Minimal Change Disease Patients Research Articles

#1389 Identification of serum lipidomic profile in nephrotic syndrome patients

Abstract Background and Aims Nephrotic syndrome describes a collection of symptoms, mainly heavy proteinuria leading to kidney function loss, that can be caused by different underlying kidney diseases. Common primary causes of nephrotic syndrome include focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD) and membranous nephropathy (MN). Nephrotic syndrome is often characterized by plasma lipid abnormalities with elevations in cholesterol, triglycerides and lipoproteins. Here we set out to generate a detailed lipidomic analysis of FSGS, MCD and MN patient's plasma to find lipid changes common to nephrotic syndrome or specific for the underlying disease. Method For this lipidomic study, we included patients with primary FSGS (2 cohorts with n = 5), genetic FSGS (n = 5), MCD (n = 5) and MN (n = 5) in whom serum had been collected at the time they presented at our center with active nephrotic syndrome. We compared the serum lipidome of nephrotic syndrome patients with age matched healthy controls (n = 5), and with age matched patients with familial hypercholesterolemia (n = 5) who, like patients with nephrotic syndrome, have significantly elevated lipid values. Serum was analyzed using the Shotgun Lipidomics platform by Lipotype GmbH (Dresden, Germany), as previously described [1]. Results The lipidomic profile of patients with nephrotic syndrome was markedly different compared to control groups (Fig. 1A). In particular, lower levels of lyso-phophatidylcholine (LPC) and higher concentrations of phosphatidylethanolamine (PE) and lyso-PE (LPE) compared to control groups were most prominent (Fig. 1B). Subspecies analysis identified LPC 16:0;0 to be highly downregulated in patients with nephrotic syndrome (Fig. 2A), whereas LPE 18:0;0 and nearly all PE subspecies were increased compared to control groups (Fig. 2B and C). The lipidomic profile was largely comparable between different underlying diseases and we could not identify lipid classes specifically different for certain diseases. Conclusion Our lipidomic data show that patients with nephrotic syndrome have a distinct lipid profile compared to healthy controls or other disease controls. We identified LPCs, PEs and LPEs to be changed in nephrotic syndrome. We could not identify lipids specific for certain diseases underlying nephrotic syndrome, but rather identified a general nephrotic syndrome lipid profile. This suggests that lipid changes are rather a consequence of disease manifestation in these patients with various underlying causes. Further research should focus on confirming this lipid profile in larger cohorts and unraveling the mechanisms leading to the observed lipid changes.

The efficacy and safety of rituximab with or without glucocorticoid in inducing remission of MCD with different clinical presentations in adults: a retrospective study

Abstract Background To investigate the efficacy and safety of rituximab (RTX) with or without glucocorticoid (GC) in inducing remission of minimal change disease (MCD) in adults. Methods Twenty-one adult MCD patients were included in the study. The patients were assigned to the following three groups according to their background before RTX treatment: an RTX single drug direct induction treatment group (Group A; n = 9), a short-term, low-dose GC combined with RTX induction treatment group (Group B; n = 4) and a short-term, adequate-dose GC-induced remission and RTX maintenance treatment group (Group C; n = 8). The primary endpoints were the time to induction of remission and the rate of clinical remission at 12 months. Results All patients achieved clinical remission, with 19 (90.48%) achieving complete remission (CR), and the median remission time was 4 (2.5, 12) weeks. Eight (88.89%) patients in Group A achieved CR, and the median remission time was 3 (2.25, 14) weeks. In group B, three (75.00%) patients achieved CR, with a median remission time of 4 (4, 10) weeks. In group C, eight (100.00%) patients achieved CR, and the median remission time was 3.5 (2, 4) weeks. Conclusions In MCD patients without acute kidney injury (AKI), adequate RTX alone or short-term combined treatment with low-dose GCs can effectively induce and maintain MCD remission. Adequate short-term GCs combined with RTX maintenance may be an effective alternative for MCD patients in context of AKI. There is a need to investigate different induction therapy regimens for the remission of MCD patients with different backgrounds.

