Kidney Pathology Research Articles

Kidney pathology in liver cirrhosis

Objective. To analyze the structure and frequency of kidney pathology in liver cirrhosis according to sectional analysis and to study the relationship between acute renal injury and urinary tract infection.Materials and methods. The design of the study is mixed: descriptive and analytical, which included conducting a retrospective case–control study of kidney pathology based on the results of the protocols of pathoanatomical autopsies on the basis of the state healthcare institution “Gomel Regional Clinical Pathoanatomical Bureau” for the period of January 2022 – July 2023 and clinical, laboratory, instrumental, cytological, microbiological data of patients with liver cirrhosis. The study included 98 deceased patients, including 70 (71.4%) men, 28 (28.6%) women. The average age was 53.9 years, the majority of patients were persons of working age — 72.9% of men and 60.7% of women, 21.4% were young people.Results. The most common kidney pathology in liver cirrhosis according to sectional analysis is acute renal injury (57.1%). Kidney abscesses (3%), tubulointerstitial nephritis (2%) and pyelonephritis (4%) were less frequently diagnosed. Despite the absence of a history of kidney diseases in most patients with cirrhosis, classical clinical, laboratory and instrumental signs of renal tissue damage, macroscopic and microscopic changes of the kidneys were revealed in 100% of cases at autopsy. In 84.7% of cases, acute tubular necrosis was morphologically diagnosed from focal (51%) to total (19.4%), which was not always accompanied by an increase in serum creatinine levels. A moderate relationship was established between acute kidney injury and urinary tract infection (OR = 14; 95 % CI 11.13–16.61).Conclusion. The most common complication of liver cirrhosis associated with an unfavorable prognosis is acute renal injury, which is associated with the presence of urinary tract infection.

The link between moderate COVID-19 and delayed manifestation of glomerulonephritis: Insights from cluster analysis of TGF-β1 and VEGF levels

Recent data reveal delayed pathological kidney changes occurring 8-12 months post-moderate COVID-19, often detected for the first time. While severe COVID-19 leads to interstitial and subsequent glomerular lesions, the predominant changes in moderate cases remain elusive. This study aimed to investigate the potential association between moderate COVID-19 and the manifestation of glomerulonephritis (GN).
 Methods. This cross-sectional study included 25 patients with stage 1-2 GN and a history of moderate COVID-19 8-12 months before the onset of GN, 27 individuals without GN who experienced COVID-19, and 20 healthy subjects without a history of COVID-19. Transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor (VEGF) levels in blood and urine were measured using enzyme-linked immunosorbent assay. Cluster and classification data mining methods were utilized for these markers to assess potential relationships between moderate COVID-19 and GN manifestation.
 Results. A significant increase in blood and urine TGF-β1 and VEGF levels was found in GN patients with a history of moderate COVID-19 (p<0.05), while elevated blood VEGF was observed in those without GN (p<0.05). Cluster analysis affirmed the correlation, emphasizing that urinary TGF-β1 within the range of 1.352 to 5.693 pg/ml and urinary VEGF < 214.12 pg/ml serve as classification rules for predicting GN.
 Conclusions. The cluster and classification analysis method for TGF-β1 and VEGF levels can be utilized in clinical practice to predict the development of GN in the long-term post-COVID period.

The Inhibitory Effect of Geraniol on CCL4-induced Hepatorenal Toxicity in Pregnant Mice through the PI3K/AKT Signaling Pathway.

