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.

2020 
BACKGROUND 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 longitudinal evaluation of renal structure. Thus, we evaluated renal isotopic imaging by SPECT/CT with 99mTc-DMSA to monitor renal impairment during renal insufficiency in rats. METHODS Renal insufficiency was induced by 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, 49. RESULTS Compared to control, ARD rats developed renal dysfunction characterized by increased serum creatinine and BUN, fibrosis and tubulointerstitial damage in kidneys, with 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 to control rats (P = 0.011 and P = 0.0004 respectively). 99mTc-DMSA uptake on D28 was significantly inversely correlated with sirius red staining evaluated on D49 (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 described 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 prognostic non-invasive marker of the development of renal fibrosis in animals and should be tested in humans.
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