Renal SPECT/CT with 99mTc-dimercaptosuccinic acid is a non-invasive predictive marker for the development of interstitial fibrosis in a rat model of renal insufficiency.


Journal

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
ISSN: 1460-2385
Titre abrégé: Nephrol Dial Transplant
Pays: England
ID NLM: 8706402

Informations de publication

Date de publication:
26 04 2021
Historique:
received: 16 06 2020
pubmed: 29 12 2020
medline: 23 7 2021
entrez: 28 12 2020
Statut: ppublish

Résumé

Chronic kidney disease (CKD) increases cardiovascular risk and mortality. Renal fibrosis plays a major role in the progression of CKD but, to date, histology remains the gold standard to assess fibrosis. Non-invasive techniques are needed to assess renal parenchymal impairment and to perform the longitudinal evaluation of renal structure. Thus we evaluated renal isotopic imaging by single-photon emission computed tomography/computed tomography (SPECT/CT) with technetium-99m (99mTc)-dimercaptosuccinic acid (DMSA) to monitor renal impairment during renal insufficiency in rats. Renal insufficiency was induced by an adenine-rich diet (ARD) at 0.25 and 0.5% for 28 days. Renal dysfunction was evaluated by assaying biochemical markers and renal histology. Renal parenchymal impairment was assessed by SPECT/CT isotopic imaging with 99mTc-DMSA on Days 0, 7, 14, 21, 28, 35 and 49. Compared with controls, ARD rats developed renal dysfunction characterized by increased serum creatinine and blood urea nitrogen, fibrosis and tubulointerstitial damage in the kidneys, with a dose-dependent effect of the adenine concentration. 99mTc-DMSA SPECT-CT imaging showed a significant decrease in renal uptake over time in 0.25 and 0.5% ARD rats compared with control rats (P = 0.011 and P = 0.0004, respectively). 99mTc-DMSA uptake on Day 28 was significantly inversely correlated with Sirius red staining evaluated on Day 49 (r = 0.89, P < 0.0001, R2 = 0.67). 99mTc-DMSA renal scintigraphy allows a longitudinal follow-up of risk of renal fibrosis in rats. We found that the reduction of renal parenchyma in ARD rats is inversely proportional to newly formed fibrous tissue in the kidney. Our results suggest that 99mTc-DMSA renal scintigraphy may be a useful non-invasive prognostic marker of the development of renal fibrosis in animals and should be tested in humans.

Sections du résumé

BACKGROUND
Chronic kidney disease (CKD) increases cardiovascular risk and mortality. Renal fibrosis plays a major role in the progression of CKD but, to date, histology remains the gold standard to assess fibrosis. Non-invasive techniques are needed to assess renal parenchymal impairment and to perform the longitudinal evaluation of renal structure. Thus we evaluated renal isotopic imaging by single-photon emission computed tomography/computed tomography (SPECT/CT) with technetium-99m (99mTc)-dimercaptosuccinic acid (DMSA) to monitor renal impairment during renal insufficiency in rats.
METHODS
Renal insufficiency was induced by an adenine-rich diet (ARD) at 0.25 and 0.5% for 28 days. Renal dysfunction was evaluated by assaying biochemical markers and renal histology. Renal parenchymal impairment was assessed by SPECT/CT isotopic imaging with 99mTc-DMSA on Days 0, 7, 14, 21, 28, 35 and 49.
RESULTS
Compared with controls, ARD rats developed renal dysfunction characterized by increased serum creatinine and blood urea nitrogen, fibrosis and tubulointerstitial damage in the kidneys, with a dose-dependent effect of the adenine concentration. 99mTc-DMSA SPECT-CT imaging showed a significant decrease in renal uptake over time in 0.25 and 0.5% ARD rats compared with control rats (P = 0.011 and P = 0.0004, respectively). 99mTc-DMSA uptake on Day 28 was significantly inversely correlated with Sirius red staining evaluated on Day 49 (r = 0.89, P < 0.0001, R2 = 0.67).
CONCLUSIONS
99mTc-DMSA renal scintigraphy allows a longitudinal follow-up of risk of renal fibrosis in rats. We found that the reduction of renal parenchyma in ARD rats is inversely proportional to newly formed fibrous tissue in the kidney. Our results suggest that 99mTc-DMSA renal scintigraphy may be a useful non-invasive prognostic marker of the development of renal fibrosis in animals and should be tested in humans.