Hepatotoxicity caused by CCL4 is well known. Geraniol (GNL) has high antioxidant effect that can induces liver regeneration. However, the protective effect of GNL effect on CCL4-induced hepatorenal toxicity in pregnant mice has not yet been studied. To investigate whether GNL could protect against oxidative stress induced by CCL4 via the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, which is regulated by phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT), and has been found to have protective effects on renal and hepatic tissues. Forty-eight female albino mice weighing 25-30 g were randomly allocated to 4 groups: Group I served as a control; Group II received a toxicity-inducing single dose of 15 μL of CCL4 on the 4th day after mating; Group III received 40 mg/kg GNL + CCL4 (with GNL from the 1st day of assimilation to delivery); and Group IV received GNL alone from the 1st day of assimilation to the end of the delivery period. GNL was evaluated for its protective effects on hepatotoxicity in CCL4-treated pregnant mice. Litter size, weight, survival rate, and resorption were recorded. In addition, H & E staining was done for liver and kidney pathology as well as biochemical markers and oxidative markers malondialdehyde, superoxide dismutase, and catalase were analyzed. CCL4 significantly reduced survival rate and increased resorption after exposure. Alanine transaminase and aspartate aminotransferase concentrations in the serum, tissue MDA, blood urea nitrogen, and creatinine were increased after CCL4 exposure. GNL improved enzyme and antioxidant levels and prevented CCL4-induced hepatic injury in mice. Caspase-3 cleavage was decreased by GNL, which increased PI3K, phosphorylated AKT, Nrf2, and B-cell lymphoma 2. GNL demonstrates a protective effect against CCl4-induced hepatorenal toxicity, mediated through the activation of the PI3K/AKT signaling pathway and the upregulation of Nrf2. These findings highlight the potential therapeutic implications of GNL in mitigating oxidative stress and inflammation in liver and kidney tissues.

Metagenomics and metaproteomics alterations are associated with kidney disease in opisthorchiasis hamsters fed a high-fat and high-fructose diet.

Opisthorchis viverrini (O. viverrini, Ov) infection and consumption of high-fat and high-fructose (HFF) diet exacerbate liver and kidney disease. Here, we investigated the effects of a combination of O. viverrini infection and HFF diet on kidney pathology via changes in the gut microbiome and host proteome in hamsters. Twenty animals were divided into four groups; 1) fed a normal diet not infected with O. viverrini (normal group), 2) fed an HFF diet and not infected with O. viverrini (HFF), 3) fed a normal diet and infected with O. viverrini (Ov), and 4) fed an HFF diet and infected with O. viverrini (HFFOv). DNA was extracted from fecal samples and the V3-V4 region of the bacterial 16S rRNA gene sequenced on an Illumina MiSeq sequencing platform. In addition, LC/MS-MS analysis was done. Histopathological studies and biochemical assays were also conducted. The results indicated that the HFFOv group exhibited the most severe kidney injury, manifested as elevated KIM-1 expression and accumulation of fibrosis in kidney tissue. The microbiome of the HFFOv group was more diverse than in the HFF group: there were increased numbers of Ruminococcaceae, Lachnospiraceae, Desulfovibrionaceae and Akkermansiaceae, but fewer Eggerthellaceae. In total, 243 host proteins were identified across all groups. Analysis using STITCH predicted that host proteome changes may lead to leaking of the gut, allowing molecules such as soluble CD14 and p-cresol to pass through to promote kidney disease. In addition, differential expression of TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 (Tab2, involving renal inflammation and injury) are predicted to be associated with kidney disease. The combination of HFF diet and O. viverrini infection may promote kidney injury through alterations in the gut microbiome and host proteome. This knowledge may suggest an effective strategy to prevent kidney disease beyond the early stages.

Особенности применения и возможности биоимпедансного анализа в нефрологии

The purpose — to determine the features of the body’s biocomposition using bioimpedance analysis in patients with kidney pathology. Material and methods. 39 patients from the Nephrology Department of Republican Clinical Hospital were examined. Among them were patients with acute tubulointerstitial nephritis, chronic glomerulonephritis, and nephropathy of mixed etiology. All patients underwent bioimpedance analysis of body composition using the MEDASS ABC-02 device. The study presents the results of bioimpedance analysis based on different electrical resistance of biological tissues. Bioimpedance analysis allows studying the body composition of patients with different profiles. The possibilities of bioimpedance analysis in nephrology are determined by the assessment of nutritional and volemic status. Results. Approximately half of the patients (47.8%) had an high body mass index. However, when analyzing indicators of fat mass and total body water, it was found that 36.3% of patients had normal to low levels of fat mass, with the increase in total body water being due to fluid overload. Meanwhile, 27.3% with normal body mass index had an increase in fat mass. The lean body mass, reflecting the body’s protein depot, was below normal in 15.2% of patients, which may be associated with nutritional status impairment and the development of protein-energy malnutrition. Conclusion. The study demonstrated the role of bioimpedance analysis in evaluating the volumetric and nutritional status in patients with a nephrological profile.

