Do We Now Have a Prognostic Biomarker for Progressive Diabetic Nephropathy?

Zhang

et al. 2019

NMR in Biomedicine

Excessive tissue scarring, or fibrosis, is a critical contributor to end stage renal disease, but current clinical tests are not sufficient for assessing renal fibrosis. Quantitative magnetization transfer (qMT) MRI provides indirect information about the macromolecular composition of tissues. We evaluated measurements of the pool size ratio (PSR, the ratio of immobilized macromolecular to free water protons) obtained by qMT as a biomarker of tubulointerstitial fibrosis in a well‐established murine model with progressive renal disease. MR images were acquired from 16‐week‐old fibrotic hHB‐EGFTg/Tg mice and normal wild‐type (WT) mice (N = 12) at 7 T. QMT parameters were derived using a two‐pool five‐parameter fitting model. A normal range of PSR values in the cortex and outer stripe of outer medulla (CR + OSOM) was determined by averaging across voxels within WT kidneys (mean ± 2SD). Regions in diseased mice whose PSR values exceeded the normal range above a threshold value (tPSR) were identified and measured. The spatial distribution of fibrosis was confirmed using picrosirius red stains. Compared with normal WT mice, scattered clusters of high PSR regions were observed in the OSOM of hHB‐EGFTg/Tg mouse kidneys. Moderate increases in mean PSR (mPSR) of CR + OSOM regions were observed across fibrotic kidneys. The abnormally high PSR regions (% area) detected by the tPSR were significantly increased in hHB‐EGFTg/Tg mice, and were highly correlated with regions of fibrosis detected by histological fibrosis indices measured from picrosirius red staining. Renal tubulointerstitial fibrosis in OSOM can thus be assessed by qMT MRI using an appropriate analysis of PSR. This technique may be used as an imaging biomarker for chronic kidney diseases.

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Noninvasive quantitative magnetization transfer MRI reveals tubulointerstitial fibrosis in murine kidney

Zhang

et al. 2019

NMR in Biomedicine

“…Diabetic nephropathy (DN) is a major diabetic complication that determines the morbidity and mortality of diabetic patients. However, currently available clinical tests and biomarkers do not reliably assess its severity and progression in individual patients [1, 2], making it difficult to target treatments to poor prognosis patients. Renal fibrosis is a hallmark of progressive kidney disease, including DN; therefore, it is critical to evaluate the presence and extent of fibrosis in the diabetic kidney to treat patients as well as to predict their long-term outcomes.…”

Section: Introductionmentioning

confidence: 99%

Assessment of renal fibrosis in murine diabetic nephropathy using quantitative magnetization transfer MRI

Magnetic Resonance in Med

Katagiri

et al. 2018

“…Diabetic nephropathy (DN) is a major diabetic complication that leads to renal failure and determines the morbidity and mortality of many diabetic patients. Although clinical indicators or risk factors have been described for this disease, currently available tests do not reliably detect or predict its development and progression in individual patients , making it difficult to evaluate treatments targeted to high‐risk populations. Thus, alternative techniques are required to better characterize patients with this disease.…”

Section: Introductionmentioning

confidence: 99%

Mapping murine diabetic kidney disease using chemical exchange saturation transfer MRI

Magnetic Resonance in Med

Kopylov

et al. 2015

Introduction Diabetic nephropathy (DN) is the leading cause of renal failure; however, current clinical tests are insufficient for assessing this disease. DN is associated with changes in renal metabolites, so we evaluated the utility of chemical exchange saturation transfer (CEST) imaging to detect changes characteristic of this disease. Methods Sensitivity of CEST imaging at 7T to DN was evaluated by imaging diabetic mice (db/db, db/db eNOS−/−) that show different levels of nephropathy as well as by longitudinal imaging (8 to 24 weeks). Non-diabetic (db/m) mice were used as controls. Results Compared with non-diabetic mice, the CEST contrasts of hydroxyl metabolites that correspond to glucose and glycogen were significantly increased in papilla (P), inner medulla (IM), and outer medulla (OM) in db/db and db/db eNOS−/− kidneys at 16 wks. The db/db eNOS−/− mice that showed advanced nephropathy exhibited greater CEST effects in OM and significant CEST contrasts were also observed in cortex. Longitudinally, db/db mice exhibited progressive increases in hydroxyl signals in IM+P and OM from 12 to 24 weeks and an increase was also observed in cortex at 24 weeks. Conclusions CEST MRI can be used to measure changes of hydroxyl metabolites in kidney during progression of DN.