<strong>Introduction:</strong> The evolution of primary FSGS is often marked by the occurrence of relapse and corticosteroid resistance and the therapeutic options are numerous and have limited effectivene...<strong>Introduction:</strong> The evolution of primary FSGS is often marked by the occurrence of relapse and corticosteroid resistance and the therapeutic options are numerous and have limited effectiveness. The objective of our study was to assess our practice in this lesion. <strong>Patients and Methods:</strong> We carried out a retrospective study of patients treated for primary FSGS the period January 1, 2010 to September 30, 2018. The clinical pathological, therapeutic and evolutive characteristics were studied. <strong>Results:</strong> Fifty-eight patients were included in the study. The average age was 30.74 ± 11.35 years and the sex ratio (M/F) was 2.41. Edema was found in 86.2% and hypertension in 37.9%. The average creatinine was 20.17 ± 16.06 mg/l and the average GFR according to MDRD was 82.43 ± 69.06 ml/min/1.73 m2. The average albumin level was 15.11 ± 5.78 g/l and the 24-hour proteinuria was 7.8 ± 3.79 g/24 h. Nephrotic syndrome was the main indication for renal biopsy in 84.48% and the classic form of FSGS was found in 90.9%. The average initial corticosteroid dose was 62.68 ± 10.04 mg/d and the average duration of regression was 11.78 ± 7.40 months. Forty-five patients (77.6%) were corticosensitive (27.6% complete remission and 50% partial remission). Corticosteroid resistance was observed in 19% and corticosteroid dependence in 11.1%. The proportion of relapse was 33.3% within an average of 15.4 ± 9.1 months. Cyclosporine was no longer prescribed as a second-line treatment in 8 patients. Infectious complications were more found in 19%. Two patients had progressed to ESRD and we noted 2 death cases. The male gender was correlated with the occurrence of a relapse. However, the impact of certain factors such as hypertension, proteinuria, hematuria and GFR level has not been demonstrated. <strong>Conclusion:</strong> The evolution of primary FSGS is unpredictable, often marked by relapses, hence the interest in identifying factors associated with therapeutic responses for better management.展开更多
Background:Reliable animal models are crucial to drug development for focal segmental glomerulosclerosis(FSGS),a rare kidney disease.Variability in success rates in literature and significant ethical concerns with ani...Background:Reliable animal models are crucial to drug development for focal segmental glomerulosclerosis(FSGS),a rare kidney disease.Variability in success rates in literature and significant ethical concerns with animal welfare necessitate further optimization of adriamycin(ADR)-induced FSGS model developed on BALB/c mice.Methods:High-performance liquid chromatography(HPLC)was used to assess ADR stability in water and upon light exposure.To identify the optimal ADR level,single intravenous ADR injections with dosing levels from 10 to 17 mg/kg body weight were administered to BALB/c mice to induce FSGS-like pathology.Body weight and proteinuria of FSGS mice were monitored and analyzed for FSGS model-associated morbidity.Animals were euthanized for hematological and kidney histological assessments 8 weeks post induction.To identify the suitable experiment time frame of the ADR-induced FSGS mouse model,a longitudinal study was performed,with an 11-week continuous monitoring of the symptoms.Results:ADR was found to be unstable in aqueous media and light sensitive.A dosing level of 10.5 mg/kg of ADR was optimal for consistent FSGS mouse model induction on BALB/c strain,characterized by minimal mortality and sustained FSGS-like symptoms.Findings from the longitudinal study suggest that 6 weeks post ADR induction may represent the peak of FSGS pathology severity in this mouse model.This time frame may be used for FSGS drug development projects.Conclusion:Based on the outcome from this study,we identified the optimal ADR dosing level and model testing duration.A standard operating procedure(SOP)for the ADR-induced FSGS mouse model was established to facilitate FSGS basic research and drug development.展开更多
文摘<strong>Introduction:</strong> The evolution of primary FSGS is often marked by the occurrence of relapse and corticosteroid resistance and the therapeutic options are numerous and have limited effectiveness. The objective of our study was to assess our practice in this lesion. <strong>Patients and Methods:</strong> We carried out a retrospective study of patients treated for primary FSGS the period January 1, 2010 to September 30, 2018. The clinical pathological, therapeutic and evolutive characteristics were studied. <strong>Results:</strong> Fifty-eight patients were included in the study. The average age was 30.74 ± 11.35 years and the sex ratio (M/F) was 2.41. Edema was found in 86.2% and hypertension in 37.9%. The average creatinine was 20.17 ± 16.06 mg/l and the average GFR according to MDRD was 82.43 ± 69.06 ml/min/1.73 m2. The average albumin level was 15.11 ± 5.78 g/l and the 24-hour proteinuria was 7.8 ± 3.79 g/24 h. Nephrotic syndrome was the main indication for renal biopsy in 84.48% and the classic form of FSGS was found in 90.9%. The average initial corticosteroid dose was 62.68 ± 10.04 mg/d and the average duration of regression was 11.78 ± 7.40 months. Forty-five patients (77.6%) were corticosensitive (27.6% complete remission and 50% partial remission). Corticosteroid resistance was observed in 19% and corticosteroid dependence in 11.1%. The proportion of relapse was 33.3% within an average of 15.4 ± 9.1 months. Cyclosporine was no longer prescribed as a second-line treatment in 8 patients. Infectious complications were more found in 19%. Two patients had progressed to ESRD and we noted 2 death cases. The male gender was correlated with the occurrence of a relapse. However, the impact of certain factors such as hypertension, proteinuria, hematuria and GFR level has not been demonstrated. <strong>Conclusion:</strong> The evolution of primary FSGS is unpredictable, often marked by relapses, hence the interest in identifying factors associated with therapeutic responses for better management.
基金United States Department of Defense Office of the Congressionally Directed Medical Research Programs(CDMRP),Grant/Award Number:W81XWH-22-1-0176。
文摘Background:Reliable animal models are crucial to drug development for focal segmental glomerulosclerosis(FSGS),a rare kidney disease.Variability in success rates in literature and significant ethical concerns with animal welfare necessitate further optimization of adriamycin(ADR)-induced FSGS model developed on BALB/c mice.Methods:High-performance liquid chromatography(HPLC)was used to assess ADR stability in water and upon light exposure.To identify the optimal ADR level,single intravenous ADR injections with dosing levels from 10 to 17 mg/kg body weight were administered to BALB/c mice to induce FSGS-like pathology.Body weight and proteinuria of FSGS mice were monitored and analyzed for FSGS model-associated morbidity.Animals were euthanized for hematological and kidney histological assessments 8 weeks post induction.To identify the suitable experiment time frame of the ADR-induced FSGS mouse model,a longitudinal study was performed,with an 11-week continuous monitoring of the symptoms.Results:ADR was found to be unstable in aqueous media and light sensitive.A dosing level of 10.5 mg/kg of ADR was optimal for consistent FSGS mouse model induction on BALB/c strain,characterized by minimal mortality and sustained FSGS-like symptoms.Findings from the longitudinal study suggest that 6 weeks post ADR induction may represent the peak of FSGS pathology severity in this mouse model.This time frame may be used for FSGS drug development projects.Conclusion:Based on the outcome from this study,we identified the optimal ADR dosing level and model testing duration.A standard operating procedure(SOP)for the ADR-induced FSGS mouse model was established to facilitate FSGS basic research and drug development.