Astragaloside IV alleviates renal fibrosis by inhibiting renal tubular epithelial cell pyroptosis induced by urotensin II through regulating the cAMP/PKA signaling pathway.

To explore the molecular mechanism of Astragaloside IV (AS-IV) in alleviating renal fibrosis by inhibiting Urotensin II-induced pyroptosis and epithelial-mesenchymal transition of renal tubular epithelial cells. Forty SD rats were randomly divided into control group without operation: gavage with 5ml/kg/d water for injection and UUO model group: gavage with 5ml/kg/d water for injection; UUO+ AS-IV group (gavage with AS-IV 20mg/kg/d; and UUO+ losartan potassium group (gavage with losartan potassium 10.3mg/kg/d, with 10 rats in each group. After 2 weeks, Kidney pathology, serum Urotensin II, and cAMP concentration were detected, and the expressions of NLRP3, GSDMD-N, Caspase-1, and IL-1β were detected by immunohistochemistry. Rat renal tubular epithelial cells were cultured in vitro, and different concentrations of Urotensin II were used to intervene for 24h and 48h. Cell proliferation activity was detected using the CCK8 assay. Suitable concentrations of Urotensin II and intervention time were selected, and Urotensin II receptor antagonist (SB-611812), inhibitor of PKA(H-89), and AS-IV (15ug/ml) were simultaneously administered. After 24 hours, cells and cell supernatants from each group were collected. The cAMP concentration was detected using the ELISA kit, and the expression of PKA, α-SMA, FN, IL-1β, NLRP3, GSDMD-N, and Caspase-1 was detected using cell immunofluorescence, Western blotting, and RT-PCR. Renal tissue of UUO rats showed renal interstitial infiltration, tubule dilation and atrophy, renal interstitial collagen fiber hyperplasia, and serum Urotensin II and cAMP concentrations were significantly higher than those in the sham operation group (p <0.05). AS-IV and losartan potassium intervention could alleviate renal pathological changes, and decrease serum Urotensin II, cAMP concentration levels, and the expressions of NLRP3, GSDMD-N, Caspase-1, and IL-1β in renal tissues (p <0.05). Urotensin II at a concentration of 10-8 mol/L could lead to the decrease of cell proliferation, (p<0.05). Compared with the normal group, the cAMP level and the PKA expression were significantly increased (p<0.05). After intervention with AS-IV and Urotensin II receptor antagonist, the cAMP level and the expression of PKA were remarkably decreased (p<0.05). Compared with the normal group, the expression of IL-1β, NLRP3, GSDMD-N, and Caspase-1 in the Urotensin II group was increased (p<0.05), which decreased in the AS-IV and H-89 groups. AS-IV can alleviate renal fibrosis by inhibiting Urotensin II-induced pyroptosis of renal tubular epithelial cells by regulating the cAMP/PKA signaling pathway.

Thymoquinone Nanoparticles (TQ-NPs) in Kidney Toxicity Induced by Ehrlich Ascites Carcinoma (EAC): An In Vivo Study.

Cisplatin (Cis) is potent chemotherapy used to treating already many different types of cancer; however, it is found to correlate with nephrotoxicity and other adverse health consequences. Thymoquinone (TQ) is an antioxidant and anti-inflammatory molecule that may defend against the consequences of different chemotherapies. Thymoquinone uses, although, are negatively impacted by its weak solubility and inadequate biological availability. This investigation examined the efficacy of a new nanoparticle (NP) absorbing TQ in an Ehrlich Ascites Carcinoma (EAC) mice model to address its low solubility, enhance its bioavailability, and protect against Cis-induced nephrotoxicity. Following 4 treatment groups were included in this research: (1) control, (2) EAC, (3) EAC + Cis + Thymoquinone nanoparticle (TQ-NP) treated, and (4) EAC + Cis-treated. The study revealed that TQ-NP was efficacious in avoiding Cis-induced kidney problems in EAC mice, as well as restoring kidney function and pathology. Thymoquinone nanoparticle considerably reduced Cis-induced oxidative damage in renal tissue by augmenting antioxidant levels. According to tumor weight and histological investigation results, TQ-NP did not impair Cis's anticancer efficacy. Thymoquinone nanoparticle might be used as a potential drug along with Cis anticancer therapy to reduce nephrotoxicity and other side effects while maintaining Cis anticancer properties.