Adult primary glomerular diseases due to podocytopathies: a single center experience on patient characteristics, treatment and outcomes

Purpose: This study aims to evaluate the demographic, clinical, and pathologic characteristics and response to immunosuppressive therapy, particularly corticosteroids, in adult patients with primary focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD), which are classified as podocytopathies. 
 Materials and Methods: Between January 1998 and December 2014, this study included 44 patients (27 with primary FSGS and 17 with MCD) aged older than 18 years with a histopathologic diagnosis, symptoms of nephrotic syndrome, and a minimum follow-up of six months. Patients were divided into two groups according to the treatment they received and three groups according to their response to treatment. Patients diagnosed with primary FSGS and MCD were evaluated based on clinical, demographic, and laboratory findings, as well as response to treatment, and a comparison was conducted between the two groups.
 Results: 59.1% of the patients were male with a mean age of 44.8±17.7 years. At the time of diagnosis, there were no statistically significant differences in clinical and demographic characteristics between MCD and primary FSGS patients. However, in patients with MCD, the mean creatinine clearance (118.0±46.7 ml/min) was higher and the rate of microscopic hematuria (11.8%) was lower at the time of diagnosis. There was an increased need for alternative immunosuppressive treatments besides corticosteroids in patients with primary FSGS to achieve partial or complete remission. At both the third and sixth-month follow-ups, MCD patients achieved a higher rate of complete remission (proteinuria

Inhibition of RAC attenuates Adriamycin-induced podocyte injury

Minimal Change Disease (MCD), which is associated with podocyte injury, is the leading cause of nephrotic syndrome in children. A considerable number of patients experience relapses and require prolonged use of prednisone and immunosuppressants. Multi-drug resistance and frequent relapses can lead to disease progression to focal and segmental glomerulosclerosis (FSGS).To identify potential targets for therapy of podocyte injury, we examined microarray data of mRNAs in glomerular samples from both MCD patients and healthy donors, obtained from the GEO database. Differentially expressed genes (DEGs) were used to construct the protein-protein interactions (PPI) network through the application of the search tool for the retrieval of interacting genes (STRING) tool. The most connected genes in the network were ranked using cytoHubba. 16 hub genes were selected and validated by qRT-PCR. RAC2 was identified as a potential therapeutic target for further investigation. By downregulating RAC2, Adriamycin (ADR)-induced human podocytes (HPCs) injury was attenuated. EHT-1864, a small molecule inhibitor that targets the RAC (RAC1, RAC2, RAC3) family, proved to be more effective than RAC2 silencing in reducing HPCs injury. In conclusion, our research suggests that EHT-1864 may be a promising new molecular drug candidate for patients with MCD and FSGS.

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

IntroductionC4d 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 methodsIn 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. ResultsC4d 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 conclusionThe expression of C4d marker had a good sensitivity and negative predictive value in the diagnosis of FSGS.

Exploring the significance of interleukin-33/ST2 axis in minimal change disease

Minimal change disease (MCD), a common cause of idiopathic nephrotic syndrome, has been postulated to exhibit an association with allergic conditions. Recent studies revealed the crucial role of interleukin (IL)-33 in type 2 innate immunity. We hypothesized that development of MCD involves an IL-33–related immune response. We examined 49 patients with biopsy-proven MCD, 6 healthy volunteers, and 29 patients in remission. In addition to clinical features, serum and urinary levels of IL-33 and soluble suppression of tumorigenicity 2 protein (sST2), a secreted form of the receptor of IL-33, were analyzed. Although IL-33 was barely detectable in either MCD or control samples, sST2 levels at diagnosis were elevated in MCD patients. Serum sST2 levels of MCD patients were correlated with serum total protein level (r = − 0.36, p = 0.010) and serum creatinine level (r = 0.34, p = 0.016). Furthermore, the elevated sST2 levels were observed to decrease following remission. Immunofluorescence revealed IL-33 expression in the podocytes among MCD patients, with a significant increase compared with controls. In vitro, mouse podocyte cells incubated with serum from a MCD patient at disease onset showed increased IL-33 secretion. These results suggest an IL-33–related immune response plays a role in MCD.

