Efficacy of abatacept treatment for focal segmental glomerulosclerosis and minimal change disease: A systematic review of case reports, case series, and observational studies

Hansrivijit, Panupong; Puthenpura, Max; Ghahramani, Nasrollah

doi:10.5414/cn110134

Cited by 11 publications

(6 citation statements)

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“…Notably, abatacept has been approved by FDA for the treatment of rheumatoid arthritis [106], while belatacept has been approved by FDA for use as an immunosuppressive therapy to prevent kidney allograft rejection [107]. Additionally, several case reports showed abatacept to have mixed success in the treatment of glomerular diseases such as minimal change disease [108, 109] and focal segmental glomerulosclerosis [110-113]. A phase II trial is currently underway to evaluate the use of abatacept in adults and children with minimal change disease and focal segmental glomerulosclerosis [114].…”

Section: Kp In Ckdmentioning

confidence: 99%

The Kynurenine Pathway in Acute Kidney Injury and Chronic Kidney Disease

et al. 2021

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Background: The kynurenine pathway (KP) is the major catabolic pathway for tryptophan degradation. The KP plays an important role as the sole de novo nicotinamide adenine dinucleotide (NAD+) biosynthetic pathway in normal human physiology and functions as a counter-regulatory mechanism to mitigate immune responses during inflammation. Although the KP has been implicated in a variety of disorders including Huntington’s disease, seizures, cardiovascular disease, and osteoporosis, its role in renal diseases is seldom discussed. Summary: This review summarizes the roles of the KP and its metabolites in acute kidney injury (AKI) and chronic kidney disease (CKD) based on current literature evidence. Metabolomics studies demonstrated that the KP metabolites were significantly altered in patients and animal models with AKI or CKD. The diagnostic and prognostic values of the KP metabolites in AKI and CKD were highlighted in cross-sectional and longitudinal human observational studies. The biological impact of the KP on the pathophysiology of AKI and CKD has been studied in experimental models of different etiologies. In particular, the activation of the KP was found to confer protection in animal models of glomerulonephritis, and its immunomodulatory mechanism may involve the regulation of T cell subsets such as Th17 and regulatory T cells. Manipulation of the KP to increase NAD+ production or diversion toward specific KP metabolites was also found to be beneficial in animal models of AKI. Key Messages: KP metabolites are reported to be dysregulated in human observational and animal experimental studies of AKI and CKD. In AKI, the magnitude and direction of changes in the KP depend on the etiology of the damage. In CKD, KP metabolites are altered with the onset and progression of CKD all the way to advanced stages of the disease, including uremia and its related vascular complications. The activation of the KP and diversion to specific sub-branches are currently being explored as therapeutic strategies in these diseases, especially with regards to the immunomodulatory effects of certain KP metabolites. Further elucidation of the KP may hold promise for the development of biomarkers and targeted therapies for these kidney diseases.

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Section: Kp In Ckdmentioning

confidence: 99%

The Kynurenine Pathway in Acute Kidney Injury and Chronic Kidney Disease

et al. 2021

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“…There have been reports after our initial publication [ 26 ] that either (1) could not identify B7-1 on KT biopsies [ 28 – 31 ], or (2) did not demonstrate a response to CTLA-4Ig, including abatacept and belatacept in rFSGS [ 28 , 32 , 33 ]. Although there has been controversy regarding tissue podocyte B7-1 staining [ 30 , 31 , 38 ], the reproducibility is apparent, given staining of positive controls (lymph nodes) by others [ 28 ] and by our group (Fig. 3D ).…”

Section: Discussionmentioning

confidence: 69%

Benefit of B7-1 staining and abatacept for treatment-resistant post-transplant focal segmental glomerulosclerosis in a predominantly pediatric cohort: time for a reappraisal

et al. 2022

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Background Primary FSGS manifests with nephrotic syndrome and may recur following KT. Failure to respond to conventional therapy after recurrence results in poor outcomes. Evaluation of podocyte B7-1 expression and treatment with abatacept (a B7-1 antagonist) has shown promise but remains controversial. Methods From 2012 to 2020, twelve patients developed post-KT FSGS with nephrotic range proteinuria, failed conventional therapy, and were treated with abatacept. Nine/twelve (< 21 years old) experienced recurrent FSGS; three adults developed de novo FSGS, occurring from immediately, up to 8 years after KT. KT biopsies were stained for B7-1. Results Nine KTRs (75%) responded to abatacept. Seven of nine KTRs were B7-1 positive and responded with improvement/resolution of proteinuria. Two patients with rFSGS without biopsies resolved proteinuria after abatacept. Pre-treatment UPCR was 27.0 ± 20.4 (median 13, range 8–56); follow-up UPCR was 0.8 ± 1.3 (median 0.2, range 0.07–3.9, p < 0.004). Two patients who were B7-1 negative on multiple KT biopsies did not respond to abatacept and lost graft function. One patient developed proteinuria while receiving belatacept, stained B7-1 positive, but did not respond to abatacept. Conclusions Podocyte B7-1 staining in biopsies of KTRs with post-transplant FSGS identifies a subset of patients who may benefit from abatacept. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information

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“…MCD in children is common in male preschool children. NS is the main clinical manifestation, and it can be mitigated by hormone therapy in 90%-95% of cases[ 12 ]. We summarize the differences between IMN and MCD to better identify and address IMN at the early stage, as shown in Table 3 .…”

Section: Discussionmentioning

confidence: 99%

Idiopathic membranous nephropathy in children: A case report

Cui¹,

Zhang²,

Tao³

2022

WJCC

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BACKGROUND Minimal change disease is a common cause of nephrotic syndrome (NS) in children and has a good prognosis. Idiopathic membranous nephropathy (IMN), a rare cause of NS in children, may progress to chronic kidney disease. However, there is little data on how to evaluate and treat IMN in children. CASE SUMMARY In this article, we report the case of a 7-year-old boy with steroid-resistant NS. After cyclophosphamide pulse therapy combined with oral prednisone, the urinary protein results remained positive. Renal biopsy confirmed the pathological diagnosis of stage II MN, with positivity for phospholipase A 2 receptor. Other immunological and infectious diseases relevant to secondary MN were ruled out by laboratory tests. Subsequently, tacrolimus plus prednisone was administered, and the therapeutic effect was satisfactory. CONCLUSION IMN is rare in children. The main clinical manifestation is NS. The diagnosis depends on renal biopsy. There is little evidence-based data on the treatment of IMN in children. Therefore, large-sample randomized controlled trials need to be performed. Individualized treatment should be used to improve the prognosis of the disease.

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Efficacy of abatacept treatment for focal segmental glomerulosclerosis and minimal change disease: A systematic review of case reports, case series, and observational studies

Cited by 11 publications

References 0 publications

The Kynurenine Pathway in Acute Kidney Injury and Chronic Kidney Disease

The Kynurenine Pathway in Acute Kidney Injury and Chronic Kidney Disease

Benefit of B7-1 staining and abatacept for treatment-resistant post-transplant focal segmental glomerulosclerosis in a predominantly pediatric cohort: time for a reappraisal

Idiopathic membranous nephropathy in children: A case report

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