Common Renal Disease Research Articles

Renal Disease in Nepal, Under Microscope: One Year Study

Introduction: Renal disease is a significant health problem in Nepal that is creating an increasing health and economic burden. Renal disease usually does not cause symptoms until reaching an advanced stage. Correct diagnosis of renal biopsy requires correlation of clinical, biochemical, and serological parameters and histopathological examination by light microscopy, immunofluorescence, and sometimes electron microscopic examination. The present study was conducted to study the histopathological patterns of all renal biopsy specimens in Nepal with the help of information obtained from Light microscopy and Immunofluorescence examination. Materials and Methods: In this cross-sectional (Prospective study) undertaken at the Pathology Department at Pratham Pathology Laboratory, Lazimpat for 1year duration (January 1ST - December 31ST 2022), all renal biopsy specimens of patients with different glomerular diseases were enrolled. The final diagnosis was made by a pathologist correlating with the histopathological along with immunofluorescence and other clinical and laboratory findings. Results: A total of 195 patient renal biopsy specimens between ages (1-80 years) were enrolled. The majority of patients were in the age group of 21-30 years (23.60%). The study showed slight female predominance with a male-to-female ratio of 1: 1.34. The most common renal disease was Lupus Nephritis with a frequency of 64 with a predominance of Lupus Type IV with a frequency of 34 (17.45. Among all, 21 cases were of Chronic Glomerulonephritis and the most common leading cause for it was IgA Nephropathy with a frequency of 8 (38.10%). Conclusions: The most commonly diagnosed renal disease under a microscope was Lupus Nephritis with a frequency of 34 (17.45%). The leading primary glomerular disease for Chronic glomerulonephritis was IgA Nephropathy with a frequency of 8 (38.10%).

Exploring the Potential of Claude 3 Opus in Renal Pathological Diagnosis: Performance Evaluation.

Artificial intelligence (AI) has shown great promise in assisting medical diagnosis, but its application in renal pathology remains limited. We evaluated the performance of an advanced AI language model, Claude 3 Opus (Anthropic), in generating diagnostic descriptions for renal pathological images. We carefully curated a dataset of 100 representative renal pathological images from the Diagnostic Atlas of Renal Pathology (3rd edition). The image selection aimed to cover a wide spectrum of common renal diseases, ensuring a balanced and comprehensive dataset. Claude 3 Opus generated diagnostic descriptions for each image, which were scored by 2 pathologists on clinical relevance, accuracy, fluency, completeness, and overall value. Claude 3 Opus achieved a high mean score in language fluency (3.86) but lower scores in clinical relevance (1.75), accuracy (1.55), completeness (2.01), and overall value (1.75). Performance varied across disease types. Interrater agreement was substantial for relevance (κ=0.627) and overall value (κ=0.589) and moderate for accuracy (κ=0.485) and completeness (κ=0.458). Claude 3 Opus shows potential in generating fluent renal pathology descriptions but needs improvement in accuracy and clinical value. The AI's performance varied across disease types. Addressing the limitations of single-source data and incorporating comparative analyses with other AI approaches are essential steps for future research. Further optimization and validation are needed for clinical applications.

Efficacy of Ultrasound-Guided Renal Access for Percutaneous Nephrolithotomy in Combination with Fluoroscopy versus Fluoroscopy as a Single Imaging Modality