Identifiants

pubmed: 33367913
pii: 6046936
doi: 10.1093/ndt/gfaa374
doi:

Substances chimiques

Biomarkers 0
Technetium Tc 99m Dimercaptosuccinic Acid 494JNQ8L28

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

804-810

Informations de copyright

© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Auteurs

Mickaël Bobot (M)

Centre de Néphrologie et Transplantation Rénale, Hôpital de la Conception, Assistance Publique-Hôpitaux de Marseille, Marseille, France.
Centre Européen de Recherche en Imagerie Médicale, Aix-Marseille Université, Marseille, France.
C2VN, INSERM 1263, INRAE 1260, Aix-Marseille Université, Marseille, France.

Guillaume Hache (G)

Centre Européen de Recherche en Imagerie Médicale, Aix-Marseille Université, Marseille, France.
C2VN, INSERM 1263, INRAE 1260, Aix-Marseille Université, Marseille, France.
Pharmacie, Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille, Marseille, France.

Anaïs Moyon (A)

Centre Européen de Recherche en Imagerie Médicale, Aix-Marseille Université, Marseille, France.
C2VN, INSERM 1263, INRAE 1260, Aix-Marseille Université, Marseille, France.
Service de Radiopharmacie, Assistance Publique-Hôpitaux de Marseille, Marseille, France.

Samantha Fernandez (S)

Centre Européen de Recherche en Imagerie Médicale, Aix-Marseille Université, Marseille, France.

Laure Balasse (L)

Centre Européen de Recherche en Imagerie Médicale, Aix-Marseille Université, Marseille, France.

Laurent Daniel (L)

C2VN, INSERM 1263, INRAE 1260, Aix-Marseille Université, Marseille, France.
Laboratoire d'Anatomopathologie, Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille, Marseille, France.

Philippe Garrigue (P)

Centre Européen de Recherche en Imagerie Médicale, Aix-Marseille Université, Marseille, France.
C2VN, INSERM 1263, INRAE 1260, Aix-Marseille Université, Marseille, France.
Service de Radiopharmacie, Assistance Publique-Hôpitaux de Marseille, Marseille, France.

Pauline Brige (P)

Centre Européen de Recherche en Imagerie Médicale, Aix-Marseille Université, Marseille, France.
Laboratoire d'Imagerie Interventionnelle Expérimentale, EA, 4264, Aix Marseille Université, Marseille, France.

Sophie Chopinet (S)

Centre Européen de Recherche en Imagerie Médicale, Aix-Marseille Université, Marseille, France.
Laboratoire d'Imagerie Interventionnelle Expérimentale, EA, 4264, Aix Marseille Université, Marseille, France.
Service de Chirurgie Digestive, Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille, Marseille, France.

Françoise Dignat-George (F)

C2VN, INSERM 1263, INRAE 1260, Aix-Marseille Université, Marseille, France.

Philippe Brunet (P)

Centre de Néphrologie et Transplantation Rénale, Hôpital de la Conception, Assistance Publique-Hôpitaux de Marseille, Marseille, France.
C2VN, INSERM 1263, INRAE 1260, Aix-Marseille Université, Marseille, France.

Stéphane Burtey (S)

Centre de Néphrologie et Transplantation Rénale, Hôpital de la Conception, Assistance Publique-Hôpitaux de Marseille, Marseille, France.
C2VN, INSERM 1263, INRAE 1260, Aix-Marseille Université, Marseille, France.

Benjamin Guillet (B)

Centre Européen de Recherche en Imagerie Médicale, Aix-Marseille Université, Marseille, France.
C2VN, INSERM 1263, INRAE 1260, Aix-Marseille Université, Marseille, France.
Service de Radiopharmacie, Assistance Publique-Hôpitaux de Marseille, Marseille, France.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH