Kidney Lesions Research Articles

Hematological manifestations of paraneoplastic syndromes in dogs

Hematological paraneoplastic syndromes are common but poorly studied complications in veterinary oncology, manifested by a variety of hematological changes associated with the system effects of malignant neoplasms on the animal's body. The article presents the results of studying hematological paraneoplastic syndromes, the research involves 131 dogs with spontaneous malignant neoplasms. We used a comprehensive methodological approach, including clinical, instrumental, morphological and hematological research methods. During the morphological study we found out that carcinomas were diagnosed in 33.6% of cases in dogs, of which breast carcinoma was registered in 24.4%, in other cases lung, liver, kidney and abdominal lesions were noted. We also discovered: sarcomas in 22.1% of cases, including hemangiosarcoma of the spleen in 7.6%; and gastrointestinal lymphoma in 16.8% of cases and lymph nodes; in 16.8% of mastocytomas. in 4.6% of melanomas of the skin and mucous membranes; squamous cell carcinoma in 6.1% of cases. As a result of hematological studies, it was revealed that anemia syndrome (18.4%), lymphopenia (16.8%) and thrombocytopenia (15.4%) are the most frequent changes in clinical blood analysis in dogs with oncological diseases. Neutrophilic leukocytosis, leukopenia and thrombocytosis had an identical incidence, which was 12.2% of cases. Monocytosis and lymphocytosis were diagnosed less frequently, in 4.6% of cases. Leukogram changes were observed in 75.4% of cases: in 66.2%, an increase in the percentage of neutrophils was found, with a shift to the left in 38.5% of cases, a decrease in the percentage of lymphocytes in 18.5% of cases, monocytes in 6.2% of cases, eosinophils in 4.6% of cases. The frequency of hematological changes in the general clinical blood analysis of dogs depended on the histogenesis of the tumor. Hematological paraneoplastic syndromes can be used as an early marker of the oncological process, and they can also prevent timely prescription of treatment. Anemia and thrombocytopenia are absolute contraindications for chemotherapy and radiation therapy.

Outer membrane vesicles as nanovaccine candidates against pathogenic Leptospira in experimental Guinea pig model

Leptospira interrogans serovar Hardjo is a long slender bacterium of size 0.1–0.3 μm × 5–50 μm. It is one of the major causes of bovine leptospirosis and is of economical importance because of the reproductive failure, still birth, abortion, and reduced productivity in cattle. It is also a zoonotic disease-causing infection in humans characterized by headaches, fever, chills, sweats and myalgia, lethargy, aching joints, pulmonary haemorrhages, and death in severe cases. Control of the disease involves antibiotic therapy, management and vaccination, of which immunization is the cheapest and effective means of disease prevention. The present study was developed to isolate and characterize the outer membrane vesicles of Leptospira interrogans serovar Hardjo and to evaluate their vaccine potential in guinea pig model. The OMVs were isolated from the culture by sonication and ultracentrifugation. In transmission electron microscopy, the isolated OMVs appeared as small spherical structures of 50–200 nm size. In Western blot and indirect ELISA, antibodies specific to OMVs were observed as indicative of a good humoral immune response elicited by L. interrogans serovar Hardjo OMV. The OMV-based Leptospira vaccine was able to prevent kidney lesions and renal colonization compared to the control and bacterin vaccinated group as proven by histopathology and PCR.

Histopathological Spectrum of Kidney Lesions in an Autopsy 2 Years Study at Tertiary Care Hospital

Histopathological Spectrum of Kidney Lesions in an Autopsy 2 Years Study at Tertiary Care Hospital

Abstract 1738: Precise detection of benign and malignant renal tumor via epigenetic characteristics of urinary cell-free DNA

