Diagnosis Of Glomerular Diseases Research Articles

Approach to Glomerular Disease in Pregnancy

The presence of glomerular diseases in pregnancy presents challenges to both patients and nephrologists. The preconception planning in patients with kidney disease involves comprehensive stratification, treatment optimization, and comorbidity assessment, requiring nephrologists to engage in well-informed decision-making processes alongside their patients. There is a necessity for a multidisciplinary approach to meet their complex healthcare needs. Effective control of blood pressure, proteinuria, and disease activity are pivotal in mitigating adverse pregnancy events. This comprehensive review intends to equip nephrologists with the requisite knowledge and understanding to navigate the intricate landscape of glomerular diseases in pregnancy. It delves into the challenges associated with the diagnosis of glomerular diseases, the significance of preconception counseling, and the nuances of antenatal and postnatal care. Additionally, the article provides insights into the management and prognosis of glomerular diseases, shedding light on the judicious use of immunosuppression as a therapeutic tool.

Accurate classification of glomerular diseases by hyperspectral imaging and transformer

Background and objectiveIn renal disease research, precise glomerular disease diagnosis is crucial for treatment and prognosis. Currently reliant on invasive biopsies, this method bears risks and pathologist-dependent variability, yielding inconsistent results. There is a pressing need for innovative diagnostic tools that enhance traditional methods, streamline processes, and ensure accurate and consistent disease detection. MethodsIn this study, we present an innovative Convolutional Neural Networks-Vision Transformer (CVT) model leveraging Transformer technology to refine glomerular disease diagnosis by fusing spectral and spatial data, surpassing traditional diagnostic limitations. Using interval sampling, preprocessing, and wavelength optimization, we also introduced the Gramian Angular Field (GAF) method for a unified representation of spectral and spatial characteristics. ResultsWe captured hyperspectral images ranging from 385.18 nm to 1009.47 nm and employed various methods to extract sample features. Initial models based solely on spectral features achieved a accuracy of 85.24 %. However, the CVT model significantly outperformed these, achieving an average accuracy of 94 %. This demonstrates the model's superior capability in utilizing sample data and learning joint feature representations. ConclusionsThe CVT model not only breaks through the limitations of existing diagnostic techniques but also showcases the vast potential of non-invasive, high-precision diagnostic technology in supporting the classification and prognosis of complex glomerular diseases. This innovative approach could significantly impact future diagnostic strategies in renal disease research. Concise abstractThis study introduces a transformative hyperspectral image classification model leveraging a Transformer to significantly improve glomerular disease diagnosis accuracy by synergizing spectral and spatial data, surpassing conventional methods. Through a rigorous comparative analysis, it was determined that while spectral features alone reached a peak accuracy of 85.24 %, the novel Convolutional Neural Network-Transformer (CVT) model's integration of spatial-spectral features via the Gramian Angular Field (GAF) method markedly enhanced diagnostic precision, achieving an average accuracy of 94 %. This methodological innovation not only overcomes traditional diagnostic limitations but also underscores the potential of non-invasive, high-precision technologies in advancing the classification and prognosis of complex renal diseases, setting a new benchmark in the field.

#1927 Efficacy and safety of ripertamab in paediatic glomerular disease

Abstract Background and Aims Anti-B-cell treatment has been shown to be an efficient tactic for glomerular disease. Ripertamab as a novel anti-CD20 monoclonal antibody developed by China, has been structurally optimized to specifically bind to the transmembrane antigen CD20, with an amino acid difference in the constant region sequence compared to rituximab. This study reports the efficacy and safety of ripertamab in children with different glomerular diseases. Method We retrospectively report the data of 140 children with a diagnosis of glomerular disease and a treatment with ripertamab in a single center Results A total of 140 children (age, 11.2 ± 3.7 years; 58.6% boys) were included, 69/140 (49.3%) steroid-dependent nephrotic syndrome (SDNS), 38/140 (27.1%) steroid-resistant but CNIs-dependent nephrotic syndrome, 18/140 (12.9%) Lupus nephritis, 5/140 (3.6%) atypical hemolytic uremic syndrome, 4/140 (2.9%) ANCA associated vasculitis, 3/140 (2.1%) membranous nephropathy and 3/140 (2.1%) IgA vasculitis nephritis. The Median (IQR) duration of disease before the application of ripertamab was 4.4 (2.3, 7.4) years. They totally received 200 courses of ripertamab. A total of 83, 55, 1, and 1 patient received one, two, three, and four courses, respectively. Ripertamab 375 mg/m2 (maximum 500 mg) were injected per course. B cell depletion could be observed in 129/140 (92.1%) children one month after ripertamab. An additional course was administered due to recovery of B-cells or relapse. Median (IQR) follow-up was 0.8 (0.5, 1.1) years. The median relapse-free period after the first course was 4.7 months (IQR, 3.8, 5.6 months). Most of the relapses developed simultaneously with recovery of B-cells. About 36.7% of these children stopped steroid during the follow-up. One or more immunosuppressant (IS) drugs needed before ripertamab infusion could be withdrawn or reduced in 109/140 patients (77.9%). None of the patients developed life-threatening adverse events. Conclusion This study suggests that ripertamab could be an effective and safe treatment for various pediatric glomerular diseases.

