Gene Expression as a Guide to the Development of Novel Therapies in Primary Glomerular Diseases

Despite improvements in understanding the pathogenic mechanisms of primary glomerular diseases, therapy still remains nonspecific. We sought to identify novel therapies targeting kidney-intrinsic injury of distinct primary glomerulonephritides through computational systems biology approaches. We defined the unique transcriptional landscape within kidneys from patients with focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), immunoglobulin A nephropathy (IgAN), membranous nephropathy (MN) and thin basement membrane nephropathy (TBMN). Differentially expressed genes were functionally annotated with enrichment analysis, and distinct biological processes and pathways implicated in each primary glomerular disease were uncovered. Finally, we identified novel drugs and small-molecule compounds that may reverse each glomerulonephritis phenotype, suggesting they should be further tested as precise therapy in primary glomerular diseases.

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

Background The 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. Methods Data 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. Results The 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. Conclusions The 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.

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

Background Minimal 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. Method A 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. Results Of 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. Conclusions A 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.

P0453BIOSIMILAR RITUXIMAB AND BRAND RITUXIMAB: RELAPSES AND PROTEINURIA IN THE GLOMERULAR PRYMARY DISEASES

Background and Aims Biosimilar drugs need to prove similar effectiveness to the brand name drug, in order to have their authorization from regulatory agencies. Rituximab initially developed as a treatment for non-Hodgkin lymphoma, is used as a therapeutic alternative to several autoimmune diseases, including primary glomerular diseases. The objective of this study is to observe if there were differences in terms of effects measured in proteinuria and relapse episodes between rituximab brand versus biosimilar in primary glomerular diseases Method This is a retrospective descriptive study that included patients receiving rituximab brand or biosimilar for the first time between March 2018 to March 2019, collecting information from the reported medical records with primary glomerulopathy were included. The collected laboratory data included creatinine, proteinuria, leukocyte and lymphocyte count before (0-60 days before) and after (0-60 days after) administration of rituximab. Results A total of 19 patients with primary glomerulopathy were included. Six patients (59-years-old (26-74); 50% female) with baseline 6.52±2.00x10^9/L leucocyte count, 2.28±1.10x10^9/L lymphocyte count, 1.63±1.04 mg/dL creatinine and 6.84±3.36g/24h proteinuria, were treated with biosimilar-rituximab. Thirteen patients (58-years-old (25-81); 30% female) with baseline 9.80±4.62x10^9/L leucocyte count, 1.92±1.13 x10^9/L lymphocyte count, 1.61±0.85 mg/dL creatinine and 5.81±4.55 g/24h proteinuria, were treated with brand-rituximab. After the rituximab administration, these values were 6.13±1.94x10^9/L leucocyte count, 1.30±0.59x10^9/L lymphocyte count, 1.16±1.19 mg/dL creatinine, 3.29±0.58g/24h and proteinuria for the biosimilar group; and 8.77±3.78x10^9/L leucocyte count, 1.67±1.13x10^9/L lymphocyte count, 1.56±1.19 mg/dL creatinine and 3.36±2.20g/24h proteinuria for the brand group. After rituximab administration CD19+ lymphocytes become negative in both groups (5/5 for the biosimilar group; 6/6 for the brand group). There were 2 total remissions, 1 partial remission and 3 without response with the biosimilar and 1 total remission, 5 partial remissions and 7 without response with the rituximab brand. Biosimilar was well tolerated in 6/6 patients and Rituximab brand infection did not develop was well tolerated in 11/13 patients and 4/13 patients showed an episode of infection. No statistically significant results were observed for the response to treatment between both groups. Conclusion The biosimilar shows a similar profile in terms of proteinuria and remissions against rituximab mark in the reported follow-up period, however our study is limited since it has a small sample, so a larger study is necessary to demonstrate these results with statistical significance

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

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.