Primary Glomerular Disease Research Articles

Pattern of kidney diseases in Northern India: an overview through histopathological findings in biopsy-proven cases

BackgroundA kidney biopsy is being increasingly performed for the diagnosis of renal diseases. It is a reasonably safe procedure that helps not only to reach the correct diagnosis based on histopathological findings but also helps in predicting the clinical course and outcome. The pattern of kidney diseases varies not only in far apart geographical regions but also in the same country. This study was done to evaluate the demographic pattern and spectrum of kidney diseases in renal biopsy-proven cases in an admitted patient of a tertiary care hospital of northern India.ResultsThe mean age of patients was 41.3 years ± 18.39 years, and the male-to-female ratio was 1.7:1. The most common indication for biopsy in this study was nephrotic syndrome (40.5%). The primary glomerular disease was most common, accounting for 57.5% of cases. Membranous nephropathy (MN) was the most frequently observed histopathological diagnosis not only in the primary glomerular disease category (22.9%) but of all cases (13.2%) as well. Among secondary cases, diabetic nephropathy was most frequent, constituting 43.4% cases. Interstitial and vascular diseases accounted for 18.8% and 1.8% of total cases, respectively. While minimal change disease (MCD) was the most common diagnosis in < 18-year age group, membranous nephropathy was most common above this age. Regarding the gender factor, membranoproliferative glomerulonephritis had an equal distribution among both genders, while MCD had a female preponderance.ConclusionsPrimary glomerular disease is the predominant kidney disease in northern India with MN being the most common histopathological diagnosis. The spectrum of kidney diseases varied with patient’s age and gender.

Predicting Factors for Rapid Progressive Chronic Kidney Disease in Primary Glomerular Disease Patients with Moderate-to-Severe Stage.

Objective To investigate the predictive factors associated with rapid progressive chronic kidney disease (CKD) in patients with primary glomerular disease (PGD). Methods Baseline data, clinical biochemistry, laboratory data, and imaging data were collected from 112 PGD patients in CKD stages 3 and 4 who were hospitalized at the Third Xiangya Hospital. Patients were divided into rapid progression group (Group R) and no rapid progression group (NR) according to the definition of rapid progression of CKD. Results The age, systolic blood pressure (SBP), serum β2-microglobulin (sβ2-MG), urinary α1-microglobulin (uα1-MG), and cardiothoracic ratio (CTR) of the R group were significantly higher than the NR group. However, the size of the kidney, high-dense lipoprotein (HDL), hemoglobin (Hb), and hematocrit of the R group were significantly lower than the NR group (P < 0.05). Binary logistic regression analysis showed that baseline CTR, SBP, size of the kidney, and HDL were independent risk factors for rapid progression of PGD. At the end of follow-up, CTR and SBP of group R were higher than the NR group, and the size of the kidney and HDL of group R were lower than the NR group. Conclusion Increased baseline CTR and SBP and decreased baseline HDL and renal volume could be the predictors of rapid progression in patients of PGD at the CKD stages 3 and 4.

MicroRNA-630 Regulates Underglycosylated IgA1 Production in the Tonsils by Targeting TLR4 in IgA Nephropathy.

IgA nephropathy (IgAN) is the most common primary glomerular disease. The characteristic pathology involves immune complexes formed by the deposition of IgA1 and underglycosylated IgA1 aggregates in the mesangial area, which may be accompanied by the deposition of IgG and/or IgM and complement components. However, the molecular mechanisms of IgAN remain unclear. In the present study, microarray analysis showed that the expression of microRNA-630 (miR-630) was significantly reduced in palatal tonsils from IgAN patients compared with chronic tonsillitis. Additionally, bioinformatic analysis showed that Toll-like receptor 4 (TLR4) was the predicted target gene of miR-630 and was regulated by miR-630. When miR-630 was overexpressed in palatal tonsil mononuclear cells from IgAN patients, the expression of TLR4 was reduced and the content of IgA1 in the cell culture supernatant was decreased, and the level of galactosylation in the IgA1 hinge region was increased. Moreover, immunohistochemical analysis showed that the expression of TLR4 in IgAN patients was significantly increased. After knocking down the expression of TLR4, both the concentration of IgA1 and the binding force of IgA1 with broad bean lectin were significantly reduced in IgAN. Furthermore, the mechanism study demonstrated that TLR4 might regulate the expression of IL-1β and IL-8 through NF-κB signaling pathway to modulate the concentration of IgA1 and the glycosylation level of IgA1. This interesting finding may offer new insight into the molecular mechanism of IgAN.

