Background Uncontrolled hyperphosphatemia in chronic kidney disease (CKD) patients commonly results in vascular calcification leading to increased risk of cardiovascular disease. Phosphate binders (PBs) are used for hyperphosphatemia and can be calcium-based (CBPBs) or non-calcium-based (NCBPBs), the latter being more expensive than CBPBs. In this study, we used meta-analysis approaches to assess the cost-utility of PBs for hyperphosphatemia in CKD patients. Methods Relevant studies published prior to June 2019 were identified from PubMed, Scopus, the Cochrane Library, the National Health Service Economic Evaluation Database, and the Cost-Effectiveness Analysis Registry. Studies were eligible if they included CKD patients with hyperphosphatemia, compared any PBs and reported economic outcomes. Meta-analysis was applied to pool incremental net benefit (INB) across studies stratified by country income. Results A total of 25 studies encompassing 32 comparisons were eligible. Lanthanum carbonate, a NCBPB, was a more cost-effective option than CBPBs in high-income countries (HICs), with a pooled INB of $3984.4 (599.5–7369.4), especially in pre-dialysis patients and used as a second-line option with INBs of $4860.2 (641.5–9078.8), $4011.0 (533.7–7488.3), respectively. Sevelamer, also a NCBPB, was not more cost-effective as a first-line option compared to CBPBs with a pooled INB of $6045.8 (− 23,453.0 to 35,522.6) and $34,168.9 (− 638.0 to 68,975.7) in HICs and upper middle-income countries, respectively. Conclusions Lanthanum carbonate was significantly more cost-effective than CBPBs as a second-line option for hyperphosphatemia in pre-dialysis patients in HICs. However, the use of sevelamer is not more cost-effective as a first-line option compared to CBPBs.
Background Asymptomatic hyperuricemia was found to be associated with increased cardiovascular disease risk but the potential benefits of urate-lowering therapy (ULT) remain controversial. We conducted a systematic review and network meta-analysis (NMA) with frequentist model to estimate the efficacy and safety of ULT in asymptomatic hyperuricemia. Methods MEDLINE, Embase, and Scopus were searched without language restrictions. Randomized controlled trials (RCT) of adults with asymptomatic hyperuricemia were eligible if they compared any pair of ULTs (i.e., allopurinol, febuxostat, probenecid, benzbromarone, sulfinpyrazone, rasburicase, lesinurad, and topiroxostat) and placebo or no ULT, and had outcomes of interest, including composite renal events, major adverse cardiovascular events, serum urate levels, estimated glomerular filtration rate (eGFR), systolic blood pressure, and adverse events. Results NMA with frequentist approach was applied to estimate relative treatment effects, i.e., risk ratio (RR) and mean difference (MD). A total of 23 RCTs were eligible. NMA identified beneficial effects of ULT on composite renal events and eGFR but not for other outcomes. Allopurinol and febuxostat had significantly lower composite renal events than placebo (RR 0.39, 95% confidence interval [CI] 0.23 to 0.66, and RR 0.68, 95% CI 0.46 to 0.99, respectively). Both treatments also resulted in significantly higher eGFR than placebo (MD 3.69 ml/min/1.73 m2, 95% CI 1.31 to 6.08, and MD 2.89 ml/min/1.73 m2, 95% CI 0.69 to 5.09, respectively). No evidence of inconsistency was identified. Conclusions Evidence suggests that allopurinol and febuxostat are the ULTs of choice in reducing composite renal events and improving renal function. Trial registration. This study was registered with PROSPERO: CRD42019145908. The date of the first registration was 12th November 2019.
Summary Cytomegalovirus (CMV) infection is common in kidney transplantation (KT). Antiviral‐agents are used as universal prophylaxis. Our purpose aimed to compare and rank efficacy and safety. MEDLINE, Embase, SCOPUS, and CENTRAL were used from inception to September 2020 regardless language restriction. We included randomized clinical trials (RCTs) comparing the CMV infection/disease prophylaxis among antiviral‐agents in adult KT recipients. Of 24 eligible RCTs, prophylactic valganciclovir (VGC) could significantly lower the overall CMV infection and disease risks than placebo with pooled risk differences (RDs) [95% confidence interval (CI)] of −0.36 (−0.54, −0.18) and −0.28 (−0.48, −0.08), respectively. Valacyclovir (VAC) and ganciclovir (GC) significantly decreased risks with the corresponding RDs of −0.25 (−0.32, −0.19) and −0.30 (−0.37, −0.22) for CMV infection and −0.26 (−0.40, −0.12) and −0.22 (−0.31, −0.12) for CMV disease. For subgroup analysis by seropositive‐donor and seronegative‐recipient (D+/R−), VGC and GC significantly lowered the risk of CMV infection/disease with RDs of −0.42 (−0.84, −0.01) and −0.35 (−0.60, −0.12). For pre‐emptive strategies, GC lowered the incidence of CMV disease significantly with pooled RDs of −0.33 (−0.47, −0.19). VGC may be the best in prophylaxis of CMV infection/disease follow by GC. VAC might be an alternative where VGC and GC are not available.
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