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1.
Pediatr Nephrol ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38980322

ABSTRACT

BACKGROUND: To investigate the clinical features, kidney pathology, treatment regimens, and clinical outcomes of IgA vasculitis nephritis (IgAVN) with nephrotic-range proteinuria in children. METHODS: A retrospective review of children diagnosed with IgAVN between January 2019 and December 2022 was conducted. Participants were divided into two groups based on their urine protein/creatinine (UPCR) levels. Biodata, clinical characteristics, laboratory findings, pathologic features, treatment regimens, and outcomes were abstracted from case records and analyzed. RESULTS: A total of 255 children were identified, 94 with nephrotic-range proteinuria (UPCR ≥ 200 mg/mmol) and 161 with non-nephrotic proteinuria (UPCR < 200 mg/mmol). Patients in the nephrotic-range proteinuria group were significantly younger and had worse grades of glomerular and acute tubulointerstitial injury compared to those in the non-nephrotic proteinuria group. Higher levels of blood urea nitrogen (BUN), D-dimer (DD), and fibrin degradation products (FDP), and lower levels of total protein (TP), albumin (ALB), urine creatinine (Cr), prothrombin time (PT), activated partial thromboplastin time (APTT), IgG, CD3 + cells, and CD4 + cells were found in patients in the nephrotic-range proteinuria group. Clinical outcome of patients with nephrotic-range proteinuria was significantly associated with ISKDC grading, proportion of glomerular crescents and severity of acute tubulointerstitial injury. CONCLUSIONS: Children with nephrotic-range proteinuria exhibit more severe disordered immunologic function, hypercoagulability, glomerular and tubulointerstitial pathological damage, and have worse outcomes than those with lower proteinuria levels. Clinicians should pay great attention to the kidney injury and more extensive studies are required to identify optimal treatment regimens to improve outcomes in patients.

2.
Cureus ; 16(5): e60568, 2024 May.
Article in English | MEDLINE | ID: mdl-38894774

ABSTRACT

Primary squamous cell carcinoma (SCC) of the renal pelvis is one of the extremely rare tumors encountered in the kidney. It poses a diagnostic challenge for both the clinician and pathologist alike due to the sheer rarity of its occurrence and the multitude nature of its clinical presentation. A review of the literature over the last few decades shows just a countable number of cases documented, each bearing the testimony of the aggressive nature of this subtype. We hereby report three cases of SCC of the renal pelvis origin received at a tertiary care hospital in North India.

4.
Glomerular Dis ; 4(1): 49-63, 2024.
Article in English | MEDLINE | ID: mdl-38600956

ABSTRACT

Background: The first spatially resolved transcriptomics platforms, GeoMx (Nanostring) and Visium (10x Genomics) were launched in 2019 and were recognized as the method of the year by Nature Methods in 2020. The subsequent refinement and expansion of these and other technologies to increase -plex, work with formalin-fixed paraffin-embedded tissue, and analyze protein in addition to gene expression have only added to their significance and impact on the biomedical sciences. In this perspective, we focus on two platforms for spatial transcriptomics, GeoMx and Visium, and how these platforms have been used to provide novel insight into kidney disease. The choice of platform will depend largely on experimental questions and design. The application of these technologies to clinically sourced biopsies presents the opportunity to identify specific tissue biomarkers that help define disease etiology and more precisely target therapeutic interventions in the future. Summary: In this review, we provide a description of the existing and emerging technologies that can be used to capture spatially resolved gene and protein expression data from tissue. These technologies have provided new insight into the spatial heterogeneity of diseases, how reactions to disease are distributed within a tissue, which cells are affected, and molecular pathways that predict disease and response to therapy. Key Message: The upcoming years will see intense use of spatial transcriptomics technologies to better define the pathophysiology of kidney diseases and develop novel diagnostic tests to guide personalized treatments for patients.

