Cargando…

A Single Oral Dose of Diclofenac Causes Transition of Experimental Subclinical Acute Kidney Injury to Chronic Kidney Disease

Nephrotoxic drugs can cause acute kidney injury (AKI) and analgesic nephropathy. Diclofenac is potentially nephrotoxic and frequently prescribed for pain control. In this study, we investigated the effects of single and repetitive oral doses of diclofenac in the setting of pre-existing subclinical A...

Descripción completa

Detalles Bibliográficos
Autores principales: Störmer, Johanna, Gwinner, Wilfried, Derlin, Katja, Immenschuh, Stephan, Rong, Song, Jang, Mi-Sun, Shushakova, Nelli, Haller, Hermann, Gueler, Faikah, Greite, Robert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9138744/
https://www.ncbi.nlm.nih.gov/pubmed/35625934
http://dx.doi.org/10.3390/biomedicines10051198
_version_ 1784714695674953728
author Störmer, Johanna
Gwinner, Wilfried
Derlin, Katja
Immenschuh, Stephan
Rong, Song
Jang, Mi-Sun
Shushakova, Nelli
Haller, Hermann
Gueler, Faikah
Greite, Robert
author_facet Störmer, Johanna
Gwinner, Wilfried
Derlin, Katja
Immenschuh, Stephan
Rong, Song
Jang, Mi-Sun
Shushakova, Nelli
Haller, Hermann
Gueler, Faikah
Greite, Robert
author_sort Störmer, Johanna
collection PubMed
description Nephrotoxic drugs can cause acute kidney injury (AKI) and analgesic nephropathy. Diclofenac is potentially nephrotoxic and frequently prescribed for pain control. In this study, we investigated the effects of single and repetitive oral doses of diclofenac in the setting of pre-existing subclinical AKI on the further course of AKI and on long-term renal consequences. Unilateral renal ischemia–reperfusion injury (IRI) for 15 min was performed in male CD1 mice to induce subclinical AKI. Immediately after surgery, single oral doses (100 mg or 200 mg) of diclofenac were administered. In a separate experimental series, repetitive treatment with 100 mg diclofenac over three days was performed after IRI and sham surgery. Renal morphology and pro-fibrotic markers were investigated 24 h and two weeks after the single dose and three days after the repetitive dose of diclofenac treatment using histology, immunofluorescence, and qPCR. Renal function was studied in a bilateral renal IRI model. A single oral dose of 200 mg, but not 100 mg, of diclofenac after IRI aggravated acute tubular injury after 24 h and caused interstitial fibrosis and tubular atrophy two weeks later. Repetitive treatment with 100 mg diclofenac over three days aggravated renal injury and caused upregulation of the pro-fibrotic marker fibronectin in the setting of subclinical AKI, but not in sham control kidneys. In conclusion, diclofenac aggravated renal injury in pre-existing subclinical AKI in a dose and time-dependent manner and already a single dose can cause progression to chronic kidney disease (CKD) in this model.
format Online
Article
Text
id pubmed-9138744
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-91387442022-05-28 A Single Oral Dose of Diclofenac Causes Transition of Experimental Subclinical Acute Kidney Injury to Chronic Kidney Disease Störmer, Johanna Gwinner, Wilfried Derlin, Katja Immenschuh, Stephan Rong, Song Jang, Mi-Sun Shushakova, Nelli Haller, Hermann Gueler, Faikah Greite, Robert Biomedicines Article Nephrotoxic drugs can cause acute kidney injury (AKI) and analgesic nephropathy. Diclofenac is potentially nephrotoxic and frequently prescribed for pain control. In this study, we investigated the effects of single and repetitive oral doses of diclofenac in the setting of pre-existing subclinical AKI on the further course of AKI and on long-term renal consequences. Unilateral renal ischemia–reperfusion injury (IRI) for 15 min was performed in male CD1 mice to induce subclinical AKI. Immediately after surgery, single oral doses (100 mg or 200 mg) of diclofenac were administered. In a separate experimental series, repetitive treatment with 100 mg diclofenac over three days was performed after IRI and sham surgery. Renal morphology and pro-fibrotic markers were investigated 24 h and two weeks after the single dose and three days after the repetitive dose of diclofenac treatment using histology, immunofluorescence, and qPCR. Renal function was studied in a bilateral renal IRI model. A single oral dose of 200 mg, but not 100 mg, of diclofenac after IRI aggravated acute tubular injury after 24 h and caused