Abstract Early detection of clear cell renal cell carcinoma (ccRCC) and accurate differentiation between malignant and benign lesions pose clinical challenges. Profiling the epigenetic pattern of patients through liquid biopsy offers a promising strategy for non-invasive cancer identification. This study utilizes the methylation characteristics of urinary cell-free DNA to enhance the precise diagnosis of ccRCC. In this study, 32 patients with malignant RCC, 20 patients with benign kidney lesions, and 28 age- and sex-matched healthy donors were enrolled. Urine samples were collected and applied by PredicineEPIC assay to analyze the whole genome methylation profiles. We assessed the methylation differences on cancer-specific altered regions and constructed a machine learning model for malignant and benign classification. Beta values were calculated for differentially methylated regions identified through literature mining and our current work. These features carry methylation signals that are recognized by gradient boosting machine and used for classification training. The leave-one-out cross-validation method compensated for the shotage of sample size. The sensitivity and specificity of the optimal model in the training set are both greater than 0.97, and it can achieve an accuracy of 0.95 on the validation set. This performance surpasses traditional diagnostic methods such as contrast-enhanced CT and MRI. This study demonstrated the technical feasibility of leveraging epigenetics profiles to discriminate malignant from benign lesions, suggesting a promising liquid biopsy-based approach for the precise detection of renal cell carcinoma. Citation Format: Wen Kong, Hang Dong, Haoran Tang, Pan Du, Shidong Jia, Jin Zhang. Precise detection of benign and malignant renal tumor via epigenetic characteristics of urinary cell-free DNA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1738.

BMP9 is a key player in endothelial identity and its loss is sufficient to induce arteriovenous malformations.

BMP9 is a high affinity ligand of ALK1 and endoglin receptors that are mutated in the rare genetic vascular disorder hereditary hemorrhagic telangiectasia (HHT). We have previously shown that loss of Bmp9 in the 129/Ola genetic background leads to spontaneous liver fibrosis via capillarization of liver sinusoidal endothelial cells (LSEC) and kidney lesions. We aimed to decipher the molecular mechanisms downstream of BMP9 to better characterize its role in vascular homeostasis in different organs. For this, we performed an RNA-seq analysis on LSEC from adult WT and Bmp9-KO mice and identified over 2000 differentially expressed genes. Gene ontology analysis showed that Bmp9 deletion led to a decrease in BMP and Notch signalling, but also LSEC capillary identity while increasing their cell cycle. The gene ontology term 'glomerulus development' was also negatively enriched in Bmp9-KO mice vs. WT supporting a role for BMP9 in kidney vascularization. Through different imaging approaches (electron microscopy, immunostainings), we found that loss of Bmp9 led to vascular enlargement of the glomeruli capillaries associated with alteration of podocytes. Importantly, we also showed for the first time that the loss of Bmp9 led to spontaneous arteriovenous malformations (AVMs) in the liver, gastrointestinal tract, and uterus. Altogether, these results demonstrate that BMP9 plays an important role in vascular quiescence both locally in the liver by regulating endothelial capillary differentiation markers and cell cycle but also at distance in many organs via its presence in the circulation. It also reveals that loss of Bmp9 is sufficient to induce spontaneous AVMs, supporting a key role for BMP9 in the pathogenesis of HHT.

MicroRNA-630 alleviates inflammatory reactions in rats with diabetic kidney disease by targeting toll-like receptor 4.