5.
Am J Clin Pathol ; 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38567909

ABSTRACT

OBJECTIVES: ChatGPT (OpenAI, San Francisco, CA) has shown impressive results across various medical examinations, but its performance in kidney pathology is not yet established. This study evaluated proficiencies of GPT-4 Vision (GPT-4V), an updated version of the platform with the ability to analyze images, on kidney pathology questions and compared its responses with those of nephrology trainees. METHODS: Thirty-nine questions (19 text-based questions and 20 with various kidney biopsy images) designed specifically for the training of nephrology fellows were employed. RESULTS: GPT-4V displayed comparable accuracy rates in the first and second runs (67% and 72%, respectively, P = .50). The aggregated accuracy, however-particularly, the consistent accuracy-of GPT-4V was lower than that of trainees (72% and 67% vs 79%). Both GPT-4V and trainees displayed comparable accuracy in responding to image-based and text-only questions (55% vs 79% and 81% vs 78%, P = .11 and P = .67, respectively). The consistent accuracy in image-based, directly asked questions for GPT-4V was 29%, much lower than its 88% consistency on text-only, directly asked questions (P = .02). In contrast, trainees maintained similar accuracy in directly asked image-based and text-based questions (80% vs 77%, P = .65). Although the aggregated accuracy for correctly interpreting images was 69%, the consistent accuracy across both runs was only 39%. The accuracy of GPT-4V in answering questions with correct image interpretation was significantly higher than for questions with incorrect image interpretation (100% vs 0% and 100% vs 33% for the first and second runs, P = .001 and P = .02, respectively). CONCLUSIONS: The performance of GPT-4V in handling kidney pathology questions, especially those including images, is limited. There is a notable need for enhancement in GPT-4V proficiency in interpreting images.

6.
Front Med (Lausanne) ; 11: 1369225, 2024.
Article in English | MEDLINE | ID: mdl-38549873

ABSTRACT

Although a few registry-based studies have shown associations between receiving kidney allografts from Black donors and shorter allograft survival, detailed, large, single-center studies accounting for common confounding factors are lacking. Furthermore, pathologic alterations underlying this potential disparity have not been systematically studied. We performed a retrospective clinical-pathological study of kidney transplant recipients who received kidney allografts from either Black (n = 407) or White (n = 1,494) donors at Columbia University Irving Medical Center from 2005 to 2018, with median follow-up of 4.5 years post-transplantation. Black donor race was independently associated with allograft failure (adjusted HR = 1.34, p = 0.02) and recipients of kidney allografts from Black donors had a higher incidence of collapsing glomerulopathy [7.4% vs. 1.9%, OR = 4.17, p < 0.001]. When causes of allograft failure were examined, only allograft failure following development of collapsing glomerulopathy was more frequent in recipients of allografts from Black donors [15% vs. 5%, OR = 3.16, p = 0.004]. Notably, when patients who developed collapsing glomerulopathy were excluded from analysis, receiving kidney allografts from Black donors was not independently associated with allograft failure (adjusted HR = 1.24, p = 0.10). These findings revealed that, compared with recipients of kidney allografts from White donors, recipients of kidneys from Black donors have modestly shorter allograft survival and a higher probability of developing collapsing glomerulopathy, which negatively impacts allograft outcome. Identification of collapsing glomerulopathy risk factors may help decrease this complication and improve allograft survival, which optimally may reduce racial disparities post-transplantation.

