Clinical relevance of proteinuria selectivity index and fractional excretion of sodium in patients with nephrotic syndrome.

Proteinuria selectivity index (PSI) is a potential tool for histological classification and prediction of treatment response in nephrotic syndrome, but evidence is insufficient. Clinical relevance of fractional excretion of sodium (FENa) in nephrotic syndrome remains largely unexplored. This multicenter retrospective study included patients with nephrotic syndrome who underwent kidney biopsy between January 2012 and June 2022. Optimal cutoffs for predicting complete remission based on PSI and FENa were determined using receiver operating characteristic curves. Patients were divided into two groups using these cutoffs and followed until complete remission. Of the 611 patients included, 177 had minimal change disease (MCD), 52 had focal segmental glomerulosclerosis (FSGS), and 149 had membranous nephropathy (MN). Median (interquartile range) PSI were 0.14 (0.09-0.19) for MCD, 0.33 (0.23-0.40) for FSGS, and 0.20 (0.14-0.30) for MN. FENa were 0.24 (0.09-0.68), 1.03 (0.50-2.14), and 0.78 (0.41-1.28). Patients with low PSI and FENa had a higher incidence of complete remission. Cox regression analyses demonstrated that both parameters were associated with achieving complete remission (HR 2.73 [95% CI 1.97-3.81] and HR 1.93 [95% CI 1.46-2.55], respectively). PSI and FENa may be useful for histological classification and predicting remission in nephrotic syndrome.

Minimal Change Disease: Pathogenetic Insights from Glomerular Proteomics.

The mechanism underlying podocyte dysfunction in minimal change disease (MCD) remains unknown. This study aimed to shed light on the potential pathophysiology of MCD using glomerular proteomic analysis. Shotgun proteomics using label-free quantitative mass spectrometry was performed on formalin-fixed, paraffin-embedded (FFPE) renal biopsies from two groups of samples: control (CTR) and MCD. Glomeruli were excised from FFPE renal biopsies using laser capture microdissection (LCM), and a single-pot solid-phase-enhanced sample preparation (SP3) digestion method was used to improve yield and protein identifications. Principal component analysis (PCA) revealed a distinct separation between the CTR and MCD groups. Forty-eight proteins with different abundance between the two groups (p-value ≤ 0.05 and |FC| ≥ 1.5) were identified. These may represent differences in podocyte structure, as well as changes in endothelial or mesangial cells and extracellular matrix, and some were indeed found in several of these structures. However, most differentially expressed proteins were linked to the podocyte cytoskeleton and its dynamics. Some of these proteins are known to be involved in focal adhesion (NID1 and ITGA3) or slit diaphragm signaling (ANXA2, TJP1 and MYO1C), while others are structural components of the actin and microtubule cytoskeleton of podocytes (ACTR3 and NES). This study suggests the potential of mass spectrometry-based shotgun proteomic analysis with LCM glomeruli to yield valuable insights into the pathogenesis of podocytopathies like MCD. The most significantly dysregulated proteins in MCD could be attributable to cytoskeleton dysfunction or may be a compensatory response to cytoskeleton malfunction caused by various triggers.

Characterizing Glomerular Barrier Dysfunction with Patient-Derived Serum in Glomerulus-on-a-Chip Models: Unveiling New Insights into Glomerulonephritis.

Glomerulonephritis (GN) is characterized by podocyte injury or glomerular filtration dysfunction, which results in proteinuria and eventual loss of kidney function. Progress in studying the mechanism of GN, and developing an effective therapy, has been limited by the absence of suitable in vitro models that can closely recapitulate human physiological responses. We developed a microfluidic glomerulus-on-a-chip device that can recapitulate the physiological environment to construct a functional filtration barrier, with which we investigated biological changes in podocytes and dynamic alterations in the permeability of the glomerular filtration barrier (GFB) on a chip. We also evaluated the potential of GN-mimicking devices as a model for predicting responses to human GN. Glomerular endothelial cells and podocytes successfully formed intact monolayers on opposite sides of the membrane in our chip device. Permselectivity analysis confirmed that the chip was constituted by a functional GFB that could accurately perform differential clearance of albumin and dextran. Reduction in cell viability resulting from damage was observed in all serum-induced GN models. The expression of podocyte-specific marker WT1 was also decreased. Albumin permeability was increased in most models of serum-induced IgA nephropathy (IgAN) and membranous nephropathy (MN). However, sera from patients with minimal change disease (MCD) or lupus nephritis (LN) did not induce a loss of permeability. This glomerulus-on-a-chip system may provide a platform of glomerular cell culture for in vitro GFB in formation of a functional three-dimensional glomerular structure. Establishing a disease model of GN on a chip could accelerate our understanding of pathophysiological mechanisms of glomerulopathy.