Epidemiological features of primary glomerular disease in Turkey: a multicenter study by the Turkish Society of Nephrology Glomerular Diseases Working Group

BackgroundThe largest data on the epidemiology of primary glomerular diseases (PGDs) are obtained from the databases of countries or centers. Here, we present the extended results of the Primary Glomerular Diseases Study of the Turkish Society of Nephrology Glomerular Diseases (TSN-GOLD) Working Group.MethodsData of patients who underwent renal biopsy and received the diagnosis of PGD were recorded in the database prepared for the study. A total of 4399 patients from 47 centers were evaluated between May 2009 and May 2019. The data obtained at the time of kidney biopsy were analyzed. After the exclusion of patients without light microscopy and immunofluorescence microscopy findings, a total of 3875 patients were included in the study.ResultsThe mean age was 41.5 ± 14.9 years. 1690 patients were female (43.6%) and 2185 (56.3%) were male. Nephrotic syndrome was the most common biopsy indication (51.7%). This was followed by asymptomatic urinary abnormalities (18.3%) and nephritic syndrome (17.8%). The most common PGD was IgA nephropathy (25.7%) followed by membranous nephropathy (25.6%) and focal segmental glomerulosclerosis (21.9%). The mean total number of glomeruli per biopsy was 17 ± 10. The mean baseline systolic blood pressure was 130 ± 20 mmHg and diastolic blood pressure was 81 ± 12 mmHg. The median proteinuria, serum creatinine, estimated GFR, and mean albumin values were 3300 (IQR: 1467–6307) mg/day, 1.0 (IQR: 0.7–1.6) mg/dL, 82.9 (IQR: 47.0–113.0) mL/min and 3.2 ± 0.9 g/dL, respectively.ConclusionsThe distribution of PGDs in Turkey has become similar to that in other European countries. IgA nephropathy diagnosed via renal biopsy has become more prevalent compared to membranous nephropathy.

Characteristics of primary glomerular diseases patients with hematuria in Turkey: the data from TSN-GOLD Working Group.

Hematuria is one of the most common laboratory findings in nephrology practice. To date, there is no enough data regarding the clinical and histopathologic characteristics of primary glomerular disease (PGD) patients with hematuria in our country. Data were obtained from national multicenter (47 centers) data entered into the Turkish Society of Nephrology Glomerular Diseases (TSN-GOLD) database between May 2009 and June 2019. The data of all PGD patients over the age of 16years who were diagnosed with renal biopsy and had hematuria data were included in the study. Demographic characteristics, laboratory and biopsy findings were also recorded. Data of 3394 PGD patients were included in the study. While 1699 (50.1%) patients had hematuria, 1695 (49.9%) patients did not have hematuria. Patients with hematuria had statistically higher systolic blood pressure, serum blood urea nitrogen, creatinine, albumin, levels and urine pyuria. However, these patients had statistically lower age, body mass index, presence of hypertension and diabetes, eGFR, 24-h proteinuria, serum total, HDL and LDL cholesterol, and C3 levels when compared with patients without hematuria. Hematuria was present 609 of 1733 patients (35.8%) among the patients presenting with nephrotic syndrome, while it was presented in 1090 of 1661 (64.2%) patients in non-nephrotics (p < 0.001). This is the first multicenter national report regarding the demographic and histopathologic data of PGD patients with or without hematuria. Hematuria, a feature of nephritic syndrome, was found at a higher than expected in the PGDs presenting with nephrotic syndrome in our national database.

Intracellular Calcium Homeostasis and Kidney Disease.

Kidney disease is a serious health problem that burdens our healthcare system. It is crucial to find the accurate pathogenesis of various types of kidney disease to provide guidance for precise therapies for patients suffering from these diseases. However, the exact molecular mechanisms underlying these diseases have not been fully understood. Disturbance of calcium homeostasis in renal cells plays a fundamental role in the development of various types of kidney disease, such as primary glomerular disease, diabetic nephropathy, acute kidney injury and polycystic kidney disease, through promoting cell proliferation, stimulating extracellular matrix accumulation, aggravating podocyte injury, disrupting cellular energetics as well as dysregulating cell survival and death dynamics. As a result, preventing the disturbance of calcium homeostasis in specific renal cells (such as tubular cells, podocytes and mesangial cells) is becoming one of the most promising therapeutic strategies in the treatment of kidney disease. The endoplasmic reticulum and mitochondria are two vital organelles in this process. Calcium ions cycle between the endoplasmic reticulum and mitochondria at the conjugation of these two organelles known as the mitochondria-associated endoplasmic reticulum membrane, maintaining calcium homeostasis. The pharmacologic modulation of cellular calcium homeostasis can be viewed as a novel therapeutic method for renal diseases. Here, we will introduce calcium homeostasis under physiological conditions and the disturbance of calcium homeostasis in kidney diseases. We will focus on the calcium homeostasis regulation in renal cells (including tubular cells, podocytes and mesangial cells), especially in the mitochondria- associated endoplasmic reticulum membranes of these renal cells.

Crescentic glomerulonephritis in renal transplant; a case series

Crescentic glomerulonephritis (GN) is a severe proliferative renal lesion with an aggressive clinical scenario. The occurrence of crescentic GN post-transplant is mainly related to the recurrence of the primary glomerular disease. De novo crescentic GN in renal allografts is rare. We present five patients diagnosed with crescentic GN post-transplantation during 10 years period. There were two males and three females with age range 20-50 years. Three cases were crescentic phenotypes of recurrent disease and two were de novo. The post-transplant time range was (7-144 months). Three patients lost their grafts and returned to dialysis. One patient had chronic allograft dysfunction and one patient died because of severe renal failure. Recurrent or de novo crescentic GN is not uncommon, especially in a live donor program. It leads to graft loss in most cases.

