Treatment of Recurrent Focal Segmental Glomerulosclerosis in Pediatric Kidney Transplant Recipients: Effect of Rituximab

Sethna, Christine B.; Benchimol, Corinne; Hotchkiss, Hilary; Frank, Rachel; Infante, Lulette; Vento, Suzanne; Trachtman, Howard

doi:10.1155/2011/389542

Cited by 20 publications

(30 citation statements)

References 22 publications

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“…Despite successful results having been obtained [77][78][79][80][81][82][83][84][85][86] , other studies have shown a transient or even absent response to Rituximab ® [62,[87][88][89][90][91][92][93][94] (Table 1).…”

Section: Novel Therapeutic Optionsmentioning

confidence: 99%

Update on the treatment of focal segmental glomerulosclerosis in renal transplantation

Messina¹,

Gallo²,

Mella³

et al. 2016

WJT

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Focal segmental glomerulosclerosis (FSGS) represents one of the most severe glomerular diseases, with frequent progression to end-stage renal disease and a high rate of recurrence in renal allografts (30%-50%). Recurrent FSGS portends a negative outcome, with the hazard ratio of graft failure being two-fold higher then that of other glomerulonephritis. Two patterns of clinical presentations are observed: Early recurrence, which is characterized by massive proteinuria within hours to days after implantation of the renal graft, and late recurrence, which occurs several months or years after the transplantation. Many clinical conditions have been recognized as risk factors for recurrence, including younger age, rapid progression of the disease to end-stage renal disease on native kidneys, and loss of previous renal allografts due to recurrence. However, much less is known about the incidence and risk factors of the so-called "de novo " type of FSGS, for which sufferers are transplanted patients without disease on native kidneys; but, rapid development of allograft failure is frequently observed. Management of both forms is challenging, and none of the approaches proposed to date have been demonstrated as consistently beneficial or effective. In the present review we report an update on the available therapeutic strategies for FSGS in renal transplantation within the context of a critical overview of the current literature.

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Section: Novel Therapeutic Optionsmentioning

confidence: 99%

Update on the treatment of focal segmental glomerulosclerosis in renal transplantation

Messina¹,

Gallo²,

Mella³

et al. 2016

WJT

View full text Add to dashboard Cite

show abstract

“…Since the year 2000, numerous case reports and small studies of the efficacy of rituximab in treating FSGS have been published [62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78]. The larger case series are summarized in Table 3.…”

Section: Treatmentmentioning

confidence: 99%

Recurrent focal segmental glomerulosclerosis after kidney transplantation

2015

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Focal segmental glomerulosclerosis (FSGS) is an important cause of glomerular disease in children and adolescents and nearly 50 % of affected patients will progress to endstage kidney disease over a 5 to 10-year period. Unfortunately, there is no established treatment for disease in the native kidney. Moreover, up to 55 % of patients develop recurrent disease after receiving a kidney transplant, with a substantially higher risk in patients who have already experienced recurrent disease in a prior transplant. A number of clinical and laboratory factors have been identified as risk factors for this complication. In addition, new investigations into podocyte biology and circulating permeability factors have shed light on the cause of recurrent the disease. While a number of novel therapeutic agents have been applied in the management of this problem, there still is no proven treatment. In this review, we summarize recent advances in the epidemiology, pathophysiology, and treatment of recurrent FSGS in pediatric patients who have received a kidney transplant.

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“…9,10 Furthermore, recent reports suggest that rituximab, a mAb to CD20 that depletes mature B cells, may be beneficial in some patients with the nephrotic syndrome. [11][12][13][14][15][16] However, the mechanisms by which rituximab alleviates the nephrotic syndrome are not yet known. Recent work has demonstrated that "natural antibody" contributes to tissue injury in a number of different diseases.…”

mentioning

confidence: 99%

IgM Contributes to Glomerular Injury in FSGS

Strassheim

Renner

Panzer

et al. 2013

Journal of the American Society of Nephrology

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Glomerular IgM and C3 deposits frequently accompany idiopathic FSGS and secondary glomerulosclerosis, but it is unknown whether IgM activates complement, possibly contributing to the pathogenesis of these diseases. We hypothesized that IgM natural antibody binds to neoepitopes exposed in the glomerulus after nonimmune insults, triggering activation of the complement system and further injury. We examined the effects of depleting B cells, using three different strategies, on adriamycin-induced glomerulosclerosis. First, we treated wild-type mice with an anti-murine CD20 antibody, which depletes B cells, before disease induction. Second, we evaluated adriamycin-induced glomerulosclerosis in Jh mice, a strain that lacks mature B cells. Third, we locally depleted peritoneal B cells via hypotonic shock before disease induction. All three strategies reduced deposition of IgM in the glomerulus after administration of adriamycin and attenuated the development of albuminuria. Furthermore, we found that glomerular IgM and C3 were detectable in a subset of patients with FSGS; C3 was present as an activation fragment and colocalized with glomerular IgM, suggesting that glomerular IgM may have bound a cognate ligand. Taken together, these results suggest that IgM activates the complement system within the glomerulus in an animal model of glomerulosclerosis. Strategies that reduce IgM natural antibody or that prevent complement activation may slow the progression of glomerulosclerosis.

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Treatment of Recurrent Focal Segmental Glomerulosclerosis in Pediatric Kidney Transplant Recipients: Effect of Rituximab

Cited by 20 publications

References 22 publications

Update on the treatment of focal segmental glomerulosclerosis in renal transplantation

Update on the treatment of focal segmental glomerulosclerosis in renal transplantation

Recurrent focal segmental glomerulosclerosis after kidney transplantation

IgM Contributes to Glomerular Injury in FSGS

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