High-dose oral cyclosporin therapy for recurrent focal segmental glomerulosclerosis in children

2004 ◽  
Vol 44 (1) ◽  
pp. 50-56 ◽  
Author(s):  
Reem H Raafat ◽  
Alok Kalia ◽  
Luther B Travis ◽  
Steven C Diven
Keyword(s):  
Focal Segmental Glomerulosclerosis ◽  
High Dose ◽  
Cyclosporin Therapy ◽  
Oral Cyclosporin ◽  
Segmental Glomerulosclerosis ◽  
Dose Oral

P1757RITUXIMAB FOR RECURRENCE OF PRIMARY FOCAL SEGMENTAL GLOMERULOSCLEROSIS AFTER KIDNEY TRANSPLANTATION: RESULTS OF A NATIONWIDE STUDY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Camille Lanaret ◽  
Dany Anglicheau ◽  
Audard Vincent ◽  
Celine Lambert ◽  
Lionel Couzi ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Focal Segmental Glomerulosclerosis ◽  
Standard Of Care ◽  
High Dose ◽  
Infectious Risk ◽  
Segmental Glomerulosclerosis ◽  
Group 2 ◽  
Retrospective Multicenter Study ◽  
Group 1 ◽  
Rejection Rates

Abstract Background and Aims The indication of rituximab (RTX) in the treatment of primary focal segmental glomerulosclerosis (FSGS) recurrence after kidney transplantation (KT) remains controversial. The objective of our study was to evaluate the benefit and tolerability of adding RTX to the standard of care (SOC) comprising plasmapheresis (PP), corticosteroids, and high-dose anticalcineurins for the treatment of FSGS recurrence after KT. Method This retrospective, multicenter study reports on 148 patients, transplanted between 31 December 2004 and 31 December 2018, aged 39.9 + 13.4 years, who developed FSGS recurrence at 7 [3–23] days. In all 109 patients received a SOC (Group 1). RTX was introduced in this group after more than 28 days of SOC for failure or for therapeutic intensification (n = 19, Group 1a), or for early discontinuation of PP (n = 12, Group 1b); 39 patients received RTX associated at the outset with SOC (Group 2). Results We observed 46.6% complete remission (CR) and 33.1% partial remission (PR). Ten-year graft survival was 65.6% [51.4–76.6] and 13.4% [3.4–30.0] in responders and non-responders respectively. There was no difference in CR + PR rate between G1 (82.5%) and G2 (71.8%), p = 0.08, confirmed by propensity score +4.3% (95% CI [−9.0%-17.5%], p = 0.53). Following addition of RTX (Group 1a), we observed a CR rate of 26.3% and a PR rate of 31.6%. Patients with and without RTX experienced similar rejection rates (18.6% and 28.2%, p = 0.17) and infection rates (71.4% and 79.5%, p = 0.40). In multivariate analysis, the infections were associted with hypogammaglobulinemia <5g/l (OR = 8.04, 95% CI [1.65,39.25], p = 0.01). Conclusion Rituximab could be used in cases of SOC failure or in remission patients for early weaning of plasmapheresis, without increasing infectious risk.

Primary focal segmental glomerulosclerosis

2018 ◽  
Author(s):  
Alain Meyrier ◽  
Patrick Niaudet
Keyword(s):  
Focal Segmental Glomerulosclerosis ◽  
Viral Infections ◽  
Therapy Response ◽  
High Dose ◽  
African Origin ◽  
Donor Kidney ◽  
Progressive Loss ◽  
Segmental Glomerulosclerosis ◽  
Collapsing Fsgs ◽  
Focal Segmental Sclerosis

Primary focal segmental glomerulosclerosis (FSGS) causes nephrotic syndrome and by definition is not caused by any of the known causes of podocyte toxicity or focal segmental sclerosis such as viral infections or toxins. A number of genetic causes of FSGS are commonly diagnosed in early childhood. Other causes of segmental scarring need to be distinguished. Genotypes in APOL1 of African origin are associated with higher incidence of FSGS and poorer responses to treatment. Cellular and collapsing FSGS are variants of FSGS in which there is overt acute podocytopathy and they have a relatively poor prognosis. A glomerular tip lesion is thought to have a slightly better prognosis than other types. Some cases of primary FSGS respond to high-dose corticosteroids, sometimes only after prolonged therapy. Response to steroids is a good prognostic sign, and without a response, progressive loss of renal function is likely. A circulating factor is implicated by the observation that proteinuria can recur in a donor kidney within hours of transplant. Plasma exchange appears to remove this factor but it is not conclusively identified.

scholarly journals Focal segmental glomerulosclerosis: current status of the problem

2020 ◽  
Vol 10 (1) ◽  
pp. 38-46
Author(s):  
I. T. Murkamilov ◽  
I. S. Sabirov ◽  
V. V. Fomin ◽  
Zh. A. Murkamilova
Keyword(s):  
Focal Segmental Glomerulosclerosis ◽  
Ace Inhibitors ◽  
Daily Intake ◽  
Adult Patients ◽  
Response To Treatment ◽  
Current Status ◽  
Chronic Glomerulonephritis ◽  
High Dose ◽  
Converting Enzyme Inhibitors ◽  
Segmental Glomerulosclerosis