Generation of PAS-stained images of glomerular tissue units using a generative adversarial network with spectral normalization colorization method

In recent years, the pathological diagnosis of glomerular diseases typically involves the study of glomerular his-to pathology by specialized pathologists, who analyze tissue sections stained with Periodic Acid-Schiff (PAS) to assess tissue and cellular abnormalities. In recent years, the rapid development of generative adversarial networks composed of generators and discriminators has led to further developments in image colorization tasks. In this paper, we present a generative adversarial network by Spectral Normalization colorization designed for color restoration of grayscale images depicting glomerular cell tissue elements. The network consists of two structures: the generator and the discriminator. The generator incorporates a U-shaped decoder and encoder network to extract feature information from input images, extract features from Lab color space images, and predict color distribution. The discriminator network is responsible for optimizing the generated colorized images by comparing them with real stained images. On the Human Biomolecular Atlas Program (HubMAP)—Hacking the Kidney FTU segmentation challenge dataset, we achieved a peak signal-to-noise ratio of 29.802 dB, along with high structural similarity results as other colorization methods. This colorization method offers an approach to add color to grayscale images of glomerular cell tissue units. It facilitates the observation of physiological information in pathological images by doctors and patients, enabling better pathological-assisted diagnosis of certain kidney diseases.

Generation of PAS-Stained images of glomerular tissue units using a generative adversarial network with spectral normalization colorization method

In recent years, the pathological diagnosis of glomerular diseases typically involves the study of glomerular his-to pathology by specialized pathologists, who analyze tissue sections stained with Periodic Acid-Schiff (PAS) to assess tissue and cellular abnormalities. In recent years, the rapid development of generative adversarial networks composed of generators and discriminators has led to further developments in image colorization tasks. In this paper, we present a generative adversarial network by Spectral Normalization colorization designed for color restoration of grayscale images depicting glomerular cell tissue elements. The network consists of two structures: the generator and the discriminator. The generator incorporates a U-shaped decoder and encoder network to extract feature information from input images, extract features from Lab color space images, and predict color distribution. The discriminator network is responsible for optimizing the generated colorized images by comparing them with real stained images. On the Human Biomolecular Atlas Program (HubMAP)—Hacking the Kidney FTU segmentation challenge dataset, we achieved a peak signal-to-noise ratio of 29.802 dB, along with high structural similarity results as other colorization methods. This colorization method offers an approach to add color to grayscale images of glomerular cell tissue units. It facilitates the observation of physiological information in pathological images by doctors and patients, enabling better pathological-assisted diagnosis of certain kidney diseases.

Identifying and matching 12‐level multistained glomeruli via deep learning for diagnosis of glomerular diseases

