate risk. In this review we will present a 6R framework to identify and mange drug induced kidney injury - risk, recognition, response, renal support, rehabilitation and research.

Albuminuria, a hallmark of diabetic nephropathy, reflects not only injury and dysfunction of the filtration apparatus, but is also affected by altered glomerular hemodynamics and hyperfiltration, as well as by the inability of renal tubular cells to fully retrieve filtered albumin. Albuminuria further plays a role in the progression of diabetic nephropathy, and the suppression of glomerular albumin leak is a key factor in its prevention. Although microalbuminuria is a classic manifestation of diabetic nephropathy, often progressing to macroalbuminuria or overt proteinuria over time, it does not always precede renal function loss in diabetes. The various components leading to diabetic albuminuria and their associations are herein reviewed, and the physiologic rationale and efficacy of therapeutic interventions that reduce glomerular hyperfiltration and proteinuria are discussed. With these perspectives, we propose that these measures should be initiated early, before microalbuminuria develops, as substantial renal injury may already be present in the absence of proteinuria. We further advocate that the inhibition of the renin–angiotensin axis or of sodium–glucose co-transport likely permits the administration of a normal recommended or even high-protein diet, highly desirable for sarcopenic diabetic patients. [ABSTRACT FROM AUTHOR]

Background: ANCA-associated vasculitis (AAV), and nephrotic syndrome encompassing diseases including minimal change disease (MCD), focal and segmental glomerulosclerosis (FSG), membranous nephropathy (MN), remain a challenge due to their varied immunological characteristics. Recent therapeutic advancements have highlighted the importance of understanding these diseases' immunological landscapes., Methods: This study analyzed transcriptomics data from renal glomerular tissues of patients with AAV, FSG, MCD, MN, and normal controls. Utilizing an immune-related gene set of 883 genes, methods including Gene Set Variation Analysis (GSVA), LASSO regression, and Weighted Correlation Network Analysis (WGCNA) were used. Predictions of immune cell compositions were made through CIBERSORT, TIMER, MCPcounter, and quanTIseq algorithms., Results: The study revealed distinct immunogenetic pathways enriched in each disease: hematopoietic cell lineage in ANCA, linoleic acid metabolism in FSG, PPAR signaling in MCD, and drug metabolism in MN. Classifiers based on immune gene expression showed high accuracy (AUC: ANCA 0.812, FSG 0.99, MCD 1, MN 0.888). Co-expression modules and PPI networks highlighted unique pathways for each disease. Predictions of immune cell composition showed elevated macrophages in FSG and MN, with Treg levels elevated across all four diseases compared to normal controls and highest in FSG. Correlation analyses demonstrated significant associations between classifier scores and immune cell types., Conclusion: This study offers accurate classifiers for AAV, FSG, MCD, and MN, and reveals distinct immunological pathways. These findings advance personalized treatments and highlight potential therapeutic targets in AAV and nephrotic syndrome. Further research should validate these results for clinical applications.

Background and aim: The harmful effects of nicotine have been reported on the lungs and cardiovascular system in many studies, but the most unexplored profile of the effect of nicotine has been the genitourinary organs. In the current study, we planned to evaluate the effects of nicotine smoke on one of the important genitourinary organs, i.e., the testes and kidneys.Materials and methods: The study was conducted on 12 inbred adult Wistar albino rats; 6 animals acting as a control, and the remaining six acting as a test group. The control group animals were given only sterile water, whereas animals of the test group were exposed to smoke produced from the nicotine wrapped in cotton wool in the dose of 6mg/day three times a day for each session of 5 minutes each for five days. Each rat was exposed to the smoke produced due to nicotine separately in a closed inhalational chamber and not in groups. The rats were euthanized after experimentation, and testis and kidneys were removed and subjected further to tissue processing for histological examination.Results: The histological examination of tissue sections of the test group revealed marked distortion and degeneration of seminiferous tubules and germ cell lineage and distorted and widened interstitial spaces with loss of Leydig cells. On the other hand, the tissue sections of the control group showed normal histological architecture of testes with normal interstitial spaces and Leydig cells. Additionally, the renal sections of the test group showed dilation of urinary space, shrunken and distorted glomeruli. On the contrary, the renal specimens of the control group also demonstrated normal renal architectural patterns.Conclusion: the results of the present study concluded that even passive smoke exposure has drastic effects on the genitourinary organs, and hence, its use in public places should be checked.

