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OBJECTIVE: Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are podocytopathies characterized by damage to the glomerular filtration barrier, leading to proteinuria and nephrotic syndrome. The production of anti-podocyte antibodies has been proposed as potential circulating factors contributing to the development of these conditions. The aim of the study is to evaluate the levels of anti-nephrin antibodies in patients with podocytopathies and healthy subjects.
METHODS: In this study, a total of 77 patients with active glomerulopathy and 11 healthy subjects were included. Forty one patients were diagnosed with FSGS, 11 with MCD, and 25 with MN. To measure the levels of anti-nephrin antibodies, enzyme-linked immunosorbent assay was used.
RESULTS: The levels of antibodies to nephrin were significantly higher in patients with MCD 61.2 [28.9-66.3] ng/mL and FSGS 32.5 [17.2-58.4] ng/mL compared to MN 20.3 [14.4-38.4] and healthy individuals 15.3 [12-18.9] ng/mL, p < .05. In patients with primary FSGS, the levels of antibodies to nephrin were significantly higher 45.2 [20-64.3] ng/mL compared to patients with secondary FSGS 26.7 [11.2-44.1] ng/mL, p < .05. There were no significant differences in the remission rate between the anti-nephrin antibodies positive and negative groups (log-rank test: p = .158).
CONCLUSIONS: The level of anti-nephrin antibodies was found to be significantly higher in patients with MCD and pFSGS compared to those with sFSGS, MN, and healthy subjects. Anti-nephrin antibodies in MCD and primary FSGS may be associated with the severity of podocytopathies, however they did not have an impact on the response to therapy.

Introduction  Focal and segmental glomerulosclerosis (FSGS) is a leading cause of nephrotic syndrome in both adults and children. The \"Columbia classification of FSGS\" includes five variants; not otherwise specified (NOS), tip, perihilar, cellular, and collapsing variants that may have different prognostic and therapeutic implications. Materials and Methods  This is a retrospective study and was carried out in the Department of Histopathology, Apollo Hospitals, Hyderabad. Of a total of 11,691 kidney biopsies over a 7-year period, from 2006 to 2012, 824 cases were diagnosed as FSGS, of which 610 cases in which detailed clinical findings were available were included in this study. FSGS was then categorized according to the Columbia classification. Results  FSGS, NOS was the predominant histomorphological variant. Serum creatinine was significantly high in the collapsing variant, followed by NOS. Follow-up data was available for 103 cases,72.8% had complete remission, 10.6% had partial remission, and in 16.5 % there was no remission. Relapses were observed in 6.7% cases, two patients (1.9%) succumbed, and 4.8% cases progressed to chronic kidney disease. Conclusion  This study showed that perihilar variant was less prevalent, with tip and cellular variants being more prevalent in Indian subcontinent compared to Western literature. Collapsing variant was also less common.

UNASSIGNED: Minimal change disease and focal segmental glomerulosclerosis are primary podocytopathies that are clinically presented in adults presenting with severe nephrotic syndrome. The pathogenesis of these diseases is not clear and many questions remain to be answered. A new concept about the role of changes in the antigenic determinant of podocytes and the production of anti-podocyte antibodies that cause podocyte damage is being developed. The aim of the study is to evaluate the levels of anti-CD40 and anti-ubiquitin carboxyl-terminal hydrolase L1 (anti-UCH-L1) antibodies in patients with podocytopathies in comparison with other glomerulopathies.
UNASSIGNED: One hundred and six patients with glomerulopathy and 11 healthy subjects took part in the study. A histological study revealed primary FSGS in 35 patients (genetic cases of FSGS and secondary FSGS in the absence of NS were excluded), 15 had MCD, 21 - MN, 13 - MPGN, 22 patients - IgA nephropathy. The effect of steroid therapy was evaluated in patients with podocytopathies (FSGS and MCD). The serum levels of anti-UCH-L1 and anti-CD40 antibodies were measured by ELISA before steroid treatment.
UNASSIGNED: The levels of anti-UCH-L1 antibodies were significantly higher in MCD patients and anti-CD40 antibodies were higher in MCD and FSGS than in the control group and other groups of glomerulopathies. In addition, the level of anti-UCH-L1 antibodies was higher in patients with steroid-sensitive FSGS and MCD, and anti-CD40 antibodies were lower than in patients with steroid-resistant FSGS. An increase in anti-UCH-L1 antibody levels above 6.44 ng/mL may be a prognostic factor of steroid-sensitivity. The ROC curve (AUC = 0.875 [95% CI 0.718-0.999]) for response to therapy showed a sensitivity of 75% and specificity of 87.5%.
UNASSIGNED: An increase in the level of anti-UCH-L1 antibodies is specific for steroid-sensitive FSGS and MCD, while an increase in anti-CD40 antibodies - for steroid-resistant FSGS, compared with other glomerulopathies. It suggests that these antibodies could be a potential factor for differential diagnosis and treatment prognosis.

