WT-1 and NPHS2 mutation analysis in patients with non-familial steroid-resistant focal-segmental glomerulosclerosis

2003 ◽  
Vol 59 (02) ◽  
pp. 143-146 ◽  
Author(s):  
M.M. Löwik ◽  
E.N. Levtchenko ◽  
L.A.H. Monnens ◽  
L.P.W.J. van den Heuvel
Keyword(s):  
Focal Segmental Glomerulosclerosis ◽  
Mutation Analysis ◽  
Steroid Resistant ◽  
Segmental Glomerulosclerosis

scholarly journals Clinical and laboratory features that differentiate familial from sporadic focal segmental glomerulosclerosis in adolescents and adults

2021 ◽  
Vol 6 (1) ◽  
pp. 1-5
Author(s):  
Maria Goretti Polito ◽  
Michelle Tiveron Passos ◽  
Danilo Euclides Fernandes ◽  
Gianna Mastroianni-Kirsztajn
Keyword(s):  
Serum Albumin ◽  
Focal Segmental Glomerulosclerosis ◽  
Steroid Resistance ◽  
End Stage Kidney Disease ◽  
Steroid Resistant ◽  
Best Management ◽  
Segmental Glomerulosclerosis ◽  
Laboratory Features ◽  
Adolescents And Adults ◽  
End Stage

Background: Focal segmental glomerulosclerosis (FSGS) is an important cause of end-stage kidney disease in children and adults. Although most cases are sporadic (s), familial (f) presentation is also described. The purpose of the present study was to establish clinical and laboratory profiles of fFSGS vs. primary sFSGS, contributing to the distinguishing diagnosis in clinical practice and best management, in particular when mutation analysis is not available. Methods: Demographic, clinical and laboratorial parameters were studied in 124 patients 12 years and older with FSGS, subdivided in sFSGS (n=89) and fFSGS (n=35). Results: General and clinical features were similar, as well as serum creatinine at disease presentation. Proteinuria levels were more frequently ≥ 3g/day in sFSGS (63.8%) than in fFSGS (44%, p=0.080), and serum albumin levels were < 3.0 g/dL in 45.8% and 20%, respectively (p=0.046). The groups were statistically different regarding steroid resistance, corresponding to 60% in sFSGS and 100% in fFSGS (p=0.001). Conclusions: The studied groups were clinically similar, except that proteinuria tended to be higher (nephrotic range) and serum albumin was lower in sFSGS vs. fFSGS. In addition, all treated fFSGS patients were steroid resistant. At presentation it is important to characterize if the patient has fFSGS, that will contribute to further disease management, and disease history will be the first clue for such differential diagnosis.

Rituximab and low-dose cyclosporine combination therapy for steroid-resistant focal segmental glomerulosclerosis

2016 ◽  
Vol 58 (3) ◽  
pp. 219-223 ◽  
Author(s):  
Kazuhide Suyama ◽  
Yukihiko Kawasaki ◽  
Kyohei Miyazaki ◽  
Syuto Kanno ◽  
Atsushi Ono ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Focal Segmental Glomerulosclerosis ◽  
Low Dose ◽  
Steroid Resistant ◽  
Segmental Glomerulosclerosis

scholarly journals P0372RITUXIMAB IN IDIOPATHIC FOCAL SEGMENTAL GLOMERULOSCLEROSIS OF THE ADULT: A MULTICENTRE RETROSPECTIVE SURVEY OF 31 PATIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Martina Tedesco ◽  
Isabella Pisani ◽  
Marco Allinovi ◽  
Giovanni Casazza ◽  
Lucia Del Vecchio ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Focal Segmental Glomerulosclerosis ◽  
Immunosuppressive Treatment ◽  
Case Series ◽  
Post Transplantation ◽  
Steroid Resistant ◽  
Segmental Glomerulosclerosis ◽  
Steroid Dependent ◽  
Stage Renal Disease