Renal hypoxia has recently been implicated as a key contributor and indicator of various glomerular diseases. As such, monitoring changes in renal oxygenation in these disorders may provide an early diagnostic advantage that could prevent potential adverse outcomes. Blood oxygen level-dependent magnetic resonance imaging (BOLD MRI) is an emerging noninvasive technique for assessing renal oxygenation in glomerular disease. Although BOLD MRI has produced promising initial results for the use in certain renal pathologies, the use of BOLD imaging in glomerular diseases, including primary and secondary nephrotic and nephritic syndromes, is relatively unexplored. Early BOLD studies on primary nephrotic syndrome, nephrotic syndrome secondary to diabetes mellitus, and nephritic syndrome secondary to systemic lupus erythematosus have shown promising results to support its future clinical utility. In this review, we outline the advancements made in understanding the use of BOLD MRI for the assessment, diagnosis, and screening of these pathologies.

Haibo Xie,1,2,* Hui Wang,1,2,* Qifeng Wu,3 Jiale Peng,4 Hua Huang,4 Yican Wang,4 Meng Huang,4 Wei Jiang,4 Yi Yang,4 Xuesong Zhang,4 Jiaxiang Zhang,2,4 Qixing Zhu1,2 1Department of Dermatology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 2Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, People’s Republic of China; 3Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou, Guangdong Province, People’s Republic of China; 4Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jiaxiang ZhangDepartment of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui, People’s Republic of ChinaTel +86-055163869267Email zhangjiaxiang@ahmu.edu.cnQixing ZhuDepartment of Dermatology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of ChinaEmail zqxing@yeah.netIntroduction: This study aimed to investigate the mechanism in regulating the cross talk between glomerular endothelial cells and podocytes in “occupational medicamentosa-like dermatitis induced by trichloroethylene (OMLDT)” patients.Methods: Totally 6 OMLDT patients, 18 controls, and 102 BALB/c female mice were involved in this study. Patient’s serum endothelin-1 (ET-1), angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2), blood urea nitrogen (BUN), and podocalyxin (PCX) were detected. All the mice were used to establish the trichloroethylene (TCE) sensitized mouse model. Transmission electron microscope results were used to reflect renal glomerulus injury. Protein levels were detected by Western blot. Ang-1/Ang-2 gene level was reflected by RT-PCR. Cell apoptosis level was detected by using TUNEL assay kit.Results: We found that in OMLDT patients, ET-1, Ang-2, BUN, and PCX were highly expressed but Ang-1 was inhibited. In TCE sensitized positive mouse, the downregulation of Ang-1, pTie-2 and the upregulation of Ang-2 were mediated by ET-1/ETAR but not ET-1/ETBR. The promotor of apoptosis proteins was downregulated and the inhibitor of apoptosis proteins was upregulated by treating with BQ123.Discussion: ET-1/ETAR-Angs/Tie-2 pathway mediated the cross talk between glomerular endothelial cells and podocytes. BQ123 can alleviate glomerulus immune injury.Keywords: trichloroethylene, glomerular, endothelin-1, endothelin receptor type A, angiopoietin-1, angiopoietin-2

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Podocytopathy is the most common feature of glomerular disorder characterized by podocyte injury- or dysfunction-induced excessive proteinuria, which ultimately develops into glomerulosclerosis and results in persistent loss of renal function. Due to the lack of self-renewal ability of podocytes, mild podocyte depletion triggers replacement and repair processes mostly driven by stem cells or resident parietal epithelial cells (PECs). In contrast, when podocyte recovery fails, activated PECs contribute to the establishment of glomerular lesions. Increasing evidence suggests that PECs, more than just bystanders, have a crucial role in various podocytopathies, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, diabetic nephropathy, IgA nephropathy, and lupus podocytopathy. In this review, we attempt to dissect the diverse role of PECs in the pathogenesis of podocytopathy based on currently available information. [ABSTRACT FROM AUTHOR]

Podocytopathy is the most common feature of glomerular disorder characterized by podocyte injury- or dysfunction-induced excessive proteinuria, which ultimately develops into glomerulosclerosis and results in persistent loss of renal function. Due to the lack of self-renewal ability of podocytes, mild podocyte depletion triggers replacement and repair processes mostly driven by stem cells or resident parietal epithelial cells (PECs). In contrast, when podocyte recovery fails, activated PECs contribute to the establishment of glomerular lesions. Increasing evidence suggests that PECs, more than just bystanders, have a crucial role in various podocytopathies, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, diabetic nephropathy, IgA nephropathy, and lupus podocytopathy. In this review, we attempt to dissect the diverse role of PECs in the pathogenesis of podocytopathy based on currently available information.

