Renal dysfunction can occur in advanced‐stage Duchenne muscular dystrophy

Motoki, Takayuki; Shimizu‐Motohashi, Yuko; Saito, Isao; Komaki, Hirofumi; Ishiyama, Akihiko; Aibara, Kaori; Jogamoto, Toshihiro; Tezuka, Yuko; Kawabe, Mika; Makino, Akihiro; Nagatani, Koji; Tatara, Katsunori; Kuwabara, Kozue; Kikuchi, Chiya; Fukuda, Mitsumasa; Ishii, Eiichi; Eguchi, Mariko

doi:10.1002/mus.26757

Cited by 10 publications

(9 citation statements)

References 23 publications

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“…Instead, we focused on the value of native T1 mapping rather than ECV quantification with contrast material. Native T1 measurement may be a replaceable method of ECV or LGE for detecting myocardial involvement, which is important in DMD patients because recent reports suggested that renal disease may be under-recognized in advanced-stage DMD patients [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Global, segmental and layer specific analysis of myocardial involvement in Duchenne muscular dystrophy by cardiovascular magnetic resonance native T1 mapping

et al. 2021

Journal of Cardiovascular Magnetic Resonance

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Background Progressive cardiomyopathy accounts for almost all mortality among Duchenne muscular dystrophy (DMD) patients.‍ Thus, our aim was to comprehensively characterize myocardial involvement by investigating the heterogeneity of native T1 mapping in DMD patients using global and regional (including segmental and layer-specific) analysis across a large cohort. Methods We prospectively enrolled 99 DMD patients (8.8 ± 2.5 years) and 25 matched male healthy controls (9.5 ± 2.5 years). All subjects underwent cardiovascular magnetic resonance (CMR) with cine, T1 mapping and late gadolinium enhancement (LGE) sequences. Native T1 values based on the global and regional myocardium were measured, and LGE was defined. Results LGE was present in 49 (49%) DMD patients. Global native T1 values were significantly longer in LGE-positive (LGE +) patients than in healthy controls, both in basal slices (1304 ± 55 vs. 1246 ± 27 ms, p < 0.001) and in mid-level slices (1305 ± 57 vs. 1245 ± 37 ms, p < 0.001). No significant difference in global native T1 was found between healthy controls and LGE-negative (LGE−) patients. In segmental analysis, LGE + patients had significantly increased native T1 in all analyzed segments compared to the healthy control group. Meanwhile, the comparison between LGE− patients and healthy controls showed significantly elevated values only in the basal anterolateral segment (1273 ± 62 vs. 1234 ± 40 ms, p = 0.034). Interestingly, the epicardial layer had a significantly higher native T1 in LGE− patients than in healthy controls (p < 0.05), whereas no such pattern was noticed in the global myocardium. Epicardial layer native T1 resulted in the highest diagnostic performance for distinguishing between healthy controls and DMD patients in receiver operating curve analyses (area under the curve [AUC] 0.84 for basal level and 0.85 for middle level) when compared to global native T1 and endocardial layer native T1. Conclusions Myocardial regional native T1, particularly epicardial native T1, seems to have potential as a novel robust marker of very early cardiac involvement in DMD patients. Trial registration: Chinese Clinical Trial Registry (http://www.chictr.org.cn/index.aspx) ChiCTR1800018340, 09/12/2018, Retrospectively registered.

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Section: Discussionmentioning

confidence: 99%

Global, segmental and layer specific analysis of myocardial involvement in Duchenne muscular dystrophy by cardiovascular magnetic resonance native T1 mapping

et al. 2021

Journal of Cardiovascular Magnetic Resonance

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“…However, LGE requires administration of gadolinium contrast agents. While these agents have an excellent safety profile in patients without renal disease, recent reports suggest that renal disease may be under-recognized in older DMD patients [12], coupled with growing concern over possible longterm brain deposition after repeated scans has raised concerns about long-term safety in children and young adults [8,13].…”

Section: Introductionmentioning

confidence: 99%

Non-contrast cardiovascular magnetic resonance detection of myocardial fibrosis in Duchenne muscular dystrophy