Clinical and prognostic significance of C1q deposition in IgAN patients-a retrospective study

Background/AimIgA nephropathy (IgAN) is the most prevalent primary glomerular disease worldwide and is responsible for 45–50% of primary glomerular diseases in China. We are essentially dependent on the degree of proteinuria to determine prognosis and it has been reported that histopathologic lesions are risk factors for the progression of IgAN. The aim of this study was to investigate the clinicopathologic features and prognosis of IgAN with C1q deposition in adult Chinese patients. MethodsThe patients of primary IgAN diagnosed by renal biopsy from January 2002 to December 2018 at the Second Hospital of Shanxi Medical University were retrospectively analyzed and divided into C1q deposit group and C1q negative group according to glomerular immunofluorescence examination. We evaluated their serologic and histopathologic findings. We collected data of patients during January 1, 2015 to December 31, 2018 and performed the clinical follow-up until the patient's estimated glomerular filtration rate (eGFR) decreased by more than 30%, entering end-stage renal disease (ESRD). Kaplan-Meier survival analysis was used to evaluate the cumulative incidence of renal progression in two groups. Univariate and multivariate Cox proportional hazard regression models were used to analyze the effect of C1q deposition on the prognosis of patients with IgA nephropathy. ResultsThe baseline data of total 491 cases were available and 172 cases had the follow-up data. The baseline eGFR and plasma albumin (ALB) levels in C1q deposit group were lower than those in the C1q negative group, while the levels of serum creatinine (Scr), total cholesterol (TC), 24 h urine protein, low-density lipoprotein (LDL), β2 microglobulin, etc. were higher than those in C1q negative group (all P < 0.05). Pathological indexes: glomerular segment sclerosis and adhesion (S), renal tubular atrophy/interstitial fibrosis (T), and cell/fibroblastic crescent (C) scores in C1q deposit group were higher than those in C1q negative group (all P < 0.05). With a median follow-up time of 32.5 (24,42) months, a total of 18 patients (C1q deposit: 11; C1q negative: 7) developed to endpoints. Kaplan-Meier survival curve analysis showed that there was significant decrease in cumulative incidence of renal progression between the two groups (Log-rank test χ2 = 4.78, P = 0.029). Cox regression analysis showed that the risk of renal end-point events in IgAN patients with C1q deposit group was 6.35 times higher than that in C1q negative group (HR = 6.35, 95% CI: 1.21–33.30, P = 0.029). ConclusionThe clinical and renal pathological changes of IgAN patients with C1q deposition are more severe than those of C1q negative patients, and has a worse outcome. C1q deposition is an independent risk factor for the progression of renal function and contributes to a poor renal prognosis in adult IgAN patients.

Kidney transplantation in children with CAKUT and non-CAKUT causes of chronic kidney disease: Do they have the same outcomes?

Almost half the children who undergo kidney transplantation (KTx) have congenital abnormalities of the kidney and urinary tract (CAKUT). We compared patient, graft survival, and kidney function at last follow-up between CAKUT and non-CAKUT patients after KTx. We divided the analysis into two eras: 1988-2000 and 2001-2019. Of 923 patients, 52% had CAKUT and 48% non-CAKUT chronic kidney disease (CKD). Of the latter, 341 (77%) had glomerular disease, most frequently typical HUS (32%) and primary FSGS (27%); 102 had non-glomerular disease. CAKUT patients were more often boys, younger at KTx, transplanted more frequently preemptively, but with longer time on chronic dialysis. They had less delayed graft function (DGF) and better eGFR, but higher incidence of urinary tract infection (1 year post-KTx). In both eras, 1-, 5-, and 10-year patient survival was similar in the groups, but graft survival was better in CAKUT recipients vs those with primary glomerular and primary recurrent glomerular disease: Era 1, 92.3%, 80.7%, and 63.6% vs 86.9%, 70.6%, and 49.5% (P=.02), and 76.7%, 56.6%, and 34% (P=.0003); Era 2, 96.2%, 88%, and 73.5% vs 90.3%, 76.1%, and 61% (P=.0075) and 75.4%, 54%, and 25.2% (P<.0001), respectively. Main predictors of graft loss were DGF, late acute rejection (AR), and age at KTx in CAKUT group and disease relapse, DGF, early AR, and number of HLA mismatches in recipients with glomerular disease. Graft survival was better in CAKUT patients. DGF was the main predictor of graft loss in all groups. Disease recurrence and early AR predicted graft failure in patients with glomerular disease.