Hematuria is an important and common symptom of urinary system pathologies in children, and careful evaluation is required for its definitive diagnosis. This study aimed to determine the demographic and clinical characteristics and etiological causes of patients who applied to our pediatric nephrology clinic with hematuria. In this study, the record of 434 patients who were followed up in our clinic for macroscopic and/or microscopic hematuria were evaluated retrospectively. Demographic data, clinical findings, laboratory and imaging examinations, and final diagnosis of the patients were recorded. Out of 434 patients with hematuria, 239 (55%) were males and 195 (45%) females. Of the patients, 291 (67%) had macroscopic hematuria, and 83 (19.1%) had glomerular hematuria. Non-glomerular causes were found in 80.9%, with a significantly higher rate. Most of the causes of non-glomerular hematuria were urinary tract infection and renal stones. Acute post-streptococcal glomerulonephritis (APSGN) was found to be responsible for the majority of glomerular diseases. This study shows that most pathologies that may cause hematuria can be detected with a detailed history, careful physical examination, and simple laboratory tests. [ABSTRACT FROM AUTHOR]

Albuminuria, a hallmark of diabetic nephropathy, reflects not only injury and dysfunction of the filtration apparatus, but is also affected by altered glomerular hemodynamics and hyperfiltration, as well as by the inability of renal tubular cells to fully retrieve filtered albumin. Albuminuria further plays a role in the progression of diabetic nephropathy, and the suppression of glomerular albumin leak is a key factor in its prevention. Although microalbuminuria is a classic manifestation of diabetic nephropathy, often progressing to macroalbuminuria or overt proteinuria over time, it does not always precede renal function loss in diabetes. The various components leading to diabetic albuminuria and their associations are herein reviewed, and the physiologic rationale and efficacy of therapeutic interventions that reduce glomerular hyperfiltration and proteinuria are discussed. With these perspectives, we propose that these measures should be initiated early, before microalbuminuria develops, as substantial renal injury may already be present in the absence of proteinuria. We further advocate that the inhibition of the renin–angiotensin axis or of sodium–glucose co-transport likely permits the administration of a normal recommended or even high-protein diet, highly desirable for sarcopenic diabetic patients.

Tithonia diversifolia can be used as an antidiabetic, so it is necessary to study the safety of its use, especially the side effects on the liver and kidneys. This study aimed to determine the effect of using T. diversifolia leaf extract through histomorphometry observations of the liver and kidneys of hyperglycemic albino rats. The study design used a completely randomized design (CRD). This study used 20 male albino rats which were divided into five treatment groups, there were T0 (rat normal/control), T1 (hyperglycemic rat without T. diversifolia leaf extract), T2 (hyperglycemic rat administered with Glibenclamide 10 mg/kg BW), T3 (hyperglycemic rat administered with T. diversifolia leaf extract 150 mg/kg BW), T4 (hyperglycemic rat administered with T. diversifolia leaf extract 300 mg/kg BW). Every treatment was repeated four times. The damage of hepatocyte and the glomerular cell was observed through histological structure observation by histomorphometry method using a photomicrography microscope (Olympus BX51). The results indicate that there were significant differences (P < 0.05) in the variable of hepatocytes diameter and there was no significant different (P > 0.05) result on glomerular diameter, as well as kidney and liver weight. It was concluded that T. diversifolia leaf extract of 150 mg/kg BW and 300 mg/kg BW are safe to be used as antidiabetic. It does not cause any side effects on the liver and kidneys of hyperglycemic albino rats. Thereby T. diversifolia leaf extract can be further tested as preparation of biopharmaca which can be used as herbal medicines for diabetics [ABSTRACT FROM AUTHOR]

