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2017 ; 12
(9
): e0184398
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Comparative effectiveness and tolerance of immunosuppressive treatments for
idiopathic membranous nephropathy: A network meta-analysis
#MMPMID28898290
Ren S
; Wang Y
; Xian L
; Toyama T
; Jardine M
; Li G
; Perkovic V
; Hong D
PLoS One
2017[]; 12
(9
): e0184398
PMID28898290
show ga
BACKGROUND: Immunosuppressive agents in general are shown to prevent renal
progression and all-cause mortality in idiopathic membranous nephropathy (IMN)
patients with nephrotic syndrome. However, the efficacy and safety of different
immunosuppressive treatments have not been systematic assessed and compared. A
network meta-analysis was performed to compare different immunosuppressive
treatment in IMN. METHODS: Cochrane library, MEDLINE, EMBASE and trial register
system were searched for randomized controlled trials reporting the treatments
for IMN to May 3, 2016. Composite endpoint of mortality or end-stage kidney
disease (ESKD), complete or partial proteinuria remission and withdrawal because
of treatment adverse events were compared combing direct and indirect comparison
using network meta-analysis. Ranking different immunosuppressive treatments in
the outcomes were analyzed by using surface under the cumulative ranking curve
(SUCRA). RESULTS: Total 36 randomized controlled trials (n = 2018) covering 11
kinds of treatments were included. Compared with non-immunosuppressive treatment,
only cyclophosphamide (CTX) and chlorambucil significantly reduced the risk of
composite outcome of mortality or ESKD while combining the direct and indirect
comparison (OR = 0.31, 95%CI: 0.12-0.81 and OR = 0.33, 95%CI: 0.12-0.92). CTX
increased the composite outcome of complete remission (CR) or partial remission
(PR) (OR = 4.29, 95%CI: 2.30-8.00) but chlorambucil did not (OR = 1.58, 95%CI:
0.80-3.12) as compared with non-immunosuppressive treatment. Chlorambucil also
significantly increased the withdrawal risk (OR = 3.34, 95%CI: 1.37-8.17) as
compared to CTX. Both tacrolimus (OR = 3.10, 95%CI: 1.36-7.09) and cyclosporine
(CsA) (OR = 2.81, 95%CI: 1.08-7.32) also significantly increased the rate of CR
or PR as compared with non-immunosuppressive treatment (without significant
difference as compared with CTX), while ranking results showed that cyclosporine
or tacrolimus was with less possibility of drug withdrawal as compared to CTX.
CONCLUSIONS: Cyclophosphamide and chlorambucil reduce risk of ESKD or death in
IMN with nephrotic range proteinuria, but carry substantial toxicity that may be
lower for cyclophosphamide. Tacrolimus and cyclosporine increase the possibility
of proteinuria remission with less drug withdrawal, but the effects on kidney
failure remain uncertain.
|Chlorambucil/administration & dosage/*adverse effects/therapeutic use
[MESH]
|Cyclophosphamide/administration & dosage/*adverse effects/therapeutic use
[MESH]
|Cyclosporine/administration & dosage/*adverse effects/therapeutic use
[MESH]