Proteomic Analysis of Idiopathic Nephrotic Syndrome Triggered by Primary Podocytopathies in Adults: Regulatory Mechanisms and Diagnostic Implications.

Idiopathic nephrotic syndrome (NS) is a heterogeneous group of glomerular disorders which includes two major phenotypes: minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). MCD and FSGS are classic types of primary podocytopathies. We aimed to explore the molecular mechanisms in NS triggered by primary podocytopathies and evaluate diagnostic value of the selected proteomic signatures by analyzing blood proteome profiling. Totally, we recruited 90 participants in two cohorts. The first cohort was analyzed using label-free quantitative (LFQ) proteomics to discover differential expressed proteins and identify enriched biological process in NS which were further studied in relation to clinical markers of kidney injury. The second cohort was analyzed using parallel reaction monitoring-based quantitative proteomics to verify the data of LFQ proteomics and assess the diagnostic performance of the selected proteins using receiver-operating characteristic curve analysis. Several biological processes (such as immune response, cell adhesion, and response to hypoxia) were found to be associated with kidney injury during MCD and FSGS. Moreover, three proteins (CSF1, APOC3, and LDLR) had over 90% sensitivity and specificity in detecting adult NS triggered by primary podocytopathies. The identified biological processes may play a crucial role in MCD and FSGS pathogenesis. The three blood protein markers are promising for diagnosing adult NS triggered by primary podocytopathies.

Analysis of glomerular deposition of IgM and C3 in patients with podocytopathies.

Minimal Change Disease (MCD) and Focal Segmental Glomerulosclerosis (FSGS) are the main causes of nephrotic syndrome in the world. The complement system appears to play an important role in the pathogenesis of these diseases. To evaluate the deposition of immunoglobulins and particles of the complement system in renal biopsies of patients with FSGS and MCD and relate to laboratory data, we selected 59 renal biopsies from patients with podocytopathies, 31 from patients with FSGS and 28 with MCD. Epidemiological, clinical, laboratory information and the prognosis of these patients were evaluated. Analysis of the deposition of IgM, IgG, C3, C1q and C4d in renal biopsies was performed. We related IgM and C3 deposition with laboratory parameters. Statistical analysis was performed using GraphPad Prism version 7.0. Glomerular deposition of IgM was significantly higher in the FSGS group, as was codeposition of IgM and C3. The clinical course of patients and laboratory data were also worse in cases of FSGS, with a higher percentage progressing to chronic kidney disease and death. Patients with C3 deposition had significantly higher mean serum creatinine and significantly lower eGFR, regardless of disease. Patients with FSGS had more IgM and C3 deposition in renal biopsies, worse laboratory data and prognosis than patients with MCD. C3 deposition, both in FSGS and MCD, appears to be related to worsening renal function.

Bicellular Localization of Tricellular Junctional Protein Angulin-3/ILDR2 Allows Detection of Podocyte Injury.

Podocytes serve as part of the renal filtration unit with slit diaphragms. Although the structure of slit diaphragms between two cells is well characterized, how the tricellular contact of podocytes is organized and how it changes in injured podocytes remains unknown. This study focused on a tricellular junction protein, angulin-3, and its localization in healthy podocytes, in developmental stages, and in pathologic conditions, using a newly established monoclonal antibody. Angulin-3 was confined at tricellular junctions of primordial podocytes, then transiently localized at bicellular junctions as foot process interdigitation developed and the intercellular junctions rearranged into slit diaphragm, and eventually distributed in a sparse punctate pattern on the foot processes of adult podocytes. In the rodent podocyte injury models, angulin-3 showed bicellular localization between the foot processes, and the localization turned from punctate to dashed linear pattern along the effaced foot processes with the progression of podocyte injury. Angulin-3 also accumulated between foot processes in a linear pattern in kidney biopsy samples of human nephrotic syndrome. Additionally, the line length of angulin-3 staining signal correlated with risk of relapse under glucocorticoid therapy in patients with minimal change nephrotic syndrome. This study proposes an image program to score the linearity of the accumulation pattern of angulin-3 to evaluate the relapse risk of patients with minimal change nephrotic syndrome.

