Review Article

CD80 Insights as Therapeutic Target in the Current and Future Treatment Options of Frequent-Relapse Minimal Change Disease

Table 4

CD80 in human studies’ summary.

StudiesType of studiesSubject numberMain findingConclusion

Garin et al., 2009 [22]Clinical studiesMCD patients:
Control subjects:
FSGS patients:
Urinary CD80 was significantly higher in relapse MCD patients than MCD in remission.Urinary CD80 is elevated in idiopathic MCD and relevant to diagnosis and prognosis.
Garin et al., 2010 [100]Clinical studiesMCD patients:
FSGS patients:
CD80 is not elevated in FSGS patients.CD80 may be a useful marker, supported hypothesis that MCD and FSGS were two different diseases.
Ishimoto et al., 2013 [101]Basic science studiesHuman podocyte cell lineAn impaired CTLA4 response, the rapid upregulation of CTLA4 in glomeruli could be responsible for the transient CD80 expression.CD80 production in podocytes with transient proteinuria; CD80 was relevant in the pathogenesis of proteinuria in MCD.
Yu et al., 2013 [23]Clinical and basic science studiesFSGS patients: CD80 could be a useful biomarker in the treatment of some glomerulopathies.Abatacept induced complete or partial remission of proteinuria in patients.
Cara-Fuentes et al., 2014 [26]Clinical studiesMCD:
In relapse:
In remission:
FSGS patients:
FSGS patients have significant higher level of suPAR than relapse-MCD patients which showed correlation with proteinuria.Urinary CD80 is elevated in MCD patients compared with FSGS patients.
Novelli et al., 2016 [20]Clinical and basic science studiesMCD patients:
FSGS patients:
Male Balb/c mice for basic science studies
The therapeutic effect of abatacept might not be because of podocyte CD80.Podocyte CD80 was not observed in mice or patients of MCD and FSGS.
Mishra et al., 2017 [151]Clinical studiesNephrotic syndrome patients:
Healthy controls:
MCD patients had higher median in expressing potential biomarkers than FSGS patients but no significant difference.Urinary creatine/CD80 could be useful biomarkers in steroid-sensitive nephrotic syndrome in relapse.
Liao et al., 2017 [94]Clinical studiesNephrotic syndrome patients:
Healthy controls:
Higher urinary CD80 in recurrent phase steroid-sensitive nephrotic syndrome than healthy control or remission patients.Urinary CD80 was strongly associated with relapse nephrotic syndrome but cannot be used as frequency of relapse prediction.
Minamikawa et al., 2018 [152]ClinicalMCD patients:
FSGS:
Healthy controls:
Urinary CD80 was present in all active chronic kidney disease. Urinary CD80 was correlated with the urinary protein levels.Urinary CD80 was an unreliable biomarker to differentiate relapse MCD and FSGS.
Zhao et al., 2018 [153]ClinicalMCD patients: CTLA4 absent or in minimum amount could distinguish steroid-sensitive MCD patients from steroid-resistant MCD patients.Glucocorticoid was useful to result complete remission only in MCD patients, with strong CD80 level and minimum level of CTLA4.
Ling et al., 2018 [8]ClinicalNephrotic syndrome patients: Urinary CD80 level could affect the response towards the initial treatment of steroid. High urinary CD80 level reacted 100% at the initial steroid treatment.Urinary CD80 could predict the progression and remission of MCD in children, while also able to identify high-risk patients at an early stage.
Ahmed et al., 2018 [154]ClinicalMCD patients:
FSGS patients:
Other glomerulopathies:
Healthy controls:
Urinary CD80 in MCD was significantly higher than FSGS and other glomerulopathies.Urinary CD80 was significantly higher in MCD child patients.
Bhatia et al., 2018 [155]ClinicalSteroid-dependent nephrotic syndrome patients: The first study to report the effect of rituximab on urinary CD80 excretion.Reduced urinary CD80 was observed after rituximab therapy.
Isom et al., 2019 [78]Clinical case studyMCD patients: The longest successful abatacept treatment that has ever been reported; 6 years of follow up, abatacept tremendously changed the pattern of relapse.Strongly encourage the investigation of urinary CD80 as therapeutic and potential treatment target.
Cara-Fuentes et al., 2020 [156]Clinical and basic science studiesMCD patients:
FSGS patients:
Relapse MCD patients had less CTLA4+ in glomeruli which caused the imbalance ratio of CD80/CTLA4 locally. There was a link between CD80 and endothelial cell activation. A second hit to the glomerulus could result in more significant podocytes injury and proteinuria.Both podocytes and endothelial cells could be the potential sources of CD80 in human and animal model.
Chen et al., 2020 [157]ClinicalMCD patients in relapse:
MCD patients in remission:
Healthy controls:
No correlation between urinary CD80 and proteinuria in adult onset MCD. Urinary CD80 was not a reflection of proteinuria.Imbalance level of Th1/TH2/TH17 and elevated CD80 could be the pathogenesis of developing adult onset MCD.
Gonzalez et al., 2020 [158]ClinicalMCD patients:
FSGS patients:
Healthy controls:
Urinary CD80 could serve as predictive marker for the potential responsiveness towards specific immunosuppressive agents.Urinary CD80 could discriminate MCD from other nephrotic syndrome diseases.