APOL1 risk variants and kidney transplantation: a protocol for systematic review andmeta-analysis

<jats:title>Abstract</jats:title>
<jats:p><jats:bold>Background</jats:bold>Graft survival post-kidney transplant may be influenced by APOL1 risk variant status of both donors and recipients. There are several conflicting reports on screening, eligibility and inclusion of APOL1 risk variant testing in the Kidney Donor Risk Index. We aimed to produce a protocol for synthesizing evidence from available data on Apoprotein L1 risk variants and kidney transplantation.<jats:bold>METHODS:</jats:bold>We developed a search strategy using MeSH, text words and entry terms. Nine databases will be searched: PubMed, Embase, CINAHL, AJOL, Google Scholar, Web of Science, Cochrane Library, Research gate and Scopus. Only observational studies retrievable in the English Language will be included. The primary measurable outcome is the recipient’s post-transplant graft survival time from APOL1 high-risk variant donors. The secondary outcomes are the proportion of APOL1 high-risk variants in End-Stage Kidney Disease requiring a kidney transplant, the proportion in graft recipients and kidney donors; the effect of APOL1 high-risk variant on donor's kidney function post-kidney donation, recipient kidney allograft survival in APOL1 low and high-risk recipients. Deduplication, screening, and selection of identified studies will be done using Covidence software while CMA software version 3 will be used for meta-analysis. All studies will be assessed for methodological, clinical, and statistical heterogeneity. Publication bias will be visually assessed using the funnel plot. Results will be presented in forest plots with pooled survival time, standard error, and variance. Subgroup analysis will be performed using moderators such as socio-demographics: race, age, gender, and socio-economic status; hypertension, HIV status, forms of rejection, and other environmental factors.<jats:bold>Discussion</jats:bold>: The effect size for the primary outcome is a standardized mean difference in survival time for APOL1 high-risk variants in kidney transplants. The changes in kidney functions of donors and recipients pre and post-transplantation would be examined. The suitability of donors who have APOL1 high-risk variants will be explored in relation to graft survival time, donors' kidney function, and moderating effects of socio-demographic and environmental determinants.<jats:bold>Trial Registration Number</jats:bold>: This protocol is registered in PROSPERO, with registration number CRD42021230358</jats:p>