Evaluation of C4d expression and staining patterns by immunohistochemistry in renal biopsy samples with focal segmental glomerulosclerosis and minimal change disease.

INTRODUCTION: C4d is an activation product of lectin pathway of complement. Glomerular deposition of C4d is associated with poor prognosis in different types of immune-related glomerulonephritis. The present study was conducted to investigate expression level of C4d and its staining pattern in renal biopsy of patients with focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) by immunohistochemistry method. MATERIALS AND METHODS: In this retrospective cross-sectional study, renal biopsy specimens from 46 samples of MCD, 47 samples of FSGS, and 15 samples without glomerular disease as the controls, were subjected to immunohistochemistry staining with C4d. Demographic characteristics and information obtained from light and electron microscopy (EM) of patients were also extracted from their files. RESULTS: C4d positive staining was observed in 97.9 % of FSGS and 43.5 % of MCD samples, which showed a statistically significant difference (P < 0.001). The sensitivity and specificity of C4d expression for diagnosing FSGS were 97.9 % and 56.5 %, respectively. There was no significant correlation between C4d expression and any of the light and electron microscopy findings, including presence of foam cells, mesangial matrix expansion, interstitial fibrosis and tubular atrophy, and basement membrane changes in MCD patients. Also, no significant correlation was observed between C4d expression and clinical symptoms of proteinuria or prolonged high level of creatinine in patients with MCD. DISCUSSION AND CONCLUSION: The expression of C4d marker had a good sensitivity and negative predictive value in the diagnosis of FSGS.

Drug-induced glomerular diseases.

Drug-induced kidney diseases represent a wide range of diseases that are responsible for a significant proportion of all acute kidney injuries and chronic kidney diseases. In the present review, we focused on drug-induced glomerular diseases, more precisely podocytopathies - minimal change diseases (MCD), focal segmental glomerulosclerosis (FSGS) - and membranous nephropathies (MN), from a physiological and a pharmacological point of view. The glomerular filtration barrier is composed of podocytes that form foot processes tightly connected and directly in contact with the basal membrane and surrounding capillaries. The common clinical feature of these diseases is represented by the loss of the ability of the filtration barrier to retain large proteins, leading to massive proteinuria and nephrotic syndrome. Drugs such as non-steroidal anti-inflammatory drugs (NSAIDs), D-penicillamine, tiopronin, trace elements, bisphosphonate, and interferons have been historically associated with the occurrence of MCD, FSGS, and MN. In the last ten years, the development of new anti-cancer agents, including tyrosine kinase inhibitors and immune checkpoint inhibitors, and research into their renal adverse effects highlighted these issues and have improved our comprehension of these diseases.

The influence of calcitriol and methylprednisolone on podocytes function in minimal change disease in vitro model.

Minimal change disease (MCD), considered one of the major causes of nephrotic syndrome, is a complex pathological condition with disturbances in podocytes' foot processes. Numerous studies suggested the essential role of vitamin D3 in maintaining proper glomerulus function. However, the data on direct potential of that compound in reference to podocytes are scarce. Thus, here we assessed the influence of calcitriol (active vitamin D3) on podocyte function, apart from commonly used steroids (methylprednisolone). CIHP-1 podocyte cell line was used to implement the LPS-PAN-induced MCD in vitro model. Viability, podocyte-related slit diaphragm proteins, morphology, function as a barrier was evaluated using flow cytometry, RT-PCR, confocal microscopy, and TEER analysis. Calcitriol or methylprednisolone did not affect cell viability. Podocyte-related proteins demonstrated different responses to in vitro treatment compared to previously reported changes in total glomeruli. Podocyte morphology was partially restored in the presence of the tested compounds. In addition, TEER analysis revealed improvement of LPS-PAN-induced cells' function as a barrier when vitamin D3 or steroid was used. In conclusion, a significant potential for modulation of MCD in vitro model podocytes with calcitriol or selected steroids was reported. Further studies on vitamin D3 in context of podocyte-related phenomenon accompanying MCD are of great importance.