Demographics and treatment of patients with primary nephrotic syndrome in Japan using a national registry of clinical personal records

The nationwide clinical features of Japanese patients with primary nephrotic syndrome (NS), including minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), or membranous nephropathy (MN), have not yet been reported. We collected the clinical personal records of patients with primary NS between 2015 and 2018 from the national registry organized by the Japanese Ministry of Health, Labour, and Welfare. Overall, the demographics, chronic kidney disease classification based on glomerular filtration rate and albuminuria, and treatment of 6036 patients were collected: 3394 (56.2%) with MCD, 677 (11.2%) with FSGS, 1455 (24.1%) with MN, and 510 (8.5%) with others. MN patients were older than MCD and FSGS patients (67 vs. 42 and 47 years, respectively). Steroid-dependent NS or frequently relapsing NS was found in 70.2%, 40.5%, and 24.6%, whereas steroid-resistant NS was found in 6.4%, 36.0%, and 37.9% of patients in the MCD, FSGS, and MN, respectively. The present oral prednisolone use (mean dose, mg/day) was 87.2% (21.2), 80.9% (20.0), and 77.5% (18.8) of patients in the MCD, FSGS, and MN, respectively. The national registry of clinical personal records of primary NS could provide an informative insight into the characteristics, clinical features, and treatment approaches for patients with primary NS in Japan.

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.

Outcomes of minimal change disease without nephrotic range proteinuria.

Minimal change disease (MCD) is characterized by edema and nephrotic range proteinuria (NS). However, the fate of MCD without nephrotic proteinuria requires elucidation. We retrospectively reviewed 79 adults diagnosed with primary MCD at their initial renal biopsy at a tertiary hospital between May 2003 and June 2017. Clinicopathologic features were compared between patients with and without NS. The frequency of flaring to nephrotic proteinuria and renal outcomes were assessed during follow-up. There were 20 and 59 patients in the Non-NS and NS groups, respectively. The Non-NS group had a lower frequency of acute kidney injury (AKI) during the follow-up period [5.0% vs. 59.3%, p <0.001]. The response rate to steroid treatment was 100% in the Non-NS group and 92.3% in the NS group (p = 1.000). Except for one patient, the Non-NS group was treated with steroids when their proteinuria increased to a nephrotic level. There were no differences in the frequency of the first relapse or the number of relapses among patients with initial remission from nephrotic range proteinuria. At the final visit, the complete remission rate was 73.4%. The estimated glomerular filtration rate during follow-up was significantly better in the NS group than the Non-NS group, given the higher rates of AKI at renal biopsy. The rates of renal events, end-stage renal disease, and mortality did not differ between the groups. Adult MCD patients with nephrotic and non-nephrotic range proteinuria showed similar outcomes. Accordingly, this population must be carefully managed, regardless of the amount of proteinuria at renal biopsy.

Mechanisms and Clinical Research Progress of Rituximab in the Treatment of Adult Minimal Change Disease