One of the most prognostically unfavorable variants of glomerulopathy is focal segmental glomerulosclerosis (FSHC), which is detected by nephrobiopsy in 5-20% of patients with nephrotic syndrome (NS) and in 15% of adult patients with chronic glomerulonephritis. FSGS recurs in a transplanted kidney in 30-50% of patients. Among adult patients with FSH, men predominate. A poor prognosis of FSHC is explained by the heterogeneity of the disease and is exacerbated by a poor response to treatment. According to current data, FSGS is characterized by sclerosis of the mesangial matrix, hyalinosis, damage to capillaries, an increase in foam cells and their adhesion between the glomerular bundle and the Bowman capsule. In 2004, the following histological variants of FSGS were proposed: apical, perichillary, collaborating, cellular and classical. Each histological variant of FSGS differs in etiology, response to treatment, and prognosis. The clinical diagnosis of primary FSHC should be based on the exclusion of secondary causes of the disease. Focal sclerotic changes in the glomeruli can be caused by various factors and occur in various conditions, including the existing kidney pathology. According to international recommendations for the treatment of FSHS, one should focus on the amount of daily proteinuria. For patients with FSHS without pronounced proteinuria, the use of angiotensin converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor blockers (ARBs) is recommended. In FSGS and NS, immunosuppressive therapy is used along with ACE inhibitors or ARB II. For adult patients, glucocorticoids (HA) are prescribed daily in a single dose at a dose of 1 mg / kg per day, the maximum dose is 80 mg with a daily intake and 120 mg with an alternating regimen. Resistance to HA is detected in the absence of effect after 16 weeks. In the presence of contraindications or intolerance to HA, calcineurin inhibitors are used. The recommended initial dose of cyclosporine is 2 mg / kg / day, taken twice a day with a gradual increase to 3.5-4 mg / kg / day. The duration of therapy with satisfactory tolerance to cyclosporine is more than six months. After achieving complete remission, the dose of cyclosporin is gradually reduced by 0.5 mg / kg / day to the minimum effective dose (1.5-2 mg / kg / day) and such maintenance therapy is carried out for 1-2 years. A treatment option is possible using lower doses of HA and cyclosporine, or a combination of mycophenolate mofetil with a high dose of dexamethasone.

scholarly journals Treatment of childhood nephrotic syndrome.

1992 ◽  
Vol 3 (4) ◽  
pp. 889-894
Author(s):  
S A Mendoza ◽  
B M Tune
Keyword(s):  
Nephrotic Syndrome ◽  
Focal Segmental Glomerulosclerosis ◽  
Alkylating Agent ◽  
Controlled Trial ◽  
Current Data ◽  
High Dose ◽  
Converting Enzyme Inhibitors ◽  
Childhood Nephrotic Syndrome ◽  
Segmental Glomerulosclerosis ◽  
Daily Prednisone

This review examines selected aspects of the treatment of the nephrotic syndrome in children. Particular attention has been paid to two groups of nephrotic children. First, children with steroid-responsive nephrotic syndrome are discussed. Recently, a series of controlled studies have provided important information regarding the optimal duration of steroid therapy. Initial episodes of the nephrotic syndrome are best treated with "long" courses of prednisone therapy (6 wk of high-dose daily prednisone followed by 6 wk of alternate-day prednisone). In contrast, relapses do as well with "short" courses (about 2 wk of daily prednisone and 2 wk of alternate-day therapy). Some children who are steroid responsive require high doses of prednisone to remain in remission. These patients may require alkylating agent therapy. The most common cause of steroid-resistant nephrotic syndrome is focal segmental glomerulosclerosis. Over the past 10 yr, these patients have been treated with an intensive protocol involving multiple infusions of high-dose methylprednisolone and, in many cases, oral alkylating agent therapy. Current experience with this treatment is presented. The protocol appears to improve the outcome in children with focal segmental glomerulosclerosis, although it is believed that it is essential that these observations be confirmed by a controlled trial. There is also interest in the use of angiotensin-converting enzyme inhibitors and cyclosporine in the treatment of childhood nephrotic syndrome. The experience with these agents is briefly reviewed, but the current data are inadequate to indicate their role(s) in this condition.

scholarly journals High-Dose Rituximab Ineffective for Focal Segmental Glomerulosclerosis: A Long-Term Observation Study

2017 ◽  
Vol 46 (2) ◽  
pp. 108-113 ◽  
Author(s):  
Dario Roccatello ◽  
Savino Sciascia ◽  
Daniela Rossi ◽  
Mirella Alpa ◽  
Carla Naretto ◽  
...  
Keyword(s):  
Renal Function ◽  
Focal Segmental Glomerulosclerosis ◽  
B Lymphocyte ◽  
Adult Patients ◽  
High Dose ◽  
Observation Study ◽  
Positive Effects ◽  
Segmental Glomerulosclerosis ◽  
Investigation Methods ◽  
Long Term Observation