In single-center studies, both preterm birth and low birth weight (LBW) are associated with worse outcomes in childhood nephrotic syndrome. Using the Nephrotic Syndrome Study Network (NEPTUNE) observational cohort, we tested the hypothesis that in patients with nephrotic syndrome, hypertension, proteinuria status, and disease progression would be more prevalent and more severe in subjects with LBW and prematurity singly or in combination (LBW/prematurity).
Three hundred fifty-nine adults and children with focal segmental glomerulosclerosis (FSGS) or minimal change disease (MCD) and available birth history were included. Estimated glomerular filtration rate (eGFR) decline and remission status were primary outcomes, and secondary outcomes were kidney histopathology, kidney gene expression, and urinary biomarkers. Logistic regression was used to identify associations with LBW/prematurity and these outcomes.
We did not find an association between LBW/prematurity and remission of proteinuria. However, LBW/prematurity was associated with greater decline in eGFR. This decline in eGFR was partially explained by the association of LBW/prematurity with APOL1 high-risk alleles, but the association remained after adjustment. There were no differences in kidney histopathology or gene expression in the LBW/prematurity group compared to normal birth weight/term birth.
LBW and premature babies who develop nephrotic syndrome have a more rapid decline in kidney function. We did not identify clinical or laboratory features that distinguished the groups. Additional studies in larger groups are needed to fully ascertain the effects of (LBW) and prematurity alone or in combination on kidney function in the setting of nephrotic syndrome.

BACKGROUND: This study aimed to investigate the role of neurofascin186 (NF186) in the pathogenesis of the concurrent focal segmental glomerulosclerosis (FSGS) in CIDP-like autoimmune nodopathy patients.
METHODS: We presented a case of CIDP-like autoimmune nodopathy complicated with FSGS. We measured NF186 antibodies by cell-binding assay (CBA) method. We performed immunofluorescence analysis in the renal cryosection samples from a patient with minimal nephropathy with rabbit anti-NF186 antibody or NF186 antibody positive human serum. Then we performed western blotting of recombinant NF186 protein and component of NF186 including Ig and FNIII domains incubating with human serum and corresponding rabbit polyclonal antibody. Cases of CIDP complicated with FSGS were searched form PubMed and reviewed.
RESULTS: We reported a 66-year-old Chinese woman with CIDP-like autoimmune nodopathy and concurrent FSGS. Her NF186 antibody was positive. The fluorescent signal for NF186 was detected in the renal tissue sections of the patient with minimal nephropathy. The staining for NF186 matched the podocyte spatially. In western blotting analysis, patients had antibodies in their serum recognizing the NF186 protein and their antibodies recognized the Ig domain of NF186. 3 cases of CIDP-like autoimmune nodopathy with positive NF186 antibody and FSGS have been reported. All these patients were responsive to corticosteroids rather than the intravenous immunoglobulin, in terms of both the neuropathy and renal disease.
CONCLUSIONS: NF186 was probably a targeted antigen in the pathogenesis of concurrent FSGS in CIDP-like autoimmune nodopathy with positive NF186 antibody. CIDP-like autoimmune nodopathy with positive NF186 antibody and FSGS is a rare entity, which may be responsive to corticosteroids combined with immunosuppressant.

Background Focal segmental glomerulosclerosis (FSGS) is characterized by the presence of glomerular damage on histopathological examination. The major defining symptom of FSGS is proteinuria, which indicates damage to the glomerular filtration barrier. Additionally, FSGS is the most common cause of primary nephrotic syndrome. However, in Saudi Arabia, there is a paucity of research on this topic. Therefore, this study was designed to examine the clinical features, laboratory findings, and presence of comorbidities in patients with FSGS to determine their effects on clinical outcomes. Methods We retrospectively analyzed the histopathological and clinical data of patients diagnosed with FSGS via biopsy at King Abdulaziz University Hospital, Jeddah, Saudi Arabia, during the period 1989-2020. Biopsy samples were labeled according to the Columbia classification as tip, perihilar, cellular, collapsing, or not otherwise specified (NOS). Results We included 39 children and 21 adults. Males accounted for 54.1% of the sample. Hypertension was the most common comorbidity. Regarding FSGS subtypes, 60.9% of the lesions in the adult patients were collapsing lesions, followed by NOS (26.1%). In pediatric patients, 36.8% of the lesions were NOS, followed by collapsing lesions (28.9%). We also observed a very low rate of remission. In both age groups, the most common clinical presentation was nephrotic syndrome. Conclusion We found a high prevalence of collapsing and NOS FSGS subtypes in both the adult and pediatric age groups. The most prevalent outcome was the persistence of nephrotic syndrome with low rates of remission.