Diabetic kidney disease (DKD) is a major complication of diabetes mellitus. Renal tubular epithelial cell (TEC) damage, which is strongly associated with the inflammatory response and mesenchymal trans-differentiation, plays a significant role in DKD; However, the precise molecular mechanism is unknown. The recently identified microRNA-630 (miR-630) has been hypothesized to be closely associated with cell migration, apoptosis, and autophagy. However, the association between miR-630 and DKD and the underlying mechanism remain unknown. To investigate how miR-630 affects TEC injury and the inflammatory response in DKD rats. Streptozotocin was administered to six-week-old male rats to create a hyperglycemic diabetic model. In the second week of modeling, the rats were divided into control, DKD, negative control of lentivirus, and miR-630 overexpression groups. After 8 wk, urine and blood samples were collected for the kidney injury assays, and renal tissues were removed for further molecular assays. The target gene for miR-630 was predicted using bioinformatics, and the association between miR-630 and toll-like receptor 4 (TLR4) was confirmed using in vitro investigations and double luciferase reporter gene assays. Overexpression of miR-630 in DKD rats led to changes in body weight, renal weight index, basic blood parameters and histopathological changes. The expression level of miR-630 was reduced in the kidney tissue of rats with DKD (P < 0.05). The miR-630 and TLR4 expressions in rat renal TECs (NRK-52E) were measured using quantitative reverse transcription polymerase chain reaction. The mRNA expression level of miR-630 was significantly lower in the high-glucose (HG) and HG + mimic negative control (NC) groups than in the normal glucose (NG) group (P < 0.05). In contrast, the mRNA expression level of TLR4 was significantly higher in these groups (P < 0.05). However, miR-630 mRNA expression increased and TLR4 mRNA expression significantly decreased in the HG + miR-630 mimic group than in the HG + mimic NC group (P < 0.05). Furthermore, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and IL-6 were significantly higher in the HG and HG + mimic NC groups than in NG group (P < 0.05). However, the levels of these cytokines were significantly lower in the HG + miR-630 mimic group than in the HG + mimic NC group (P < 0.05). Notably, changes in protein expression were observed. The HG and HG + mimic NC groups showed a significant decrease in E-cadherin protein expression, whereas TLR4, α-smooth muscle actin (SMA), and collagen IV protein expression increased (P < 0.05). Conversely, the HG + miR-630 mimic group exhibited a significant increase in E-cadherin protein expression and a notable decrease in TLR4, α-SMA, and collagen IV protein expression than in the HG + mimic NC group (P < 0.05). The miR-630 targets TLR4 gene expression. In vivo experiments demonstrated that DKD rats treated with miR-630 agomir exhibited significantly higher miR-630 mRNA expression than DKD rats injected with agomir NC. Additionally, rats treated with miR-630 agomir showed significant reductions in urinary albumin, blood glucose, TLR4, and proinflammatory markers (TNF-α, IL-1β, and IL-6) expression levels (P < 0.05). Moreover, these rats exhibited fewer kidney lesions and reduced infiltration of inflammatory cells. MiR-630 may inhibit the inflammatory reaction of DKD by targeting TLR4, and has a protective effect on DKD.

Nutritional status as a predictive factor for paediatric tuberous sclerosis complex-associated kidney angiomyolipomas: a retrospective analysis

The purpose of this study is to determine the predictive factors of tuberous sclerosis complex (TSC)-associated kidney disease and its progression in children. Retrospective review of children with TSC in a tertiary children’s hospital was performed. Relevant data were extracted, and Cox proportional hazards regression was used to establish predictors of kidney lesions. Logistic regression was conducted to identify factors predicting chronic kidney disease (CKD) and high-risk angiomyolipomas (above 3 cm). Kidney imaging data were available in 145 children with TSC; of these, 79% (114/145) had abnormal findings. The only significant predictive factor for cyst development was being female (HR = 0.503, 95% CI 0.264–0.956). Being female (HR = 0.505, 95% CI 0.272–0.937) and underweight (HR = 0.092, 95% CI 0.011–0.800) both lowers the risk of having angiomyolipomas, but TSC2 mutations (HR = 2.568, 95% CI 1.101–5.989) and being obese (HR = 2.555, 95%CI 1.243–5.255) increases risks. Ten (12%) of 81 children with kidney function tested demonstrate CKD stages II–V, and only angiomyolipomas above 3 cm predict CKD. Additionally, 13/145 (9%) children had high-risk angiomyolipomas, whereby current age (adjusted odds ratio (aOR) 1.015, 95% CI 1.004–1.026) and being overweight/obese (aOR 7.129, 95% CI 1.940–26.202) were significantly associated with angiomyolipomas above 3 cm.Conclusions: While gender and genotype are known predictors, this study includes the novel finding of nutritional status as a predictor of TSC-associated kidney disease. This study sheds light on a possible complex interplay of hormonal influences, obesity, and kidney angiomyolipomas growth, and further investigations focusing on the impact of nutritional status on TSC-associated kidney disease are warranted.What is Known:• Gender and genotype are well-studied predictive factors in TSC kidney disease.What is New:• Nutritional status may influence the development and the progression of kidney lesions in children with TSC and should not be overlooked.• Management guidelines of TSC-associated kidney disease can address nutritional aspects.