Kidney pathology alters cell-clustering in single cell RNA sequencing

Kidney pathology alters cell-clustering in single cell RNA sequencing

KIM-1 is a universal biomarker of kidney pathologies: True or false?

KIM-1 is a universal biomarker of kidney pathologies: True or false?

MicroRNA-216a-5p Alleviates Acute Kidney Injury of Mice via Suppressing FAS Ligand Expression.

The aim of this present work was to investigate the mechanism of the microRNA (miR)-216a-5p/FASL axis in mice with acute kidney injury (AKI). Mice kidney ischemia/reperfusion (I/R) injury was used as AKI models in this study. I/R mice were injected with miR-216a-5p- and FASL-related constructs to investigate potential mechanisms of kidney protection. Kidney function, inflammation, oxidative stress, and kidney cell apoptosis were assessed after 24 h of reperfusion. In vitro, the hypoxia-reoxygenation (H/R) model was used with kidney tubular epithelial cells (TECs) to mimic kidney I/R injury. H/R-treated TECs were transfected with miR-216a-5p- and FASL-related constructs to detect cell viability, inflammation, and oxidative stress. MiR-216a-5p and FASL expression levels in mouse kidney tissues and in H/R-treated TECs were detected. MiR-216a-5p was downregulated and FASL was upregulated in kidney tissues of I/R mice and H/R-treated TECs. Upregulating miR-216a-5p attenuated kidney cell apoptosis and the damage of kidney function, and reduced inflammatory factor levels and oxidative stress response in kidney tissues of I/R mice. Upregulating miR-216a-5p advanced cell viability and reduced inflammatory factor levels and oxidative stress response in H/R-treated TECs. Downregulation of FASL effectively reversed the influences of downregulation of miR-216a-5p on kidney injury in mice and kidney TEC survival. Our study reveals that miR-216a-5p reduces I/R-induced pathological kidney damage in AKI via suppressing FASL.

Total Knee Arthroplasty in Hemodialysis Patients: Routine or Complex Surgery?

Background. Chronic hemodialysis significantly increases the risks associated with knee replacement. Among the late complications of knee arthroplasty in hemodialysis patients, deep periprosthetic joint infection (PJI) and aseptic loosening are more frequent. The frequency of revision interventions in patients with end-stage kidney disease (ESKD) is substantially higher compared to patients with normal kidney function.&#x0D; The aim of the study — based on the perioperative parameters and midterm outcomes to justify the primary knee replacement in chronic hemodialysis patients as complex case of arthroplasty.&#x0D; Methods. A retrospective randomized single-center cohort study was conducted, including 62 patients with various forms of knee osteoarthritis. Patients were divided into two groups: Group 1 — 29 (46.8%) patients with end-stage renal disease (ESRD) undergoing dialysis, Group 2 — 33 (53.2%) patients without kidney pathology. The average follow-up period in both groups was 3.7 years (min — 1, max — 6). The following parameters were assessed: patient age, length of hospital stay, morphocortical index, body mass index (BMI), duration of hemodialysis, functional assessment of the knee joint using the KSS Function Score and Forgotten Joint Score-12 (FJS-12), radiological results on the KRESS, and the frequency of various complications.&#x0D; Results. In Group 1, patients had significantly lower BMI compared to Group 2. Length of hospital stay in Group 1 were 1.7 times longer. According to the KSS Function Score, no significant differences were observed between the groups in the first 36 months after the operation. However, by the 4th year of follow-up, average KSS Function Score in Group 1 decreased to 77.3 points, which was due to infectious complications. The FJS-12 showed worse scores in Group 2, averaging 68.7 points. After more than three years post-operation, no statistically significant differences were observed between the groups, which was associated with an increase in the number of complications in Group 1. Results on the KRESS after 43 months did not differ between the groups and averaged 4.8 points. Group 1 had more orthopedic complications and cases of PJI, accounting for 7 out of 37.&#x0D; Conclusion. Age and constitutional characteristics of patients undergoing hemodialysis significantly differ from the normal population. The frequency of complications in Group 1 was 23.5%. These patients require the implantation of more constrained implant components and modular systems. Therefore, primary knee replacement in hemodialysis patients can be classified as a complex case of arthroplasty.