Abstract Background Renal stone is one of the most common renal diseases worldwide. There are several modalities for treatment of renal stone disease, one of these modalities is the use of percutaneous nephrolithatomy (PCNL) surgery which can be done either under fluoroscopic or ultrasound guidance which has significantly reduced x-ray exposure risk to medical personnel and patients. Objective To evaluate the efficacy of the ultrasound-guided PCNL in combination with fluoroscopy to minimize exposure time to radiation, risk of accidental injury to adjacent organs, blood loss and increased stone clearance rate versus usage of fluoroscopy as a single imaging modality in PCNL. Patients and Methods This prospective randomized comparative clinical trial study was conducted on 40 patients for the treatment of stone(s) located in the kidney more than 2 cm or refractory to shockwave therapy, patients were divided into 2 groups, 20 patients each; Group I: ultrasound-guided PCNL in combination with fluoroscopy and Group II: use of fluoroscopy as a single imaging modality, the study was carried on at Urology department, Faculty of medicine, Ain Shams University and Urology department, Theodor Bilharz Research Institute. Results As regard post operative complications in studied groups, in group I, there were 3 patients (15%) with post-operative fever versus 4 patients (20%) in group II. In group I, there was 1 patient (5%) with post-operative leakage versus 3 patients (15%) in group II. In group II, there was 1 patient (5%) with post-operative blood transfusion versus 0 patients (0%) in group I with no statistical difference. With respect to post-operative hospital stay and need for second operation between studied groups, there was a highly statistical significant (p-value < 0.001) increased post- operative hospital stay in group II (3.5 ± 1.05) when compared with group I (1.9 ± 0.9). While, as regard need for second operation and type of the operation, there were no statistical differences between the studied groups. But, there was high statistical significant difference (p-value < 0.001) decreased x-ray exposure time in group I (43.2 ± 11.3 sec) when compared to group II (314 ± 84.2 sec). Conclusion Combined ultrasonic and fluoroscopic guided PCNL had shorter x-ray exposure time. Combined ultrasonic and fluoroscopic guided PCNL had less Hb drop and intraoperative complications. However it still had longer surgery duration. Combined ultrasonic and fluoroscopic guided PCNL showed less postoperative pain and analgesic consumption. Combined ultrasonic and fluoroscopic guided PCNL had shorter hospital stay. Regarding the outcome and complications, in general, there is no statistical significant difference between these two groups.

Applying a Deep Learning Model for Total Kidney Volume Measurement in Autosomal Dominant Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease leading to end-stage renal disease. Total kidney volume (TKV) measurement has been considered as a surrogate in the evaluation of disease severity and prognostic predictor of ADPKD. However, the traditional manual measurement of TKV by medical professionals is labor-intensive, time-consuming, and human error prone. In this investigation, we conducted TKV measurements utilizing magnetic resonance imaging (MRI) data. The dataset consisted of 30 patients with ADPKD and 10 healthy individuals. To calculate TKV, we trained models using both coronal- and axial-section MRI images. The process involved extracting images in Digital Imaging and Communications in Medicine (DICOM) format, followed by augmentation and labeling. We employed a U-net model for image segmentation, generating mask images of the target areas. Subsequent post-processing steps and TKV estimation were performed based on the outputs obtained from these mask images. The average TKV, as assessed by medical professionals from the testing dataset, was 1501.84 ± 965.85 mL with axial-section images and 1740.31 ± 1172.21 mL with coronal-section images, respectively (p = 0.73). Utilizing the deep learning model, the mean TKV derived from axial- and coronal-section images was 1536.33 ± 958.68 mL and 1636.25 ± 964.67 mL, respectively (p = 0.85). The discrepancy in mean TKV between medical professionals and the deep learning model was 44.23 ± 58.69 mL with axial-section images (p = 0.8) and 329.12 ± 352.56 mL with coronal-section images (p = 0.9), respectively. The average variability in TKV measurement was 21.6% with the coronal-section model and 3.95% with the axial-section model. The axial-section model demonstrated a mean Dice Similarity Coefficient (DSC) of 0.89 ± 0.27 and an average patient-wise Jaccard coefficient of 0.86 ± 0.27, while the mean DSC and Jaccard coefficient of the coronal-section model were 0.82 ± 0.29 and 0.77 ± 0.31, respectively. The integration of deep learning into image processing and interpretation is becoming increasingly prevalent in clinical practice. In our pilot study, we conducted a comparative analysis of the performance of a deep learning model alongside corresponding axial- and coronal-section models, a comparison that has been less explored in prior research. Our findings suggest that our deep learning model for TKV measurement performs comparably to medical professionals. However, we observed that varying image orientations could introduce measurement bias. Specifically, our AI model exhibited superior performance with axial-section images compared to coronal-section images.

