Abstract

D-serine administration prevents kidney damage in murine models of acute kidney injury, and risperidone inhibits the activity of D-amino acid oxidase, which regulate plasma D-amino acid levels. This pilot randomized controlled trial investigated the effects of risperidone on glucose, amino acid metabolism, and kidney function in healthy adults. Healthy adults with a homeostasis model assessment of insulin resistance (HOMA-IR) of ≥ 1.6 and estimated glomerular filtration rate (eGFR) of ≥ 60 mL/min/1.73m2 were randomly assigned to the risperidone and control groups. The risperidone group received 0.5 mg/day risperidone for 4 days. The primary outcome was mean change in HOMA-IR on day 5, and the secondary outcomes were changes in D-amino acid levels, eGFR, and urinary albumin. Seven participants were randomized to the risperidone and control groups. The changes in HOMA-IR, eGFR, and urinary albumin on day 5 were not significantly different between the two groups (all p>0.05). Mean changes in plasma D-serine level and urinary D-serine/creatinine ratio were significantly higher in the risperidone group than in the control group (0.2 vs. −0.3 nmol/mL, p=0.03 and 38.2 vs. −25.8 nmol/mL, p=0.01, respectively). Short-term risperidone affects D-serine metabolism without instigating acute adverse effects on kidney or glucose homeostasis in healthy individuals.

Clinical Trial Registry number This study was registered with the Japan Registry for Clinical Trials (jRCTs041210165).

Competing Interest Statement

MM is the founder and CEO of KAGAMI INC.

Clinical Trial

jRCTs041210165

Clinical Protocols

https://jrct.mhlw.go.jp/latest-detail/jRCTs041210165

Funding Statement

Yes

Author Declarations

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study protocol was approved by the Medical Ethics Committee of Kanazawa University (approval no: 2021-004)

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AbbreviationsCKDchronic kidney diseaseeGFRestimated glomerular filtration rateHOMA-IRhomeostasis model assessment of insulin resistanceUACRurine albumin to creatinine ratiorRNAribosomal ribonucleic acid