Specific Alternation of Gut Microbiota and the Role of Ruminococcus gnavus in the Development of Diabetic Nephropathy.

In this study, we aim to investigate the precise alterations in the gut microbiota during the onset and advancement of diabetic nephropathy (DN) and examine the impact of Ruminococcus gnavus (R. gnavus) on DN. Eight-week-old male KK-Ay mice were administered antibiotic cocktails for a duration of two weeks, followed by oral administration of R. gnavus for an additional eight weeks. Our study revealed significant changes in the gut microbiota during both the initiation and progression of DN. Specifically, we observed a notable increase in the abundance of Clostridia at the class level, higher levels of Lachnospirales and Oscillospirales at the order level, and a marked decrease in Clostridia_UCG-014 in DN group. Additionally, there was a significant increase in the abundance of Lachnospiraceae, Oscillospiraceae, and Ruminococcaceae at the family level. Moreover, oral administration of R. gnavus effectively aggravated kidney pathology in DN mice, accompanied by elevated levels of urea nitrogen (UN), creatinine (Cr), and urine protein. Furthermore, R. gnavus administration resulted in down-regulation of tight junction proteins such as Claudin-1, Occludin, and ZO-1, as well as increased levels of uremic toxins in urine and serum samples. Additionally, our study demonstrated that orally administered R. gnavus up-regulated the expression of inflammatory factors, including nucleotide-binding oligomerization domain-like receptor pyrin domain-containing protein 3 (NLRP3) and Interleukin (IL)-6. These changes indicated the involvement of the gut-kidney axis in DN, and R. gnavus may worsen diabetic nephropathy by affecting uremic toxin levels and promoting inflammation in DN.

Рrevention of contrast-induced nephropathy during interventional treatment of acute coronary syndrome

The aim of the work was to determine the risk factors of contrast-induced nephropathy in patients with acute coronary syndrome and to evaluate the effectiveness of methods of its prevention. There were examined 62 patients admitted to the interventional cardiology department during 9 months of routine practice with a diagnosis of acute coronary syndrome and concomitant chronic kidney disease. Among them, 56.45% have diabetic nephropathy, 21% – hypertensive nephro­pathy, 19.35% – chronic pyelonephritis, 3.2% – gouty nephropathy. According to the stages of chronic kidney disease: I stage – 8.1%, II stage – 46.8%, III A stage – 30.6%, III B stage – 14.5% of patients. The control group consisted of 32 patients with acute coronary syndrome without kidney pathology. All patients underwent urgent percutaneous coronary intervention using a water-soluble low-osmolarity radiocontrast medium. The risk of contrast-induced nephropathy was determined according to the Mehran scale. Contrast-induced nephropathy was diagnosed by an increase in serum creatinine over 24-48 hours by &gt;25%. Prevention of contrast-induced nephropathy according to existing recommendations was carried out by prescribing early statin therapy and diuresis-controlled combined hydration in 22 patients with concomitant chronic kidney disease. Mathematical processing was performed using Statistica 8.0 software (StatSoft Inc, USA). Patients with chronic kidney disease had a high and very high risk of contrast-induced nephropathy in 19.4% and 3.2% of cases, among them in 91.6% of high and in 100% very high-risk contrast-induced nephropathy developed. Patients in the control group had a low to moderate risk, none of them developed contrast-induced nephropathy. It has been shown that the risk of contrast-induced nephropathy depends on the stage of chronic kidney disease and is associated with a decrease in the ejection fraction of the left ventricle (≤40%), acute left ventricle failure of the III and IV classes according to Killip, a decrease in diuresis in the first 12-24 hours after urgent percutaneous coronary intervention up to ≤0.6 ml/h/kg; in patients with diabetic nephropathy taking metformin 6-12 hours before the administration of the X-ray contrast medium and the glomerular filtration rate ≤45 ml/min./1.73 m2. In patients who underwent prevention of contrast-induced nephropathy in its entirety, its development was not registered.