Changes in the spectrum of biopsy-proven renal diseases over 11 years: a single-center study in China

Background There have been some shifts in the frequency and distribution of biopsy-proven renal diseases in China over recent years. The aim of the study was to investigate the changing spectrum of renal diseases from the view of kidney biopsy data in a single center of China. Methods and results A total of 10,996 cases of native renal biopsies from patients aged ≥15 years old in Huashan Hospital, Fudan University, between 2008 and 2018 were analyzed retrospectively. The results showed that primary glomerular nephropathy (PGN) remained the most common biopsy-proven renal disease (69.42% of total), with IgA nephropathy (IgAN) accounting for 44.40% of PGN, membranous nephropathy (MN) for 28.55%, minimal change disease (MCD) for 13.26% and focal segmental glomerulosclerosis (FSGS) for 8.00%. During the study period, the proportion of MN in PGN appeared an increasing tendency, while that of IgAN and MCD remained stable and that of FSGS showed a decline. Secondary glomerular nephropathy (SGN) constituted 21.54% of total cases, among which the leading two diseases were lupus nephritis (LN) and Henoch-Schonlein purpura nephritis (HSN) which accounted for 41.08% and 19.11% respectively. Conclusions The 11-year retrospective study revealed that PGN was the predominant histologic diagnosis among patients undergoing renal biopsy and the most frequent type of PGN remained to be IgAN, followed by MN which increased dramatically.

#1636 Treatment of Tolvaptan related polyuria with bendroflumethiazide for ADPKD: Does it really work?

Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease worldwide and accounts for 10% of patients on renal replacement therapy. Currently, the arginine vasopressin (AVP) V2 receptor antagonist Tolvaptan is the only available treatment for ADPKD which slows cyst formation and thus the progression of kidney disease by inducing AVP resistance. However, its aquaretic side effects can be debilitating and is the most common reason for medication discontinuation. Thiazides such as bendroflumethiazide are natriuresis-promoting diuretics through their action on the sodium-chloride channel in the distal convoluted tubule that are widely used to treat polyuria in inherited AVP deficiency or resistance. However, there is limited information about their effect in patients treated with Tolvaptan. The aim of this observational study is to review the impact on patients’ quality of life by using a low dose bendroflumethiazide with Tolvaptan in patients with ADPKD who are suffering from Tolvaptan induced aquaretic side effects. Method Details of all patients with ADPKD who are on Tolvaptan with or without bendroflumethiazide who are currently attending the polycystic kidney disease (PKD) clinic at Royal Free London NHS Foundation Trust were obtained, and their medications reviewed. Patients who have previously been or were currently on bendroflumethiazide to enable them to continue Tolvaptan therapy were identified. Information about the impact of bendroflumethiazide on their quality of life and their aquaretic side effects were obtained via phone call. If they discontinued bendroflumethiazide, the reason for this was explored. In addition, eGFR, sodium, potassium, and calcium at the time of bendroflumethiazide initiation as well as at three, six, nine and twelve months post bendroflumethiazide initiation were obtained. Results Out of 136 patients receiving Tolvaptan for treatment of ADPKD at our centre, eight (5.8%) were prescribed bendroflumethiazide for treatment of their aquaretic side effects from Tolvaptan. Two of these eight patients (25%) stopped bendroflumethiazide due to adverse reactions. The remaining six patients (75%) remained on the medication, and all reported significant subjective improvement in their symptoms of polyuria, nocturia and in their overall quality of life. Two of the six patients (33.3%) that remained on bendroflumethiazide had also subsequently increased their Tolvaptan dose. No electrolyte disturbances were noted after initiation of bendroflumethiazide. Conclusion Using bendroflumethiazide appears to improve the quality of life through reduction of polyuria and nocturia in patients suffering from Tolvaptan-induced aquaretic side effects with some patients subsequently able to increase their Tolvaptan dose by taking bendroflumethiazide which might result in augmented therapeutic benefit of Tolvaptan. Further placebo-controlled randomised studies with longitudinal will be needed to determine the true benefit-disbenefit balance of thiazide therapy in patients taking tolvaptan, especially to determine whether there is a negative effect on efficacy of tolvaptan on the underlying ADPKD. However, based on our small observational study, the number of patients needed to determine whether bendroflumethiazide improves the tolerability and medication adherence in patients who are debilitated by the aquaretic side effects of Tolvaptan would be small.

Adipocentric origin of the common cardiometabolic complications of obesity in the young up to the very old: pathophysiology and new therapeutic opportunities.