AN UNUSUAL CASE OF ACUTE HYPOXIC RESPIRATORY FAILURE IN A PATIENT WITH FIBRILLARY GLOMERULONEPHRITIS

SESSION TITLE: Fellows Critical Care Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Fibrillary glomerulonephritis (FGN) is a rare primary glomerular disease (incidence <1%) characterized by immune-complex mediated GN with amyloid-like fibrils which are IgG positive and Congo red negative(1). We present a case of refractory respiratory failure with co-existing FGN. CASE PRESENTATION: A 58-year-old woman with hypertension and chronic hematuria/ proteinuria (presumed IgA nephropathy but no biopsy) presented to the hospital with fever and dyspnea for 2 days. Due to moderate hypoxemia she required invasive mechanical ventilation (IMV). CXR showed bilateral diffuse airspace opacities. Lab work up showed proteinuria, hematuria, elevated CRP and normal creatinine. ANCA panel, complements, anti-GBM antibody, anti-SSA/SSB, RF and anti Scl-70 were negative. BAL showed no evidence of DAH, neutrophilic alveolitis and sterile cultures. Echocardiogram was normal. Despite lung protective IMV, PEEP adjustment as per ARDS net and adjuvant therapies (inhaled nitric oxide, steroids and paralytics), severe hypoxemia persisted. She developed AKI requiring renal replacement therapy. She received appropriate antibiotics for ESBL E. coli UTI and C. diff. colitis. Kidney biopsy showed FGN. She underwent plasma exchange, intravenous immunoglobulin therapy followed by rituximab per management protocol used in other pulmonary renal syndromes. Due to worsening of severe ARDS refractory to medical therapy, VV-ECMO was initiated in week 4. She was unable to be weaned off ECMO support (>30 days) which lead to her death. DISCUSSION: FGN was first described in 1977(2). Fibrils characterizing FGN are confined to glomeruli and stain intensely by IF for IgG, C3, ?, and ?, strongly suggesting that the fibrils are composed of a complex of antibodies and antigens as seen in our case(3). It was described in association with underlying malignancy, hepatitis C, diabetes or autoimmune disease. Nephrotic range proteinuria, hematuria and hypertension are usual presentations. Recent discovery of major fibril component, DNA-J heat-shock protein family member B9 (DNAJB9), has made the diagnosis of FGN by immunohistochemistry possible(4,5). Nearly half of patients with FGN progress to ESRD within 4 years. Benefit from immunosuppressive therapy is unestablished. Transplant is not curative as recurrence is not uncommon. Very few cases of extra-renal manifestations of FGN have been reported. Only cases associated with pulmonary hemorrhage were successfully treated with steroids(6). CONCLUSIONS: Our case reports a rare extra-renal manifestation of FGN causing refractory respiratory failure. Further research to identify exact pathogenesis and successful treatment is imperative. Reference #1: 1. Fibrillary Glomerulonephritis: Clinicopathological features and atypical cases from a multi-institutional cohort, CJASN Dec 2019, 14 (12) 1741-50 2. Nephrotic syndrome associated with amyloid-like glomerular deposits. Nephron. 1977;18:301-308 Reference #2: 3. Fibrillary Glomerulonephritis: An update, Kidney Int Rep. 2019 Jul; 4(7): 917-922 4. DNA J heat shock protein family B member 9 is a novel biomarker for fibrillary GN. J Am Soc Nephrol. 2018;29:51–56 Reference #3: 5. DNA J homolog subfamily B member 9 is a putative autoantigen in fibrillary GN. J Am Soc Nephrol. 2018; 29:231–239 6. Fibrillary Glomerulonephritis: Another cause of bleeding lung. Case reports, ATS 2017 conference DISCLOSURES: No relevant relationships by Moises Cossio, source=Web Response No relevant relationships by Domingo Franco-Palacios, source=Web Response No relevant relationships by Kushagra Gupta, source=Web Response No relevant relationships by Shahzad Hussain, source=Web Response No relevant relationships by Venkateswara Kollipara, source=Web Response No relevant relationships by Toribiong Uchel, source=Web Response

Nuclear receptors in podocyte biology and glomerular disease.

Nuclear receptors have a broad spectrum of biological functions in normal physiology and in the pathology of various diseases, including glomerular disease. The primary therapies formany glomerular diseases are glucocorticoids, which exert their immunosuppressive and direct podocyte protective effects via the glucocorticoid receptor (GR). As glucocorticoids are associated with important adverse effects and a substantial proportion of patients show resistance to these therapies, the beneficial effects of selective GR modulators are now being explored. Peroxisome proliferator-activated receptor-γ (PPARγ) agonism using thiazolidinediones has potent podocyte cytoprotective and nephroprotective effects. Repurposing of thiazolidinediones or identification of novel PPARγ modulators are potential strategies to treat non-diabetic glomerular disease. Retinoic acid receptor-α is the key mediator of the renal protective effects of retinoic acid, and repair of the endogenous retinoic acid pathway offers another potential therapeutic strategy for glomerular disease. Vitamin D receptor, oestrogen receptor and mineralocorticoid receptor modulators regulate podocyte injury in experimental models. Further studies are needed to better understand the mechanisms of these nuclear receptors, evaluate their synergistic pathways and identify their novel modulators. Here, we focus on the role of nuclear receptors in podocyte biology and non-diabetic glomerular disease.

Establishment of a novel nomogram for the clinically diagnostic prediction of minimal change disease, \u2212a common cause of nephrotic syndrome