Introduction: Minimal change disease (MCD) is a common subtype of primary nephrotic syndrome in adults. The pathogenesis of MCD is still not well understood, but some studies suggest that MCD is a T cell-mediated disease related to podocyte dysfunction. Previous research has also indicated the crucial role of B cells in the pathogenesis of MCD. Rituximab (RTX) is a recombinant chimeric mouse/human antibody targeting CD20 antigen. In recent years, RTX has been increasingly used in adult MCD patients. Methodology: We searched the PubMed database using the keywords “Minimal change disease”, “Nephrotic syndrome”, and “Rituximab” and obtained a total of 140 articles. We will now provide a literature review based on these 140 articles, according to our research topic. Discussion: This article provides an overview of the mechanisms and clinical research progress of RTX in the treatment of adult MCD. We have also discussed the current treatment methods for MCD, exploring the potential of using RTX as a first-line therapy for refractory adult MCD. Conclusion: MCD is a common pathological type of nephrotic syndrome, and the exact mechanisms are still not fully understood. Although RTX as a treatment of adult MCD has shown promising clinical results in patients with refractory adult MCD, the safety and efficacy of RTX still lack high-quality clinical evidence. Further research is needed to explore the pathogenesis of MCD and the RTX treatment for MCD.

Serum IgE levels are a risk factor with prognosis of pediatric minimal change disease.

Minimal change disease (MCD) is one of the most common primary glomerular disorders with high serum IgE levels. This study was aimed to investigate the clinical features of different serum IgE levels in pediatric MCD and evaluate the prognostic significance of serum IgE levels with regard to remission and relapse in pediatric cohort. This study enrolled 142 new-onset children diagnosed with biopsy-proven MCD from January 2010 to December 2021 at the Jinling Hospital in Nanjing, China. These cases were divided into three groups according to serum IgE levels. MCD patients' demographics, clinical parameters, and follow-up data were collected and analyzed. The primary and secondary outcomes were defined as the time to the first complete remission (CR) and the first relapse. The results manifested that 85.2% (121/142) of MCD children had high serum IgE levels (IgE > 90.0 IU/ml). A total of 142 patients were divided into the normal-, low-, and high-IgE groups based on the normal reference value level (90.0 IU/ml) and median serum IgE level (597.5 IU/ml). The high-IgE group had a significantly lower cumulative rate of the first CR (log-rank, P = 0.032) and a higher rate of the first relapse (log-rank, P = 0.033) than the normal-IgE and low-IgE groups. Multivariate Cox analysis showed that IgE ≥597.5 IU/ml was independently associated with the delayed first CR [hazard ratio (HR) = 0.566, 95% confidence interval (CI) = 0.330-0.972, P = 0.039] and the early first relapse (HR = 2.767, 95% CI = 1.150-6.660, P = 0.023). Serum IgE levels were an independent correlation factor for pediatric MCD-delayed remissions and early relapses.

#5801 EXTENDED LOW DOSE RITUXIMAB REGIMEN FOR THE TREATMENT OF ADULT PATIENTS WITH STEROID-DEPENDENT AND FREQUENTLY RELAPSING MINIMAL CHANGE DISEASE

Abstract Background and Aims Patients with frequently relapsing and steroid-dependent minimal change disease (MCD) imply a therapeutic challenge for nephrologists. The use of steroid sparing agents such as cyclosporine, rituximab and mycophenolate, allows minimization of steroids exposure among these patients. In children and adults, Rituximab has demonstrated safety and efficacy in some studies although there is no established treatment regimen. This study aims to demonstrate that a low dose extended regimen of rituximab is an effective alternative for preventing relapses among these patients. Method This is a single-centre retrospective descriptive study of a case series of adult MCD patients from Ramón y Cajal’ Hospital in Madrid, Spain. Since 2019, patients with steroids-dependent or frequently relapsing MCD were treated with a low dose extended protocol of Rituximab as follows; 500 mg of rituximab once remission is achieved with steroid therapy, and four additional doses at month +6, +18 and +30 during the follow-up. Relapse free survival was analyzed after rituximab therapy. Results Eight patients with a median age of 42 years (22–70 years) who received at least one dose of intravenous rituximab were included. Four of the patients (50%) had previously received additional immunosuppressive regimens (including cyclophosphamide, chlorambucil cyclosporine, mycophenolate or ACTH). Two of them (25%) had frequent relapses and the remaining six (75%) had steroid-dependent behaviour. After a median of 2 years (IQR, 1,4-3,3) of follow-up, 6 out of 8 (75%) patients stayed under remission, experiencing the remaining two one relapse at one month and at one year, respectively, after the first rituximab dose. Comparing relapses during the two years-period before and after rituximab use, the median relapse rate per patient dropped from 2.8 (IQR, 2-4) to 0.5 (IQR, 0-1; P = 0.001) (Fig. 1). No patient experienced rituximab related side effects nor infections during the study period. Conclusion In MCD patients, the administration of rituximab in an extended low-dose regimen as corticosteroid-sparing therapy appears to be safe and effective in most of the patients for preventing relapses. This regimen allows minimization exposure to rituximab as well as disease remission during a longer period of time.

