Boonpheng Boonphiphop, Thongprayoon Charat, Bathini Tarun, Sharma Konika, Mao Michael A, Cheungpasitporn Wisit
Department of Internal Medicine, East Tennessee State University, Johnson City, TN37614, United States.
Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN55905, United States.
World J Transplant. 2019 Jun 28;9(2):35-47. doi: 10.5500/wjt.v9.i2.35.
The adverse renal effects of proton pump inhibitors (PPIs) are increasingly recognized in both the general population and patients with chronic kidney disease. Several pharmacokinetic studies have also raised concerns regarding the interaction between PPIs and immunosuppressive drugs in transplant patients. Whether the adverse effects of PPIs have a clinical significance in kidney transplant recipients remains unclear. We performed this meta-analysis to assess the risk of adverse effects in kidney transplant recipients on PPI compared with those without PPI exposure.
To investigate the risk of acute rejection, graft loss, hypomagnesemia, renal dysfunction, and overall mortality in kidney transplant recipients on PPI compared with those without PPI exposure.
A systematic review was conducted in MEDLINE, EMBASE, and Cochrane databases from inception through October 2018 to identify studies that evaluated the adverse effects of PPIs in kidney transplant recipients, including biopsy-proven acute rejection, graft loss, hypomagnesemia, renal function, and overall mortality. Effect estimates from the individual studies were extracted and combined using random-effect, generic inverse variance method of DerSimonian and Laird. The protocol for this meta-analysis is registered with PROSPERO, No. CRD42018115676.
Fourteen observational studies with 6786 kidney transplant recipients were enrolled. No significant association was found between PPI exposure and the risk of biopsy-proven acute rejection at ≥ 1 year [pooled odds ratio (OR), 1.25; 95% confidence interval (CI), 0.82-1.91, = 55%], graft loss at 1 year (pooled OR = 1.30, 95%CI: 0.75-2.24, = 0%) or 1-year mortality (pooled OR = 1.53, 95%CI: 0.90-2.58, = 34%). However, PPI exposure was significantly associated with hypomagnesemia (pooled OR = 1.56, 95%CI: 1.19-2.05, = 27%). Funnel plots and Egger regression asymmetry test were performed and showed no publication bias.
PPI use was not associated with significant risks of higher acute rejection, graft loss, or 1-year mortality. However, the risk of hypomagnesemia was significantly increased with PPI use. Thus, future studies are needed to assess the impact of PPIs on long-term outcomes.
质子泵抑制剂（PPIs）对肾脏的不良影响在普通人群和慢性肾脏病患者中日益受到关注。多项药代动力学研究也引发了对PPIs与移植患者免疫抑制药物之间相互作用的担忧。PPIs的不良反应在肾移植受者中是否具有临床意义仍不明确。我们进行了这项荟萃分析，以评估使用PPIs的肾移植受者与未接触PPIs的受者相比出现不良反应的风险。
调查使用PPIs的肾移植受者与未接触PPIs的受者相比发生急性排斥反应、移植肾丢失、低镁血症、肾功能不全及总体死亡率的风险。
在MEDLINE、EMBASE和Cochrane数据库中进行了一项系统评价，检索从建库至2018年10月的研究，以确定评估PPIs对肾移植受者不良反应的研究，包括经活检证实的急性排斥反应、移植肾丢失、低镁血症、肾功能及总体死亡率。提取各研究的效应估计值，并采用DerSimonian和Laird的随机效应、通用逆方差法进行合并。该荟萃分析的方案已在PROSPERO注册，注册号为CRD42018115676。
纳入了14项观察性研究，共6786例肾移植受者。使用PPIs与≥1年经活检证实的急性排斥反应风险之间未发现显著关联[合并比值比（OR）为1.25；95%置信区间（CI）为0.82 - 1.91，I² = 55%]，与1年时移植肾丢失风险（合并OR = 1.30，95%CI：0.75 - 2.24，I² = 0%）或1年死亡率（合并OR = 1.53，95%CI：0.90 - 2.58，I² = 34%）之间也未发现显著关联。然而，使用PPIs与低镁血症显著相关（合并OR = 1.56，95%CI：1.19 - 2.05，I² = 27%）。进行了漏斗图和Egger回归不对称性检验，未显示发表偏倚。
使用PPIs与较高的急性排斥反应、移植肾丢失或1年死亡率的显著风险无关。然而，使用PPIs会显著增加低镁血症的风险。因此，需要进一步研究来评估PPIs对长期结局的影响。
