Urinary Excretion of microRNAs in Young Fabry Disease Patients with Mild or Absent Nephropathy

Jaurretche, Sebastián; Venera, Graciela Delia; Antongiovanni, Norberto; Perretta, Fernando; Pérez, Germán

doi:10.4236/ojneph.2018.83009

Cited by 6 publications

(13 citation statements)

References 41 publications

(49 reference statements)

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“…In Argentina, a recent analysis of young patients with classic FD forms and mild or absent nephropathy showed urinary microRNAs suggestive of kidney fibrosis, even in non-albuminuric cases (22). Riccio et al reported that GHF may be an early marker of renal involvement in FD patients, even before the onset of signs, symptoms, or laboratory changes (20).…”

Section: Discussionmentioning

confidence: 99%

Variables Associated with Glomerular Hyperfiltration in Fabry Disease Patients

Perretta¹,

Antongiovanni²,

Jaurretche

2020

Nephro-Urol Mon

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Background: Fabry disease is a genetic disorder caused by the deficiency of the lysosomal α-galactosidase A enzyme. This failure generates the storage of globotriaosylceramide in different cells with a progressive multi-organ involvement. Objectives: To report the prevalence of glomerular hyperfiltration in Fabry disease patients and the association with clinical variables. Methods: Adult patients (≥ 18 years) at the moment of FD diagnosis were evaluated. The variables studied were: central and peripheral nervous system compromise, presence of arterial hypertension, cardiac arrhythmia, left ventricular hypertrophy, albuminuria/proteinuria, cornea verticillata, gastrointestinal involvement, treatment with inhibitors of the renin-angiotensin-aldosterone system, deafness, and presence of angiokeratomas. Results: Forty-eight adults with Fabry disease (35.9 ± 11.7 years), 28 women (58.3%), and 20 men (41.7%) were analyzed. Nine (18.8%) patients with glomerular hyperfiltration, including six females and three males (mean age: 28.8 years), were detected. A significant association between and central nervous system (P = 0.021) and peripheral nervous system (P = 0.001) compromise, cardiac arrhythmia (P = 0.001), cornea verticillata (P = 0.009), and gastrointestinal involvement (P = 0.009) was observed. However, no association was found between glomerular hyperfiltration and proteinuria or treatment with inhibitors of the renin-angiotensin-aldosterone system. Conclusions: This research showed a higher prevalence of glomerular hyperfiltration in the younger group and a significant association between glomerular hyperfiltration and some typical manifestations of classic Fabry patients. Although more studies are needed, it is concluded that other mechanisms than glomerular hyperfiltration, like injury by glycosphingolipids deposit into the filtration barrier, might influence the protein loss in Fabry nephropathy.

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Section: Discussionmentioning

confidence: 99%

Variables Associated with Glomerular Hyperfiltration in Fabry Disease Patients

Perretta¹,

Antongiovanni²,

Jaurretche

2020

Nephro-Urol Mon

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“…To detect the relative excretion urinary levels of miR-21, miR-29, miR-192, miR-200, and miR-433, reverse transcription reaction with a stem-loop primer was used. The resulting cDNA was amplified using a miRNA-specific forward primer and the universal reverse primer [12]. Relative miRNAs expression levels were calculated using the 2 -ΔΔCt method as previously described [13] (Figure 2).…”

Section: Case Presentation and Methodsmentioning

confidence: 99%

“…We have recently demonstrated that young FD patients present a miRNAs urinary profile excretion indicative of renal fibrosis in correlation with decreased α GalA activity, even in non-albuminuric patients [12]. This work includes the study of miRNAs families regulated by TGF- β .…”

Section: Introductionmentioning

confidence: 99%

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High Lyso-Gb3 Plasma Levels Associated with Decreased miR-29 and miR-200 Urinary Excretion in Young Non-Albuminuric Male Patient with Classic Fabry Disease

Jaurretche

Pérez

Venera

2019

Case Reports in Nephrology

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Renal involvement is associated with a greater morbidity and mortality in Fabry disease. Pathological albuminuria, the first Fabry nephropathy clinical manifestation, can occur from early childhood, although histological lesions such as tubulo-interstitial fibrosis and glomerulosclerosis are present or may precede the onset of pathological albuminuria. In renal cells, exposure to Lyso-Gb3 is correlated with increased expression of Transforming Growth Factor-βeta (TGF-β). miR-21, miR-192, and miR-433 that promote fibrosis are activated by TGF-β, and miR-29 and miR-200 that suppress fibrosis are inhibited by TGF-β. A 23-year-old male was diagnosed with FD. αGalA decreased enzyme activity: 0.1 nmol/hour/liter; genotype: [c.317T>G (p.L106R)]; GFR: 104.4 mL/min/m2; urinary albumin excretion: 6.00 mg/day; plasma Lyso-Gb3: 124.5 nmol/L. A decrease urinary excretion of miR-29 and miR-200 was found (p <0.005) compared to controls. In addition to its usefulness as a phenotype marker, Lyso-Gb3 has been proposed as an indicator of therapeutic response. We detect an association of high Lyso-Gb3 plasma values with decreased urinary excretion of miRNAs with known antifibrotic effect (miR-29 and miR-200). Although the present work is a case report, it could be hypothesized that one of the harmful Lyso-Gb3 effects could be the miRNAs regulation through changes in TGF-β expression.

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“…There are some limited studies focused on the selected urinary miRNA expression in FD. Decrease of certain miRNA species, namely, miR-29 and miR-200, have been associated to the renal fibrosis prior to onset of pathological albuminuria [80,81]. In serum, specific miRNAs species, namely, miR-1307-5p, miR-21-5p, miR-152-5p, and miR-26a-5p, were significantly down-regulated in Fabry patients with ERT, compared to those without.…”

Section: Transcriptomicsmentioning

confidence: 99%

Biomarkers of Fabry Nephropathy: Review and Future Perspective

Levstek

Vujkovac

Podkrajšek

2020

Genes

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Progressive nephropathy is one of the main features of Fabry disease, which largely contributes to the overall morbidity and mortality burden of the disease. Due to the lack of specific biomarkers, the heterogeneity of the disease, and unspecific symptoms, diagnosis is often delayed. Clinical presentation in individual patients varies widely, even in patients from the same family carrying the same pathogenic GLA variant. Therefore, it is reasonable to anticipate that additional genomic, transcriptomic, proteomic, and metabolomics factors influence the manifestation and progression of the disease. The aim of this article is to provide an overview of nephropathy in Fabry patients and the biomarkers currently used in the diagnosis and follow-up. Current biomarkers are associated with late signs of kidney damage. Therefore, there is a need to identify biomarkers associated with early stages of kidney damage that would enable early diagnosis, which is crucial for effective treatment and prevention of severe irreversible complications. Recent advances in sequencing and -omics technologies have led to several studies investigating new biomarkers. We will provide an overview of the novel biomarkers, critically evaluate their clinical utility, and propose future perspectives, which we believe might be in their integration.

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Urinary Excretion of microRNAs in Young Fabry Disease Patients with Mild or Absent Nephropathy

Cited by 6 publications

References 41 publications

Variables Associated with Glomerular Hyperfiltration in Fabry Disease Patients

Variables Associated with Glomerular Hyperfiltration in Fabry Disease Patients

High Lyso-Gb3 Plasma Levels Associated with Decreased miR-29 and miR-200 Urinary Excretion in Young Non-Albuminuric Male Patient with Classic Fabry Disease

Biomarkers of Fabry Nephropathy: Review and Future Perspective

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