BackgroundMinimal change disease (MCD) is one of the major causes of nephrotic syndrome (NS). A confirmed MCD diagnosis mainly depends on renal biopsy at present, which is an invasive procedure with many potential risks. The overall incidence of complications caused by renal biopsy procedures has been reported as approximately 11 and 6.6% outside and within China, respectively. Unfortunately, there is currently no noninvasive procedure or practical classification method for distinguishing MCD from other primary glomerular diseases available.MethodA total of 1009 adult patients who underwent renal biopsy between January 2017 and November 2019 were enrolled in this study. Twenty-five parameters extracted from patient demographics, clinical manifestations, and laboratory test results were statistically analysed. LASSO regression analysis was further performed on these parameters. The parameters with the highest area under the curve (AUC) were selected and used to establish a logistic diagnostic prediction model.ResultsOf the 25 parameters, 14 parameters were significantly different (P < 0.05). MCD patients were mostly younger (36 (22, 55) vs. 41 (28.75, 53)) and male (59% vs. 52%) and had lower levels of diastolic blood pressure (DBP) (79 (71, 85.5) vs. 80 (74, 89)) and IgG (5.42 (3.17, 6.36) vs. 9.38 (6.79, 12.02)) and higher levels of IgM (1.44 (0.96, 1.88) vs. 1.03 (0.71, 1.45)) and IgE (160 (46.7, 982) vs. 47.3 (19, 126)) than those in the non-MCD group. Using the LASSO model, we established a classifier for adults based on four parameters: DBP and the serum levels of IgG, IgM, IgE. We were able to clinically classify adult patients with NS into MCD and non-MCD using this model. The validation accuracy of the logistic regression model was 0.88. A nomogram based on these four classifiers was developed for clinical use that could predict the probability of MCD in adult patients with NS.ConclusionsA LASSO model can be used to distinguish MCD from other primary glomerular diseases in adult patients with NS. Combining the model and the nomogram potentially provides a novel and valuable approach for nephrologists to diagnose MCD, avoiding the complications caused by renal biopsy.

Secretion of the epithelial sodium channel chaperone PCSK9 from the cortical collecting duct links sodium retention with hypercholesterolemia in nephrotic syndrome

The proprotein PCSK9 functions as a chaperone for the epithelial sodium channel in the cortical collecting duct (CCD), is highly expressed in the liver, and plays a significant role in the pathogenesis of hypercholesterolemia. Lower levels of PCSK9 expression also occur in the normal kidney and intestine. Here, we found increased PCSK9 expression in the CCD of biopsies of patients with primary glomerular disease and explored a possible relationship with hypercholesterolemia of nephrotic syndrome. Significantly elevated serum PCSK9 and cholesterol levels were noted in two models of focal and segmental glomerulosclerosis, the Rrm2b-/- mouse and the Buffalo/Mna rat. Increased expression of PCSK9 in the kidney occurred when liver expression was reduced in both models. The impact of reduced or increased PCSK9 in the CCD on hypercholesterolemia in nephrotic syndrome was next studied. Mice with selective deficiency of PCSK9 expression in the collecting duct failed to develop hypercholesterolemia after injection of nephrotoxic serum. Blocking epithelial sodium channel activity with Amiloride in Rrm2b-/- mice resulted in increased expression of its chaperone PCSK9 in the CCD, followed by elevated plasma levels and worsening hypercholesterolemia. Thus, our data suggest that PCSK9 in the kidney plays a role in the initiation of hypercholesterolemia in nephrotic syndrome and make a case for depletion of PCSK9 early in patients with nephrotic syndrome to prevent the development of hypercholesterolemia.

Longitudinal Changes in Health-Related Quality of Life in Primary Glomerular Disease: Results From the CureGN Study

IntroductionPrior cross-sectional studies suggest that health-related quality of life (HRQOL) worsens with more severe glomerular disease. This longitudinal analysis was conducted to assess changes in HRQOL with changing disease status.MethodsCure Glomerulonephropathy (CureGN) is a cohort of patients with minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, IgA vasculitis, or IgA nephropathy. HRQOL was assessed at enrollment and follow-up visits 1 to 3 times annually for up to 5 years with the Patient-Reported Outcomes Measurement Information System (PROMIS). Global health, anxiety, and fatigue domains were measured in all; mobility was measured in children; and sleep-related impairment was measured in adults. Linear mixed effects models were used to evaluate HRQOL responsiveness to changes in disease status.ResultsA total of 469 children and 1146 adults with PROMIS scores were included in the analysis. HRQOL improved over time in nearly all domains, though group-level changes were modest. Edema was most consistently associated with worse HRQOL across domains among children and adults. A greater number of symptoms also predicted worse HRQOL in all domains. Sex, age, obesity, and serum albumin were associated with some HRQOL domains. The estimated glomerular filtration rate (eGFR) was only associated with fatigue and adult physical health; proteinuria was not associated with any HRQOL domain in adjusted models.ConclusionHRQOL measures were responsive to changes in disease activity, as indicated by edema. HRQOL over time was not predicted by laboratory-based markers of disease. Patient-reported edema and number of symptoms were the strongest predictors of HRQOL, highlighting the importance of the patient experience in glomerular disease. HRQOL outcomes inform understanding of the patient experience for children and adults with glomerular diseases.

A single-center analysis of primary nephrotic syndrome with acute pancreatitis in children.