AbstractThe assessment of glomerular lesions is a fundamental step toward the diagnosis of glomerular diseases. This requires diagnosis and fusion of information from all the glomeruli at multiple levels and stainings. The lack of research on multi‐level multistained glomerular identification and matching has resulted in renal pathologists devoting much time and attention to this time‐consuming and labor‐intensive process. This limits the overall efficiency of the diagnosis of glomerular diseases. This paper constructed a dataset consisting of 600 cases, each containing 12 levels of whole slide images from H&E, PAS, Masson trichrome, and PASM staining. The glomeruli identifying and matching was proposed. First, a multistained transformer‐based Mask R‐CNN is proposed to extract the position and contours of the glomeruli. Second, coherent point drift‐based coarse matching and hybrid feature‐based fine matching achieve pairwise matching. Finally, the voting‐based cross‐matching realizes 12‐level multistained matching. This system constitutes a practical human‐computer interface. Intensive experiments were conducted to validate the ability to identify and match 12‐level multistained glomeruli. The mAP@50 for detection and segmentation reached 95.40% and 95.70%, respectively. The basic and comprehensive matching rates of the glomeruli matching reached 98.25% and 74.59%, respectively. Visualization results further demonstrate that the model achieved accurate identification and matching. The proposed system achieves accurate identification and matching of 12 levels of multistained glomeruli and can serve as a tool for pathological diagnosis of glomerular diseases by simplifying the diagnostic process. More importantly, this system can lay the foundation for the fully automated assisted diagnosis of glomerular diseases.

Efficacy and Safety of CT-Guided Kidney Biopsy for the Diagnosis of Glomerular Diseases in Complicated Patients

Introduction: Kidney biopsy is the cornerstone for the diagnosis of glomerular diseases and to guide treatment. Percutaneous ultrasound-guided kidney biopsy is currently the gold standard to obtain cortical specimens. However, in cases where ultrasound-guided kidney biopsy is not deemed safe (obese patients, deep kidneys, or kidneys with a complicated anatomy), CT-guided kidney biopsy could be a convenient alternative to obtain renal tissue samples. The aim of this study was to describe the diagnostic yield and complications of CT-guided kidney biopsies in patients with glomerular diseases that were previously discarded for ultrasound-guided kidney biopsy. Material and Methods: We performed a retrospective, single-center, observational study including patients who underwent CT-guided native kidney biopsies in our center after being contraindicated for ultrasound-guided biopsy. Patients’ records were reviewed retrieving baseline characteristics and pre-biopsy clinical, laboratory parameters and concomitant medication. The biopsy needle gauge, site of puncture, and number of needle passes were recorded. The diagnostic yield was evaluated by the number of glomeruli obtained, the rate of specimens that were adequate to reach diagnosis, and the number of biopsies that had to be repeated. Complications were defined as minor (hypotension, hematoma) and major (arteriovenous fistulae, major bleeding requiring embolization, or nephrectomy). The diagnostic yield and complications were compared to ultrasound-guided native kidney biopsies performed during the same period. Results: 56 CT-guided native kidney biopsies were performed during the study period. The number of glomeruli obtained per patient was 11.5 ± 6.3, which was inferior to that obtained from ultrasound-guided biopsies (14.08 ± 8.47, p < 0.05). However, the rate of specimens that were adequate to reach a diagnosis was similar (92.9% vs. 90.8%, p = 0.437). The number of needle passes was higher in CT-guided kidney biopsies (2.0 ± 0.7 vs. 1.7 ± 0.5, p < 0.05), as well as the incidence of post-biopsy perirenal asymptomatic hematomas (66.1% vs. 24.5%, p < 0.01). There were no significant differences in other post-biopsy minor complications (1.8% vs. 2.5%, p = 0.621). There were no major complications after CT-guided kidney biopsies. Conclusions: CT-guided percutaneous kidney biopsy is a valid alternative for the diagnosis of glomerular diseases in patients with special characteristics such as obesity or deep kidneys that contraindicate ultrasound-guided biopsy. In this population, CT-guided kidney biopsies are safe and provide a high diagnostic yield, reaching a diagnosis in >90% of patients that had been previously discarded for ultrasound-guided biopsy.

CureGN-Diabetes Study: Rationale, Design, and Methods of a Prospective Observational Study of Glomerular Disease Patients with Diabetes.