Background: A beneficial effect of rituximab (RTX) on focal segmental glomerulosclerosis (FSGS) in pediatric patients or in transplant recipients has been reported in isolated cases. However, the use of RTX in adult patients with idiopathic FSGS needs further investigation. Methods: Eight patients who had biopsy-proven FSGS (63.9 ± 14.0, range 40-81 years, 4 women, 4 men) with major risk factors precluding corticosteroids or conventional immunosuppression were treated with a high dose of RTX (8 weekly doses of 375 mg/m2) and prospectively followed up for at least 2 years (29.1 ± 8.8 months, range 24-42 months). Results: RTX failed to improve proteinuria in 7 out of 8 patients, who had persistent nephrotic proteinuria. In one case, a rapidly deteriorating renal function was also observed. Only one patient showed an improvement in renal function and a remarkable reduction in proteinuria. There were no differences in clinical or laboratory characteristics or in the CD20 B lymphocyte count after RTX between the responder and the 7 nonresponder patients. Conclusions: Only a minority (1 of 8) in our series of adult patients with FSGS showed positive effects of high doses of RTX. Future studies are warranted to investigate more promising therapeutic options in the management of FSGS.

scholarly journals Collapsing Focal Segmental Glomerulosclerosis Following Treatment with High-Dose Pamidronate

2001 ◽  
Vol 12 (6) ◽  
pp. 1164-1172 ◽  
Author(s):  
GLEN S. MARKOWITZ ◽  
GERALD B. APPEL ◽  
PAUL L. FINE ◽  
ANDREW Z. FENVES ◽  
NICHOLAS R. LOON ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Renal Insufficiency ◽  
Focal Segmental Glomerulosclerosis ◽  
Metastatic Breast ◽  
Recommended Dose ◽  
Temporal Association ◽  
High Dose ◽  
Metastatic Breast Carcinoma ◽  
Segmental Glomerulosclerosis ◽  
Collapsing Fsgs

Abstract. Collapsing focal segmental glomerulosclerosis (FSGS) is a distinct clinicopathologic entity seen most commonly in young African American patients who present with renal insufficiency and nephrotic syndrome. The only epidemiologic factor previously linked to collapsing FSGS is HIV infection. Here clinicopathologic findings are reported for a distinctive population of seven patients, who were older, Caucasian, and HIV negative and developed collapsing FSGS during active treatment of malignancy (multiple myeloma in six patients and metastatic breast carcinoma in one). Although oncologic treatment regimens included vincristine for four patients, doxorubicin for five patients, cisplatin for two patients, and total-body irradiation for one patient, the only agent common to all patients was pamidronate (Aredia). All patients had normal renal function before the administration of pamidronate. Patients began therapy with pamidronate at or below the recommended dose of 90 mg, intravenously, monthly, which was increased to 180 mg monthly in two patients and 360 mg monthly in three patients. Patients received pamidronate for 15 to 48 mo before presentation with renal insufficiency (mean serum creatinine, 3.6 mg/dl) and full nephrotic syndrome (mean 24-h urinary protein excretion, 12.4 g/d). Pamidronate, which is a member of the class of bisphosphonates, is widely used in the treatment of hypercalcemia of malignancy and osteolytic metastases. At the recommended dose of 90 mg, intravenously, monthly, renal toxicity is infrequent; however, higher doses have produced nephrotoxicity in animal models. The temporal association between pamidronate therapy and the development of renal insufficiency, the use of escalating doses that exceed recommended levels, and the distinctive pattern of glomerular and tubular injury strongly suggest a mechanism of drug-associated podocyte and tubular toxicity. These data provide the first association of collapsing FSGS with toxicity to a therapeutic agent.

Primary focal segmental glomerulosclerosis

2018 ◽  
Author(s):  
Alain Meyrier ◽  
Patrick Niaudet
Keyword(s):  
Nephrotic Syndrome ◽  
Focal Segmental Glomerulosclerosis ◽  
Remission Rate ◽  
Calcineurin Inhibitors ◽  
Steroid Treatment ◽  
High Dose ◽  
Glomerular Injury ◽  
Asian Patients ◽  
Segmental Glomerulosclerosis ◽  
Black Patients

The proportion of cases of primary focal segmental glomerulosclerosis responsive to treatment with corticosteroids is variable and depends on histological type, patient age and duration, and dose of steroid treatment, but overall complete remission rate is estimated at 20–25% in white and Asian patients, and lower in black patients. Partial response dependent on a high dose of steroids is common. Despite anxieties about nephrotoxicity, there may be justification for adding calcineurin inhibitors to control nephrotic syndrome if it is severe. Data for additional agents is not very encouraging. Plasma exchange appears to remove a circulating factor that causes proteinuria in focal segmental glomerulosclerosis, as illustrated by responses to this treatment when proteinuria recurs acutely after kidney transplantation. This is rarely pursued clinically except after transplantation, in advance of severe glomerular injury.

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