Glomerular parietal epithelial expression of CD44 in minimal change nephrotic syndrome and primary focal segmental glomerulosclerosis: A clinico-pathological study.

Introduction: Minimal change nephrotic syndrome (MCNS) and focal segmental glomerulosclerosis (FSGS) are the two common causes of nephrotic syndrome (NS) in both children and adults with overlapping clinical features, but with distinct prognostic and therapeutic implications. The distinction between these relies entirely on histopathology, which can sometimes be difficult. CD44 is expressed by activated parietal epithelial cells, plays a role in matrix deposition and thus in the pathogenesis of FSGS. Aims: To assess the expression of CD44 in MCNS and FSGS and to evaluate its association with the known clinical and histopathological prognostic factors. Materials and Methods: Thirty cases each of MCNS and FSGS were studied. The clinical, laboratory, histopathological, and CD 44 immunohistochemical data were recorded. The findings were analyzed and correlated. A P value of < 0.05 was considered statistically significant. Results: Statistical association was noted between CD44 positivity and serum creatinine (p = 0.031), estimated glomerular filtration rate (p = 0.040), segmental sclerosis (p < 0.001), tubular atrophy (p = 0.027), interstitial fibrosis (p = 0.027), and histological diagnosis (p < 0.001). The sensitivity, specificity, positive predictive, and negative predictive values were 90%, 76.67%, 79.41% and 88.46%, respectively. Conclusions: CD44 immunostain can effectively distinguish MCNS from FSGS. The congruent results of CD44 positivity with known prognostic factors support the possibility of using the CD44 marker as a predictive tool in selecting high-risk patients and offering appropriate therapeutic measures.

The kinetics of mTORC1 activation associates with FOXP3 expression pattern of CD4+ T cells and outcome of steroid-sensitive minimal change disease.

Minimal change disease (MCD) usually responds to glucocorticoids (GCs) but relapses in most cases. Relapse pathogenesis after complete remission (CR) remains unclear. We hypothesized that FOXP3+ T regulatory cell (Treg) dysregulation may drive early relapses (ER). In this study, a cohort of 23 MCD patients were treated with a conventional GC regimen for the initial onset of nephrotic syndrome. Upon GC withdrawal, seven patients suffered from ER, while 16 patients sustained remission (SR) during the 12-month follow-up. Patients with ER had reduced FOXP3+ Treg proportions compared with healthy controls. Treg reduction, accompanied by IL-10 impairment, was ascribed to a proportional decline of FOXP3medium rather than FOXP3high cells. GC-induced CR was marked by a rise in the proportions of FOXP3+ and FOXP3medium cells compared to baseline levels. These increases declined in patients with ER. The expression level of phosphorylated ribosomal protein S6 was used to track the dynamic shifts in mTORC1 activity within CD4+ T cells of MCD patients at various stages of treatment. Baseline mTORC1 activity was inversely correlated with FOXP3+ and FOXP3medium Treg proportion. The mTORC1 activity in CD4+ T cells served as a reliable indicator for ER and demonstrated improved performance when paired with FOXP3 expression. Mechanically, targeting mTORC1 intervention by siRNAs sufficiently altered the conversion pattern of CD4+ T cell to FOXP3+ Treg. Taken together, the activity of mTORC1 in CD4+ T cells can act as a credible predictor for ER in MCD, especially when combined with FOXP3 expression, and may offer a potential therapeutic avenue for the treatment of podocytopathies.

Analysis of glucocorticoid receptor and microRNAs expression in pathological renal tissues.