Glomerular diseases (GDs) represent the third leading cause of end-stage kidney disease (ESKD) in the US Diabetes was excluded from the CureGN Study, an NIH/NIDDK-sponsored observational cohort study of four leading primary GDs: IgA nephropathy (IgAN), membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), and minimal change disease (MCD). CureGN-Diabetes, an ancillary study to CureGN, seeks to understand how diabetes influences the diagnosis, treatment, and outcomes of GD. It is a multicenter, prospective cohort study, targeting an enrollment of 300 adults with prevalent type 1 or type 2 diabetes and MCD, FSGS, MN, or IgAN, with first kidney biopsy obtained within 5 years of enrollment in 80% (20% allowed if biopsy after 2010). CureGN and Transformative Research in DiabEtic NephropaThy (TRIDENT) provide comparator cohorts. Retrospective and prospective clinical data and patient-reported outcomes are obtained. Blood and urine specimens are collected at study visits annually. Kidney biopsy reports and digital images are obtained, and standardized pathologic evaluations performed. Light microscopy images are uploaded to the NIH pathology repository. Outcomes include relapse and remission rates, changes in proteinuria and estimated glomerular filtration rate, infections, cardiovascular events, malignancy, ESKD, and death. Multiple analytical approaches will be used leveraging the baseline and longitudinal data to compare disease presentation and progression across subgroups of interest. With 300 patients and an average of 3 years of follow-up, the study has 80% power to detect a HR of 1.4-1.8 for time to complete remission of proteinuria, a rate ratio for hospitalizations of 1.18-1.56 and difference in eGFR slope of 6.0-8.6 mL/min/year between two groups of 300 participants each. CureGN-Diabetes will enhance our understanding of diabetes as a modifying factor of the pathology and outcomes of GDs and support studies to identify disease mechanisms and improve patient outcomes in this understudied patient population.

Alport syndrome misdiagnosed with IgA nephropathy from familial history: a case report and brief review

BackgroundAlport syndrome is a rare inherited disease resulting from a primary disorder of the glomerular basement membrane. This disease results from mutations in genes encoding alpha chains of type IV collagen. In the differential diagnosis of this disease, IgA nephropathy is the most common primary glomerular disease with gross or microscopic hematuria.Case presentationA 50-year-old woman was presented with microscopic hematuria and proteinuria of under one gram. Due to the diagnosis of IgA nephropathy in family members, she was treated and followed up for 4 years as a possible case of IgA nephropathy. Eye examination and audiometry were normal. She underwent renal biopsy with an exacerbation of proteinuria. There was no finding in favor of IgA nephropathy in the histological examination, but the findings of electron microscopy and family history favored Alport syndrome.ConclusionsThis case demonstrates the importance of accurate history and electron microscopy in the complete histological evaluation and diagnosis of glomerular disease. Although in most cases the two can be differentiated based on clinical manifestations, laboratory findings, and histopathological examination, sometimes the association of these two diseases in the families involved or the lack of accurate history and complete histological examinations can complicate the diagnosis.

Precision nephrology: from molecular diagnostics to an individualized therapy

The diagnosis of glomerular disease still mostly relies on the conventional histologic and immunohistochemical analysis of biopsies, thereby failing to provide a molecular disease understanding and stratification as the fundamental basis for an individualized therapy. It is out of the question that nephrology will be transformed into a field of systemic molecular precision diagnostics and individualized therapies. However, the time scale and efficiency of such transformation will depend on more studies exemplifying successful translational strategies. The highly heterogeneous glomerular disease entities of minimal change disease and focal segmental glomerular sclerosis seem ideally suited to exploring and ensuring the advancement of an individualized precision nephrology.

Pregnancy History and Kidney Disease Progression Among Women Enrolled in Cure Glomerulonephropathy

Preeclampsia increases the risk for future chronic kidney disease (CKD). Among those diagnosed with CKD, it is unclear whether a prior history of preeclampsia, or other complications in pregnancy, negatively impact kidney disease progression. In this longitudinal analysis, we assessed kidney disease progression among women with glomerular disease with and without a history of a complicated pregnancy. Adult women enrolled in the Cure Glomerulonephropathy study (CureGN) were classified based on a history of a complicated pregnancy (defined by presence of worsening kidney function, proteinuria, or blood pressure; or a diagnosis of preeclampsia, eclampsia, or hemolysis, elevated liver enzymes, and low platelets [HELLP] syndrome), pregnancy without these complications, or no pregnancy history at CureGN enrollment. Linear mixed models were used to assess estimated glomerular filtration rate (eGFR) trajectories and urine protein-to-creatinine ratios (UPCRs) from enrollment. Over a median follow-up period of 36 months, the adjusted decline in eGFR was greater in women with a history of a complicated pregnancy compared to those with uncomplicated or no pregnancies (-1.96 [-2.67,-1.26] vs.-0.80 [-1.19,-0.42] and-0.64 [-1.17,-0.11] ml/min per 1.73 m2 per year, P= 0.007). Proteinuria did not differ significantly over time. Among those with a complicated pregnancy history, eGFR slope did not differ by timing of first complicated pregnancy relative to glomerular disease diagnosis. A history of complicated pregnancy was associated with greater eGFR decline in the years following glomerulonephropathy (GN) diagnosis. A detailed obstetric history may inform counseling regarding disease progression in women with glomerular disease. Continued research is necessary to better understand pathophysiologic mechanisms by which complicated pregnancies contribute to glomerular disease progression.