Obesity is a multifactorial chronic disease characterized by an excess of adipose tissue, affecting people of all ages. In the last 40 years, the incidence of overweight and obesity almost tripled worldwide. The accumulation of "visceral" adipose tissue increases with aging, leading to several cardio-metabolic consequences: from increased blood pressure to overt arterial hypertension, from insulin-resistance to overt type 2 diabetes mellitus (T2DM), dyslipidemia, chronic kidney disease (CKD), and obstructive sleep apnea. The increasing use of innovative drugs, namely glucagon-like peptide-1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2-i), is changing the management of obesity and its related cardiovascular complications significantly. These drugs, first considered only for T2DM treatment, are now used in overweight patients with visceral adiposity or obese patients, as obesity is no longer just a risk factor but a critical condition at the basis of common metabolic, cardiovascular, and renal diseases. An adipocentric vision and approach should become the cornerstone of visceral overweight and obesity integrated management and treatment, reducing and avoiding the onset of obesity-related multiple risk factors and their clinical complications. According to recent progress in basic and clinical research on adiposity, this narrative review aims to contribute to a novel clinical approach focusing on pathophysiological and therapeutic insights.

Monocytes and Macrophages in Kidney Disease and Homeostasis.

The monocyte-macrophage lineage of inflammatory cells is characterized by significant morphologic and functional plasticity. Macrophages have broad M1 and M2 phenotype subgroups with distinctive functions and dual reno-toxic and reno-protective effects. Macrophages are a major contributor to injury in immune-complex-mediated, as well as pauci-immune, glomerulonephritis. Macrophages are also implicated in tubulointerstitial and vascular disease, though there have not been many human studies. Patrolling monocytes in the intravascular compartment have been reported in auto-immune injury in the renal parenchyma, manifesting as acute kidney injury. Insights into the pathogenetic roles of macrophages in renal disease suggest potentially novel therapeutic and prognostic biomarkers and targeted therapy. This review provides a concise overview of the macrophage-induced pathogenetic mechanism as a background for the latest findings about macrophages' roles in different renal compartments and common renal diseases.

Human umbilical cord mesenchymal stem cell therapy for renal dysfunction in Alport syndrome: protocol for an open-label, single-arm trial in China

IntroductionAlport syndrome (AS) is one of the most common fatal hereditary renal diseases in human, with a high risk of progressing to end-stage renal disease without effective treatments. Mesenchymal stem...

Cardiovascular and renal diseases in type 2 diabetes patients: 5-year cumulative incidence of the first occurred manifestation and hospitalization cost: a cohort within the French SNDS nationwide claims database

BackgroundMyocardial infarction (MI), stroke, peripheral arterial disease (PAD), heart failure (HF) and chronic kidney disease (CKD) are common cardiovascular renal diseases (CVRD) manifestations for type 2 diabetes. The objective was to estimate the incidence of the first occurring CVRD manifestation and cumulative hospitalization costs of each CVRD manifestation for type 2 diabetes without CVRD history.MethodsA cohort study of all type 2 diabetes free of CVRD as of January 1st 2014, was identified and followed-up for 5 years within the French SNDS nationwide claims database. The cumulative incidence of the first occurring CVRD manifestation was estimated using the cumulative incidence function, with death as a competing risk. Cumulative hospitalization costs of each CVRD manifestations were estimated from the perspective of all payers.ResultsFrom 2,079,089 type 2 diabetes without cancer or transplantation, 76.5% were free of CVRD at baseline with a mean age of 65 years, 52% of women and 7% with microvascular complications history. The cumulative incidence of a first CVRD manifestation was 15.3% after 5 years of follow-up with a constant linear increase over time for all CVRD manifestations: The most frequent was CKD representing 40.6% of first occurred CVRD manifestation, followed by HF (23.0%), then PAD (13.5%), stroke (13.2%) and MI (9.7%). HF and CKD together reached about one patient out of ten after 5 years and represented 63.6% of first CVRD manifestations. The 5-year global cost of all CVRD hospitalizations was 3.9 billion euros (B€), i.e. 2,450€ per patient of the whole cohort, with an exponential increase over time for each specific CVRD manifestation. The costliest was CKD (2.0 B€), followed by HF (1.2 B€), then PAD (0.7 B€), stroke (0.6 B€) and MI (0.3 B€).Conclusions/interpretationWhile MI, stroke and PAD remain classic major risks of complications for CVRD-free type 2 diabetes, HF and CKD nowadays represent individually a higher risk and cost than each of these classic manifestations, and jointly represents a risk and a cost twice as high as these three classic manifestations all together. This should encourage the development of specific HF and CKD preventive strategies.