Effect of selenium on physiological and reproductive parameters in males of the catfish Sorubim cuspicaudus

Selenium is a trace mineral that participates in the body's homeostasis as an antioxidant by forming selenoproteins. In aquaculture, supplementation with this mineral influences zootechnical parameters and blood biochemistry while strengthening the immune system. This work aimed to evaluate the effect of organic selenium on physiological and zootechnical parameters in males of the catfish Sorubim cuspicaudus. Male breeders of S. cuspicaudus (n=56) with an average weight and length of 485.6 g and 39.3 cm, respectively, were distributed in 6.5 m3 pools in four treatments by triplicate. The fish were fed diets enriched with Se: 0.07 (control), 1.57, 2.07, and 2.57 mg Se/kg diet for 14 weeks. Length, weight, condition factor, and survival were recorded. In blood samples transaminases and cortisol were measured. Also, liver, kidney, and gonad histological analyses were realized. The zootechnical parameters and blood chemistry between treatments showed no significant difference (p>0.05). At the histological level, the fish fed 2.0 and 2.5 mg Se/kg diet showed moderate to severe kidney and mild liver lesions associated with selenium toxicity. The results of this study allow us to conclude that selenium doses of 2 mg or more generate toxicity in male breeders of the catfish S. cuspicaudus.

Microalbuminuria sensitive near‐infrared AIE probe for point‐of‐care evaluating kidney diseases

AbstractUrinary microalbumin (mALB) serves as an exceptionally sensitive indicator for the early detection of kidney damage, playing a pivotal role in identifying chronic renal failure and kidney lesions in individuals. Nevertheless, the current fluorescent methodologies for point‐of‐care (POC) diagnosis of mALB in real urine still exhibit suboptimal performance. Herein, the development and synthesis of QM‐N2, an albumin‐activated near‐infrared (NIR) aggregation‐induced emission (AIE) fluorescent probe, are presented. The strategic incorporation and positioning of quaternary ammonium salts within the quinoline‐malononitrile (QM) scaffold significantly influence solubility and luminescence characteristics. Specifically, the quaternary ammonium salt‐free variant, QM‐OH, and the quaternary ammonium salt integrated at the donor function group (DFG) site, QM‐N1, display limited solubility in aqueous solutions while demonstrating a distinct fluorescence signal. Conversely, the incorporation of quaternary ammonium salt at the conformational functional group (CFG) site in QM‐N2 imparts superior dispersibility in water and reduces the initial fluorescence. Furthermore, the integration of a well‐defined D‐π‐A structure within QM‐N2 enables itself with near‐infrared emission, which is crucial for mitigating interference from autofluorescence present in urine samples. Upon interaction with albumin, QM‐N2 forms a tight bond with the IIA site of the subdomain of human serum albumin (HSA), inducing alterations in protein configuration and constraining the intrinsic motion of fluorescent molecules. This interaction induces fluorescence, facilitating the sensitive detection of trace albumin. Ultimately, QM‐N2 is applied for POC testing of mALB using portable equipment, particularly in the diagnosis of mALB‐related diseases, notably chronic renal failure. This positioning underscores its potential as an ideal candidate for self‐health measurement at home or in community hospitals.