Risk of glomerular diseases, proteinuria and hematuria following mRNA (BNT162b2) and inactivated (CoronaVac) SARS-CoV-2 vaccines.

With accruing case reports on de novo or relapsing glomerular diseases (GD) following different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, we evaluated the risk of GD following BNT162b2 and CoronaVac vaccines. A modified self-controlled case series analysis was conducted using anonymized, territory-wide SARS-CoV-2 vaccination records in Hong Kong. All Hong Kong residents aged 18 years or above with outcomes of interest were included. Outcomes of interest were GD, proteinuria or hematuria within 42 days following each dose of SARS-CoV-2 vaccines. Incidence per 100000 doses of SARS-CoV-2 vaccines administered was calculated, and incidence rate ratios (IRRs) were estimated using conditional Poisson regression with seasonality adjustment. Between 23 February 2021 and 31 March 2022, 4062 patients had an incident diagnosis of GD, proteinuria or hematuria, with 2873 of them being vaccinated during the observation period. The incidences of the composite events 1-41 days after vaccination were 3.7 (95% CI 3.1-4.4) per 100000 doses of BNT162b2 administered, and 6.5 (95% CI 5.7-7.5) per 100000 doses CoronaVac administered. There was no significant increase in the risks of composite events following the first (BNT162b2: IRR=0.76, 95% CI 0.56-1.03; CoronaVac: IRR=0.92, 95% CI 0.72-1.19), second (BNT162b2: IRR=0.92, 95% CI 0.72-1.17; CoronaVac: IRR=0.88. 95% CI 0.68-1.14) or third (BNT162b2: IRR=0.39. 95% CI 0.15-1.03; CoronaVac: IRR=1.18. 95% CI 0.53-2.63) dose of SARS-CoV-2 vaccines. There was no evidence of increased risks of de novo or relapsing GD with either BNT162b2 or CoronaVac vaccines.

Urine testing to differentiate glomerular from tubulointerstitial diseases on kidney biopsy

BackgroundDifferentiating between glomerular and tubulointerstitial diseases can guide selection of appropriate patients for kidney biopsy. The aim of this study is to identify urine tests that can differentiate between these histological diagnoses. MethodsIn this sub-study of a prospectively enrolled cohort of participants with urine samples concurrent with their kidney biopsy, we tested the association of 24 features on urinalysis, urine sediment microscopy, and biomarkers of glomerular and tubular injury and inflammation with histological diagnosis of glomerular or tubulointerstitial disease. We selected a combination of features associated with glomerular disease using stepwise forward and backward regression, and LASSO algorithm after dividing the cohort into training (70%) and test (30%) sets. ResultsOf 359 participants, 121 had glomerular, 89 had tubulointerstitial diseases, and 149 were classified as mixed. Compared to patients with tubulointerstitial diseases, those with glomerular diseases had more dipstick hematuria (3+ vs. 1+, P < 0.001) and urine albumin (1.25 vs. 0.09 mg/mg, P < 0.001). Patients with glomerular diseases had higher levels of tubular health biomarkers (Uromodulin, 1.22 vs. 0.92, P = 0.03). In a multivariable model, higher urine albumin, dipstick blood, and urine uromodulin were independently associated with higher odds of glomerular diseases (test set AUC, 0.81 (0.69, 0.93)). ConclusionUrine tests, including urine albumin, dipstick blood, and urine uromodulin, were associated with the histological diagnosis of glomerular disease. These findings can help clinicians differentiate between glomerular and tubulointerstitial diseases and guide clinical decisions regarding a kidney biopsy.