Objective: Kidney biopsy is essential to evaluate the activity of underlying kidney disease and the risk factors related to kidney disease progression. Glomerular morphometry is a simple but uncommonly used qualitative predictor of long-term kidney function. But it is mysterious if glomerular morphometry changes due to underlying glomerulonephritis. Measurement quantification is also necessary for reliable interpretation. We aimed to evaluate glomerular morphometry with glomerular area measurements quantitatively with digitally scanned slides in the primary glomerular diseases. Methods: We retrospectively analyzed 198 patients with nephrotic syndrome that underwent kidney biopsy between 2017 and 2019. 48 patients enrolled into the study after the exclusion criteria. We measured the glomerular area as maximum, minimum, and mean areas, using image analysis software. Results: Forty-eight kidney biopsies were analyzed retrospectively under three primary glomerular disease groups as IgA nephropathy (37.5%), focal segmental glomerulosclerosis (29.2%), and membranous glomerulonephritis (33.3%). The glomerular area measured as maximum, minimum, and mean, were similar between 3 groups. The maximum glomerular area was negatively correlated with serum albumin and positively correlated with 24hr proteinuria (r= -0.592, p=0.044, and r=0.531, p=0.022) at the time of diagnosis. At the end of one year, maximum glomerular area was positively correlated with serum creatinine (r=0.385, p=0.019) and negatively correlated with eGFR (r= -0.493, p=0.043). Conclusions: At the time of diagnosis of glomerular diseases, maximum glomerular area measurement during the pathological assessment might be an additional marker to estimate the ultrastructure of the kidney and the clinical course of the disease. [ABSTRACT FROM AUTHOR]

Urinary plasminogen/plasmin, or plasmin (ogen) uria, has been demonstrated in proteinuric patients and exposure of cultured podocytes to plasminogen results in injury via oxidative stress pathways. A causative role for plasmin (ogen) as a "second hit" in kidney disease progression has yet to have been demonstrated in vivo. Additionally, association between plasmin (ogen) uria and kidney function in glomerular diseases remains unclear. We performed comparative studies in a puromycin aminonucleoside (PAN) nephropathy rat model treated with amiloride, an inhibitor of plasminogen activation, and measured changes in plasmin (ogen) uria. In a glomerular disease biorepository cohort (n = 128), we measured time‐of‐biopsy albuminuria, proteinuria, and plasmin (ogen) uria for correlations with kidney outcomes. In cultured human podocytes, plasminogen treatment was associated with decreased focal adhesion marker expression with rescue by amiloride. Increased glomerular plasmin (ogen) was found in PAN rats and focal segmental glomerulosclerosis (FSGS) patients. PAN nephropathy was associated with increases in plasmin (ogen) uria and proteinuria. Amiloride was protective against PAN‐induced glomerular injury, reducing CD36 scavenger receptor expression and oxidative stress. In patients, we found associations between plasmin (ogen) uria and edema status as well as eGFR. Our study demonstrates a role for plasmin (ogen)‐induced podocyte injury in the PAN nephropathy model, with amiloride having podocyte‐protective properties. In one of the largest glomerular disease cohorts to study plasminogen, we validated previous findings while suggesting a potentially novel relationship between plasmin (ogen) uria and estimated glomerular filtration rate (eGFR). Together, these findings suggest a role for plasmin (ogen) in mediating glomerular injury and as a viable targetable biomarker for podocyte‐sparing treatments. [ABSTRACT FROM AUTHOR]

Objective: The present study investigated withdrawal effects of caffeinated energy drink on renal histological and biochemical parameters of adult albino rats. Material and method: Thirty adult male rats weighing 250±10gm were equally divided into 3 groups. Rats in control group I received normal diet and water for 8 weeks. Rats in energy drink group II received 3.57ml/kg body weight red bull daily by gavage for 8 weeks. Withdrawal group III received 3.57ml/kg body weight red bull for 4weeks daily, followed by normal diet and water for next 4 weeks. Blood samples were taken through tail vein at end of 4 and 8 weeks for determination of serum urea and creatinine levels. After completion of 8 weeks' rats were sacrificed, kidneys were removed and slides were prepared using Periodic acid-Schiff stain. Readings were taken through image j software and results were analyzed by SPSS. Results: On histological examination decrease in diameter of glomerulus along with widening of bowman capsule space was observed. In withdrawal group, the histological changes were not reverted to normal since no significant difference was observed when compared to energy drink group with P=0.05. Amongst the biochemical parameters, serum urea levels were increased significantly in the energy drink group. In the withdrawal group, serum urea levels were not reduced at the end of 8 weeks, results were significant when compared with control group with p value 0.000. The results were not significant in case of serum creatinine levels. Conclusion: Histological and biochemical changes in adult albino rats kidneys are not reversible after withdrawal of caffeinated energy drinks. [ABSTRACT FROM AUTHOR]