#3057 OUTCOMES IN SRNS (FSGS) PATIENTS IN THE UK RADAR IDIOPATHIC NEPHROTIC SYNDROME REGISTRY AND THEIR RELATIONSHIP WITH TIME-AVERAGED PROTEINURIA

Abstract Background and Aims Idiopathic Steroid Resistant Nephrotic Syndrome, SRNS (incorporating FSGS) is an important cause of proteinuric renal disease leading to kidney failure. Here we describe the outcomes of SRNS using the UK National Registry of Rare Kidney Diseases Idiopathic Nephrotic Syndrome (RaDaR-INS) Cohort, including retrospective and prospective data from 4274 patients with nephrotic syndrome (NS) not attributable to glomerulonephritis or systemic disorders, recruited from 107 adult and paediatric kidney units across the UK since 2010. In patients with FSGS, severity of proteinuria at onset and during follow up is associated with renal failure. In this study, we tested for associations between defined proteinuria endpoints with both eGFR slope and renal survival, in children and adults. Method Participants included those with renal biopsy diagnosis of FSGS or minimal change disease (MCD), or monogenic NS. Patients with no proteinuria measurement ≥1.0 g/g &amp;gt;6 months after disease onset were excluded as likely fully steroid-sensitive. Patients with kidney failure (KF) (CKD stage 5 or on renal replacement therapy) at or prior to first proteinuria measurement after baseline were excluded. Disease onset was defined as time of renal biopsy; primary renal diagnosis (PRD) date if no biopsy date recorded, and first proteinuria ≥1 g/g if neither biopsy/PRD date was available. Baseline was defined as first proteinuria ≥1 g/g &amp;gt;6 months after disease onset. Kaplan-Meier methods were used to analyze renal survival, defined as absence of KF or death with survival time calculated from baseline to last follow up. eGFR slope was measured from 6 months after baseline for the duration of follow up. Results Of 612 MCD and FSGS patients meeting eligibility, median time from disease onset to baseline was 1.2 years (IQR 0.6-4.4). Median baseline age was 38 years (IQR 21–56) with paediatric patients representing 21% of the study population. Median proteinuria at baseline was 3.4 g/g (IQR 1.9-6.2), while mean eGFR was 89 mL/min/1.73 m2 (SD 39). Mean rate of loss of eGFR over follow-up was 4.4mL/min/1.73 m2/year (SD 10.9). Complete proteinuria remission (CR) and FSGS partial remission (FPR) were defined as shown in Table 1 using values of time-averaged proteinuria (TA-PU) over months 6–24 from baseline. For patients achieving CR or FPR, the rate of loss of eGFR was slower (Table 1), with a higher probability of survival from KF/death (Table 1 &amp; Figure 1), than patients failing to achieve CR or FPR. Conclusion This is a study of proteinuria and outcomes in a population of patients with FSGS or steroid-resistant MCD. We regard the latter group as likely also to have FSGS. In this population of patients with overt proteinuria, achieving partial or complete remission of proteinuria is associated with slower disease progression and reduced risk of KF/death.