The Development and Use of an EHR-Linked Database for Glomerular Disease Research and Quality Initiatives

Background and Objective: The use of electronic health record (EHR) data can facilitate efficient research and quality initiatives. The imprecision of ICD-10 codes for kidney diagnoses has been an obstacle to discrete data-defined diagnoses in the EHR. This manuscript describes the Kidney Research Network (KRN) registry and database that provide an example of a prospective, real-world data glomerular disease registry for research and quality initiatives. Methods: KRN is a multicenter collaboration of patients, physicians, and scientists across diverse health-care settings with a focus on improving treatment options and outcomes for patients with glomerular disease. The registry and data warehouse amasses retrospective and prospective data including EHR, active research study, completed clinical trials, patient reported outcomes, and other relevant data. Following consent, participating sites enter the patient into KRN and provide a physician-confirmed primary kidney diagnosis. Kidney biopsy reports are redacted and uploaded. Site programmers extract local EHR data including demographics, insurance type, zip code, diagnoses, encounters, laboratories, procedures, medications, dialysis/transplant status, vitals, and vital status monthly. Participating sites transform data to conform to a common data model prior to submitting to the Data Analysis and Coordinating Center (DACC). The DACC stores and reviews each site’s EHR data for quality before loading into the KRN database. Results: As of January 2021, 1,192 patients have enrolled in the registry. The database has been utilized for research, clinical trial design, clinical trial end point validation, and supported quality initiatives. The data also support a dashboard allowing enrolling sites to assist with clinical trial enrollment and population health initiatives. Conclusion: A multicenter registry using EHR data, following physician- and biopsy-confirmed glomerular disease diagnosis, can be established and used effectively for research and quality initiatives. This design provides an example which may be readily replicated for other rare or common disease endeavors.

Recovering histological sections for ultrastructural diagnosis of glomerular diseases through the pop-off technique.

Electron microscopy (EM) represents an indispensable technique for the diagnosis of kidney glomerular diseases. When dedicated tissue is not available, histological and cryostat sections can be reprocessed for EM using the pop-off technique. Here the practical value of this technique is analysed with emphasis on its accuracy in measuring basement membrane thickness and detecting immune deposits. Ninety-four histological sections of kidney tissues fixed in Serra's solution, stained with H&E, PAS, and Masson's Trichrome; for EM analysis, the sections were recovered from either treated or untreated microscope slides through the pop-off technique. Some sections were recovered from cryosections allocated for immunofluorescence. The ultrastructural details were sufficiently maintained on tissues fixed with Serra's solution despite being considered disadvantageous for EM. The type of microscope slides and the time of biopsy storage did not affect the quality of section recovery. The histological stains had only moderate effects on the electron-density of the glomerular basement membrane (GBM). The pop-off technique reduced the GBM thickness when compared to the conventional EM processing but preserved the electron density of immune deposits. The application of the pop-off method to renal biopsy is a useful recovery method that produces limited but satisfactory results when there is no suitable material for EM. The ultrastructural morphology was retained even from tissues fixed with Serra's solution, and deposits maintained the expected electron density, however, we observed an overall thickness reduction of the GBM that could have a potential impact on thin membrane disease diagnosis.

