Belatacept in recurrent focal segmental glomerulosclerosis after kidney transplantation

Grellier, Jimmy; Bello, Arnaud Del; Milongo, David; Guilbeau‐Frugier, Céline; Rostaing, Lionel; Kamar, Nassim

doi:10.1111/tri.12574

Cited by 19 publications

(26 citation statements)

References 4 publications

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“…However, if these results are in contrast with the recent report by Yu et al, 8 they are consistent with a few case reports showing the ineffectiveness of B7-1 blockade at inducing post-transplant proteinuria remission. 9,10 In the post-transplant course, Yu et al 8 used one or two infusions of abatacept, a sufficient dosage to induce prolonged proteinuria remission. Following this approach, we did not induce any remission.…”

Section: Discussionmentioning

confidence: 99%

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B7–1 Blockade Does Not Improve Post–Transplant Nephrotic Syndrome Caused by Recurrent FSGS

Delville

Baye

Dürrbach

et al. 2015

JASN

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FSGS is a common glomerular disorder that has a high propensity for recurrence after kidney transplant. The pathophysiology of FSGS is unknown, but podocytes seem to be the target of one or several circulating factors that lead to cytoskeleton reorganization and proteinuria. Research on podocytes has identified B7-1 as an important factor in podocyte biology and a new therapeutic target in renal disease. Indeed, in four patients with recurrent FSGS after transplant, treatment with the B7-1 blocker abatacept was associated with proteinuria remission. Here, we prospectively treated nine patients with recurrent FSGS after transplant using either abatacept or belatacept, a B7-1 blocker with higher affinity, and did not induce proteinuria remission. Furthermore, we did not detect B7-1 expression by immunofluorescence in podocytes of biopsy specimens from these or other kidney grafts or podocytes of native kidney biopsy specimens. In conclusion, B7-1 blockade did not induce FSGS remission after transplant in our study.

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Section: Discussionmentioning

confidence: 99%

“…9,10 We decided to prospectively administer either abatacept or belatacept to nine consecutive patients with a resistant form of recurrent FSGS after Tx. We did not induce any remission in the patients even using several drug infusions.…”

mentioning

confidence: 99%

B7–1 Blockade Does Not Improve Post–Transplant Nephrotic Syndrome Caused by Recurrent FSGS

Delville

Baye

Dürrbach

et al. 2015

JASN

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“…Garin et al [105] Abatacept (1 or [106] Abatacept (3 doses; 10 mg/kg) 1 patient (< 18 yr) No response Grellier et al [107] Belatacept (days 1, 15, 30 and monthly thereafter, 5 mg/kg) had achieved sustained remission. In a second series, remission was induced in 13/16 patients (81%), which also included PE sessions for 4 of the cases; CyA doses were from 6 to 25 mg/kg per day [46] .…”

Section: Patients (≥ 18 Yr) No Responsementioning

confidence: 99%

“…Nevertheless, other studies of patients with FSGS recurrence have shown a slight/absent response after treatment with CTLA4-Ig [104][105][106][107] , despite the fact that in some of these cases belatacept (able to bind B71 with an higher affinity than abatacept) was adopted.…”

Section: Abataceptmentioning

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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“…However, the excitement was dampened by subsequent studies, as several groups faced problems trying to reproduce previous data. First, following a thorough experimental design, B7-1 expression by podocytes was not confirmed in human or murine diabetic nephropathy [14,15,16], nor in focal segmental glomerulosclerosis, either primary or recurrent post-transplantation [14,17,18,19,20,21], while multiple artifacts due to non-specific staining obtained with immunofluorescence (IF) analyses were described [14,15,17,18]. Second, the efficacy of B7-1 blockers, abatacept and belatacept, in inducing proteinuria remission was challenged in patients with FSGS, either primary or recurrent post-transplantation [11,19,20,21,22].…”

Section: Introductionmentioning

confidence: 99%

Another Piece of the Puzzle of Podocyte B7-1 Expression: Lupus Nephritis

Novelli

Gagliardini²,

Ruggiero

et al. 2016

Nephron

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Background/Aims: Lupus nephritis (LN) is a frequent complication and a major predictor of poor prognosis of systemic lupus erythematosus. Immune complex deposition and T cell infiltration are crucial events in LN pathogenesis. B7-1 (CD80), normally expressed by antigen-presenting cells, is one of the major co-stimulators of T-cell activation through the binding with its counter-receptors CD28 and cytotoxic T-lymphocyte antigen-4. Unexpectedly, B7-1 induction was described at the podocyte level in patients affected by different renal diseases, including LN. These observations suggested a novel exciting function for B7-1 as a biomarker of podocyte injury, and hence that B7-1 inhibitory drugs could serve as podocyte-targeted treatment of intractable renal diseases. However, subsequent studies hardly questioned the reliability of B7-1 detection assays and the therapeutic efficacy of B7-1 blockade in proteinuric patients, casting doubts on B7-1 expression by podocytes. Here, we thoroughly investigated whether B7-1 was indeed expressed by podocytes in LN, before even considering employing B7-1 blockade in patients with severe manifestations of LN and unfavourable prognosis. Methods: Applying different immunohistochemical assays with 4 primary antibodies, we analysed kidney biopsies from 42 LN patients at different stages of the disease, and from NZB/NZW mice, an LN model. Results: B7-1 was not induced in podocytes in human and murine LN; instead its expression was confined to infiltrating inflammatory cells. Conclusion: B7-1 is not expressed by podocytes in LN. A renoprotective effect of B7-1 blockade in LN patients cannot be ruled out but, if confirmed, cannot be the result of an effect on podocyte B7-1.

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Belatacept in recurrent focal segmental glomerulosclerosis after kidney transplantation

Cited by 19 publications

References 4 publications

B7–1 Blockade Does Not Improve Post–Transplant Nephrotic Syndrome Caused by Recurrent FSGS

B7–1 Blockade Does Not Improve Post–Transplant Nephrotic Syndrome Caused by Recurrent FSGS

Update on the treatment of focal segmental glomerulosclerosis in renal transplantation

Another Piece of the Puzzle of Podocyte B7-1 Expression: Lupus Nephritis

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