Loss of glomerular podocytes is the crucial event in the progression of chronic kidney disease (CKD). tRNA-derived fragments (tRFs), a newfangled branch of small non-coding RNA (sncRNA), recently reported to play a vital part in several diseases. In present study, we aimed to detect and reveal the role of tRFs in podocyte differentiation. The expression levels of tRFs between undifferentiated and differentiated podocytes were sequenced by illumina nextseq 500, and further verified by quantitative RT-PCR. 69 upregulated and 70 downregulated tRFs in total were singled out (Fold change > 2, P < 0.05). Gene ontology (GO) analysis indicated they are involved in the biological processes of transcription, DNA-templated, positive regulation of transcription from RNA polymerase II promoter, angiogenesis, cell adhesion. Besides, KEGG analysis suggested that these differentially tRFs are associated with PI3K-Akt signaling pathway, Rap1 signaling pathway, Ras signaling pathway, MAPK signaling pathway, and Wnt signaling pathway. Therefore, the differentially tRFs might regulate the differentiation of podocyte and the process of CKD. The functions and mechanisms of tRFs in podocytes are needed to be further explored. • Various of tRNA-derived fragments (tRFs) differed between undifferentiated podocytes and differentiated podocytes. • tRFs may play an important role of regulation in podocyte differentiation. • Potential target genes of differential tRFs were related to signaling pathways involved in podocyte injury. • Further research on differentially expressed tRFs is useful for understanding diseases associated with podocyte injury and discovering new targets. [ABSTRACT FROM AUTHOR]

Purpose of Review: To summarize the literature regarding alterations in bone health in patients with glomerular kidney disease and highlight areas in need of additional investigation. Recent Findings: There is mounting evidence that children and adults with glomerular conditions, with or without compromised kidney function, comprise a distinct subgroup of patients with unique risk factors for altered bone health. Summary: Patients with glomerular kidney disease are exposed to both disease-related and treatment-related factors that affect bone structure and function. In addition to chronic kidney disease–related risk factors for impaired bone health, high rates of exposure to osteotoxic medications, varying degrees of systemic inflammation, and altered vitamin D metabolism may contribute to compromised bone health in individuals with glomerular disease. Further study is needed to better understand these risk factors and the complex interaction between the immune system and bone cells in glomerular disease. [ABSTRACT FROM AUTHOR]

Background: The 24-hour (24-h) creatinine clearance (CrCl) is the most common method for measuring GFR in clinical laboratories. However, the limitations of CrCl have resulted in the widespread acceptance of mathematically derived estimated glomerular filtration rate (eGFR) using Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in predicting eGFR. The aim of the study was to compare 24-h CrCl with eGFR derived from these formulae and to identify which could be the best alternative. Method: A prospective study was conducted involving 140 CKD patients. Creatinine and cystatin C concentrations were determined using the cobas 6000 analyzer. The eGFR was calculated using the CG formula, 4-variable MDRD and CKD-EPI equations, and Bland-Alman plots bias was determined. Results: The CG and MDRD formulas had mean eGFR values similar to CrCl and correlation coefficients (r) were highest for CG (0.906) and lowest for MDRD (0.799). The CG equation was in agreement with 24-h CrCl in all but stage V CKD while the MDRD equation compared well in all except Stage IV CKD. The CG equation was positively biased (0.9857) while the MDRD had a negative bias (−0.05). Conclusion: The Cockcroft-Gault formula provides a more accurate assessment of GFR than 24-h CrCl and would be recommended as a substitute to provide the best estimate of GFR in our population.