Primary nephrotic syndrome in children in Cape Town, South Africa

Background. Histopathological patterns of childhood primary nephrotic syndrome (PNS) and clinical response to steroids have beenassociated with certain race groups in parts of South Africa. However, there are no recent studies of childhood PNS in Cape Town.Objectives. To describe the demographics, histological subtypes and steroid response of patients with PNS who underwent kidney biopsiesat Red Cross War Memorial Children’s Hospital (RCWMCH) over a 10-year period.Methods. Details of patients with PNS who underwent kidney biopsies in the Paediatric Nephrology Department at RCWMCH between2006 and 2015 were retrospectively recorded.Results. A total of 103 patients were included in the study. Most patients were either of mixed race (42%) or black (36%), with a mean age of6.8 years and a male-to-female ratio of 1.19:1. The most identified histopathological subtype was mesangioproliferative glomerulonephritis(MesPGN; 60% (n/N=62/103)). Of the patients with focal segmental glomerulosclerosis (FSGS), MesPGN and minimal change disease(MCD) 45% (n/N=43/95) were steroid-resistant, and 54% (n/N=51/95) were steroid-sensitive. There was no significant associationbetween any race group and steroid response. Patients with FSGS were more likely to be black, while MCD was more common in mixed-race patients (p=0.04). There was no difference in the likelihood of being mixed race or black between patients with FSGS and MesPGN(p=0.472).Conclusion. MesPGN was the most common histopathological subtype found in our study. There was no significant association betweenrace and steroid response. Patients with FSGS were more likely to be black than mixed race when compared with MCD patients. Race wasnot otherwise significantly associated with any histopathological subtype

Rituximab as Initial Therapy in Adult Patients With Minimal Change Disease

Rituximab as Initial Therapy in Adult Patients With Minimal Change Disease

Urinary matrix metalloproteinase-7 is a sensitive biomarker to evaluate renal tubular injury in patients with minimal change disease and focal segmental glomerulosclerosis.

To explore the advantages of urinary matrix metalloproteinase-7 (MMP-7) in evaluating renal tubular injury in minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) patients compared with urinary cystatin C (CysC) and retinol-binding protein (RBP). Serum and urine samples were collected from 20 healthy volunteers, and 40 MCD and 20 FSGS patients. Serum and urinary MMP-7 levels were measured by enzyme-linked immunosorbent assay. Urinary total protein, CysC and RBP levels were measured by automatic specific protein analyzer and compared with urinary creatinine level for calibration. The renal tissue serial sections were stained by MMP-7 immunohistochemistry and periodic acid-Schiff. Under light microscopy, MMP-7 granular weak positive expression was showed sporadically in the cytoplasm of a few renal tubular epithelial cells without obvious morphological changes in MCD patients, and MMP-7-positive expression was observed in the cytoplasm of some renal tubular epithelial cells in FSGS patients. There was no significant difference in serum MMP-7 level among the three groups. Compared with the control group, the urinary MMP-7 level in MCD patients was higher, but urinary CysC and RBP levels were not increased significantly. Compared with the control group and MCD patients, urinary MMP-7, CysC and RBP levels in FSGS patients were upregulated significantly. Urinary MMP-7 could not only evaluate the mild renal tubular epithelial cells injury in MCD patients with massive proteinuria, but also evaluate the continuous renal tubular epithelial cells injury in FSGS patients.

Clinico-biochemical Profile of Biopsy-proven Minimal Change Disease in Adults from a Tertiary Care Center in South India.