Survival by depth of response and efficacy by International Metastatic Renal Cell Carcinoma Database Consortium Subgroup with lenvatinib plus pembrolizumab versus sunitinib in advanced renal cell carcinoma: analysis of the phase 3 randomized CLEAR study

Background: The extent of tumor shrinkage has been deemed a predictor of survival for advanced/metastatic renal cell carcinoma (RCC), a disease with historically poor survival.Objective: To perform an exploratory analysis of overall survival (OS) by tumor response by 6 mo, and to assess the efficacy and survival outcomes in specific subgroups.Design, setting, and participants: CLEAR was an open-label, multicenter, randomized, phase 3 trial of first-line treatment of advanced clear cell RCC.Intervention: Patients were randomized 1:1:1 to lenvatinib 20mg orally daily with pembrolizumab 200 mg intravenously once every 3 wk, lenvatinib plus everolimus (not included in this analysis), or sunitinib 50 mg orally daily for 4 wk on treatment/2 wk of no treatment.Outcome measurements and statistical analysis: Landmark analyses were conducted to assess the association of OS with tumor shrinkage and progressive disease status by 6 mo. Progression-free survival, duration of response, and objective response rate (ORR) were analyzed by the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk subgroup and by the presence of target kidney lesions. Efficacy was assessed by an independent review committee as per Response Evaluation Criteria in Solid Tumors version 1.1.Results and limitations: Landmark analyses by tumor shrinkage showed that patients enrolled to lenvatinib plus pembrolizumab arm with a confirmed complete response or &gt;75 % target-lesion reduction by 6 mo had a 24-mo OS probability of 91.7 %. A landmark analysis by disease progression showed that patients with no progression by 6 mo had lower probabilities of death in both arms. Patients with an IMDC risk classification of intermediate/poor had longer median progression-free survival (22.1 vs 5.9 mo) and a higher ORR (72.4 % vs 28.8 %) with lenvatinib plus pembrolizumab versus sunitinib. Similarly, results favored lenvatinib plus pembrolizumab in IMDC-favorable patients and those with/without target kidney lesions. Limitations of the study are that results were exploratory and not powered/stratified.Conclusions: Lenvatinib plus pembrolizumab showed improved efficacy versus sunitinib for patients with advanced RCC; landmark analyses showed that tumor response by 6 mo correlated with longer OS.Patient summary: In this report of the CLEAR trial, we explored the survival of patients with advanced renal cell carcinoma by assessing how well they initially responded to treatment. We also explored how certain groups of patients responded to treatment overall. Patients were assigned to cycles of either lenvatinib 20 mg daily plus pembrolizumab 200 mg every 3 wk or sunitinib 50 mg daily for 4 wk (followed by a 2-wk break). Patients who either had a ‘‘complete response’’ or had their tumors shrunk by &gt;75 % within 6 mo after starting treatment with lenvatinib plus pembrolizumab had better survival than those with less tumor reduction by 6 mo. Additionally, patients who had more severe disease (as per the International Metastatic Renal Cell Carcinoma Database Consortium) at the start of study treatment survived for longer without disease progression with lenvatinib plus pembrolizumab than with sunitinib.

IgG4-Related Infiltrative Kidney Disease without Extrarenal Organ Involvement: A Case Report

Background: IgG4-related disease (RD) is a systemic condition that can affect nearly all organs. Renal involvement encompasses interstitial nephritis, membranous nephropathy, and renal infiltrative lesions. Symptomatic IgG4-related kidney disease (RKD) without extrarenal organ manifestations is an exceptionally rare occurrence. Case Report: The authors present a case of 48-year-old male with isolated renal IgG4-RD presented with abdominal pain. Laboratory investigations revealed acute kidney injury, proteinuria, and hypoalbuminemia. Whole abdominal computed tomography (CT) scan disclosed infiltrative lesions in both kidneys and ureters, accompanied by hydronephrosis. Kidney biopsy demonstrated lymphocytic and plasma cell infiltration, with 82 plasma cells per high power field (HPF), storiform fibrosis, and the absence of obliterative phlebitis. After receiving corticosteroid treatment, the patient’s renal function improved, and the infiltrative lesions went into remission. Conclusion: Isolated renal IgG4-RD is a rare and challenging diagnosis. The disease can manifest as acute interstitial nephritis, glomerular disease, retroperitoneal fibrosis, or, rarely, as mass or infiltrative lesions. Corticosteroid therapy is likely to yield favorable responses, hence, prompt diagnosis is crucial. Delayed diagnosis may result in organ fibrosis and dysfunction. Keywords: IgG4-related disease; IgG4-related kidney disease; Infiltrative renal disease

Insights into Hyperparathyroidism-Jaw Tumour Syndrome: From Endocrine Acumen to the Spectrum of CDC73 Gene and Parafibromin-Deficient Tumours.