Primary nephrotic syndrome (PNS) is one of the most common primary glomerular diseases in children. Patients complicated nephrotic syndrome with pancreatic lesions are rarely reported, and the clinical manifestations in children are atypical. This study has observed the incidence, clinical types, and prognosis of acute pancreatitis (AP) in children with primary nephrotic syndrome, and analyzed its related factors, early diagnosis, and treatment.Seven children with PNS and AP in Shanghai Children's Hospital from January 2015 to December 2017 were reviewed. The clinical data including age, height, weight, body mass index (BMI), diet, biliary tract disease, PNS durations, drugs, proteinuria, creatinine, glucose, glycated hemoglobin, amylase and lipase, albumin, cholesterol, triglyceride, ultrasound, computerized tomography (CT), renal pathology and estimated glomerular filtration rate (eGFR) were retrospectively analyzed. All patients were followed for >2 years.Ten in 589 patients with PNS were detected pancreatic lesions by abdominal ultrasound. Seven were diagnosed as AP, which the incidence was 1.2%. Only 1 of 7 patients had elevated serum amylase. Lesions of pancreas were found by ultrasound and/or enhanced CT. Four of 7 patients had been treated with tacrolimus. All patients with AP were improved after octreotide acetate injection and supportive treatment. Only 1 patient suffered recurrent AP during the relapse of PNS 10 months later.AP in children with PNS is not common, and the clinical manifestations are not typical. Abdominal ultrasound and enhanced CT are of high value in diagnosis. The adverse effects of tacrolimus should be concerned. Early diagnosis and timely treatment can be helpful for a prognosis.

P0448CHARACTERISTICS OF PRIMARY GLOMERULAR DISEASE PATIENTS WITH HEMATURIA IN TURKEY: THE DATA FROM TSN-GOLD WORKING GROUP

Abstract Background and Aims Hematuria is one of the most common laboratory findings in nephrology practice. In different regions of the world, the etiologic causes differ. To date, there is no enough data regarding the clinical and histopathologic characteristics of primary glomerular diseases (PGD) patients with hematuria in our country. Method Data were obtained from national multicenter (47 centers) data entered into the Turkish Society of Nephrology Glomerular Diseases (TSN-GOLD) database between May 2009 and June 2019. The data of all PGD patients over the age of 16 years who were diagnosed with renal biopsy and had hematuria data were included in the study. The biopsy samples were processed using a light microscopy and immunofluorescence examination. Demographic characteristics such as age, sex, indications for biopsy, primary glomerular diseases, comorbidities, laboratory and biopsy findings of all patients were also recorded. Hematuria was defined as the presence of at least 5 red blood cells/hpf. Results Data of 3394 patients were included to the study after the exclusion of patients with secondary glomerulonephritis and patients with missing biopsy findings. While 1699 (50.1%) patients had hematuria, 1695 (49.9%) patients did not have hematuria. Demographic, laboratory, and histopathological characteristics of patients with and without hematuria are given in Table. Patients with hematuria had statistically higher systolic blood pressure (SBP), serum blood urea nitrogen, creatinine, albumin, levels and urine pyuria, however, these patients had statistically lower age, body mass index, presence of hypertension and diabetes, eGFR, 24-hour proteinuria, serum total, HDL and LDL-cholesterol and C3 levels when compared with patients without hematuria. Figure depicted the etiologic causes of patients with and without hematuria. According to histopathological findings, number of global sclerotic glomeruli, cellular and fibrocellular crescents, the levels of mesangial proliferation, endocapillary proliferation, exudative changes in glomeruli, severe tubular atrophy, interstitial inflammation, subendothelial deposition, moderate and severe IgA and C3 deposition were found to be significantly higher and the levels of basal membrane thickening, interstitial fibrosis, subepithelial deposition, severe IgG staining were found to be significantly lower in patients with hematuria. Conclusion This is the first multicenter national report regarding the demographic and histopathologic data of PGD patients with or without hematuria. Hematuria, a feature of nephritic syndrome, was found at a higher than expected in the PGDs presenting with nephrotic syndrome in our national database.

P0389THE PREVALENCE, CLINICAL AND PATHOLOGICAL CHARACTERISTICS OF PRIMARY FOCAL SEGMENTAL GLOMERULOSCLEROSIS IN TURKISH ADULTS: THE DATA FROM TSN-GOLD ( TURKISH SOCIETY OF NEPHROLOGY GLOMERULAR DISEASES) WORKING GROUP

Abstract Background and Aims Focal segmental glomerulosclerosis (FSGS) is one of the primary glomerulopathies which is the most common cause of end-stage renal disease among all primary glomerular diseases. In adults, nephrotic syndrome develops 10-35% due to FSGS. However, its frequency has been increasing in recent years. This study was aimed to present the data and the prevalence of primary FSGS patients in Turkey. Method These data were obtained from the National Multicenter (47 centers) Primary Glomerular Diseases registry system, which was entered into the Turkish Society of Nephrology Glomerular Diseases (TSN-GOLD) database between May 2009 and June 2019. The presented data in this study is cross-sectional and includes the recorded data of the patients in the hospitalization period for the kidney biopsy. These demographic, clinic and pathological data of patients were evaluated with using statistically. Results Of the 3875 patients enrolled in the Primary Glomerular Diseases database, 850 (21.9%) had FSGS. The mean age of the patients was 47.1 ± 13.7 and 435 (52%) of patients were male. Two hundred and eighty one (33.1%) had hypertension and 93 (11%) had diabetes. Five hundred and four patients (59.3%) were diagnosed as nephrotic syndrome. At the time of diagnosis, the mean systolic blood pressure was 13.8 ± 18.6 mm Hg and the mean diastolic blood pressure was 81.4± 11.4 mm Hg. The laboratory findings at the time of diagnosis on following; serum creatinine 1.2 ± 0.04 mg / dl, albumin 3.3 ± 0.03 g / dl, and 24 hours urinary proteinuria amounts to 4743 ± 181 mg / day. Demographical and clinical data of the patients at the time of diagnosis were presented on Table 1. In pathological examination; the mean number of glomeruli was 16.8 ± 0.3, global sclerotic glomeruli were 3.1 ± 0.1, and segmental sclerotic glomeruli were 2.4 ± 0.1. Summary of Pathological Findings were presented on Table 2 Conclusion It is very difficult to determine the absolute incidence and prevalence of primary FSGS. Incidence rates have been reported to range from 0.2 to 1.8 / 100,000 per year in the literature. In a United States study, the most common diagnosis in 2501 kidney biopsies was FSGS (35.9%). According to this database, the prevalence of FSGS in primary glomerular diseases in our country is 21.9%.

