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.
Nephrol Dial Transplant. 2021 Apr 26;36(5):804-810. doi: 10.1093/ndt/gfaa374.
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.
慢性肾脏病（CKD）会增加心血管风险和死亡率。肾纤维化在 CKD 的进展中起着重要作用，但迄今为止，组织学仍然是评估纤维化的金标准。需要非侵入性技术来评估肾实质损伤，并对肾脏结构进行纵向评估。因此，我们评估了应用单光子发射计算机断层扫描/计算机断层扫描（SPECT/CT）技术用 99mTc-二巯丁二酸（99mTc-DMSA）进行肾同位素成像，以监测腺嘌呤丰富饮食（ARD）诱导的大鼠肾功能不全期间的肾功能障碍。
在 28 天内用含 0.25%和 0.5%腺嘌呤的饮食诱导肾功能不全。通过检测生化标志物和肾脏组织学来评估肾功能障碍。用 99mTc-DMSA 进行 SPECT/CT 同位素成像，在第 0、7、14、21、28、35 和 49 天评估肾实质损伤。
与对照组相比，ARD 大鼠出现肾功能障碍，表现为血清肌酐和血尿素氮升高，肾脏纤维化和肾小管间质损伤，且腺嘌呤浓度呈剂量依赖性。与对照组相比，0.25%和 0.5%ARD 大鼠的 99mTc-DMSA SPECT-CT 成像显示随时间推移肾摄取量显著减少（P=0.011 和 P=0.0004）。第 28 天的 99mTc-DMSA 摄取量与第 49 天的天狼星红染色评估值呈显著负相关（r=0.89，P<0.0001，R2=0.67）。
99mTc-DMSA 肾闪烁显像可对大鼠肾纤维化风险进行纵向随访。我们发现 ARD 大鼠肾实质减少与肾脏内新形成的纤维组织呈反比关系。我们的结果表明，99mTc-DMSA 肾闪烁显像可能是评估动物肾纤维化发展的有用的非侵入性预后标志物，应该在人类中进行测试。