Abstract Background and Aims Idiopathic Focal Segmental Glomerulosclerosis (FSGS) is a rare glomerulonephritis often complicated by a chronic relapsing course frequently characterized by dependency or resistance to immunosuppressive treatment. Moreover, about half of the patients with active disease would develop end-stage renal disease within 10 years from the diagnosis, highlighting the need of novel therapeutic approaches. Rituximab (RTX), a chimeric monoclonal antibody against CD20, showed promising results in pediatric steroid-dependent/frequently relapsing FSGS and in post-transplantation recurrence. However, evidence about its role in the FSGS of the adult is still lacking with small case series suggesting conflicting results. In this study we assess the efficacy of RTX in the largest cohort of adults with FSGS currently available in literature. Methods Adults with biopsy proven idiopathic FSGS treated with RTX were retrospectively identified among several Italian nephrology units. Response to RTX was evaluated at 3, 6, 12 months and, when available, during the long-term follow-up. A positive response (POR) was defined as: (1) proteinuria &lt;3.5 g/die with a decrease &gt;50% compared to baseline, (2) stable renal function (3) decreased or stable dose of glucocorticoids and other immunosuppressants. Severe Adverse Events (SAEs) have been recorded. Results 31 patients have been identified: 18 steroid-dependent, 11 steroid-resistant, and 2 patients with major contraindication to steroid therapy. RTX has been administered at a median of 87 months (IQR 54–96) from the diagnoses using heterogeneous schedules of administration. Overall, the POR rate at 6 months was 52% (steroid-dependent=69%; steroid-resistant=22%). At univariate analyses, POR to RTX at 6 months was associated to the steroid-dependent status (p=0.0347) and a proteinuria at RTX &lt;5 g/die (p=0.0173); a trend towards better response was observed in patients with IgG at RTX &lt;500 mg/dl (p=0.0774). Over the first year of follow-up, the proteinuria and serum albumin significantly improved (respectively, p=0.0021 and p=0.0277 at 12 months), while serum creatinine remained stable (figure). Among treated patients, the median dose of prednisone decreased from 15 mg/die (IQR 12.5–25) at baseline to 10 mg/die (IQR 5–15) at 12 months, while the proportion of patients free from glucocorticoids respectively increased from 42% to 54%. Six patients have been retreated within a year since the first RTX: of these only the 2 patients who have experienced a POR to the first administration obtained a further POR after retreatment. After the 12th month, 11 patients have been followed for a median time of 17 months (IQR 15–33.5): of the 5/11 with a POR at the 12th month, 2/5 maintained a POR without needing further immunosuppression, 2/5 maintained a POR with a pre-emptive RTX based maintenance treatment, 1/5 experienced a relapse successfully managed with RTX needing then a pre-emptive RTX based maintenance therapy able to allow a persistent POR. Overall, 9 SAEs have been recorded with requirement of hospital admission for clinical deterioration being the most frequent. Conclusion RTX may be an option in the FSGS of the adult, especially in the steroid-dependent patients and the ones with less severe nephrotic syndrome. In the responders, a RTX based maintenance therapy may be required.

scholarly journals Recent Advances in Treatments of Primary Focal Segmental Glomerulosclerosis in Children

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Kyoung Hee Han ◽  
Seong Heon Kim
Keyword(s):  
Focal Segmental Glomerulosclerosis ◽  
Calcineurin Inhibitors ◽  
Steroid Treatment ◽  
Renal Survival ◽  
Steroid Resistant ◽  
Segmental Glomerulosclerosis ◽  
Risk Of Progression ◽  
Traditional Therapies ◽  
Stage Renal Disease ◽  
End Stage