Bacteriological investigation of pyelonephritis in AL-Najaf Governorate, Iraq: a cross-Sectional study

Pyelonephritis is an inflammation caused by bacteria that primarily effects the interstitial area and the renal pelvis or, less often, the renal tubules. It is one of the most common renal diseases. The main objective of the study is to know and to compare the bacterial species that cause pyelonephritis in its three types, acute, chronic and emphysematous for patients in Iraq, specifically in the Al-Najaf Governorate. 663 (82.88%) samples gave a positive result for bacterial growth, and they belonged to patients with acute pyelonephritis 128 samples, chronic pyelonephritis patients had 288 samples and 247 samples for pyelonephritis emphysematous patients. The chronic pyelonephritis type had the most diverse bacterial species (11) bacterial species, the acute pyelonephritis (9) bacterial species, and the emphysematous pyelonephritis (6) species only. Escherichia coli bacteria was the most widespread of all types pyelonephritis, with a percentage of 34.41% (53/ 154) .For the acute type, percentage of 49.83% (152/305) was for the chronic type and a percentage of 56.07% (157/280) for the emphysematous type. 15 types of antibiotics were tested, and the antibiotics Imipenem and Amikacin were the best for most isolated bacterial species. In terms of gender, age and residence of the patients, females were the most susceptibility 341 (51.43%), and the age group (41-55) years is the most influential 211 (31.83%) and the percentage of residents of urban areas 379 (57.16%) gave the highest percentage of residents of rural areas.

Assessment of rhabdomyolysis-induced acute kidney injury with chemical exchange saturation transfer magnetic resonance imaging.

Rhabdomyolysis (RM)-induced acute kidney injury (AKI) is a common renal disease with low survival rate and inadequate prognosis. In this study, we investigate the feasibility of chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) for assessing the progression of RM-induced AKI in a mouse model. AKI was induced in C57BL/6J mice via intramuscular injection of 7.5 mL/kg glycerol (n=30). Subsequently, serum creatinine (SCr), blood urea nitrogen (BUN), and hematoxylin-eosin (HE) and Masson staining, were performed. Longitudinal CEST-MRI was conducted on days 1, 3, 7, 15, and 30 after AKI induction using a 7.0-T MRI system. CEST-MRI quantification parameters including magnetization transfer ratio (MTR), MTR asymmetric analysis (MTRasym), apparent amide proton transfer (APT*), and apparent relayed nuclear Overhauser effect (rNOE*) were used to investigate the feasibility of detecting RM-induced renal damage. Significant increases of SCr and BUN demonstrated established AKI. The HE staining revealed various degrees of tubular damage, and Masson staining indicted an increase in the degree of fibrosis in the injured kidneys. Among CEST parameters, the cortical MTR presented a significant difference, and it also showed the best diagnostic performance for AKI [area under the receiver operating characteristic curve (AUC) =0.915] and moderate negative correlations with SCr and BUN. On the first day of renal damage, MTR was significantly reduced in cortex (22.7%±0.04%, P=0.013), outer stripe of outer medulla (24.7%±1.6%, P<0.001), and inner stripe of outer medulla (27.0%±1.5%, P<0.001) compared to the control group. Longitudinally, MTR increased steadily with AKI progression. The MTR obtained from CEST-MRI is sensitive to the pathological changes in RM-induced AKI, indicating its potential clinical utility for the assessment of kidney diseases.

The ERA Registry Annual Report 2021: a summary.

The European Renal Association (ERA) Registry collects data on kidney replacement therapy (KRT) in patients with end-stage kidney disease (ESKD). This paper is a summary of the ERA Registry Annual Report 2021, including a comparison across treatment modalities. Data was collected from 54 national and regional registries from 36 countries, of which 35 registries from 18 countries contributed individual patient data and 19 registries from 19 countries contributed aggregated data. Using this data, incidence and prevalence of KRT, kidney transplantation rates, survival probabilities and expected remaining lifetimes were calculated. In 2021, 533.2 million people in the general population were covered by the ERA Registry. The incidence of KRT was 145 per million population (pmp). In incident patients, 55% were 65 years or older, 64% were male, and the most common primary renal disease (PRD) was diabetes (22%). The prevalence of KRT was 1040pmp. In prevalent patients, 47% were 65 years or older, 62% were male, and the most common PRDs were diabetes and glomerulonephritis/sclerosis (both 16%). On 31 December 2021, 56% of patients received haemodialysis, 5% received peritoneal dialysis, and 39% were living with a functioning graft. The kidney transplantation rate in 2021 was 37 pmp, a majority coming from deceased donors (66%). For patients initiating KRT between 2012-2016, 5-year survival probability was 52%. Compared to the general population, life expectancy was 65% and 68% shorter for males and females receiving dialysis, and 40% and 43% shorter for males and females living with a functioning graft.