interstitial fibrosis and tubular atrophy two weeks later. Repetitive treatment with 100 mg diclofenac over three days aggravated renal injury and caused upregulation of the pro-fibrotic marker fibronectin in the setting of subclinical AKI, but not in sham control kidneys. In conclusion, diclofenac aggravated renal injury in pre-existing subclinical AKI in a dose and time-dependent manner and already a single dose can cause progression to chronic kidney disease (CKD) in this model. MDPI 2022-05-22 /pmc/articles/PMC9138744/ /pubmed/35625934 http://dx.doi.org/10.3390/biomedicines10051198 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Störmer, Johanna
Gwinner, Wilfried
Derlin, Katja
Immenschuh, Stephan
Rong, Song
Jang, Mi-Sun
Shushakova, Nelli
Haller, Hermann
Gueler, Faikah
Greite, Robert
A Single Oral Dose of Diclofenac Causes Transition of Experimental Subclinical Acute Kidney Injury to Chronic Kidney Disease
title A Single Oral Dose of Diclofenac Causes Transition of Experimental Subclinical Acute Kidney Injury to Chronic Kidney Disease
title_full A Single Oral Dose of Diclofenac Causes Transition of Experimental Subclinical Acute Kidney Injury to Chronic Kidney Disease
title_fullStr A Single Oral Dose of Diclofenac Causes Transition of Experimental Subclinical Acute Kidney Injury to Chronic Kidney Disease
title_full_unstemmed A Single Oral Dose of Diclofenac Causes Transition of Experimental Subclinical Acute Kidney Injury to Chronic Kidney Disease
title_short A Single Oral Dose of Diclofenac Causes Transition of Experimental Subclinical Acute Kidney Injury to Chronic Kidney Disease
title_sort single oral dose of diclofenac causes transition of experimental subclinical acute kidney injury to chronic kidney disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9138744/
https://www.ncbi.nlm.nih.gov/pubmed/35625934
http://dx.doi.org/10.3390/biomedicines10051198
work_keys_str_mv AT stormerjohanna asingleoraldoseofdiclofenaccausestransitionofexperimentalsubclinicalacutekidneyinjurytochronickidneydisease
AT gwinnerwilfried asingleoraldoseofdiclofenaccausestransitionofexperimentalsubclinicalacutekidneyinjurytochronickidneydisease
AT derlinkatja asingleoraldoseofdiclofenaccausestransitionofexperimentalsubclinicalacutekidneyinjurytochronickidneydisease
AT immenschuhstephan asingleoraldoseofdiclofenaccausestransitionofexperimentalsubclinicalacutekidneyinjurytochronickidneydisease
AT rongsong asingleoraldoseofdiclofenaccausestransitionofexperimentalsubclinicalacutekidneyinjurytochronickidneydisease
AT jangmisun asingleoraldoseofdiclofenaccausestransitionofexperimentalsubclinicalacutekidneyinjurytochronickidneydisease
AT shushakovanelli asingleoraldoseofdiclofenaccausestransitionofexperimentalsubclinicalacutekidneyinjurytochronickidneydisease
AT hallerhermann asingleoraldoseofdiclofenaccausestransitionofexperimentalsubclinicalacutekidneyinjurytochronickidneydisease
AT guelerfaikah asingleoraldoseofdiclofenaccausestransitionofexperimentalsubclinicalacutekidneyinjurytochronickidneydisease
AT greiterobert asingleoraldoseofdiclofenaccausestransitionofexperimentalsubclinicalacutekidneyinjurytochronickidneydisease
AT stormerjohanna singleoraldoseofdiclofenaccausestransitionofexperimentalsubclinicalacutekidneyinjurytochronickidneydisease
AT gwinnerwilfried singleoraldoseofdiclofenaccausestransitionofexperimentalsubclinicalacutekidneyinjurytochronickidneydisease
AT derlinkatja singleoraldoseofdiclofenaccausestransitionofexperimentalsubclinicalacutekidneyinjurytochronickidneydisease
AT immenschuhstephan singleoraldoseofdiclofenaccausestransitionofexperimentalsubclinicalacutekidneyinjurytochronickidneydisease
AT rongsong singleoraldoseofdiclofenaccausestransitionofexperimentalsubclinicalacutekidneyinjurytochronickidneydisease
AT jangmisun singleoraldoseofdiclofenaccausestransitionofexperimentalsubclinicalacutekidneyinjurytochronickidneydisease
AT shushakovanelli singleoraldoseofdiclofenaccausestransitionofexperimentalsubclinicalacutekidneyinjurytochronickidneydisease
AT hallerhermann singleoraldoseofdiclofenaccausestransitionofexperimentalsubclinicalacutekidneyinjurytochronickidneydisease
AT guelerfaikah singleoraldoseofdiclofenaccausestransitionofexperimentalsubclinicalacutekidneyinjurytochronickidneydisease
AT greiterobert singleoraldoseofdiclofenaccausestransitionofexperimentalsubclinicalacutekidneyinjurytochronickidneydisease