Familial collapsing focal segmental glomerulosclerosis

The majority of patients with non-HIV-related collapsing focal segmental glomerular sclerosis (FSGS) have idiopathic disease. Only a few genetic forms associated with rare syndromes have been described in families. Here we report two families with multiple members who have collapsing FSGS with no clear associated secondary etiology. Genetic analysis revealed a defect in the TRPC6 gene in one family, but excluded all known common inherited podocyte defects in the other family. The course and response to treatment differed dramatically among members of the same family.     

Successful treatment of recurrent focal segmental glomerulosclerosis with a low dose rituximab in a kidney transplant recipient

Recurrence of focal segmental glomerulosclerosis (FSGS) is a major therapeutic challenge in kidney transplantation (KT). Although intensive plasmapheresis and high-dose rituximab have been introduced to treat recurrent FSGS, the most effective dosage and regimen of rituximab have not been determined. Herein we reported the first case of successful treatment of recurrent FSGS with a low-dose rituximab. The patient showed marked proteinuria (3.5?g/d) and oliguria 2?d after KT. Two courses of plasmapheresis and immunoglobulin were applied to the patient, however, nephrotic range proteinuria persisted and creatinine level increased to 3.56?mg/dL. Five months post-transplant, the patient received injection with only one dose of rituximab 100?mg, without further plasmapheresis, which resulted in immediate reduction of serum creatinine and full remission of proteinuria during the following 18 months. This case suggested that recurrent FSGS, which frequently relapses after plasmapheresis, could be treated successfully with a low-dose rituximab even without plasmapheresis.     

Successful treatment of recurrent focal segmental glomerulosclerosis after kidney transplantation by plasmapheresis and rituximab

A 22-year-old patient whose primary kidney disease was focal segmental glomerulosclerosis (FSGS) developed severe recurrence of proteinuria (up to 57 g/24 h) immediately after a haploidentic living donor kidney transplantation despite pre-operative plasmapheresis. The immunosuppressive treatment consisted of tacrolimus, mycophenolate mofetil, basiliximab and steroids. He underwent 10 plasmapheresis sessions in the first 3-week post-transplantation. In addition, he received 2 i.v. doses of rituximab (RTX) 600 mg (375 mg/m(2)) on days 7 and 15. Proteinuria decreased below nephrotic range at day 14 and serum creatinine returned progressively to normal values. A short course of oral ciclophosphamide (100 mg/j) was administrated between days 22 and 40 and three additional plasmapheresis sessions on days 34, 39 and 49. This strategy allowed obtaining sustained full remission of the nephrotic syndrome (NS) and excellent graft function, which persists over 2 years after transplantation. No notable adverse events related to RTX or plasmapheresis were observed. This case suggests that RTX associated with plasmapheresis may be an effective treatment of recurrent NS because of FSGS.     

A prospective study of collapsing focal segmental glomerulosclerosis

Collapsing focal segmental glomerulosclerosis (cFSGS) is characterized by rapid progression to end-stage renal disease (ESRD). We evaluated the clinicopathological spectrum of cFSGS and compared its clinical behavior to steroid and tacrolimus (TAC)-resistant noncollapsing focal segmental glomerulosclerosis (FSGS). All patients (>14 years) diagnosed with cFSGS were enrolled in the study. Staining for differentiated podocyte markers such as WT 1, PAX and KI67 were performed in all patients. The outcome and histological features of cFSGS was compared with a prospectively followed cohort of steroid and TAC-resistant noncollapsing FSGS. The study included 22 cFSGS patients and 19 cases of steroid and TAC-resistant FSGS. Complete remission, partial remission, steroid resistance, progression to ESRD and death were observed in 13.6%, 4.5%, 27.3%, 36.4% and 18.2% patients, respectively. Patients with cFSGS had higher serum creatinine and more advanced tubulointerstitial changes compared to resistant FSGS. Twenty-six percent of therapy resistant noncollapsing FSGS progressed to ESRD after two years of stopping TAC. However, there was no difference in progression to ESRD between cFSGS and therapy-resistant noncollapsing FSGS at the end of two years. Glomerular collapse in the setting of FSGS is poorly responsive to treatment and has a high rate of progression to ESRD. The long-term prognosis of cFSGS and steroid and TAC-resistant FSGS are similar.     

Idiopathic collapsing focal segmental glomerulosclerosis in pediatric patients

The aim of this study was to evaluate the clinical outcome of our patients with idiopathic collapsing focal segmental glomerulosclerosis (FSGS) as compared to those with non-collapsing FSGS. The study included a total of 39 patients with idiopathic FSGS. Of these, 11 had collapsing FSGS and the remaining 28 were collectively grouped as non-collapsing FSGS. The mean ages, gender ratio (M:F), and percentage of African-American patients in collapsing versus non-collapsing FSGS groups were 12.7 ± 3.1 and 8.9 ± 5.1 years, 1.2:1 and 4.6:1, and 90.9 and 53.6%, respectively. After a mean followup period of 31.5 ± 22.3 months, 8 patients (73%) with collapsing FSGS had chronic renal impairment as compared to 8 (29%) patients with non-collapsing FSGS group after a mean follow-up period of 18.7 ± 12.9 months. However, the cumulated renal survival at 30 months did not reveal a significant difference. In comparison to non-collapsing FSGS, collapsing FSGS in our study was equally common in females as in males and occurred predominantly in African Americans. The outcome of our patients with collapsing FSGS at 30 months was better than in previous reports. Dr. El-Refaey’s fellowship at Children’s Hospital of Michigan was supported by a grant from the International Pediatric Nephrology Association.     