Total and Extracellular Vesicle cAMP Contents in Urine Are Associated with Autosomal Dominant Polycystic Kidney Disease (ADPKD) Progression.

ADPKD is the most common genetic renal disease, characterized by the presence of multiple cysts which, through slow and gradual growth, lead to glomerular filtration rate (GFR) decline and end-stage renal disease. Cystic growth is associated with increased intracellular levels of 3',5'-cyclic adenosine monophosphate (cAMP). Extracellular vesicles (EVs) are proposed to participate in "remote sensing" by transporting different cargoes, but their relevance to ADPKD progression is poorly understood. This study aimed to determine whether cAMP is contained in urinary EVs and, if so, how total and/or EV cAMP contents participate in disease progression. Fourteen ADPKD patients, naïve for V2 receptor antagonism treatment, and seven controls were studied. Progression was evaluated by estimating GFR (eGFR) and height-adjusted total kidney volume (htTKV). Fresh morning urine was collected to determine cAMP by the competitive radioligand assay. Urine EVs were isolated using an adapted centrifugation method and characterized by electron microscopy, dynamic light scanning, flow cytometry with FITC CD63 labeling, protein and RNA content, and AQP2 and GAPDH mRNA detection. Total and EV cAMP was measurable in both control and patient urine samples. Total cAMP was significantly correlated with eGFR and its annual change but inversely correlated with htTKV. The cAMP-EVs showed a bimodal pattern with htTKV, increasing to ~1 L/m and falling at larger sizes. Our results demonstrate that urine cAMP correlates with ADPKD progression markers, and that its extracellular delivery by EVs could reflect the architectural disturbances of the organ.

Integrated multiple-microarray analysis and mendelian randomization to identify novel targets involved in diabetic nephropathy.

Diabetic nephropathy (DN), which is the main cause of renal failure in end-stage renal disease, is becoming a common chronic renal disease worldwide. Mendelian randomization (MR) is a genetic tool that is widely used to minimize confounding and reverse causation when identifying the causal effects of complex traits. In this study, we conducted an integrated multiple microarray analysis and large-scale plasma proteome MR analysis to identify candidate biomarkers and evaluate the causal effects of prospective therapeutic targets in DN. Five DN gene expression datasets were selected from the Gene Expression Omnibus. The robust rank aggregation (RRA) method was used to integrate differentially expressed genes (DEGs) of glomerular samples between patients with DN and controls, followed by functional enrichment analysis. Protein quantitative trait loci were incorporated from seven different proteomic genome-wide association studies, and genetic association data on DN were obtained from FinnGen (3676 cases and 283,456 controls) for two-sample MR analysis. External validation and clinical correlation were also conducted. A total of 82 DEGs (53 upregulated and 29 downregulated) were identified through RRA integrated analysis. The enriched Gene Ontology annotations and Kyoto Encyclopedia of Genes and Genomes pathways of the DEGs were significantly enriched in neutrophil degranulation, neutrophil activation, proteoglycan binding, collagen binding, secretory granule lumen, gluconeogenesis, tricarboxylic acid cycle, and pentose phosphate pathways. MR analysis revealed that the genetically predicted levels of MHC class I polypeptide-related sequence B (MICB), granzyme A (GZMA), cathepsin S (CTSS), chloride intracellular channel protein 5, and ficolin-1 (FCN1) were causally associated with DN risk. Expression validation and clinical correlation analysis showed that MICB, GZMA, FCN1, and insulin-like growth factor 1 may participate in the development of DN, and carbonic anhydrase 2 and lipoprotein lipase may play protective roles in patients with DN. Our integrated analysis identified novel biomarkers, including MICB and GZMA, which may help further understand the complicated mechanisms of DN and identify new target pathways for intervention.