Glucocorticoid receptor (GR) is expressed in normal renal podocytes; however, its expression differs among renal diseases. The expression of GR as well as its epigenetic regulators microRNA (miR)30a, miR24 and miR370 was studied in the renal tissues of patients with systemic lupus nephritis (LN), minimal changes disease (MCD) and pauci-immune glumeronephritis (PIN). A total of 51 patients undergoing renal biopsy and 22 nephrectomised controls with no history of parenchymal renal disease were recruited from the Clinic of Nephrology and Renal Transplantation of General Laikon hospital between November 2016 and March 2019. All patients were newly-diagnosed and they were naïve of any treatment. The mRNA and protein expression were analyzed through reverse transcription-quantitative PCR and immunohistochemistry respectively. Written consent was obtained from all participants. GR mRNA expression was significantly reduced in all pathological samples compared with the 'normal' renal tissues used as controls (P=0.023 for LN, P=0.05 for MCD and P=0.004 for PIN). Similarly, GR protein expression was lower in all pathological samples (>6 GR positive podocytes/glomerulus in 50% of patients with LN and MCD and 18% with PIN) compared with controls (>6 positive podocytes/glomerulus in all the controls). PIN samples presented significantly lower GR mRNA and protein expression compared with LN and MCD samples. No significant differences were observed in the miR30a expression when comparing pathological with 'normal' renal samples. miR24 and miR370 expression demonstrated statistically significant difference in all pathological compared with 'normal' tissues. Moreover, GR expression was not significantly associated with either LN disease activity score or the response to the treatment. GR and miR24 expression was significantly reduced whereas miR370 significantly increased in all pathological compared with 'normal' renal tissues implying their protentional role in nephritis pathogenesis and treatment. Analysis of larger samples are required for more robust statistical analysis.

A spectrum of novel anti-vascular endothelial cells autoantibodies in idiopathic nephrotic syndrome patients.

Idiopathic nephrotic syndrome (INS) is a common renal disease characterized by disruption of the glomerular filtration barrier. In a previous study, we screened and identified podocyte autoantibodies in nephrotic syndrome patients and proposed the concept of autoimmune podocytopathy. However, circulating podocyte autoantibodies cannot reach podocytes unless glomerular endothelial cells have been damaged. Therefore, we speculate that INS patients may also have autoantibodies against vascular endothelial cells. Sera from INS patients were used as primary antibodies to screen and identify endothelial autoantibodies by hybridization with vascular endothelial cell proteins separated by two-dimensional electrophoresis. The clinical application value and pathogenicity of these autoantibodies were further verified by clinical study and in vivo and in vitro experiments. Nine kinds of autoantibodies against vascular endothelial cells were screened in patients with INS, which can cause endothelial cell damage. In addition, 89% of these patients were positive for at least one autoantibody.

Contribution of IL-33/ILC2-mediated Th2 cytokines during the progression of minimal change disease.

Minimal change disease (MCD) is a common type of nephrotic syndrome with high recurrence rate. This study aims to explore the impacts of interleukin (IL)-33 in MCD and to discuss its potential mechanism. In adriamycin (ADM) and puromycin aminonucleoside (PAN)-induced MCD rat model, IL-33 was used for treatment. H&E staining was applied for detecting histological changes. Critical proteins were examined by western blot. Corresponding commercial kits tested oxidative stress- and inflammation-related factors. Cell apoptosis was measured by TUNEL assay. ADM-induced podocyte injury model was establish to mimic MCD in vitro. Cell proliferation and apoptosis were detected by CCK-8 and TUNEL assays. Finally, podocyte was stimulated by innate lymphoid type-2 cells-secreted Th2 cytokines (ILC2s: IL-13 and IL-5 respectively), with or without incubation with M1 macrophage medium to further explore the immune-regulation of ILC2s behind the inflammatory environment of MCD. It was found that PAN-induced kidney jury, inflammation, oxidative stress and apoptosis were severer than ADM, and IL-33 treatment significantly alleviated the above injuries in PAN and ADM-induced MCD rat model. Moreover, IL-33 reversed the reduced viability and increased oxidative stress and apoptosis in ADM-induced podocyte injury model. Further, the capacities of IL-13 alone in inducing M1/M2 macrophage polarization, apoptosis, inflammation, kidney injury and reducing cell viability are stronger than IL-5. However, IL-13 reversed reduced cell viability and stimulated apoptosis, inflammation, kidney injury mediated by co-incubation with M1-conditioned medium. Collectively, IL-33 might protect against immunologic injury in MCD via mediating ILC2s-secreted IL-13.