Diabetic kidney disease (DKD) has become a global health concern, with about 40% of people living with type 1 and type 2 diabetes mellitus developing DKD. Upregulation of vascular endothelial growth factor (VEGF) in the kidney is a significant pathology of DKD associated with increased glomerular vascular permeability. To date, however, current anti-VEGF therapies have demonstrated limited success in treating DKD. Recent studies have shown that artificial sweeteners exhibit anti-VEGF potential. The aim of this study was therefore to assess the effects of aspartame, saccharin, and sucralose on VEGF-induced leak using an in vitro model of the glomerular endothelium. Saccharin and sucralose but not aspartame protected against VEGF-induced permeability. Whilst the sweeteners had no effect on traditional VEGF signalling, GC-MS analysis demonstrated that the sweetener sucralose was not able to enter the glomerular endothelial cell to exert the protective effect. Chemical and molecular inhibition studies demonstrated that sweetener-mediated protection of the glomerular endothelium against VEGF is dependent on the sweet taste receptor, T1R3. These studies demonstrate the potential for sweeteners to exert a protective effect against VEGF-induced increased permeability to maintain a healthy endothelium and protect against vascular leak in the glomerulus in settings of DKD.

Background AGT (angiotensinogen) synthesis occurs in renal proximal tubular epithelial cells, independent from systemic AGT, as a component of the intrarenal renin–angiotensin system. We investigated urinary AGT, as a biomarker for renin–angiotensin system activation, and electrolyte concentrations, in relation to glomerular volume, as a proxy for glomerular endotheliosis in renal biopsy tissue from pregnant normotensive control and hypertensive women. Methods and Results Urine samples were collected from normotensive control (n=10), gestational hypertensive (n=6), and pre‐eclamptic (n=16) women at the time a renal biopsy was obtained. Samples were collected from Lund University Hospital between November 1999 and June 2001. Urinary AGT, potassium, and sodium were measured, normalized to urinary creatinine. Mean glomerular volume was estimated from biopsy sections. AGT protein expression and localization were assessed in renal biopsies by immunohistochemistry. Urinary AGT concentrations were higher in hypertensive pregnancies (median, gestational hypertension: 11.3 ng/mmol [interquartile range: 2.8–13.6]; preeclampsia: 8.4 ng/mmol [interquartile range: 4.2–29.1]; normotensive control: 0.6 ng/mmol [interquartile range: 0.4–0.8]; P

Boxing is a combat sport linked to muscle damage (e.g., soreness, rising creatine kinase [CK]) and energetic biomarkers (e.g., urea, glucose). These factors have not, however, been examined dynamically in terms of day-to-day, lagged and reciprocal effects during normal training. This study investigated the dynamic interplay between muscle damage and energetics in male boxers during a short training block. Thirteen amateur boxers were monitored over 16 consecutive days during early-season training. The participants were assessed each morning for plasma CK, urea, glucose, and creatinine (days 1 and 16 only) concentrations, before self-reporting muscle soreness (1-10 scale). Within-person contemporaneous (lag-0) and temporal (lag-1) networks were estimated using multilevel vector autoregression. Muscle soreness, CK, urea, and glucose presented different trajectories with training, but with some heterogeneity reflecting within-person variances (47% to 78%). The contemporaneous network yielded a significant positive edge (or correlation) between CK and soreness (r = 0.44), along with negative CK-glucose and glucose-urea edges. More significant edges emerged in the temporal network, with soreness linked to CK (r = 0.19), glucose ( r = -0.28) and urea ( r = 0.22), whilst the CK-glucose edge sign switched. In summary, daily fluctuations in muscle damage and energetic activity, which presented in a normal physiological range, were highly variable among boxers during early-season training. Within-person networks indicated some interrelatedness between CK, soreness, urea, and glucose, although the nature and presence of these relationships were contingent on temporal ordering. These inconsistences reflect the pleiotropy of energetic biomarkers in training and recovery., Competing Interests: The authors declared no conflict of interest., (Copyright © Biology of Sport 2024.)