A total of 1 out of 10 patients with primary hyperparathyroidism (PHP) presents an underlying genetic form, such as multiple endocrine neoplasia types 1, 2A, etc., as well as hyperparathyroidism-jaw tumour syndrome (HJT). We aimed to summarise the recent data, thus raising more awareness regarding HJT, from the clinical perspective of PHP in association with the challenges and pitfalls of CDC73 genetic testing and parafibromin staining. This narrative review included a sample-focused analysis from the past decade according to a PubMed search. We identified 17 original human studies (≥4 patients per article). The mean age at disease onset was between 20.8 and 39.5 years, while the largest study found that 71% of patients had HJT recognised before the age of 30. Males and females seemed to be equally affected, in contrast with sporadic PHP. PHP represented the central manifestation of HJT, occurring as the first manifestation in up to 85% of HJT cases. A biochemistry panel found a mean serum calcium level above the level of 12 mg/dL in PHP. PTH was elevated in HJT as well, with average values of at least 236.6 pg/mL. The most frequent pathological type in PHP was a parathyroid adenoma, but the incidence of a parathyroid carcinoma was much higher than in non-HJT cases (15% of all parathyroid tumours), with the diagnosis being established between the age of 15 and 37.5. In some families up to 85% of carriers suffered from a parathyroid carcinoma thus indicating that certain CDC73 pathogenic variants may harbour a higher risk. An important issue in HJT was represented by the parafibromin profile in the parathyroid tumours since in HJT both parathyroid adenomas and carcinomas might display a deficient immunoreactivity. Another frequent manifestation in HJT was ossifying fibromas of the jaw (affecting 5.4% to 50% of patients; the largest study found a prevalence of 15.4%). HJT was associated with a wide variety of kidney lesion (mostly: kidney cysts, with a prevalence of up to 75%, and renal tumours involved in 19% of patients). The risk of uterine lesions seemed increased in HJT, especially with concern to leiomyomas, adenofibromas, and adenomyosis. The underlying pathogenic mechanisms and the involvement of CDC73 pathogenic variants and parafibromin expression are yet to be explored. Currently, the heterogeneous expression of parafibromin status and, the wide spectrum of CDC73 mutations including the variety of clinical presentations in HJT, make it difficult to predict the phenotype based on the genotype. The central role of HJT-PHP is, however, the main clinical element, while the elevated risk of parathyroid carcinoma requires a special awareness.

Atrophic Kidney-Like Lesion-Case Report and Review of the Literature.

Atrophic kidney-like lesion (AKLL) is a rare kidney lesion, which was recently suggested by the Genitourinary Pathology Society as a provisional entity. As of now, 16 examples of AKLL have been described in the literature. Here we report a new tumor which shows similar clinicopathologic characteristics with those previously reported in AKLL. Immunohistochemical (IHC) studies in the current lesion identified a biphasic staining pattern consisting of a mixture of WT1+/KRT7-/PAX8- large dilated cysts and WT-/KRT7+/PAX8+ small atrophic cysts. Histomorphologic features of AKLL overlap with several neoplastic and non-neoplastic entities which can lead to mischaracterization. Awareness of the differentiating features is likely important when evaluating these lesions.