7.
Clin Kidney J ; 17(2): sfae019, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38370429

ABSTRACT

Background: The Banff Classification may not adequately address protocol transplant biopsies categorized as normal in patients experiencing unexplained graft function deterioration. This study seeks to employ convolutional neural networks to automate the segmentation of glomerular cells and capillaries and assess their correlation with transplant function. Methods: A total of 215 patients were categorized into three groups. In the Training cohort, glomerular cells and capillaries from 37 patients were manually annotated to train the networks. The Test cohort (24 patients) compared manual annotations vs automated predictions, while the Application cohort (154 protocol transplant biopsies) examined predicted factors in relation to kidney function and prognosis. Results: In the Test cohort, the networks recognized histological structures with Precision, Recall, F-score and Intersection Over Union exceeding 0.92, 0.85, 0.89 and 0.74, respectively. Univariate analysis revealed associations between the estimated glomerular filtration rate (eGFR) at biopsy and relative endothelial area (r = 0.19, P = .027), endothelial cell density (r = 0.20, P = .017), mean parietal epithelial cell area (r = -0.38, P < .001), parietal epithelial cell density (r = 0.29, P < .001) and mesangial cell density (r = 0.22, P = .010). Multivariate analysis retained only endothelial cell density as associated with eGFR (Beta = 0.13, P = .040). Endothelial cell density (r = -0.22, P = .010) and mean podocyte area (r = 0.21, P = .016) were linked to proteinuria at biopsy. Over 44 ± 29 months, 25 patients (16%) reached the primary composite endpoint (dialysis initiation, or 30% eGFR sustained decline), with relative endothelial area, mean endothelial cell area and parietal epithelial cell density below medians linked to this endpoint [hazard ratios, respectively, of 2.63 (P = .048), 2.60 (P = .039) and 3.23 (P = .019)]. Conclusion: This study automated the measurement of intraglomerular cells and capillaries. Our results suggest that the precise segmentation of endothelial and epithelial cells may serve as a potential future marker for the risk of graft loss.

8.
Kidney Med ; 5(12): 100733, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38046910

ABSTRACT

Rationale & Objective: Assessment of kidney biopsies provides crucial information for diagnosis and disease activity, as well as prognostic value. Kidney-biopsy specimens occasionally contain veno-muscular complex (VMC), which consists of muscle tissues around the kidney venous system in the corticomedullary region. However, the role of VMC and the clinical significance of VMC variants are poorly understood. In the present study, we investigated kidney prognostic values of VMC variants. Study Design: Retrospective cohort study. Setting & Participants: Among 808 patients who underwent a kidney biopsy from 2011 to 2019, 246 patients whose kidney biopsy specimens contained VMC were enrolled. Predictors: VMC variants; inflammatory-VMC (an infiltration of ≥80 inflammatory cells/mm2-VMC area) and VMC hypertrophy (hyper-VMC, a VMC average width ≥850 µm), and the interstitial fibrosis/tubular atrophy (IFTA) score. Outcomes: A decline in estimated glomerular filtration rate (eGFR) ≥40% from the baseline or commencement of kidney replacement therapy. Analytical Approach: Cox proportional hazards model. Results: Among 246 patients with data on VMC, mean baseline eGFR was 56.0±25.6 ml/min per 1.73 m2; 80 had high inflammatory-VMC, and 62 had VMC hypertrophy. There were 51 kidney events over median follow-up of 2.5 years. We analyzed 2 VMC variants. Multivariable logistic regression analysis revealed that eGFR negatively correlated with the presence of both inflammatory-VMC and hyper-VMC. A Cox proportional hazards analysis revealed that inflammatory-VMC (but not hyper-VMC) was independently associated with the primary outcome after adjustments for known risk factors of progression, including proteinuria, eGFR, and the interstitial fibrosis/tubular atrophy (IFTA) score (hazard ratio, 1.97; 95% confidence interval, 1.00-3.91). Limitations: Single-center study and small sample size. Conclusions: Assessment of inflammatory-VMC provides additional kidney prognostic information to known indicators of kidney disease progression in patients who undergo kidney biopsy. Plain-Language Summary: Assessment of kidney biopsies provides crucial information for diagnosis, disease activity, and prognostic value. Kidney-biopsy specimens occasionally contain veno-muscular complex (VMC), which consists of muscle tissues around the kidney venous system. Currently, the role of VMC in kidney health and diseases and the clinical significance of VMC variants are poorly understood. In the present study, we have shown that an infiltration of ≥80 inflammatory cells/mm2-VMC area (inflammatory-VMC) is independently associated with kidney disease progression after adjustments for known risk factors of progression. Therefore, assessment of inflammatory-VMC provides additional kidney prognostic information to known indicators of kidney disease progression in patients who undergo kidney biopsy.