Sex differences in the survival benefit of kidney transplantation: a retrospective cohort study using target trial emulation.

Kidney transplantation is the preferred treatment for eligible patients with kidney failure who need renal replacement therapy. However, it remains unclear whether the anticipated survival benefit from kidney transplantation is different for women and men. We included all dialysis patients recorded in the Austrian Dialysis and Transplant Registry who were waitlisted for their first kidney transplant between 2000 and 2018. In order to estimate the causal effect of kidney transplantation on 10-year restricted mean survival time, we mimicked a series of controlled clinical trials and applied inverse probability of treatment and censoring weighted sequential Cox models. This study included 4408 patients (33% female) with a mean age of 52 years. Glomerulonephritis was the most common primary renal disease both in women (27%) and men (28%). Kidney transplantation led to a gain of 2.22 years (95% CI 1.88 to 2.49) compared with dialysis over a 10-year follow-up. The effect was smaller in women (1.95 years, 95% CI 1.38 to 2.41) than in men (2.35 years, 95% CI 1.92 to 2.70) due to a better survival on dialysis. Across ages the survival benefit of transplantation over a follow-up of 10 years was smaller in younger women and men and increased with age, showing a peak for both women and men aged about 60 years. There were few differences in survival benefit by transplantation between females and males. Females had better survival than males on the waitlist receiving dialysis and similar survival to males after transplantation.

#2524 RESOLVIN D1 ATTENUATES SEPSIS INDUCED ACUTE KIDNEY INJURY TARGETING MITOCHONDRIA AND NF-κB SIGNALING PATHWAY

Abstract Background and Aims Acute kidney injury is a highly common and multifactorial renal disease resulting in significant morbidity and mortality, especially sepsis-induced acute kidney injury. There is no effective therapy available to treat or prevent sepsis-induced acute kidney injury. One of the specialized pro-resolving mediators, Resolvin D1 exhibits special anti-inflammatory effects in several inflammatory disease models, but there is little evidence about the effect and mechanism of Resolvin D1 in sepsis-induced acute kidney injury. To explore the renal protective role of RvD1 in SI-AKI and to further explore the inherent pathophysiological mechanism, especially the role of mitochondrial function and NF-κB signaling pathway, in vitro and in vivo experiments were conducted. Method We conducted experiments to explore the effect and mechanism of Resolvin D1 in sepsis-induced acute kidney injury. In vitro, human proximal tubular epithelial cells were used to test the apoptosis ratio, cell viability and reactive oxygen species level. In vivo, C57BL/6 mice were injected with lipopolysaccharide to establish a sepsis-induced acute kidney injury model. Renal function and structure, apoptosis ratio of kidney cells, mitochondrial structure and function and related protein and gene levels were assessed. Results In vitro, the resolvin D1-treated group showed higher cell viability and lower reactive oxygen species levels and apoptosis ratios than the LPS group. In vivo, Resolvin D1 can not only improve renal function and mitochondrial function but also reduce the apoptosis ratio, while mediating mitochondrial dynamics and inhibiting NF-κB pathway. Conclusion Resolvin D1 has a good renoprotective effect by maintaining mitochondrial dynamics and inhibiting the NF-κB pathway. This provides an important basis for us to further develop the clinical therapeutic value of RvD1 in acute renal injury in sepsis.

#6120 MIRNA PROFILING OF URINARY EXTRACELLULAR VESICLES (EVS) IN TBMN AND CFHR5 NEPHROPATHY FOR THE IDENTIFICATION OF NOVEL DISEASE BIOMARKERS