Raucci

George‐Durrett

et al. 2021

Journal of Cardiovascular Magnetic Resonance

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Background Duchenne muscular dystrophy (DMD) leads to progressive cardiomyopathy. Detection of myocardial fibrosis with late gadolinium enhancement (LGE) by cardiovascular magnetic resonance (CMR) is critical for clinical management. Due to concerns of brain deposition of gadolinium, non-contrast methods for detecting and monitoring myocardial fibrosis would be beneficial. Objectives We hypothesized that native T1 mapping and/or circumferential (εcc) and longitudinal (εls) strain can detect myocardial fibrosis. Methods 156 CMRs with gadolinium were performed in 66 DMD boys and included: (1) left ventricular ejection fraction (LVEF), (2) LGE, (3) native T1 mapping and myocardial tagging (εcc-tag measured using harmonic phase analysis). LGE was graded as: (1) presence/absence by segment, slice, and globally; (2) global severity from 0 (no LGE) to 4 (severe); (3) percent LGE using full width half maximum (FWHM). εls and εcc measured using feature tracking. Regression models to predict LGE included native T1 and either εcc-tag or εls and εcc measured at each segment, slice, and globally. Results Mean age and LVEF at first CMR were 14 years and 54%, respectively. Global εls and εcc strongly predicted presence or absence of LGE (OR 2.6 [1.1, 6.0], p = 0.029, and OR 2.3 [1.0, 5.1], p = 0.049, respectively) while global native T1 did not. Global εcc, εls, and native T1 predicted global severity score (OR 2.6 [1.4, 4.8], p = 0.002, OR 2.6 [1.4, 6.0], p = 0.002, and OR 1.8 [1.1, 3.1], p = 0.025, respectively). εls correlated with change in LGE by severity score (n = 33, 3.8 [1.0, 14.2], p = 0.048) and εcc-tag correlated with change in percent LGE by FWHM (n = 34, OR 0.2 [0.1, 0.9], p = 0.01). Conclusions Pre-contrast sequences predict presence and severity of LGE, with εls and εcc being more predictive in most models, but there was not an observable advantage over using LVEF as a predictor. Change in LGE was predicted by εls (global severity score) and εcc-tag (FWHM). While statistically significant, our results suggest these sequences are currently not a replacement for LGE and may only have utility in a very limited subset of DMD patients.

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“…Disturbances in angiogenesis 2 , 3 and brain 4 , renal, and bladder dysfunctions 5 , 6 , as well as bone-health issues 7 and gastrointestinal problems 8 , reflect the range of pathological changes observed in DMD. Finally, systemic alterations in the metabolism of carbohydrates and lipids accompanied by cases of impaired glucose tolerance and insulin sensitivity are manifested by DMD patients and mouse models of the disease, including mdx mice and golden retriever muscular dystrophy (GRMD) dogs 9 – 13 .…”

Section: Introductionmentioning

confidence: 99%

miR-378 affects metabolic disturbances in the mdx model of Duchenne muscular dystrophy

Podkalicka

Mucha

Kaziród

et al. 2022

Sci Rep

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Although Duchenne muscular dystrophy (DMD) primarily affects muscle tissues, the alterations to systemic metabolism manifested in DMD patients contribute to the severe phenotype of this fatal disorder. We propose that microRNA-378a (miR-378) alters carbohydrate and lipid metabolism in dystrophic mdx mice. In our study, we utilized double knockout animals which lacked both dystrophin and miR-378 (mdx/miR-378−/−). RNA sequencing of the liver identified 561 and 194 differentially expressed genes that distinguished mdx versus wild-type (WT) and mdx/miR-378−/− versus mdx counterparts, respectively. Bioinformatics analysis predicted, among others, carbohydrate metabolism disorder in dystrophic mice, as functionally proven by impaired glucose tolerance and insulin sensitivity. The lack of miR-378 in mdx animals mitigated those effects with a faster glucose clearance in a glucose tolerance test (GTT) and normalization of liver glycogen levels. The absence of miR-378 also restored the expression of genes regulating lipid homeostasis, such as Acly, Fasn, Gpam, Pnpla3, and Scd1. In conclusion, we report for the first time that miR-378 loss results in increased systemic metabolism of mdx mice. Together with our previous finding, demonstrating alleviation of the muscle-related symptoms of DMD, we propose that the inhibition of miR-378 may represent a new strategy to attenuate the multifaceted symptoms of DMD.

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Renal dysfunction can occur in advanced‐stage Duchenne muscular dystrophy

Cited by 10 publications

References 23 publications

Global, segmental and layer specific analysis of myocardial involvement in Duchenne muscular dystrophy by cardiovascular magnetic resonance native T1 mapping

Global, segmental and layer specific analysis of myocardial involvement in Duchenne muscular dystrophy by cardiovascular magnetic resonance native T1 mapping

Non-contrast cardiovascular magnetic resonance detection of myocardial fibrosis in Duchenne muscular dystrophy

miR-378 affects metabolic disturbances in the mdx model of Duchenne muscular dystrophy

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