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Sarcopenia, a core feature of the physical frailty syndrome, is characterized by multisystem physiological dysregulation. No study has explored qualitatively the hierarchical network of relationships among different dysregulated pathways involved in the pathogenesis of sarcopenia. We used 40 blood biomarkers belonging to community‐dwelling prefrail and frail older persons to derive measures of multiple physiological pathways, and structural equation modeling to generate path network models of the multisystem physiological dysregulations associated with muscle mass and function (MMF). Insulin–leptin signaling and energy regulation, anabolic sex steroid regulation (testosterone, leptin), and tissue oxygenation (hemoglobin, red cell count) appear to be primary mediating factors exerting direct influences on MMF. There was additionally secondary mediatory involvement of myocyte‐ and adipocyte‐derived cytokines, hypothalamic pituitary adrenal (HPA) stress hormones (cortisol, DHEAS), glomerular function, and immune cell regulatory and inflammatory cytokines and glycoproteins. We conclude that within a hierarchical network of multisystem physiological dysregulations in sarcopenia, dysregulated anabolic and catabolic pathways via sex steroids and insulin–leptin dual signaling and tissue hypoxemia are primary physiological dysregulations responsible for sarcopenia and frailty. [ABSTRACT FROM AUTHOR]

Lena Succar,1 Ross A Boadle,2 David C Harris,1,3 Gopala K Rangan1,3 1Centre for Transplant and Renal Research, The Westmead Institute for Medical Research, The University of Sydney, 2Electron Microscopy Laboratory, Institute of Clinical Pathology and Medical Research, Westmead Hospital, 3Department of Renal Medicine, Westmead Hospital, Western Sydney Local Health District, Westmead, Sydney, NSW, Australia Purpose: In crescentic glomerulonephritis (CGN), the development of cellular bridges between podocytes and parietal epithelial cells (PECs) triggers glomerular crescent formation. However, the sequential changes in glomerular ultrastructure in CGN are not well defined. This study investigated the time course of glomerular ultrastructure in experimental CGN. Methods: Transmission electron microscopy (TEM) was performed using kidney samples from rats with nephrotoxic serum nephritis (NSN) from day 1 to day 14. Morphometric analysis was conducted on randomly selected glomeruli captured on TEM digital images. Results: On day 1 of NSN, there was widespread formation of focal contacts between the cell bodies of neighboring podocytes, and tight junctions were evident at the site of cell-to-cell contact. This was confirmed by the increased expression of the tight junction molecule, zonula occludens-1 (ZO-1), which localized to the points of podocyte cell–cell body contact. On day 2, the interpodocyte distance decreased and the glomerular basement membrane thickness increased. Foot process effacement (FPE) was segmental on day 3 and diffuse by day 5, accompanied by the formation of podocyte cellular bridges with Bowman’s capsule, as confirmed by a decrease in podocyte-to-PEC distance. Fibrinoid necrosis and cellular crescents were evident in all glomeruli by days 7 and 14. In vitro, the exposure of podocytes to macrophage-conditioned media altered cellular morphology and caused an intracellular redistribution of ZO-1. Conclusion: The formation of tight junctions between podocytes is an early ultrastructural abnormality in CGN, preceding FPE and podocyte bridge formation and occurring in response to inflammatory injury. Podocyte-to-podocyte tight junction formation may be a compensatory mechanism to maintain the integrity of the glomerular filtration barrier following severe endocapillary injury. Keywords: glomerular, crescent, inflammation, zonula occludens

Improving of glomerular damage diagnostics in chronic glomerulonephritis (CGN) is an actual theme. Aim. To analyze indicators of glomerular kidney damage in CGN patients. Methods and results. We examined 81 patients with CGN and saved renal function to analyze indicators of glomerular kidney damage according to vivo morphological kidney study in CGN patients with and without arterial hypertension (AH) and relationship between serum cystatin C (CysC) and histological parameters. Conclusion. Patients with hypertension had more expressed indicators of glomerular damage than patients without hypertension. We demonstrated that serum cysC is a marker of glomerular kidney damage in patients with CGN.