Viruses traverse the human proteome through peptide interfaces that can be biomimetically leveraged for drug discovery

We present a drug design strategy based on structural knowledge of protein-protein interfaces selected through virus-host coevolution and translated into highly potential small molecules. This approach is grounded on Vinland, the most comprehensive atlas of virus-human protein-protein interactions with annotation of interacting domains. From this inspiration, we identified small viral protein domains responsible for interaction with human proteins. These peptides form a library of new chemical entities used to screen for replication modulators of several pathogens. As a proof of concept, a peptide from a KSHV protein, identified as an inhibitor of influenza virus replication, was translated into a small molecule series with low nanomolar antiviral activity. By targeting the NEET proteins, these molecules turn out to be of therapeutic interest in a nonalcoholic steatohepatitis mouse model with kidney lesions. This study provides a biomimetic framework to design original chemistries targeting cellular proteins, with indications going far beyond infectious diseases.

Aminoguanidine alleviates gout in goslings experimentally infected with goose astrovirus-2 by reducing kidney lesions

Goose astrovirus (GAstV)-2, a novel pathogen identified in 2018, mainly causes visceral gout in goslings, leading to approximately 50% mortality. At present, no commercial veterinary products are available to prevent and treat the disease. Our previous studies showed that nitric oxide (NO) and inducible NO synthase (iNOS) were markedly higher in the kidney and spleen of goslings infected with GAstV-2, but their effects during GAstV-2 infection remain unclear. In the present study, goslings were intraperitoneally injected with aminoguanidine (AG)-an iNOS inhibitor-to examine the role of NO during GAstV-2 infection. AG significantly decreased the serum NO concentration and iNOS mRNA expression in the kidney. Moreover, AG reduced the mortality, serum uric acid and creatinine content, and urate deposition in visceral organs and joints. Histopathological analysis demonstrated that AG reduced renal tubular cell necrosis, inflammatory cell infiltration, glycogen deposition in glomerular mesangium, and interstitial fibrosis, suggesting alleviation of kidney lesions. Furthermore, AG decreased the expression of renal injury markers such as KIM-1 and desmin; inflammatory cytokine-related genes such as IL-1β, IL-8, and MMP-9; and autophagy-related genes and proteins such as LC3II, ATG5, and Beclin1. However, quantitative real-time PCR and immunohistochemistry showed that treatment with AG did not affect the kidney and liver viral load. These findings suggest that AG decreases the mortality rate and kidney lesions in goslings infected with GAstV-2 through mechanisms associated with autophagy and inhibition of inflammatory cytokine production in the kidney but not with GAstV-2 replication.

Points of view in nephrology: personalized management of IgA nephropathy, beyond KDIGO.

IgA nephropathyis the most common primary glomerulonephritis worldwide, and an important cause of kidney failure, as 20-40% of patients progress to renal replacement therapy 20-30years after diagnosis. Its clinical presentation ranges from isolated microscopic hematuria to nephrotic syndrome, and even to a rapidly progressive course. Ethnicity and epigenetics play a key role in its clinical aggressiveness. Selection of patients at risk needing immunosuppressive treatment is a challenge for the nephrologist. Some active and chronic kidney lesions detected on kidney biopsy have been demonstrated to have prognostic value according to the Oxford Classification of IgA nephropathy, later validated by numerous studies. However, KDIGO 2021 guidelines still consider persistent proteinuria > 1g/24h to be the most relevant risk factor for the progression of IgA nephropathy and the only one requiring immunosuppressive treatment. KDIGO guidelines have proposed a therapeutic algorithm, but many patients present peculiar characteristics that are not addressed by the current guidelines, pointing to the need for alternative approaches. In these cases, a tailored approach to each patient should be followed in which clinical, histological, laboratory, social and ethical aspects must be considered. In this manuscript we present three cases of IgA nephropathy from different countries, highlighting many of the aspects encountered in clinical practice that illustrate an individualized approach to the treatment of these patients.

Phenotype of Parathyroid-targeted Cdc73 Deletion in Mice Is Strain-dependent.