Minimal change disease (MCD) is the most common cause of nephrotic syndrome (NS) in children, and in adults, it contributes to 10%-25% of NS. MCD in adults follows a slightly different course associated with increased incidence of steroid resistance, hematuria, and HTN. This is a prospective-record analysis study aimed to analyze the profile of MCD in adults, response to treatment, and relapse rates. A retrospective observational study was carried out and data were collected retrospectively from all biopsy-proven MCD patients between 2012 and 2018. A total of 86 adults were diagnosed to have biopsy-proven MCD. Of these, 32 were excluded due to insufficient data/lost for follow-up. The IBM SPSS Statistics version 22.0 was used for the statistical analysis. Descriptive analysis includes expression of all the explanatory and outcome variables in terms of frequency and proportions for categorical variables whereas in terms of mean ± standard deviation for continuous variables. Chi-square test was used to compare the age, gender, remission, renal failure and response of different drugs, treatment durations, comorbidity conditions, relapse episodes, and different types of infections based on the degree of proteinuria among study patients. A total of 54 biopsy-proven adult MCD patients were analyzed. The mean age of the patients studied was 36.67 years, with the oldest patient being 76 years. In the study group, 37 (68.5%) patients were male and 14 (31.5%) were female. In the study population, 20 (37%) were hypertensive, 3 (5.6%) were diabetic, and 10 (18.5%) had renal failure at presentation. On treatment, 52 out of 54 patients received steroids, of which 41 (75.9%) were steroid responsive, 6 (11.1%) steroid dependent, and 7 (13%) steroid resistant. The mean time for remission in steroidsensitive patients was 8.8 weeks. Among the steroid-dependent and steroid-resistant patients, 11 patients received calcineurin inhibitors (CNIs), of which 3 were CNI resistant. In the study Group 1 patient received cyclophosphamide and two received rituximab. In the study population, two patients failed to achieve remission and one patient was initiated on hemodialysis and later lost for follow-up. Minimal change NS is a type of NS which is highly responsive to steroids with good prognosis in children. Adult MCD patients require a higher and prolonged course of steroid when compared to children. CNIs and rituximab form a promising second-line drug in patients who are steroid resistant/dependent. However, CNI dependency or relapse after stopping steroids is a concern.

Characterization and diagnostic value of the gut microbial composition in patients with minimal change disease.

Background: Minimal change disease (MCD) is one of the most common causes of primary nephrotic syndrome with high morbidity. This study aimed to explore the typical alterations of gut microbiota in MCD and establish a non-invasive classifier using key gut microbiome. We also aimed to evaluate the therapeutic efficiency of gut microbiota intervention in MCD through animal experiments. Methods: A total of 222 stool samples were collected from MCD patients and healthy controls at the First Affiliated Hospital of Zhengzhou University and Shandong Provincial Hospital for 16S rRNA sequencing. Optimum operational taxonomic units (OTUs) were obtained for constructing a diagnostic model. MCD rat models were established using doxorubicin hydrochloride for exploring the therapeutic efficiency of gut microbial intervention through fecal microbiota transplantation (FMT). Results: The α-diversity of gut microbiota decreased in MCD patients when compared with healthy controls. The relative abundance of bacterial species also changed significantly. We constructed a diagnostic model based on eight optimal OTUs and it achieved efficiency of 97.81% in discovery cohort. The high efficiency of diagnostic model was also validated in the patients with different disease states and cross-regional cohorts. The treatment partially recovered the gut microbial dysbiosis in patients with MCD. In animal experiments, likewise, the gut microbiota changed sharply in MCD rats. However, gut microbial interventions did not reduce urinary protein or pathological kidney damage. Conclusion: Gut Microbiota shifts sharply in both patients and rats with MCD. Typical microbial changes can be used as biomarkers for MCD diagnosis. The gut microbiota compositions in patients with MCD tended to normalize after treatment. However, the intervention of gut microbiota seems to have no therapeutic effect on MCD.