9.
Int J Biol Macromol ; 253(Pt 6): 127279, 2023 Dec 31.
Article in English | MEDLINE | ID: mdl-37806411

ABSTRACT

Snakebite envenomation is classified as a Neglected Tropical Disease. Bothrops jararaca venom induces kidney injury and coagulopathy. HF3, a hemorrhagic metalloproteinase of B. jararaca venom, participates in the envenomation pathogenesis. We evaluated the effects of HF3 in mouse kidney and blood plasma after injection in the thigh muscle, mimicking a snakebite. Transcriptomic analysis showed differential expression of 31 and 137 genes related to kidney pathology after 2 h and 6 h, respectively. However, only subtle changes were observed in kidney proteome, with differential abundance of 15 proteins after 6 h, including kidney injury markers. N-terminomic analysis of kidney proteins showed 420 proteinase-generated peptides compatible with meprin specificity, indicating activation of host proteinases. Plasma analysis revealed differential abundance of 90 and 219 proteins, respectively, after 2 h and 6 h, including coagulation-cascade and complement-system components, and creatine-kinase, whereas a semi-specific search of N-terminal peptides indicated activation of endogenous proteinases. HF3 promoted host reactions, altering the gene expression and the proteolytic profile of kidney tissue, and inducing plasma proteome imbalance driven by changes in abundance and proteolysis. The overall response of the mouse underscores the systemic action of a hemorrhagic toxin that transcends local tissue damage and is related to known venom-induced systemic effects.


Subject(s)
Bothrops , Crotalid Venoms , Mice , Animals , Proteome , Multiomics , Metalloproteases/metabolism , Snake Venoms/toxicity , Peptides , Plasma/metabolism , Kidney/metabolism , Bothrops/metabolism , Crotalid Venoms/toxicity , Crotalid Venoms/metabolism
10.
J Nephrol ; 36(8): 2327-2333, 2023 11.
Article in English | MEDLINE | ID: mdl-37480399

ABSTRACT

BACKGROUND: Thrombotic microangiopathy is a severe and potentially life-threatening condition inducing severe endothelial injury in many organs, particularly native and transplanted kidneys. Current pathological studies by our group have identified the use of Caveolin-1 immunohistochemistry as a potential marker of endothelial damage and progression degree of thrombotic microangiopathy. The aim of the present work was to evaluate Caveolin-1 as a marker of severity in thrombotic microangiopathy kidney disease, according to the ultrastructural progression of the disease evaluated by transmission electron microscopy. MATERIALS AND METHODS: Twenty-nine patients (17 non-transplanted and 12 transplanted) were retrospectively selected, biopsied for suspected or histologically-confirmed thrombotic microangiopathy. Transmission electron microscopy was performed in all cases, and an ultrastructural score of thrombotic microangiopathy-related glomerular disease was assessed (from 0 to 3+). Immunohistochemistry for Caveolin-1 was automatically performed. RESULTS: The mean percentage of Caveolin-1-positive glomerular capillaries was 53.2 ± 40.6% and 28.0 ± 42.8% in the active thrombotic microangiopathy versus previous thrombotic microangiopathy cases (p = 0.085), considering both native and transplanted kidneys. The presence of progressive disease correlated with diffuse Caveolin-1 immunoreactivity (p = 0.031), and ultrastructural score correlated with glomerular Caveolin-1 positivity, progressively increasing from 22.5% of the Score 0 group to 95.5% of the Score 3 group (p = 0.036). DISCUSSION: Caveolin-1 proved to be a very useful marker of early endothelial damage in the course of thrombotic microangiopathy for both native and transplanted kidneys, therefore worth considering in routine practice. Diffuse glomerular Caveolin-1 immunoreactivity correlates with the severity of the thrombotic disease and it can appear very early, even before ultrastructurally evident endothelial damage.