Potential Urine Proteomic Biomarkers for Focal Segmental Glomerulosclerosis and Minimal Change Disease.

Primary focal segmental glomerulosclerosis (FSGS), along with minimal change disease (MCD), are diseases with primary podocyte damage that are clinically manifested by the nephrotic syndrome. The pathogenesis of these podocytopathies is still unknown, and therefore, the search for biomarkers of these diseases is ongoing. Our aim was to determine of the proteomic profile of urine from patients with FSGS and MCD. Patients with a confirmed diagnosis of FSGS (n = 30) and MCD (n = 9) were recruited for the study. For a comprehensive assessment of the severity of FSGS a special index was introduced, which was calculated as follows: the first score was assigned depending on the level of eGFR, the second score-depending on the proteinuria level, the third score-resistance to steroid therapy. Patients with the sum of these scores of less than 3 were included in group 1, with 3 or more-in group 2. The urinary proteome was analyzed using liquid chromatography/mass spectrometry. The proteome profiles of patients with severe progressive FSGS from group 2, mild FSGS from group 1 and MCD were compared. Results of the label free analysis were validated using targeted LC-MS based on multiple reaction monitoring (MRM) with stable isotope labelled peptide standards (SIS) available for 47 of the 76 proteins identified as differentiating between at least one pair of groups. Quantitative MRM SIS validation measurements for these 47 proteins revealed 22 proteins with significant differences between at least one of the two group pairs and 14 proteins were validated for both comparisons. In addition, all of the 22 proteins validated by MRM SIS analysis showed the same direction of change as at the discovery stage with label-free LC-MS analysis, i.e., up or down regulation in MCD and FSGS1 against FSGS2. Patients from the FSGS group 2 showed a significantly different profile from both FSGS group 1 and MCD. Among the 47 significantly differentiating proteins, the most significant were apolipoprotein A-IV, hemopexin, vitronectin, gelsolin, components of the complement system (C4b, factors B and I), retinol- and vitamin D-binding proteins. Patients with mild form of FSGS and MCD showed lower levels of Cystatin C, gelsolin and complement factor I.

Roles of microRNAs in renal disorders related to primary podocyte dysfunction.

Through the regulation of gene expression, microRNAs (miRNAs) are capable of modulating vital biological processes, such as proliferation, differentiation, and apoptosis. Several mechanisms control the function of miRNAs, including translational inhibition and targeted miRNA degradation. Through utilizing high-throughput screening methods, such as small RNA sequencing and microarray, alterations in miRNA expression of kidneys have recently been observed both in rodent models and humans throughout the development of chronic kidney disease (CKD) and acute kidney injury (AKI). The levels of miRNAs in urine supernatant, sediment, and exosomal fraction could predict novel biomarker candidates in different diseases of kidneys, including IgA nephropathy, lupus nephritis, and diabetic nephropathy. The therapeutic potential of administrating anti-miRNAs and miRNAs has also been reported recently. The present study is aimed at reviewing the state-of-the-art research with regards to miRNAs involved in renal disorders related to primary podocyte dysfunction by laying particular emphasis on Focal Segmental Glomerulosclerosis (FSGS), Minimal Change Disease (MCD) and Membranous Nephropathy (MN).

MicroRNAs in childhood nephrotic syndrome.

The discovery of microRNAs (miRNAs) has opened up new avenues of research to understand the molecular basis of a number of diseases. Because of their conservative feature in evolution and important role in the physiological function, microRNAs could be treated as predictors for disease classification and clinical process based on the specific expression. The identification of novel miRNAs and their target genes can be considered as potential targets for novel drugs. Furthermore, currently, the circulatory and urinary exosomal miRNAs are gaining increasing attention as their expression profiles are often associated with specific diseases, and they exhibit great potential as noninvasive or minimally invasive biomarkers for the diagnosis of various diseases. The remarkable stability of these extracellular miRNAs circulating in the blood or excreted in the urine underscored their key importance as biomarkers of certain diseases. There is voluminous literature concerning the role of microRNAs in other diseases, such as cardiovascular diseases, diabetic nephropathy, and so forth. However, little is known about their diagnostic ability for the pediatric nephrotic syndrome (NS). The present review article highlights the recent advances in the role of miRNAs in the pathogenesis and molecular basis of NS with an aim to bring new insights into further research applications for the development of new therapeutic agents for NS.