P0501THE EPIDEMIOLOGICAL FEATURES OF PIRMARY GLOMERULAR DISEASES IN TURKEY: THE MULTICENTER STUDY OF TURKISH SOCIETY OF NEPHROLOGY GLOMERULAR DISEASES (TSN-GOLD) WORKING GROUP

Abstract Background and Aims The largest data on the epidemiology of primary glomerular diseases (PGD) are obtained from the databases of countries or centers. Here, we presented the extended results of the Primary Glomerular Diseases Study of the Turkish Society of Nephrology Glomerular Diseases (TSN-GOLD)Working Group. Method The data of patients who underwent renal biopsy and diagnosed as primary glomerular disease were recorded in the database prepared for the study. Between May 2009 and May 2019, a total of 4399 patients from 47 centers were evaluated. Basal data of 3875 patients were analyzed after exclusion of those lacking light microscopy and immunofluorescence findings. Results The mean age was 41.5 ± 14.9 years. Of the patients, 1690 were female (43.6%) and 2180 (56.3%) were male. Nephrotic syndrome was the most common biopsy indication (51.7%). This was followed by asymptomatic urinary abnormalities (18.3%) and nephritic syndrome (17.8%). The most common PGH was IgA nephropathy (25.7%), followed by membranous nephropathy (25.6%) and FSGS (21.9%). The mean total number of glomeruli per biopsy was 17 ± 10. Mean baseline systolic blood pressure was 130 ± 20 mmHg and diastolic blood pressure was 81 ± 12 mmHg. Median proteinuria was 3300 (IQR: 1467-6307) mg / day, mean serum creatinine, estimated GFR and albumin values were 1.4 ± 1.5 mg / dl, 80.7 ± 39.1 ml / min and 3.2 ± 0.9 g / dl, respectively. Conclusion In Turkey, the incidence of IgA nephropathy patients have become more common than membranous nephropathy among PGD patients diagnosed with renal biopsy.

P0046ZHX2 DOWNREGULATION DUE INSERTIONS AND DELETIONS IN THE HAS2-ZHX2 INTERGENIC REGION PREDISPOSE TO PODOCYTE DISEASE RELAPSE

Abstract Background and Aims ZHX2 transcriptional factor is normally found in podocyte membrane forming complexes with ZHX1 and APA or ZHX3 and Ephrin B1. Altered ZHX2 expression disrupts these interactions and is related with the worsening of different primary glomerular diseases such as focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD). A small percentage of Hodgkin lymphoma (HL) patients develop nephrotic syndrome (NS). Studies of Reed-Sternberg cell line L-1236 reveals a chromosomal rearrangement that leads to ZHX2 downregulation suggesting a possible role of ZHX2 in the development of NS in these patients. Human podocyte disease relapse is common after a common cold probably mediated by cytokines released by immune cells and the rhinovirus. Our aim is to study how the presence of insertions and deletions (InDels) between HAS2 and ZHX2 in patients with MCD, FSGS and HL could alter ZHX2 expression and the implication in podocyte disease relapse after a common cold and in HL. Method Genomic DNA between HAS2 and ZHX2 (Chr8:122624000-124001000 from UCSC hg19 GRCh37) was sequenced from 28 NS patients and 27 controls using Agilent Custom capture and high throughput Illumina sequencing. The CLC Genomics software was used to identify InDels (3-20 bp) present exclusively in patients. One of the identified InDels was replicated in human podocytes using CRISPR Cas9 and homology directed repair technology to study changes in ZHX2. A common cold cytokine cocktail containing IL-2, IL-4R, IL-6, IL-10, INF-γ, TNF-α and ICAM-1 was injected into control (BALB/c, n=5) and ZHX2 deficient mice (BALB/cJ, n=5) (Dose X); podocyte specific ZHX2 deficient (ZHX2 flox/flox cre+/+, n=3) and floxed control mice (ZHX2 flox/flox, n=3) (dose X/15). Buffalo Mna (B. Mna) rats were also injected with the cytokine cocktail (X/50) to study relapse in FSGS (n=7). Cell supernatant from HL Reed Sternberg cells (L-1236) (200µg of total protein) was injected into BALB/c (n=5) and BALB/cJ mice (n=5) and kidney function was assessed. Results Multiple InDels were found exclusively in the patient population, two of them, shared by two or more patients. The insertion at 122,533,694 was presented in patients with MCD, FSGS and HL with NS and also in L-1236 cells. This insertion was replicated in human podocytes using CRISPR/Cas9 (CRISPR B). Another insertion noted both in patients and controls was generated for comparison (CRISPR A). A reduced ZHX2 expression was detected in CRISPR B but not in CRISPR A single cell clones. The shared insertion at 122,787,088 was presented within the ZHX2 gene intron 1. BALB/cJ mice has lower ZHX2 expression in liver and podocytes due to an insertion in intron 1. To study whether this insertion could be related with relapse of MCD and FSGS following a common cold, a cytokine cocktail was injected into BALB/cJ and BALB/c mice. BALB/cJ mice developed acute albuminuria after cytokine treatment (65.3±24.3 μg per 18h), but not control BALB/c mice (10.8±1.5 μg per 18h), when compared with baseline values (BALB/cJ 5.1±1.1 μg per 18h; BALB/c 6.5±1.1 μg per 18h) (p&amp;lt;0.05). BALB/cJ mice had also higher nuclear expression of ZHX1. The cytokine cocktail also induced albuminuria in ZHX2 flox/flox/cre+/+ mice but not in control ZHX2 flox/flox, suggesting that ZHX2 deficiency in podocytes is responsible of kidney injury after cytokine injection. To study common cold related relapse in FSGS, B. Mna rats were injected with a rat cytokine cocktail, showing a significant increase in proteinuria (61.5±4.2 mg per 18h) compared with baseline (47±4.1 mg per 18h). Cell culture supernatant from L-1236 was injected into BALB/cJ and BALB/c mice to study the effect of secreted soluble mediators in NS. L-1236 supernatant (200 µg) had a nephrogenic effect in ZHX2 deficient mice but not in controls. Conclusion InDels between HAS2 and ZHX2 genes presented in patients with MCD, FSGS and HL, alter ZHX2 expression and are related to relapse following a common cold and in HL.