Subject(s)
Kidney Diseases , Thrombotic Microangiopathies , Humans , Capillaries , Retrospective Studies , Caveolin 1 , Kidney/pathology , Thrombotic Microangiopathies/diagnosis , Kidney Diseases/pathology
11.
Kidney Int ; 103(6): 1120-1130, 2023 06.
Article in English | MEDLINE | ID: mdl-36990215

ABSTRACT

Morphological alterations at the kidney filtration barrier increase intrinsic capillary wall permeability resulting in albuminuria. However, automated, quantitative assessment of these morphological changes has not been possible with electron or light microscopy. Here we present a deep learning-based approach for segmentation and quantitative analysis of foot processes in images acquired with confocal and super-resolution fluorescence microscopy. Our method, Automatic Morphological Analysis of Podocytes (AMAP), accurately segments podocyte foot processes and quantifies their morphology. AMAP applied to a set of kidney diseases in patient biopsies and a mouse model of focal segmental glomerulosclerosis allowed for accurate and comprehensive quantification of various morphometric features. With the use of AMAP, detailed morphology of podocyte foot process effacement was found to differ between categories of kidney pathologies, showed detailed variability between diverse patients with the same clinical diagnosis, and correlated with levels of proteinuria. AMAP could potentially complement other readouts such as various omics, standard histologic/electron microscopy and blood/urine assays for future personalized diagnosis and treatment of kidney disease. Thus, our novel finding could have implications to afford an understanding of early phases of kidney disease progression and may provide supplemental information in precision diagnostics.


Subject(s)
Deep Learning , Glomerulosclerosis, Focal Segmental , Kidney Diseases , Podocytes , Mice , Animals , Podocytes/pathology , Kidney Glomerulus/pathology , Kidney/diagnostic imaging , Kidney/pathology , Glomerulosclerosis, Focal Segmental/diagnostic imaging , Glomerulosclerosis, Focal Segmental/pathology , Kidney Diseases/diagnostic imaging , Kidney Diseases/pathology
12.
Life (Basel) ; 13(2)2023 Jan 31.
Article in English | MEDLINE | ID: mdl-36836756

ABSTRACT

Membranous nephropathy is one of the most prevalent conditions responsible for nephrotic syndrome in adults. It is clinically nonspecific and mainly diagnosed by kidney biopsy pathology, with three prevalent techniques: light microscopy, electron microscopy, and immunofluorescence microscopy. Manual observation of glomeruli one by one under the microscope is very time-consuming, and there are certain differences in the observation results between physicians. This study makes use of whole-slide images scanned by a light microscope as well as immunofluorescence images to classify patients with membranous nephropathy. The framework mainly includes a glomerular segmentation module, a confidence coefficient extraction module, and a multi-modal fusion module. This framework first identifies and segments the glomerulus from whole-slide images and immunofluorescence images, and then a glomerular classifier is trained to extract the features of each glomerulus. The results are then combined to produce the final diagnosis. The results of the experiments show that the F1-score of image classification results obtained by combining two kinds of features, which can reach 97.32%, is higher than those obtained by using only light-microscopy-observed images or immunofluorescent images, which reach 92.76% and 93.20%, respectively. Experiments demonstrate that considering both WSIs and immunofluorescence images is effective in improving the diagnosis of membranous nephropathy.

15.
Am J Clin Pathol ; 159(2): 129-137, 2023 02 01.
Article in English | MEDLINE | ID: mdl-36490362

ABSTRACT

OBJECTIVES: To review kidney pathology of tropical and nontropical infectious diseases in the pediatric population. METHODS: We review 4 tropical and 2 nontropical infectious diseases that affect the kidneys of children in terms of their direct and indirect pathogenetic mechanism in inducing kidney damage. RESULTS: We demonstrate clinical manifestations, pathogenesis, kidney pathology, and laboratory diagnostic methods for (1) renal cryptococcosis, which represents involvement of a pure direct pathway; (2) schistosomiasis and dengue fever as examples of dual direct and indirect pathways; and (3) congenital syphilis, visceral leishmaniasis, and Chagas disease, which represent indirect pathways. CONCLUSIONS: Infective agents affect the kidneys of children mainly through indirect mechanisms, such as through immunological mechanisms as part of an antigenic response. A direct mechanism of kidney injury, however, is less known within the medical community simply because the direct mechanism is rarely encountered in nontropical countries. In some infectious diseases, both indirect and direct pathways are responsible in inducing 2 sets of morphologically separate kidney lesions.