Exploring the pathology of liver, kidney, muscle, and stomach of fledgling seabirds associated with plastic ingestion

There remain significant gaps in knowledge about ‘sub-lethal’ impacts of plastic ingestion, particularly chronic impacts on cells, tissues, or organs. Few studies have applied traditional animal health tools, such as histopathology, to assess physiological damage to wildlife, with fewer still providing information on the dosage or exposure to plastics needed to elicit negative effects. Our study seeks to investigate a common hypothesis in plastic pollution research; that an increasing plastics burden will have an impact on an animal’s health, examining two wild species with high levels of environmental exposure to plastic through their diet. Here we assess the histopathology of the muscle, upper digestive tract, liver and kidney of two seabird species that are known to be commonly exposed to plastic, comparing exposed and non-exposed individuals. Fledgling seabirds showed histopathological evidence of cumulative pressures such as starvation, disease, and endoparasite burden. However, we observed no evidence of chronic harm that could be explicitly linked to the plastics. We found one case of haemorrhage, reaffirming that large/sharp plastic foreign bodies may cause acute physical damage. Given the numerous interacting pressures on the health of fledging seabirds, including exposure to plastic, this study highlights the need to scrutinise plastic-animal interactions and research though a One Health lens.

Convolutional Neural Network Model for Segmentation and Classification of Clear Cell Renal Cell Carcinoma Based on Multiphase CT Images.

(1) Background: Computed tomography (CT) imaging challenges in diagnosing renal cell carcinoma (RCC) include distinguishing malignant from benign tissues and determining the likely subtype. The goal is to show the algorithm's ability to improve renal cell carcinoma identification and treatment, improving patient outcomes. (2) Methods: This study uses the European Deep-Health toolkit's Convolutional Neural Network with ECVL, (European Computer Vision Library), and EDDL, (European Distributed Deep Learning Library). Image segmentation utilized U-net architecture and classification with resnet101. The model's clinical efficiency was assessed utilizing kidney, tumor, Dice score, and renal cell carcinoma categorization quality. (3) Results: The raw dataset contains 457 healthy right kidneys, 456 healthy left kidneys, 76 pathological right kidneys, and 84 pathological left kidneys. Preparing raw data for analysis was crucial to algorithm implementation. Kidney segmentation performance was 0.84, and tumor segmentation mean Dice score was 0.675 for the suggested model. Renal cell carcinoma classification was 0.885 accurate. (4) Conclusion and key findings: The present study focused on analyzing data from both healthy patients and diseased renal patients, with a particular emphasis on data processing. The method achieved a kidney segmentation accuracy of 0.84 and mean Dice scores of 0.675 for tumor segmentation. The system performed well in classifying renal cell carcinoma, achieving an accuracy of 0.885, results which indicates that the technique has the potential to improve the diagnosis of kidney pathology.