Angiotensin antagonists and steroids in the treatment of focal segmental glomerulosclerosis

The use of angiotensin converting enzyme inhibitors (ACEIs) along with good blood pressure control have been shown to significantly decrease the level of proteinuria and slow the progression of renal insufficiency in patients with nondiabetic glomerular disease including focal segmental glomerulosclerosis (FSGS). Thus, this should be part of the therapeutic approach for all proteinuric patients with FSGS and should be considered the mainstay of therapy for patients with FSGS secondary to conditions associated with hyperfiltration and/or reduced nephron mass and those patients with nonnephrotic primary FSGS. However, nephrotic patients with primary FSGS may continue to have marked proteinuria and progression of renal disease despite these measures and thus require a more aggressive approach with the use of steroids and immunosuppressive agents. Although primary FSGS was once thought to be a steroid-nonresponsive lesion, recent experience has provided a note of optimism in the use of steroids and immunosuppressive agents in treating this otherwise progressive glomerulopathy. As a result, a course of steroid therapy in primary FSGS is now warranted in nephrotic patients with reasonably well preserved renal function in whom it is not otherwise contraindicated.     

Case report: successful treatment of recurrent focal segmental glomerulosclerosis with a novel rituximab regimen

Focal segmental glomerulosclerosis (FSGS) is the cause of renal failure in more than 10% of pediatric patients undergoing renal transplantation. Recurrent FSGS is a major cause of pediatric allograft failure, with the risk increasing for patients undergoing retransplantation. Standard therapy for recurrent posttransplantation FSGS includes the use of intensive plasmapheresis (PP) in conjunction with cyclophosphamide or high-dose cyclosporine. However, many patients exhibit refractory disease, with rapid progression to allograft loss despite these interventions. Prior studies have reported conflicting data on the efficacy of adding rituximab therapy to the standard treatment regimen for recurrent posttransplantation FSGS. Here we present a successful therapeutic protocol with rapid elimination of PP after initiation of rituximab therapy for an adolescent patient with recurrent FSGS in the immediate postoperative period. The patient has maintained excellent allograft function through 12 months posttransplantation.     

Case of a focal segmental glomerulosclerosis collapsing variant associated with a hypertrophic column of Bertin

A 59-year-old Japanese man admitted to our hospital complaining of anasarca, body weight gain, and elevation of blood pressure. Serum creatinine(Cre), albumin(Alb), cholesterol(chol), and urinary protein were 1.3 mg/dL, 2.5 g/dL, 527 mg/dL, and 10 g/gCr, respectively. An abdominal echography showed a renal mass, which was diagnosed to be a hypertrophic column of Bertin by enhanced CT. His serum Cre and Alb had worsened to 1.6 mg/dL and 1.7 g/dL, respectively, and a renal biopsy was performed. The results showed a segmental sclerotic lesion associated with hypertrophy and proliferation of podocytes in several glomeruli, hence we diagnosed a focal segmental glomerulosclerosis collapsing variant. After steroid pulse therapy and LDL apheresis, his serum Cre level had decreased to 1.1 mg/dL and the urinary protein level to 2.5 g/gCr. Patients with a focal segmental glomerulosclerosis collapsing variant are poor responders to standard therapies, and have a very poor prognosis. For this case, combined steroid pulse and LDL apheresis therapy was effective.     

Post-transplant focal segmental glomerulosclerosis refractory to plasmapheresis and rituximab therapy

Sir, Primary focal segmental glomerulosclerosis (FSGS) recurs in20 to 50% of kidney transplants [1]. Recently, there have beenreports demonstrating the successful use of rituximab for recurrentpost-transplant FSGS [2–4]. We report a case of recurrentFSGS that was refractory to both     

Abrogation of nephrotic proteinuria by rituximab treatment in a renal transplant patient with relapsed focal segmental glomerulosclerosis

Relapse of focal segmental glomerulosclerosis (FSGS) after renal transplantation is 20-40%. Recurrence after a first relapse is 80%. The only current treatment is plasmapheresis and/or cyclophosphamide. We report successful treatment of a second relapse in a 48-year-old patient. At age 33, FSGS was diagnosed. The patient began hemodialysis 1 year later. In her first renal transplant, she developed recurrent FSGS and reached terminal transplant failure 3 years later. Eight years later, a second transplant was performed. Immunosuppressive regimen: steroids, mycophenolate mofetil (MMF), tacrolimus (TAC), and rabbit anti-thymocyte globulin. Proteinuria of 2-6 g/day was detected and a biopsy showed recurrent FSGS. Plasmapheresis was started without success. Another biopsy still showed FSGS. The patient received two doses of rituximab (375 mg/m2 each) i.v. Three weeks later, proteinuria was 350 mg/day (serum-creatinine 1.6 mg/dl). Twelve months later, proteinuria was at 90 mg/day. Rituximab might be an option for recurrent FSGS after renal transplantation.     

The effect of treatment of corticosteroid-resistant idiopathic (primary) focal and segmental hyalinosis and sclerosis (focal glomerulosclerosis) with ciclosporin

Nine patients with biopsy-proven primary focal and segmental hyalinosis and sclerosis (FSHS) and steroid-resistant nephrotic syndrome were randomly allocated to either a period of 4-6 months of treatment (ciclosporin; (CS); 5-8 mg/kg/24 h and warfarin) or to a control period (warfarin alone) and then crossed over to the alternative for a further 4-6 months. Serum creatinine levels increased at a similar rate during treatment and control periods of observation. Serum albumin levels increased (p less than 0.05) and urinary protein excretion decreased (p less than 0.01) in association with the CS therapy compared to the control period of observation. No patient had complete resolution of the nephrotic syndrome. In primary FSHS, CS treatment is unlikely to produce complete resolution of nephrotic-range proteinuria but does significantly decrease urinary protein excretion.