Subject(s)
Communicable Diseases , Child , Humans , Communicable Diseases/pathology , Kidney/pathology
16.
Clin Transplant ; 37(1): e14837, 2023 01.
Article in English | MEDLINE | ID: mdl-36259615

ABSTRACT

BACKGROUND: Computer-assisted scoring is gaining prominence in the evaluation of renal histology; however, much of the focus has been on identifying larger objects such as glomeruli. Total inflammation impacts graft outcome, and its quantification requires tools to identify objects at the cellular level or smaller. The goal of the current study was to use CD45 stained slides coupled with image analysis tools to quantify the amount of non-glomerular inflammation within the cortex. METHODS: Sixty renal transplant whole slide images were used for digital image analysis. Multiple thresholding methods using pixel intensity and object size were used to identify inflammation in the cortex. Additionally, convolutional neural networks were used to separate glomeruli from other objects in the cortex. This combined measure of inflammation was then correlated with rescored Banff total inflammation classification and outcomes. RESULTS: Identification of glomeruli on biopsies had high fidelity (mean pixelwise dice coefficient of .858). Continuous total inflammation scores correlated well with Banff rescoring (maximum Pearson correlation .824). A separate set of thresholds resulted in a significant correlation with alloimmune graft loss. CONCLUSIONS: Automated scoring of inflammation showed a high correlation with Banff scoring. Digital image analysis provides a powerful tool for analysis of renal pathology, not only because it is reproducible and can be automated, but also because it provides much more granular data for studies.


Subject(s)
Kidney Transplantation , Humans , Kidney Transplantation/adverse effects , Kidney/pathology , Biopsy , Inflammation/diagnosis , Inflammation/etiology , Inflammation/pathology , Allografts
17.
Pediatr Nephrol ; 38(6): 1707-1715, 2023 06.
Article in English | MEDLINE | ID: mdl-36348077

ABSTRACT

IgA nephropathy (IgAN) and IgA vasculitis-associated nephritis (IgAVN) are among the most frequent childhood glomerular diseases and are characterized by significant variability in clinical manifestations, pathological presentation and long-term outcomes. IgAVN, alternatively called purpura nephritis, is pathologically indistinguishable from kidney-limited IgAN. In Chinese children, the clinical presentations and pathological manifestations of IgAN and IgAVN are variable. The severity of proteinuria and abnormalities in kidney function and blood pressure of children in China are comparable to those of children in Europe, the USA, and Japan. Compared to Caucasian children and Japanese children, crescents were more common in Chinese children with IgAN or IgAVN. Approximately 10-20% of childhood IgAN or IgAVN progresses to impaired kidney function in China. Since 2007, a series of guidelines on the diagnosis and treatment of pediatric kidney diseases has been published following the principles of evidence-based medicine. However, a large difference exists between the Chinese evidence-based guidelines and the guidelines developed by Kidney Disease: Improving Global Outcomes (KDIGO) in 2021. Chinese children with IgAN or IgAVN were more likely to be treated with steroids or immunosuppressive agents. Further studies exploring the optimal treatment regimen for childhood IgAN or IgAVN are needed in the future.


Subject(s)
Glomerulonephritis, IGA , IgA Vasculitis , Nephritis , Humans , Child , Glomerulonephritis, IGA/complications , Glomerulonephritis, IGA/diagnosis , Glomerulonephritis, IGA/drug therapy , IgA Vasculitis/complications , IgA Vasculitis/diagnosis , IgA Vasculitis/drug therapy , East Asian People , Kidney/pathology , Nephritis/pathology , Immunoglobulin A
18.
Am J Kidney Dis ; 81(1): 114-117, 2023 01.
Article in English | MEDLINE | ID: mdl-35931341