P0440EPIDEMIOLOGICAL AND CLINICAL CHARACTERSTICS OF IGA NEPHROPATHY PATIENTS IN TURKEY: TSN-GOLD WORKING GROUP

Abstract Background and Aims According to the data of the Turkish Society of Nephrology-Glomerular Diseases Working Group (TSN-GOLD Working Group), IgA nephropathy is the most common primary glomerular disease in Turkey. The purpose of this study was to investigate the epidemiological and clinical data of IgA nephropathy patients in Turkey. Method 4399 patients with primary glomerular diseases from 47 centers who were followed up between May 2009 and May 2019 were included in the study conducted by TSN-GOLD Working Group. 524 patients were excluded due to lack of pathological data. Among the remaining patients, demographic, clinical and laboratory data of 994 patients with IgA nephropathy were analyzed. Results The median age of the patients was 37 (28-47) years, and 37.3% of them were female. The laboratory and clinical data at the time of diagnosis is presented in Figure-1, and biopsy indications are described in Figure-2. The median number of glomeruli was 16 (IQR: 3.5-4.3), sclerotic glomeruli was 2 (IQR: 1-5), and segmental sclerotic glomeruli was 1 (IQR: 1-2). Exudative changes, subendothelial and subepithelial deposition were present in 566 patients (56.9%), 46 patients (4.6%) and in 38 patients (3.8%), respectively. 662 (66.1%) and 611 of the patients (61.4%) had tubular atrophy and interstitial fibrosis in varying degrees, respectively. 672 (%67.6) and 416 patients (%41.9) had interstitial inflammation and vascular changes, respectively. In immunofluorescence staining, 18%, 30.1%, 4.4%, 68% of the patients had IgG, IgM, C1q and C3 positivity, respectively. Crescentic glomeruli were detected in 227 patients (3.3 ± 3.1 glomeruli). Patients with crescentic glomeruli had significantly higher proteinuria and lower eGFR than the patients without [2203 mg/day (15-26078) vs 1807 mg/day (15-29112); p=0.001; 55.3 ml/min/1.73 m2 (3.72-141.9) vs 72 ml/min/1.73 m2 (3.84-150.81); p&amp;lt;0.001, respectively]. Oxford classification was applied to 544 patients. Endocapillary hypercellularity (E1), mesengial hypercellularity (M1), tubular atrophy and interstitial fibrosis (T1 and T2), segmental sclerosis (S1) were present in 126 (13%), 425 (42.8%), 306 (30.8%) and 325 patients (%32.7), respectively. Proteinuria levels were higher in patients with endocapillary hypertrophy, mesengial hypercellularity, tubular atrophy-interstitial fibrosis and segmental sclerosis. eGFR levels were lower in patients with endocapillary hypertrophy, tubular atrophy-interstitial fibrosis and segmental sclerosis (Figure-3). Conclusion In this study we found that, the most common presentation of IgA nephropathy patients in our country was asymptomatic urinary abnormalities followed by nephritic and nephrotic syndrome. Higher proteinuria and lower eGFR values in patients with crescentic glomeruli, support the adoption of crescentic lesions in the new Oxford classification (MEST-C) to predict more precise outcome of IgA nephropathy patients. The high number of patients to whom the Oxford classification was applied provided us with the opportunity to examine the clinical reflections of pathological features. Evaluation of the follow-up data of the patients will give us the possibility to reveal the effect of initial clinical and pathological features on clinical findings and renal outcome.