A Prediction Model for Acute Kidney Injury in Adult Patients With Minimal Change Disease

BackgroundEarly prediction of acute kidney injury (AKI) can allow for timely interventions, but there are still few methods that are easy and convenient to apply in predicting AKI, specially targeted at patients with minimal change disease (MCD). Motivated by this, we aimed to develop a predicting model for AKI in patients with MCD within the KDIGO criteria.MethodsData on 401 hospitalized adult patients, whose biopsy was diagnosed as MCD from 12/31/2010 to 15/7/2021, were retrospectively collected. Among these data, patients underwent biopsy earlier formed the training set (n = 283), while the remaining patients formed the validation set (n = 118). Independent risk factors associated with AKI were analyzed. From this, the prediction model was developed and nomogram was plotted.ResultsAKI was found in 55 of 283 patients (19%) and 15 of 118 patients (13%) in the training and validation cohorts, respectively. According to the results from lasso regression and logistic regression, it was found that four factors, including mean arterial pressure, serum albumin, uric acid, and lymphocyte counts, were independent of the onset of AKI. Incorporating these factors, the nomogram achieved a reasonably good concordance index of 0.84 (95%CI 0.77–0.90) and 0.75 (95%CI 0.62–0.87) in predicting AKI in the training and validation cohorts, respectively. Decision curve analysis suggested clinical benefit of the prediction models.ConclusionsOur predictive nomogram provides a feasible approach to identify high risk MCD patients who might develop AKI, which might facilitate the timely treatment.

MO219: Are C4D, Nephrın and WT1 Expressıons İmportant ın the Dıfferentıal Dıagnosıs between Focal Segmental Glomerulosclerosıs and Mınımal Change Dısease?

Abstract BACKGROUND AND AIMS Focal Segmental Glomerulosclerosis (FSGS) and Minimal Change Disease (MCD) are most common seen glomerulonephritis. Differential diagnosis between FSGS and MCD by light microscopy (LM) cannot be made in some times. In this situation, electron microscopy (EM) is needed for differential diagnosis. Rarely, EM may not be sufficient for differential diagnosis. There are needed new markers for differential diagnose between FSGS and MCD. The aim of this study is to determine which of the glomerular C4d, nephrine staining is specific and sensitive for FSGS and MCD. C4d, Recent experimental data show that complement activation plays a pathogenic role in the development of FSGS. Therefore, C4d staining in the sclerotic focus of the glomeruli in FSGS patients may have an important differential diagnosis. Nephrine is the main component of the slit diaphragm that connects the foot protrusions of the podocytes. Epithelial cell and podocyte dysfunction occurs as a result of defects in the genes encoding these key proteins expressed in GBM. Wilms’ tumour suppressor gene (WT1) is a transcription factor that plays very important role in the embryonal development of the genital organs and kidney. WT-1 is expressed in podocytes and is an important transcription factor for podocyte function. METHOD This is a retrospective study, comprised of patients diagnosed as FSGS, MCD and the ones who diagnosed as having FSGS or MCD couldnot be differentiated. The patients were divided into three groups. Group 1: FSGS patients, Group 2: patients with indefinite diagnosis; either FSGS or MCD and Group 3: MCD patients. All biopsy materials were stained with C4d, WT1 and nephrine. The specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of C4d, WT1 and nephrine were evaluated for the diagnosis of both FSGS and MCD. RESULTS C4d staining in group 1 was significantly higher compared with group 2 and group 3 (P &amp;lt; .05). Nephrine was shown significantly more staining in group 3 patients than group 1 (P &amp;lt; .05). C4d was found to be associated with the presence of global or segmental sclerosis in the glomeruli, adhesion to the Bowman's capsule (P &amp;lt; .05). The specificity and sensitivity of C4d in FSGS patients were 85%, 73.9%, while it was 26.1% and 15.4% in MCD. Specificity and sensitivity of nephrine were 87%, 69% in MCD patients compared with 30.8% and 13% in FSGS (Fig. 1). PPV and NPV values of C4d and nephrine in FSGS and MCD were shown in Figure 2. CONCLUSION C4d and nephrine have predictive diagnostic value for FSGS and MCD respectively. C4d and nephrine are more specific and sensitive to FSGS and MCD, respectively. However, there is a need for randomized studies with larger study groups