Adolescent Body Mass Index and Early Chronic Kidney Disease in Young Adulthood

Despite increasing obesity rates in adolescents, data regarding early kidney sequelae are lacking. To assess the association between adolescent body mass index (BMI) and early chronic kidney disease (CKD) in young adulthood (<45 years of age). This cohort study linked screening data of mandatory medical assessments of Israeli adolescents to data from a CKD registry of a national health care system. Adolescents who were aged 16 to 20 years; born since January 1, 1975; medically evaluated for mandatory military service through December 31, 2019; and insured by Maccabi Healthcare Services were assessed. Individuals with kidney pathology, albuminuria, hypertension, dysglycemia, or missing blood pressure or BMI data were excluded. Body mass index was calculated as weight in kilograms divided by height in meters squared and categorized by age- and sex-matched percentiles according to the US Centers for Disease Control and Prevention. Follow-up started at the time of medical evaluation or January 1, 2000 (whichever came last), and ended at early CKD onset, death, the last day insured, or August 23, 2020 (whichever came first). Data analysis was performed from December 19, 2021, to September 11, 2023. Early CKD, defined as stage 1 to 2 CKD by moderately or severely increased albuminuria, with an estimated glomerular filtration rate of 60 mL/min/1.73 m2 or higher. Of 629 168 adolescents evaluated, 593 660 (mean [SD] age at study entry, 17.2 [0.5] years; 323 293 [54.5%] male, 270 367 [45.5%] female) were included in the analysis. During a mean (SD) follow-up of 13.4 (5.5) years for males and 13.4 (5.6) years for females, 1963 adolescents (0.3%) developed early CKD. Among males, the adjusted hazard ratios were 1.8 (95% CI, 1.5-2.2) for adolescents with high-normal BMI, 4.0 (95% CI, 3.3-5.0) for those with overweight, 6.7 (95% CI, 5.4-8.4) for those with mild obesity, and 9.4 (95% CI, 6.6-13.5) for those with severe obesity. Among females, the hazard ratios were 1.4 (95% CI, 1.2-1.6) for those with high-normal BMI, 2.3 (95% CI, 1.9-2.8) for those with overweight, 2.7 (95% CI, 2.1-3.6) for those with mild obesity, and 4.3 (95% CI, 2.8-6.5) for those with severe obesity. The results were similar when the cohort was limited to individuals who were seemingly healthy as adolescents, individuals surveyed up to 30 years of age, or those free of diabetes and hypertension at the end of the follow-up. In this cohort study, high BMI in late adolescence was associated with early CKD in young adulthood. The risk was also present in seemingly healthy individuals with high-normal BMI and before 30 years of age, and a greater risk was seen among those with severe obesity. These findings underscore the importance of mitigating adolescent obesity rates and managing risk factors for kidney disease in adolescents with high BMI.

Ameliorative effects of Modified Huangqi Chifeng decoction on podocyte injury via autophagy mediated by PI3K/AKT/mTOR and AMPK/mTOR pathways

Ethnopharmacological relevanceProteinuria is recognized as a risk factor for the exacerbation of chronic kidney disease. Modified Huangqi Chifeng decoction (MHCD) has distinct advantages in reducing proteinuria. Our previous experimental results have shown that MHCD can inhibit excessive autophagy. However, the specific mechanism by which MHCD regulates autophagy needs to be further explored. Aim of the studyIn this study, in vivo and in vitro experiments were conducted to further clarify the protective mechanism of MHCD on the kidney and podocytes by regulating autophagy based on phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) and adenosine monophosphate-activated protein kinase (AMPK)/mTOR signaling pathways. Materials and methodsBy a single injection via the tail vein, Sprague–Dawley rats received Adriamycin (5 mg/kg) to establish a model of proteinuria nephropathy. They were divided into control, model, MHCD, 3-methyladenine (3 MA), 3 MA + MHCD, and telmisartan groups and were administered continuously for 6 weeks. The MHCD-containing serum was prepared, and a model of podocyte injury induced by Adriamycin (0.2 μg/mL) was established. ResultsMHCD reduced the 24-h urine protein levels and relieved pathological kidney damage. During autophagy in the kidneys of rats with Adriamycin-induced nephropathy, the PI3K/AKT/mTOR signaling pathway is inhibited, while the AMPK/mTOR signaling pathway is activated. MHCD antagonized these effects, thereby inhibiting excessive autophagy. MHCD alleviated Adriamycin-induced podocyte autophagy, as demonstrated using Pik3r1 siRNA and an overexpression plasmid for Prkaa1/Prkaa2. Furthermore, MHCD could activate the PI3K/AKT/mTOR signaling pathway while suppressing the AMPK/mTOR signaling pathway. ConclusionsThis study demonstrated that MHCD can activate the interaction between the PI3K/AKT/mTOR and the AMPK/mTOR signaling pathways to maintain autophagy balance, inhibit excessive autophagy, and play a role in protecting the kidneys and podocytes.