ABSTRACT

Rare cases of immunoglobulin G (IgG)-dominant immune complex-mediated glomerulonephritis demonstrate immunoglobulin subclass restriction without light chain restriction. Some of these cases may represent proliferative glomerulonephritis with monotypic immunoglobulin deposits (PGNMID) in which monotypic immunoglobulin is obscured by coexisting polytypic immunoglobulin. However, rigorous demonstration of this possibility is lacking to date. Here, we describe a case of IgG3-restricted immune complex-mediated glomerulonephritis without light chain restriction that apparently "transformed" into IgG3κ-PGNMID in a subsequent biopsy. We demonstrate, using several ancillary techniques, including use of the newly described antibodies directed against the conformational epitope at the junctions of heavy and light chains (HLC-IF), that the first biopsy likely represents IgG3κ-PGNMID in which monotypic IgG3κ was hidden by polytypic IgM. This case underscores the need to consider PGNMID in a differential diagnosis of IgG-dominant immune complex-mediated glomerulonephritis without light chain restriction and highlights the potential utility of IgG subclass staining and HLC-IF in such cases to detect monotypic immunoglobulin that may be obscured by coexisting IgM and/or IgA deposits.


Subject(s)
Glomerulonephritis, Membranoproliferative , Glomerulonephritis , Humans , Antigen-Antibody Complex , Glomerulonephritis/pathology , Immunoglobulin G , Immunoglobulin M
19.
Int J Biol Macromol, v. 253, n. 6, 127279, dez, 2023
Article in English | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-5144

ABSTRACT

Snakebite envenomation is classified as a Neglected Tropical Disease. Bothrops jararaca venom induces kidney injury and coagulopathy. HF3, a hemorrhagic metalloproteinase of B. jararaca venom, participates in the envenomation pathogenesis. We evaluated the effects of HF3 in mouse kidney and blood plasma after injection in the thigh muscle, mimicking a snakebite. Transcriptomic analysis showed differential expression of 31 and 137 genes related to kidney pathology after 2 h and 6 h, respectively. However, only subtle changes were observed in kidney proteome, with differential abundance of 15 proteins after 6 h, including kidney injury markers. N-terminomic analysis of kidney proteins showed 420 proteinase-generated peptides compatible with meprin specificity, indicating activation of host proteinases. Plasma analysis revealed differential abundance of 90 and 219 proteins, respectively, after 2 h and 6 h, including coagulation-cascade and complement-system components, and creatine-kinase, whereas a semi-specific search of N-terminal peptides indicated activation of endogenous proteinases. HF3 promoted host reactions, altering the gene expression and the proteolytic profile of kidney tissue, and inducing plasma proteome imbalance driven by changes in abundance and proteolysis. The overall response of the mouse underscores the systemic action of a hemorrhagic toxin that transcends local tissue damage and is related to known venom-induced systemic effects.

20.
Cureus ; 14(11): e31443, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36523714

ABSTRACT

Cancer is a major health problem with a significant impact on society and healthcare systems. In 2018, approximately 18.1 million cases of cancer were diagnosed and 9.6 million deaths were documented. Urological cancers account for 12.9% of new cases recorded and 8% of deaths due to cancer worldwide. The latest cancer registries covering the Gulf Cooperation Council (GCC) countries report that 4078 cases of renal cell carcinoma were diagnosed from 1998 to 2012. Urological cancers comprised 9.4% of all cases with an incidence rate of 16.1% in males and 3.2% in females. All renal cancer cases documented in Salmaniya Medical Complex (SMC) from 2014 to 2018 were reviewed. Data collected for all patients from the electronic health record system included age at diagnosis, gender, laterality of cancer (where applicable), histological type, and TNM (tumor, node, metastasis) classification and staging. Furthermore, World Health Organization (WHO) grade and data were collected for kidney cancer cases. Statistical analysis was carried out using Statistical Package for the Social Sciences (SPSS) version 23 (IBM Corp, Armonk, NY). From 2014 to 2018, there were 65 documented cases of kidney cancer with an average caseload of 13 cases per year. The mean age at diagnosis was 57.6 years. Clear cell carcinoma was the most common histological subtype (37.5%). Stage 1 was the most common stage at diagnosis (35.4%) and the age-standardized mortality rate for males and females were 4.59 and 4.58 in 100,000, respectively. Kidney cancer is a urological malignancy that can pose a burden on both the patient and the healthcare system. There should be a national effort to better understand the etiology and epidemiology of this disease entity with regard to our population. Such efforts would make data regarding diagnosis, management, and follow-up more accessible and would add positively to our healthcare system.

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