MicroRNAs in Chronic Kidney Disease: Four Candidates for Clinical Application

Peters, Linsey J. F.; Floege, Juergen; Biessen, Erik A. L.; Jankowski, Joachim; Vorst, Emiel P. C. van der

doi:10.3390/ijms21186547

Cited by 53 publications

(51 citation statements)

References 148 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…miRNAs are thought to play a dual role both in suppressing or promoting oncogenic potential [ 23 ]. Several miRNAs have been implicated in the pathogenesis of chronic kidney diseases, especially in hypertensive nephropathy, diabetic nephropathy, and tubulointerstitial fibrosis, giving hope that they could be used for diagnostic or even therapeutic purposes in the future [ 24 ]. Modified expression of miRNAs has been documented also in different forms of glomerulonephritis including IgAN (reviewed in Nalewajska M et al [ 25 ]).…”

Section: Discussionmentioning

confidence: 99%

Serum Levels of miR-148b and Let-7b at Diagnosis May Have Important Impact in the Response to Treatment and Long-Term Outcome in IgA Nephropathy

Kouri

Stangou

Lioulios

et al. 2021

JCM

View full text Add to dashboard Cite

Background/aims: Previous studies showed that two microRNAs, let-7b and miR-148, which regulate the O-glycosylation process of IgA1, may predict diagnosis of primary IgA nephropathy (IgAN). The combined analysis of their serum levels in calculated statistical models may act as serum biomarkers for the diagnosis of primary IgAN. In the present study, we aimed to assess their impact not only on clinical and histological findings at onset but also on renal function after a long-term follow-up. Patients and methods: We enrolled 61 Caucasian patients with biopsy-proven IgAN. Serum levels of miR-148b, let-7b, and galactose-deficient IgA1 (Gd-IgA1) at the time of diagnosis were measured using real-time quantitative PCR and enzyme-linked immunosorbent assay using the monoclonal antibody KM55, respectively. Their values along with calculated Models 1 and 2 were correlated with histologic scoring system (Oxford classification system) and with renal function at diagnosis and after 11.9 ± 6.6 years. Fifty-five healthy volunteers were enrolled as controls. Results: No significant correlation was found between miRNA and Gd-IgA1 levels and eGFR and proteinuria at diagnosis. A significant negative association was detected between the presence of crescents and serum levels of let-7b (p = 0.002), miR-148b (p = 0.01), and Models 1 and 2 (p = 0.02 and p = 0.007, respectively). At the end of follow-up, eGFR correlated with let-7b levels (p = 0.01), Model 1 (p = 0.002), and Model 2 (p = 0.004). Patients with fast progression of the renal damage had significantly increased levels of let-7b (p = 0.01), Model 1 (p = 0.003), and Model 2 (p = 0.005) compared to slow progressors, as did those who reached ESKD (p = 0.002, p = 0.001, and p = 0.001, respectively). Results were most prominent in those treated with corticosteroids. Finally, cut off levels in Models 1 and 2 could also predict the renal function outcome after long-term follow-up. Conclusions: Serum levels of let-7b and miR-148b and their combination, may serve as predictors for long-term renal function outcomes, particularly in patients treated with corticosteroids.

show abstract

Section: Discussionmentioning

confidence: 99%

Serum Levels of miR-148b and Let-7b at Diagnosis May Have Important Impact in the Response to Treatment and Long-Term Outcome in IgA Nephropathy

Kouri

Stangou

Lioulios

et al. 2021

JCM

View full text Add to dashboard Cite

show abstract

“…Loss of Dicer mediated by HoxB7-Cre in the ureteric bud epithelium also increases cell proliferation and apoptosis, and disrupts ciliogenesis, which leads to development of cysts [ 25 ]. As miRNAs are widely involved in the pathogenesis of AKI and CKD, they should have promising diagnostic and therapeutic potential [ 27 , 28 ].…”

Section: Mirnasmentioning

confidence: 99%

Non-Coding RNAs in Hereditary Kidney Disorders

Zhou

2021

IJMS

View full text Add to dashboard Cite

Single-gene defects have been revealed to be the etiologies of many kidney diseases with the recent advances in molecular genetics. Autosomal dominant polycystic kidney disease (ADPKD), as one of the most common inherited kidney diseases, is caused by mutations of PKD1 or PKD2 gene. Due to the complexity of pathophysiology of cyst formation and progression, limited therapeutic options are available. The roles of noncoding RNAs in development and disease have gained widespread attention in recent years. In particular, microRNAs in promoting PKD progression have been highlighted. The dysregulated microRNAs modulate cyst growth through suppressing the expression of PKD genes and regulating cystic renal epithelial cell proliferation, mitochondrial metabolism, apoptosis and autophagy. The antagonists of microRNAs have emerged as potential therapeutic drugs for the treatment of ADPKD. In addition, studies have also focused on microRNAs as potential biomarkers for ADPKD and other common hereditary kidney diseases, including HNF1β-associated kidney disease, Alport syndrome, congenital abnormalities of the kidney and urinary tract (CAKUT), von Hippel–Lindau (VHL) disease, and Fabry disease. This review assembles the current understanding of the non-coding RNAs, including microRNAs and long noncoding RNAs, in polycystic kidney disease and these common monogenic kidney diseases.

show abstract

“…The role of miRNAs in molecular pathology has already been reported in AKI and kidney transplantation [ 65 , 66 ], polycystic kidney disease (PKD) [ 67 , 68 ], and renal fibrosis [ 69 , 70 ], which represents the final outcome and most relevant pathological event of CKD. This, together with the fact that miRNAs can be detected in exosomes in plasma and urine, indicate them as suitable and attractive new biomarkers for diagnostic purposes and disease monitoring [ 71 , 72 ]. Importantly, up/downregulated miRNAs also represent novel therapeutic targets for kidney diseases, whose potential has already begun to be explored in animal models ( Table 1 ).…”

Section: Oligonucleotides Used In Therapeuticsmentioning

confidence: 99%

Oligonucleotide-Based Therapies for Renal Diseases

et al. 2021

View full text Add to dashboard Cite

The global burden of chronic kidney disease (CKD) is increasing every year and represents a great cost for public healthcare systems, as the majority of these diseases are progressive. Therefore, there is an urgent need to develop new therapies. Oligonucleotide-based drugs are emerging as novel and promising alternatives to traditional drugs. Their expansion corresponds with new knowledge regarding the molecular basis underlying CKD, and they are already showing encouraging preclinical results, with two candidates being evaluated in clinical trials. However, despite recent technological advances, efficient kidney delivery remains challenging, and the presence of off-targets and side-effects precludes development and translation to the clinic. In this review, we provide an overview of the various oligotherapeutic strategies used preclinically, emphasizing the most recent findings in the field, together with the different strategies employed to achieve proper kidney delivery. The use of different nanotechnological platforms, including nanocarriers, nanoparticles, viral vectors or aptamers, and their potential for the development of more specific and effective treatments is also outlined.

show abstract

MicroRNAs in Chronic Kidney Disease: Four Candidates for Clinical Application

Cited by 53 publications

References 148 publications

Serum Levels of miR-148b and Let-7b at Diagnosis May Have Important Impact in the Response to Treatment and Long-Term Outcome in IgA Nephropathy

Serum Levels of miR-148b and Let-7b at Diagnosis May Have Important Impact in the Response to Treatment and Long-Term Outcome in IgA Nephropathy

Non-Coding RNAs in Hereditary Kidney Disorders

Oligonucleotide-Based Therapies for Renal Diseases

Contact Info

Product

Resources

About