CD80 Insights as Therapeutic Target in the Current and Future Treatment Options of Frequent-Relapse Minimal Change Disease.

Minimal change disease (MCD) is the most common cause of idiopathic nephrotic syndrome in children, and it is well known for its multifactorial causes which are the manifestation of the disease. Proteinuria is an early consequence of podocyte injury and a typical sign of kidney disease. Steroid-sensitive patients react well with glucocorticoids, but there is a high chance of multiple relapses. CD80, also known as B7-1, is generally expressed on antigen-presenting cells (APCs) in steroid-sensitive MCD patients. Various glomerular disease models associated with proteinuria demonstrated that the detection of CD80 with the increase of urinary CD80 was strongly associated closely with frequent-relapse MCD patients. The role of CD80 in MCD became controversial because one contradicts finding. This review covers the treatment alternatives for MCD with the insight of CD80 as a potential therapeutic target. The promising effectiveness of CD20 (rituximab) antibody and CD80 inhibitor (abatacept) encourages further investigation of CD80 as a therapeutic target in frequent-relapse MCD patients. Therapeutic-based antibody towards CD80 (galiximab) had never been investigated in MCD or any kidney-related disease; hence, the role of CD80 is still undetermined. A new therapeutic approach towards MCD is essential to provide broader effective treatment options besides the general immunosuppressive agents with gruesome adverse effects.

Morphologic Analysis of Urinary Podocytes in Focal Segmental Glomerulosclerosis.

Background: The development of glomerulosclerosis in FSGS is associated with a reduction in podocyte number in the glomerular capillary tufts. Although it has been reported that the number of urinary podocytes in FSGS exceeds that of minimal-change nephrotic syndrome, the nature of events that promote podocyte detachment in FSGS remains elusive. Methods: In this study, we provide detailed, morphologic analysis of the urinary podocytes found in FSGS by examining the size of the urinary podocytes from patients with FSGS, minimal-change nephrotic syndrome, and GN. In addition, in urinary podocytes from patients with FSGS and minimal-change nephrotic syndrome, we analyzed podocyte hypertrophy and mitotic catastrophe using immunostaining of p21 and phospho-ribosomal protein S6. Results: The size of the urinary podocytes was strikingly larger in samples obtained from patients with FSGS compared with those with minimal-change nephrotic syndrome and GN (P=0.008). Urinary podocytes from patients with FSGS had a higher frequency of positive immunostaining for p21 (P<0.001) and phospho-ribosomal protein S6 (P=0.02) than those from patients with minimal-change nephrotic syndrome. Characteristic features of mitotic catastrophe were more commonly observed in FSGS than in minimal-change nephrotic syndrome urinary samples (P=0.001). Conclusions: We posit that the significant increase in the size of urinary podocytes in FSGS, compared with those in minimal-change nephrotic syndrome, may be explained by hypertrophy and mitotic catastrophe.

Pathophysiology and Pathology of Acute Kidney Injury in Patients With COVID-19.

Acute kidney injury (AKI) is common among hospitalized patients with Coronavirus Infectious Disease 2019 (COVID-19), with the occurrence of AKI ranging from 0.5% to 80%. The variability in the occurrence of AKI has been attributed to the difference in geographic locations, race/ethnicity, and severity of illness. AKI among hospitalized patients is associated with increased length of stay and in-hospital deaths. Even patients with AKI who survive to hospital discharge are at risk of developing chronic kidney disease or end-stage kidney disease. An improved knowledge of the pathophysiology of AKI in COVID-19 is crucial to mitigate and manage AKI and to improve the survival of patients who developed AKI during COVID-19. The goal of this article is to provide our current understanding of the etiology and the pathophysiology of AKI in the setting of COVID-19.