Focal segmental glomerulosclerosis (FSGS) is a nephrotic syndrome. Up to around 80% of cases of primary FSGS are resistant to steroid treatment. A large proportion of patients with steroid-resistant FSGS progress to end-stage renal disease. The purpose of treatment is to obtain a complete remission of proteinuria, a necessary step that precedes improved renal survival and reduces the risk of progression to chronic kidney disease. When this is not possible, the secondary goal is a partial remission of proteinuria. Reduction or remission of proteinuria is the most important factor predictive of renal survival. We will review the current updated strategies for treatment of primary FSGS in children, including traditional therapies consisting of corticosteroids and calcineurin inhibitors and novel therapies such as rituximab, abatacept, adalimumab, and fresolimumab.

scholarly journals A randomized trial of cyclosporine in patients with steroid-resistant focal segmental glomerulosclerosis

1999 ◽  
Vol 56 (6) ◽  
pp. 2220-2226 ◽  
Author(s):  
Daniel C. Cattran ◽  
Gerald B. Appel ◽  
Lee A. Hebert ◽  
Lawrence G. Hunsicker ◽  
Marc A. Pohl ◽  
...  
Keyword(s):  
Randomized Trial ◽  
Focal Segmental Glomerulosclerosis ◽  
Steroid Resistant ◽  
Segmental Glomerulosclerosis

scholarly journals Bigenic heterozygosity and the development of steroid-resistant focal segmental glomerulosclerosis

2008 ◽  
Vol 23 (10) ◽  
pp. 3146-3151 ◽  
Author(s):  
M. Lowik ◽  
E. Levtchenko ◽  
D. Westra ◽  
P. Groenen ◽  
E. Steenbergen ◽  
...  
Keyword(s):  
Focal Segmental Glomerulosclerosis ◽  
Steroid Resistant ◽  
Segmental Glomerulosclerosis

APOL1 risk genotype in European steroid-resistant nephrotic syndrome and/or focal segmental glomerulosclerosis patients of different African ancestries

2018 ◽  
Vol 34 (11) ◽  
pp. 1885-1893 ◽  
Author(s):  
Olivier Gribouval ◽  
Olivia Boyer ◽  
Bertrand Knebelmann ◽  
Alexandre Karras ◽  
Jacques Dantal ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Focal Segmental Glomerulosclerosis ◽  
West Indies ◽  
African Ancestry ◽  
Compound Heterozygous ◽  
French West Indies ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Segmental Glomerulosclerosis ◽  
Risk Variants

Abstract Background Apolipoprotein L1 (APOL1) risk variants are strongly associated with sporadic focal segmental glomerulosclerosis (FSGS) in populations with African ancestry. We determined the frequency of G1/G2 variants in steroid-resistant nephrotic syndrome (SRNS)/FSGS patients with African or French West Indies ancestry in France and its relationships with other SRNS genes. Methods In a cohort of 152 patients (139 families), the APOL1 risk variants were genotyped by direct Sanger sequencing and pathogenic mutations were screened by next-generation sequencing with a panel including 35 SRNS genes. Results The two risk allele [high-risk (HR)] genotypes were found in 43.1% (66/152) of subjects compared with 18.9% (106/562) in a control population (P < 0.0001): 33 patients homozygous for APOL1 G1 alleles, 4 homozygous for G2 and 29 compound heterozygous for G1 and G2. Compared with patients in the low-risk (LR) group, patients in the HR group were more likely to originate from the French West Indies than from Africa [45/66 (68.2%) versus 30/86 (34.9%); P < 0.0001]. There were more familial cases in the HR group [27 (41.5%) versus 8 (11.4%); P < 0.0001]. However, causative mutations in monogenic SRNS genes were found in only 1 patient in the HR group compared with 16 patients (14 families) in the LR group (P = 0.0006). At diagnosis, patients in the HR group without other mutations were more often adults [35 (53.8%) versus 19 (27.1%); P = 0.003] and had a lower estimated glomerular filtration rate (78.9 versus 98.8 mL/min/1.73 m2; P = 0.02). Conclusions The HR genotype is frequent in FSGS patients with African ancestry in our cohort, especially in those originating from the West Indies, and confer a poor renal prognosis. It is usually not associated with other causative mutations in monogenic SRNS genes.

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