Hyperparathyroidism jaw-tumor syndrome is an autosomal dominant disorder caused by mutations in the CDC73/HRPT2 tumor suppressor gene, encoding parafibromin, and manifesting benign or malignant parathyroid tumors, ossifying jaw fibromas, uterine tumors, and kidney lesions. Sporadic parathyroid carcinomas also frequently exhibit inactivating CDC73 mutations and loss of parafibromin. To study the role of CDC73 in parathyroid cell proliferation in vivo, we generated mice with a parathyroid-specific deletion of Cdc73. Homozygous knockout mice on a mixed B6/129/CD1 background had decreased serum calcium and PTH and smaller parathyroid glands compared with heterozygous or wild-type littermates, whereas homozygous Cdc73-null mice on other backgrounds exhibited no abnormalities in parathyroid gland function or development. No hypercalcemia or parathyroid hypercellularity was observed in mice of any background examined at any age. Thus, although postnatally acquired complete loss of CDC73 causes parathyroid cell proliferation and hyperparathyroidism, such as seen in human hyperparathyroidism jaw-tumor syndrome, our results suggest that earlier, developmentally imposed complete loss of Cdc73 can cause a primary defect in parathyroid gland structure/function in a strain-dependent manner. This striking disparity in parathyroid phenotype related to genetic background offers a unique opportunity in an in vivo model system to precisely dissect and identify the responsible molecular mechanisms.

A Machine Learning-Driven Virtual Biopsy System For Kidney Transplant Patients

In kidney transplantation, day-zero biopsies are used to assess organ quality and discriminate between donor-inherited lesions and those acquired post-transplantation. However, many centers do not perform such biopsies since they are invasive, costly and may delay the transplant procedure. We aim to generate a non-invasive virtual biopsy system using routinely collected donor parameters. Using 14,032 day-zero kidney biopsies from 17 international centers, we develop a virtual biopsy system. 11 basic donor parameters are used to predict four Banff kidney lesions: arteriosclerosis, arteriolar hyalinosis, interstitial fibrosis and tubular atrophy, and the percentage of renal sclerotic glomeruli. Six machine learning models are aggregated into an ensemble model. The virtual biopsy system shows good performance in the internal and external validation sets. We confirm the generalizability of the system in various scenarios. This system could assist physicians in assessing organ quality, optimizing allograft allocation together with discriminating between donor derived and acquired lesions post-transplantation.

Liver and kidney damage in quail embryos hatched from eggs sprayed once with chlorpyrifos during artificial incubation.

Birds have enough conditions to be used as bioindicators for the presence of environmental contaminants. Notably, chlorpyrifos (CPF) remains extensively employed in Argentina, particularly in fruit plantations and livestock settings This study aimed to assess the potential impacts of CPF on common quail (Coturnix coturnix) embryos through external eggshell application during key embryonic stages (days 1, 4, and 14). Concentrations equivalent to those used in fruit applications, 5× and 10 × (38.4, 192, and 384µg/egg), were employed. A 48% commercial formulation of CPF (Pirfos - Icona®) was utilized. An increase in embryonic deaths, as well as a statistical association between the degree of liver or kidney lesions and CPF concentrations was observed. The results suggest that CPF can induce embryotoxic effects with a single exposure to quail embryos and compromise the viability of the organisms. The study suggests a potential exposure risk for embryos through contact with the insecticide on the eggshell's exterior.

Clinical case of Loeffler’s endomyocarditis

Eosinophilic endomyocarditis is caused by direct infiltration of heart tissue by eosinophils with the development of specific inflammation. The main etiological factor of the disease is a significant increase in the level of eosinophils in peripheral blood. Loeffler syndrome can be caused by such factors and pathological conditions as idiopathic hypereosinophilic syndrome, allergic diseases, parasitic infections, autoimmune processes, cancer. A clinical case of Loeffler syndrome in an 84-year-old patient with heart, lung, liver, kidney and pancreatic lesions is presented. Difficulties of differential diagnostics of this syndrome because of individual clinical picture and signs of the course are discussed in the article. Timely diagnosis of such a condition will prevent the rapid development of severe complications and carry out appropriate therapy, which will significantly prolong the life of patients with Loeffler syndrome. However, in the presence of nonspecific symptoms, the diagnosis of this disease may be diagnostically difficult for the physician.