Background: Markers of kidney dysfunction and damage have potential to detect chronic kidney disease (CKD) in early stages. However, data on long‐term variation of these markers in healthy dogs is lacking and is crucial for the interpretation of results. Hypothesis/Objectives: To determine temporal variations of serum cystatin C (sCysC) and urinary retinol‐binding protein (uRBP), neutrophil gelatinase‐associated lipocalin (uNGAL), immunoglobulin G (uIgG), and C‐reactive protein (uCRP) in healthy dogs. Animals Eight clinically healthy adult Beagles were evaluated. Methods: Longitudinal observational study. Serum cystatin C was determined by particle‐enhanced nephelometric immunoassay. Urinary retinol‐binding protein, uNGAL, uIgG and uCRP were determined by ELISA and concentrations were indexed to urinary creatinine. Within‐ and between‐dog variance components (VC) and within‐dog coefficients of variation (CV) were determined from blood and urine collected at eight time points over 1.5 years. Results: Urinary C‐reactive protein (uCRP) concentrations were consistently below the detection limit (5.28 ng/mL). Mean ± within‐dog standard deviation for sCysC, uRBP/c, uNGAL/c and uIgG/c was 0.15 ± 0.01 mg/L, 0.09 ± 0.03 mg/g, 2.32 ± 2.03 μg/g and 12.47 ± 10.98 mg/g, respectively. Within‐dog CV for sCysC, uRBP/c, uNGAL/c and uIgG/c was 8.1%, 33.7%, 87.2% and 88.1%, respectively. Conclusions and clinical importance: Serum cystatin C, uRBP/c, uNGAL/c and uIgG/c exhibit a wide range of long‐term within‐dog variability. Researchers and veterinarians might need to take this into account when interpreting their results. To assess their diagnostic and predictive ability, future studies need to establish reference ranges for healthy dogs and dogs with CKD. [ABSTRACT FROM AUTHOR]

It is well known that proteinuria following urinary tract obstruction is mainly of a tubular nature. However, it is unknown whether there are also changes in glomerular permeability. In this study, we compared glomerular sieving coefficients (θ) of polydisperse fluorescein isothiocyanate (FITC)-Ficoll 70/400 following a 120- or 180-min unilateral ureteral obstruction (UUO) in anesthetized Sprague-Dawley rats. Samples were collected from the obstructed kidney at 5, 15, and 30 min postrelease and analyzed by means of high-pressure size-exclusion chromatography. After 120-min UUO, mean ø for Ficoll70Å was increased (P < 0.01) from 2.2 ± 0.5 × 10-5 (baseline) to 10.6 ± 10 × 10-5 15 min postrelease (highest value). After 180-min UUO, mean ø for Ficoll70Å was further increased (P < 0.001) from 1.4 ± 0.5 × 10-5 (baseline) to 40 ± 10 × 10-5 at 5 min postrelease (highest value). Administration of a reactive oxygen species (ROS) scavenger (Tempol; 1 mg·kg-1·min-1) partly abrogated the permeability effects following 120-min UUO but not after 180 min. Moreover, administration of the RhoA kinase inhibitor Y-27632, the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester, or Rac-1 inhibition did not ameliorate glomerular hyperpermeability following 180-min UUO. We show, for the first time, that acute UUO results in marked elevations in glomerular permeability. In addition, our data suggest a timedependent pathophysiology of UUO-induced hyperpermeability, where reactive oxygen species generation may play an important role in the early stages. [ABSTRACT FROM AUTHOR]

Background: Urine protein loss is common in dogs with chronic kidney disease (CKD). Currently available noninvasive means of evaluating CKD in dogs cannot accurately predict the severity of glomerular and tubulointerstitial damage. Electrophoretic analysis of urine proteins can indicate the compromised renal compartment (glomerular vs tubular), but extensive evaluation of protein banding pattern associations with histologic damage severity has not been performed in dogs. Objectives: We aimed to evaluate electrophoretic banding patterns as indicators of the presence and severity of glomerular and tubulointerstitial damage in dogs with naturally occurring, predominantly proteinuric CKD. Methods: We performed a retrospective study using urine and renal tissue from 207 dogs with CKD. Urine protein banding patterns were correlated with histologic severity of renal damage. Sensitivity and specificity of banding patterns for the detection of glomerular and tubulointerstitial damage were determined. Results: Banding patterns were 97% sensitive and 100% specific for the detection of glomerular damage and 90% sensitive and 100% specific for the detection of tubulointerstitial damage. Correlations between composite banding patterns and the severity of renal damage were strong, while glomerular banding patterns correlated moderately with glomerular damage severity, and tubular gel scores correlated weakly to moderately with the severity of tubulointerstitial damage. Conclusions and clinical importance: Urine protein banding patterns are useful for the detection of glomerular and tubulointerstitial damage in dogs with proteinuric CKD. [ABSTRACT FROM AUTHOR]