Steroid Resistant Focal Segmental Glomerulosclerosis: Effect of Arterial Hyalinosis on Outcome: Single center study

AbstractBackground: Few data with adequate evidence exists regards the effect of Cyclosporine (CsA) and mycophenolate mofetil (MMF) on pathological prognostic parameters in patients with steroid resistant focal segmental glomerulosclerosis (FSGS). The purpose of the present study is to compare the effect of cyclosporin and mycophenolate mofetil in addition to steroids on functional and histopathologic renal parameters in patients with steroid resistant FSGS one year after treatment.Material and methods: Thirty-seven adults with primary FSGS patients resistant to steroid therapy consecutively randomized to treatment with either MMF or cyclosporine. Low dose prednisolone added to both groups. Glomerular filtration rate (GFR) and blood pressure (BP) were determined at all examinations and a second renal biopsy was taken 12 months after treatment with either of cyclosporin and mycophenolate mofetil.Results: GFR significantly increased in MMF group p <0.01 after 6 months and unchanged after 12 months. On the other hand, GFR significantly decrease in CsA group p <0.001 after 6 months and reduced more after 12 months p <0.001 compared to base line levels. Significant difference of GFR between the 2 groups at 6 months p<0.001. The extent of proteinuria decreased significantly in CsA group after 12 months p <0.001. The extent of arteriolar hyalinosis increased significantly in CsA group (0.78 to 1.81 score, p <0.001) but was unchanged in MMF group (0.93 to 0.96 score), whereas interstitial fibrosis increased to same level in both groups (grade 3).Conclusion: Conversion to MMF in those patients may be superior to CsA as regard GFR after 12 months after treatment in spite presence of greater level of protein excretion. The increased arteriolar hyalinosis during CsA treatment most likely result in higher BP compared to MMF treatment in patients with FSGS resistant to steroids.

Download Full-text

The Relationship of Vitamin D Level with Renal Prognosis in Focal Segmental Glomerulosclerosis Patients- A Retrospective Study

JOURNAL FOR CLINICAL AND DIAGNOSTIC RESEARCH ◽

10.7860/jcdr/2021/49065.15212 ◽

2021 ◽

Author(s):

Cagdas Kucukerdogan ◽

Ebru Gok Oguz ◽

Gulay Ulusal Okyay ◽

Hatice Sahin ◽

Tamer Selen ◽

...

Keyword(s):

Focal Segmental Glomerulosclerosis ◽

Interstitial Fibrosis ◽

Binary Logistic Regression ◽

Binary Logistic Regression Analysis ◽

First Year ◽

Tubular Atrophy ◽

Segmental Glomerulosclerosis ◽

Renal Prognosis ◽

One Year ◽

The Relationship

Introduction: The level of 25-hydroxyvitamin D3 is an independent predictor of disease progression and death in Chronic Kidney Disease (CKD) patients. However, there are insufficient data to evaluate the possible effects of plasma 25(OH)D3 levels on the prognosis of Focal Segmental Glomerulosclerosis (FSGS). Aim: To analyse the relationship between renal prognosis and serum 25(OH)D3 status in FSGS. Materials and Methods: The study was conducted on 56 patients, who were followed-up for at least one year and diagnosed with primary FSGS. Participants were grouped according to their baseline 25(OH)D3 levels (≤15 or >15 ng/mL) and treatment response at the end of one year (remission group or no remission group) was evaluated. Results: Mean age of the 56 participants was 44±13.92 years and 27 (48.2%) were male. Remission achievement in the first year was significantly higher and interstitial fibrosis was significantly lower for the group with a 25(OH)D3 above >15 ng/ mL (p<0.001, p=0.002, respectively). Basal serum 25(OH)D3 level was significantly lower and interstitial fibrosis and tubular atrophy percentages were higher for the ‘no remission’ group (p<0.001, p<0.001, p=0.005, respectively). Results of the binary logistic regression analysis revealed that low 25(OH)D3 level and higher interstitial fibrosis were independent predictive factors that increased the risk of no remission in the first year (p=0.036, p=0.004, respectively). Conclusion: In primary FSGS patients, low baseline 25(OH)D3 level at the time of biopsy and high interstitial fibrosis are independent predictors that reduce remission rates in the first year.

Download Full-text

SP183REMISSION INDUCTION THERAPY FOR IDIOPATHIC FOCAL SEGMENTAL GLOMERULOSCLEROSIS ACCOMPANIED BY NEPHROTIC SYNDROME AND FACTORS FOR REMISSION AT ONE YEAR AFTER THE THERAPY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfz103.sp183 ◽

2019 ◽

Vol 34 (Supplement_1) ◽

Author(s):

Hiroaki Tanaka ◽

Junya Koshizaka ◽

Nobuaki Yamauchi ◽

Mayu Morimoto ◽

Noriko Terasaki ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Focal Segmental Glomerulosclerosis ◽

Induction Therapy ◽

Segmental Glomerulosclerosis ◽

One Year

Download Full-text

Moxibustion Alleviates Injury in a Rat Focal Segmental Glomerulosclerosis Model

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/7169547 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Yi Li ◽

Yuxia Sun ◽

Chunling Zhang ◽

Ke Wang ◽

Peicheng Shen ◽

...

Keyword(s):

Focal Segmental Glomerulosclerosis ◽

Rat Model ◽

Interstitial Fibrosis ◽

Similar Efficacy ◽

Glomerular Sclerosis ◽

Control Group ◽

Therapeutic Effects ◽

Repeated Injection ◽

Moxibustion Group ◽

Segmental Glomerulosclerosis

Objectives. To evaluate the therapeutic effects of moxibustion at Shenshu (BL-23) and Geshu (BL-17) acupoints in a focal segmental glomerulosclerosis (FSGS) model in rats. Methods. A FSGS rat model was established by single nephrectomy and repeated injection of doxorubicin. The FSGS rats were randomly divided into the model group, losartan (positive control) group, Shenshu moxibustion group, and Geshu moxibustion group. Molecular indicators of kidney function and renal pathological changes were monitored. Results. Urinary protein, serum creatinine, urea nitrogen, and serum uric acid were significantly reduced after 12-week intervention with losartan, Shenshu, or Geshu moxibustion. Renal α-SMA, FN, and TGF-β were also decreased, while podocin and nephrin protein and mRNA were increased. The pathological damage in renal tissue was obviously alleviated by all three treatments, which suggests that moxibustion may have similar efficacy to losartan in the treatment of FSGS. Conclusion. Moxibustion alleviates podocyte injury and inhibits renal interstitial fibrosis in the FSGS rat model, thereby minimizing the progression of glomerular sclerosis and improving renal function.

Download Full-text

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

Journal of Rare Diseases Research & Treatment ◽

10.29245/2572-9411/2021/1.1199 ◽

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.

Download Full-text

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

Pediatrics International ◽

10.1111/ped.12804 ◽

2016 ◽

Vol 58 (3) ◽

pp. 219-223 ◽

Cited By ~ 6

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

Download Full-text

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

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0372 ◽

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 <3.5 g/die with a decrease >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 <5 g/die (p=0.0173); a trend towards better response was observed in patients with IgG at RTX <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.

Download Full-text

Recent Advances in Treatments of Primary Focal Segmental Glomerulosclerosis in Children

BioMed Research International ◽

10.1155/2016/3053706 ◽

2016 ◽

Vol 2016 ◽

pp. 1-6 ◽

Cited By ~ 5

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.

Download Full-text