Mitochondrial Dysfunction in Kidney Tubulopathies.

Mitochondria play a key role in kidney physiology and pathology. They produce ATP to fuel energy-demanding water and solute reabsorption processes along the nephron. Moreover, mitochondria contribute to cellular health by the regulation of autophagy, (oxidative) stress responses, and apoptosis. Mitochondrial abundance is particularly high in cortical segments, including proximal and distal convoluted tubules. Dysfunction of the mitochondria has been described for tubulopathies such as Fanconi, Gitelman, and Bartter-like syndromes and renal tubular acidosis. In addition, mitochondrial cytopathies often affect renal (tubular) tissues, such as in Kearns-Sayre and Leigh syndromes. Nevertheless, the mechanisms by which mitochondrial dysfunction results in renal tubular diseases are only scarcely being explored. This review provides an overview of mitochondrial dysfunction in the development and progression of kidney tubulopathies. Furthermore, it emphasizes the need for further mechanistic investigations to identify links between mitochondrial function and renal electrolyte reabsorption.

Efficient protocol for the differentiation of kidney podocytes from induced pluripotent stem cells, involving the inhibition of mTOR

The mechanistic/mammalian target of rapamycin (mTOR) is involved in a wide range of cellular processes. However, the role of mTOR in podocytes remains unclear. In this study, we aimed to clarify the role of mTOR in podocyte differentiation from human induced pluripotent stem cells (hiPSCs) and to establish an efficient differentiation protocol for human podocytes. We generated podocytes from hiPSCs by modifying protocol. The expression of the podocyte-specific slit membrane components nephrin and podocin was measured using PCR, western blotting, flow cytometry, and immunostaining; and the role of mTOR was evaluated using inhibitors of the mTOR pathway. Nephrin and podocin were found to be expressed in cells differentiated from hiPSCs, and their expression was increased by mTOR inhibitor treatment. S6, a downstream component of the mTOR pathway, was also found to be involved in podocyte differentiation. we evaluated its permeability to albumin, urea, and electrolytes. The induced podocytes were permeable to the small molecules, but only poorly permeable to albumin. We have shown that the mTOR pathway is involved in podocyte differentiation. Our monolayer podocyte differential protocol, using an mTOR inhibitor, provides a novel in vitro model for studies of kidney physiology and pathology.

Naturally occurring autoimmune disease in (NZB X NZW) F1 mice is correlated with suppression of MZ B cell development due to aberrant B Cell Receptor (BCR) signaling, which is exacerbated by exposure to inorganic mercury.

Autoimmune diseases are multifactorial and include environmental as well as genetic drivers. Although much progress has been made in understanding the nature of genetic underpinnings of autoimmune disease, by comparison much less is understood regarding how environmental factors interact with genetics in the development of autoimmunity and autoimmune disease. In this report, we utilize the (NZB X NZW) F1 mouse model of Systemic Lupus Erythematosus (SLE). Mercury is a xenobiotic that is environmentally ubiquitous and is epidemiologically linked with the development of autoimmunity. Among other attributes of human SLE, (NZB X NZW) F1 mice spontaneously develop autoimmune-mediated kidney disease. It has been previously shown that if (NZB X NZW) F1 mice are exposed to inorganic mercury (Hg2+), the development of autoimmunity, including autoimmune kidney pathology, is accelerated. We now show that in these mice the development of kidney disease is correlated with a decreased percentage of marginal zone (MZ) B cells in the spleen. In Hg2+-intoxicated mice, kidney disease is significantly augmented, and matched by a greater decrease in MZ B cell splenic percentages than found in control mice. In Hg2+- intoxicated mice, the decrease in MZ B cells appears to be linked to aberrant B Cell Receptor (BCR) signal strength in transitory 2 (T2) B cells, developmental precursors of MZ B cells.