POS-415 ELECTRON MICROSCOPY: THE GOLDEN WEAPON FOR GLOMERULAR DISORDERS

Worldwide glomerular disorders (GD) constitute one of the major causes of end-stage renal disease (ESRD). Its spectrum varies in comparison to developing countries compared to developed countries. The definitive diagnosis of requires histopathological evaluation of renal biopsy by light microscopy (LM), immunofluorescence (IF), and electron microscopy (EM). Nowadays, EM has become the standard of care practice for the evaluation of GD. The objective of this study was to analyze the role of EM for an accurate diagnosis. This was a cross-sectional study conducted in patients of age group 18-65 years presenting at a tertiary care center in North India from August 2018 to January 2020. A total of 200 consecutive renal biopsies were performed and were subjected to LM, IF, and EM. IF was performed in 100% cases and EM done in 75.5% cases. The most common indication of kidney biopsy was nephrotic syndrome (44%). Primary glomerular disorder (PGD) observed in 62% of cases. The most common PGD was IgA nephropathy [IgAN (18.5%)], followed by focal segmental glomerulosclerosis [FSGS (16%)], membranous nephropathy [MN (10%)], minimal change disease [MCD (5%)], membranoproliferative glomerulonephritis [MPGN I (2.5%)], C3 glomerulonephritis [C3GN (4%)], Crescentic GN (2.5%), diffuse proliferative GN [DPGN (2%)], IgM nephropathy [IgMN (0.5%)] and miscellaneous (1%). Secondary glomerular disorders (SGD) accounted for 21% of cases. Lupus nephritis was the most common SGD. Vascular (5.5%), tubulointerstitial disorders (9%), and ESRD (5%) were less prevalent. MCD was the most common GD in patients less than 20 years, while IgAN was most common in patients 21-50 years, followed by FSGS. Above 51 years, FSGS was the most common GD, followed by MN. In 62% of cases, the diagnosis of glomerular disease was based on LM and IF findings alone. Discrepant IF findings were obtained in 5.5% cases. In 9% of cases, EM contributed to the diagnosis. EM was essential for the final diagnosis in 23.5% of the cases. Table 1: Case series evaluation based on EM Tabled 1CategoriesLM + IFDiscrepant IFUseful EMEssential EMTotal(A). PGD124MCD2-810FSGS18111232MN1323220DPGN1-214MPGN (MPGN I / C3GN/ DDD)2/2/-1/-/--/2/-2/4/-5/8/0CresGN5---5IgAN2362637IgMN1---1Miscellaneous1--12(B). SGD42LN812415DN8-2414AA10-1-11MM2---2HSP----0(C). Vascular Nephropathy11HUS----0TMA1-214HN1-124CAN3---3(D). Tubulo-interstitial nephritis (TIN)18Acute TIN10---10Chronic TIN5---5ATN3---3(E). ESRD5---5TOTAL (%)124 (62%)11 (5.5%)18 (9%)47 (23.5%)200 Open table in a new tab The incidence of IgAN and FSGS has increased significantly over the last decade, especially in developing countries. This study has provided comprehensive information about the changing spectrum of GD in adults with a focus on EM as a routine standard of care practice.

Glomerulonephritis in AKI: From Pathogenesis to Therapeutic Intervention.

Acute kidney injury (AKI) is increasingly emerging as a global emergency. Sepsis, major surgery, and nephrotoxic drugs are the main causes of AKI in hospitalized patients. However, glomerulonephritis accounts for about 10% of AKI episodes in adults, mainly related to rapidly progressive glomerulonephritis resulting from granulomatous polyangiitis (GPA, Wegener granulomatosis), microscopic polyangiitis (MPA), and anti-glomerular basement membrane (GBM) disease. Also, diffuse proliferative lupus nephritis, immunoglobulin A nephropathy, post-streptococcal glomerulonephritis, mixed cryoglobulinemia, mesangiocapillary glomerulonephritis, membranous nephropathy, hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, and scleroderma can induce acute renal failure. Early diagnosis of AKI due to glomerulonephritis is crucial for prompt, effective management to improve short- and long-term outcomes. Kidney biopsy is the gold standard for the diagnosis of glomerular disease, but it is not frequently performed in critically ill patients because of their clinical conditions. In this setting, a growing number of diagnostic assays can support the working hypothesis, including antineutrophil cytoplasmic antibodies (ANCAs), anti-double-stranded DNA antibodies, anti-GBM antibodies, antistreptolysin O and anti-DNase B antibodies, cryoglobulins, antiphospholipid antibodies, and complement levels. Therapeutic strategies in AKI patients with glomerulonephritis include high-dose corticosteroids, cyclophosphamide, and plasma exchange. This article reviews the wide spectrum of glomerulopathies associated with AKI, describing the immunological mechanisms underlying glomerular diseases and presenting an overview of the therapeutic options.