Background Glomerulonephritis is among the most common and serious non-communicable diseases in the world, and some of them are major causes of chronic kidney disease, which eventually leads to kidney failure. In developing countries, it is the most common cause of end-stage renal disease (ESRD). Chronic kidney disease affects 10-16% of the adult population in Asia, including 21.2% in Pakistan. This study aims to determine the frequency and spectrum of glomerulonephritis at our center. Methodology This is a cross-sectional analysis of 81 renal core biopsies obtained between August 2020 and August 2021. The histopathological reports, demographic data, and relevant laboratory investigations, such as blood urea and creatinine levels, were collected. All cases were blindly reviewed by two pathologists with a special interest in medical renal pathology. Data were analyzed using SPSS version 22 (IBM Corp., Armonk, NY, USA). Results The majority of the patients (46.9%) were between the ages of 21 and 40 years. There was a slight male predominance, with 44 (54.3%) of the 81 participants being male. Hematuria was reported in 20 (24.7%) patients, with mean serum urea and creatinine levels of 75 mg/dL and 2.6 mg/dL, respectively. Nephrotic syndrome was the most common indication for a renal biopsy, accounting for 54 (67.7%) of the 81 cases. Chronic glomerulonephritis is classified into two categories, namely, primary and secondary glomerulonephritis. Focal segmental glomerulosclerosis (FSGS), the leading cause of primary glomerulonephritis, was found in 25 (30.9%) 81 patients. Furthermore, lupus nephritis (9.9%) and advanced glomerulonephritis (9.9%) were found in equal proportions among secondary glomerulonephritis. Conclusions According to our study, nephrotic syndrome was the most common indication for medical renal biopsy, with FSGS being the most common primary glomerulonephritis. Lupus nephritis and advanced glomerulonephritis were the most common secondary glomerulonephritis diagnoses.

UNASSIGNED: A critical unmet need exists for precision therapies for chronic kidney disease. GFB-887 is a podocyte-targeting, small molecule inhibitor of transient receptor potential canonical-5 (TRPC5) designed specifically to treat patients with glomerular kidney diseases characterized by an overactivation of the TRPC5-Rac1 pathway. In a first-in-human study, GFB-887 was found to be safe and well tolerated, had a pharmacokinetic (PK) profile allowing once-daily dosing, and dose dependently decreased urinary Rac1 in healthy adults.
UNASSIGNED: TRACTION-2 is a phase 2a, double-blind, placebo-controlled, multiple-ascending dose study of GFB-887 in patients with focal segmental glomerulosclerosis (FSGS), treatment-resistant minimal change disease (TR-MCD), or diabetic nephropathy (DN) (NCT04387448). Adult patients on stable renin-angiotensin system blockade and/or immunosuppression with persistent proteinuria will be randomized and dosed in 3 ascending dose levels to GFB-887 or placebo for 12 weeks. Cohorts may be expanded or biomarker-enriched depending upon results of an adaptive interim analysis.
UNASSIGNED: The primary objective is to evaluate the effect of increasing doses of GFB-887 on proteinuria. Safety and tolerability, quality of life, pharmacokinetic/pharmacodynamic profiles, and the potential association of urinary Rac1 with efficacy will also be evaluated. The projected sample size has 80% power to detect a treatment difference in proteinuria of 54% (FSGS/TR-MCD) or 44% (DN) compared to placebo.
UNASSIGNED: TRACTION-2 will explore whether targeted blockade of the TRPC5-Rac1 pathway with GFB-887 is an efficacious and safe treatment strategy for patients with FSGS, TR-MCD, and DN and the potential value of urinary Rac1 as a predictive biomarker of treatment response.

BACKGROUND: Recurrent focal and segmental glomerulosclerosis (FSGS) in kidney transplant recipients is associated with lower graft survival and increased morbidity. There are limited data to guide the decision to re-transplant patients with transplant failure due to FSGS recurrence. We aimed to evaluate outcomes in patients re-transplanted after having initial graft failure due to recurrent FSGS and to study physician attitudes and practice patterns.
METHODS: Retrospective data from 10 centers were collected on 20 patients transplanted between January 1997 and September 2018. A survey was sent to nephrologist members of the Pediatric Nephrology Research Consortium.
RESULTS: Mean patient age (years) was 9.8 ± 4.8 at first transplant and 15.9 ± 4.9 at re-transplantation. Pre-transplant plasmapheresis was used in 1 (5.3%) primary transplant vs. 7 (38.9%) re-transplants (p = .03). Nephrotic syndrome recurred in 14 patients (70%) after re-transplantation and was severe in 21.1% vs. 64.7% after first transplant (p = .04). Graft survival was significantly higher in the second transplant (p .009) with 70% having functioning grafts at a median of 25.2 months. Thirty-one physicians from 21 centers completed the survey, 94% indicated they would re-transplant such patients, 44.4% preferred a minimum waiting period before re-transplantation, 36.4% preferred living donors, and 22.2% indicated having protocols for re-transplantation at their centers.
CONCLUSIONS: Consideration for re-transplantation is high among pediatric nephrologists. Pre-transplant plasmapheresis was more frequent in re-transplanted patients. Nephrotic syndrome recurrence was less severe, with better graft survival. More data and a larger population are necessary to further evaluate outcome determinants and best practices in this special population.