Abstract Background and Aims Thin basement membrane nephropathy (TBMN) and complement factor-H related protein 5 (CFHR5) nephropathy are two of the most common renal monogenic diseases with high phenotypic heterogeneity that is only partly accounted for by locus and allelic factors. Intra-familial variability in the age of ESKD onset for some patients particularly exemplifies such highly variable phenotypes, suggesting a potential modifying role of additional factors such as non-coding regulatory RNAs. Given that miRNAs are key regulators of gene expression, miRNAs from urine-derived extracellular vesicles (EVs) were investigated for their potential use as biomarkers in TBMN and CFHR5 diagnosis and prognosis. Method MiRNA profiling of human urinary EVs was carried out by small RNA-sequencing in an initial discovery cohort of 54 patients with TBMN and 44 patients with CFHR5 nephropathy, each classified further into three subgroups based on disease severity (Grey-zone: eGFR &amp;gt;60 ml/min/1.73m2 and age &amp;lt;50 y/o; Mild: eGFR &amp;gt;60 ml/min/1.73m2 and age &amp;lt;50 y/o; Severe: eGFR &amp;lt;60 ml/min/1.73m2 independently of age). Differential expression of miRNAs from urine-derived EVs was compared with 30 age and sex matched healthy controls, whilst bioinformatic analysis was performed to delineate their associated mechanisms. Results Kidney-enriched candidate miRNA families were identified in urine-derived EVs for both TBMN and CFHR5 patients and further verified by RT-qPCR in the respective validation cohorts. Distinct miRNAs with significantly differentiated expression levels, compared to that of healthy control cohort, showed significant correlations with some of the evaluated clinical characteristics for both TBMN and CFHR5 patients suggesting a possible diagnostic and prognostic value on long follow-up. Finally, inverse correlations of miRNA expression with their predicted targeted genes identified dysregulated pathways and transcriptional networks for further investigation. Conclusion Collectively, distinct profiles of miRNAs from urine-derived EVs were identified in TBMN and CFHR5 nephropathy suggesting that a subset of differentially expressed miRNAs could serve as novel non-invasive biomarkers of disease progression and/or targets for the development of novel therapeutic approaches.

Role of abnormal glycosylated IgA1 and interstitial transformation of glomerular endothelial cells in the development and progression of IgA nephropathy

BackgroundIgA nephropathy (IgAN) is a common primary renal disease in childhood.MethodsTwenty blood samples and renal tissue from patients with IgAN, 20 blood samples from healthy children and 10 normal renal tissue were collected. Serum Gd-IgA1 and renal Gd-IgA1, CD31, α-SMA and vimentin were measured.ResultsThe serum Gd-IgA1 concentration in the IgAN group was significantly higher. Gd-IgA1 was not expressed in normal kidneys, which was positive in the IgAN group. Gd-IgA1 levels in serum and renal tissue were not related. The expression of CD31 decreased significantly in IgAN group, while the expression of α-SMA and vimentin increased significantly. There was no significant correlation between the renal concentration of Gd-IgA1 and CD31, α-SMA and vimentin.ConclusionThe increased Gd-IgA1 in the serum and kidney may promote the pathogenesis of IgAN. The serum Gd-IgA1 cannot predict the extent of its deposition in the kidney. Endothelial mesenchymal transition (EndMT) may be involved in the pathogenesis of renal fibrosis in IgAN.

Prevalence of Post Infectious Glomerulonephritis (PIGN) and Associated Complication

Introduction&#x0D; Post infectious glomerulonephritis (PIGN) is the most common renal disease in children causing significant morbidity. The affected children present with features of acute nephric syndrome (hematuria, hypertension, edema and oliguria. The objective of this study was to determine the prevalence, clinical characteristics, complications, and outcomes of children presenting with post infectious glomerulonephritis in paediatric ward of tertiary care hospital.&#x0D; Methods&#x0D; This was a prospective observational study conducted at a tertiary care hospital in Chitwan, Nepal from March 1st 2020 to February 28th 2021. Children aged 4 – 15 years satisfying 2 out of 4 features of acute nephritic syndrome were included in the study. After discharge, patients were followed up at 4 weeks and 8 weeks. Data entry was done in statistical packages for the social science version 20.&#x0D; Results&#x0D; Among 63 children recruited with acute nephritic syndrome, 73% had Post infectious glomerulonephritis. The most common etiology of PIGN was Post streptococcal glomerulonephritis (63%). The mean age of children was 11.2 (±3.2) years. Males to females’ ratio was 1.5:1. The most common presenting feature was edema (100%). The most common complication was acute kidney injury (41.3%).&#x0D; Conclusion&#x0D; Post infectious glomerulonephritis was the most common cause of acute nephritic syndrome in children. High incidence of life-threatening complications like CCF, retinopathy, encephalopathy and renal insufficiency occur that require close monitoring and timely intervention to prevent morbidity and mortality.