<?xml version="1.0" encoding="UTF-8"?>

<!--XBRL Document Created with the Workiva Platform-->
<!--Copyright 2026 Workiva-->
<!--r:019dfeb2-66ea-7295-89cb-725d503f8aa2,g:86d1e4bd-4135-4e34-a3c5-45ed91d31620-->
<link:linkbase xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/all" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#all"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#hypercube-dimension"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-default"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-domain"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/domain-member" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#domain-member"/>
  <link:roleRef roleURI="http://akebia.com/role/Cover" xlink:type="simple" xlink:href="akba-20260507.xsd#Cover"/>
  <link:definitionLink xlink:role="http://akebia.com/role/Cover" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityListingsLineItems_019dfeb2-66ea-7806-bdb0-3c4b7770908c" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityListingsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityListingsTable_019dfeb2-66ea-7639-9516-f160d4522c37" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityListingsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_dei_EntityListingsLineItems_019dfeb2-66ea-7806-bdb0-3c4b7770908c" xlink:to="loc_dei_EntityListingsTable_019dfeb2-66ea-7639-9516-f160d4522c37" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RestatementAxis_019dfeb2-66ea-70b2-9f92-fd6819d6891f" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RestatementAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_dei_EntityListingsTable_019dfeb2-66ea-7639-9516-f160d4522c37" xlink:to="loc_srt_RestatementAxis_019dfeb2-66ea-70b2-9f92-fd6819d6891f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RestatementDomain_019dfeb2-66ea-70b2-9f92-fd6819d6891f_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RestatementDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RestatementAxis_019dfeb2-66ea-70b2-9f92-fd6819d6891f" xlink:to="loc_srt_RestatementDomain_019dfeb2-66ea-70b2-9f92-fd6819d6891f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RestatementDomain_019dfeb2-66ea-7f56-8b8a-a5518c14e948" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RestatementDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RestatementAxis_019dfeb2-66ea-70b2-9f92-fd6819d6891f" xlink:to="loc_srt_RestatementDomain_019dfeb2-66ea-7f56-8b8a-a5518c14e948" xlink:type="arc" order="1"/>
  </link:definitionLink>
</link:linkbase>