Measurement of Glomerular Area in Primary Glomerular Diseases With a Digital Pathology Software

Objective: Kidney biopsy is essential to evaluate the activity of underlying kidney disease and the risk factors related to kidney disease progression. Glomerular morphometry is a simple but uncommonly used qualitative predictor of long-term kidney function. But it is mysterious if glomerular morphometry changes due to underlying glomerulonephritis. Measurement quantification is also necessary for reliable interpretation. We aimed to evaluate glomerular morphometry with glomerular area measurements quantitatively with digitally scanned slides in the primary glomerular diseases.&#x0D; Methods: We retrospectively analyzed 198 patients with nephrotic syndrome that underwent kidney biopsy between 2017 and 2019. 48 patients enrolled into the study after the exclusion criteria. We measured the glomerular area as maximum, minimum, and mean areas, using image analysis software. &#x0D; Results: Forty-eight kidney biopsies were analyzed retrospectively under three primary glomerular disease groups as IgA nephropathy (37.5%), focal segmental glomerulosclerosis (29.2%), and membranous glomerulonephritis (33.3%). The glomerular area measured as maximum, minimum, and mean, were similar between 3 groups. The maximum glomerular area was negatively correlated with serum albumin and positively correlated with 24hr proteinuria (r= - 0.592, p=0.044, and r=0.531, p=0.022) at the time of diagnosis. At the end of one year, maximum glomerular area was positively correlated with serum creatinine (r=0.385, p=0.019) and negatively correlated with eGFR (r= - 0.493, p=0.043). &#x0D; Conclusions: At the time of diagnosis of glomerular diseases, maximum glomerular area measurement during the pathological assessment might be an additional marker to estimate the ultrastructure of the kidney and the clinical course of the disease.

Distribution of proteinuria- and albuminuria-to-creatinine ratios in preterm newborns.

Urine protein assessment is important when glomerular disease or injury is suspected. Normal values of proteinuria already published for preterm newborns suffer from limitation, with small cohorts of patients. This prospective study was conducted to update the urine total protein- and albumin-to-creatinine ratio values. Urine samples were collected from 231 preterm newborns within the first 48 h (D0-1) and/or between 72-120 h of life (D3-4). Total protein, albumin, and creatinine were measured, their distribution and upper-limit values determined. At D0-1 and D3-4, respectively, the median for the total protein-to-creatinine ratio were 80 and 107 mg/mmol (upper-limit values 223 and 289 mg/mmol) in the whole studied population, 149 and 214 mg/mmol in children born before 29 weeks of gestational age, 108 and 130 mg/mmol in those born between 29 and 33 weeks, and 61 and 93 mg/mmol in those born after 33 weeks. For the albumin-to-creatinine ratio, the median were 12 and 17 mg/mmol (upper-limit values 65 and 62 mg/mmol) in the whole studied population, 22 and 50 mg/mmol in children born before 29 weeks, 21 mg/mmol in those born between 29 and 33 weeks, and 8 and 12 mg/mmol in those born after 33 weeks. The use of nephrotoxic drugs and mechanical ventilation seems to influence proteinuria and albuminuria values. We report distribution of proteinuria- and albuminuria-to-creatinine in preterm newborns, including the upper-limit values. These values should be taken into account in the detection and diagnosis of glomerular disease and/or injury in daily clinical practice. Graphical abstract.

Circulating and cellular levels of miR-193 and miR-217 in patients with common glomerular diseases

Introduction: The definitive diagnosis of the common types of glomerular disease including FSGS (focal segmental glomerulosclerosis) and MN (membranous nephropathy) is still performed by biopsy studies, which has high risks and complications. MicroRNAs (miRNAs) can open a new horizon for the treatment and diagnosis of glomerular diseases. Objectives: In the present study, we focused on miR-217, miR-193-3p, and miR-124 expression in patients with FSGS and MN. Patients and Methods: Sixty cases (30 FSGS and 30 MN) were included based on strict criteria. A group of healthy controls were also included. The relative expression of the microRNAs was evaluated in the plasma and peripheral blood mononuclear cells (PBMCs) by quantitative real-time PCR. The association between the expression levels of microRNAs and clinicopathological parameters were also assessed. Results: There were significant differences in miR-193-3p levels between FSGS and MN group in plasma samples (P = 0.036). Furthermore, significantly decreased levels of miR-217 were observed in plasma samples of patients with NS (P = 0.026) and MN (P = 0.036) groups. Conclusion: The studied miRNAs are dysregulated in clinical samples of patients with nephrotic syndrome and they may be involved in the pathogenesis of FSGS and MN. More research is needed for understanding the relationship between these microRNAs and the pathogenesis of FSGS and MGN.