Emerging Role of Circular RNAs in Kidney Diseases in Nephrology

2021 ◽  
Vol 22 ◽  
Author(s):  
Cong Ma ◽  
Junjun Luan ◽  
Jeffrey B. Kopp ◽  
Hua Zhou

Background: Circular RNAs (circRNAs) have been identified to be involved in a variety of human diseases such as cancers, cardiovascular diseases, and autoimmune diseases. In recent years, the role of circRNAs in the development of kidney diseases in nephrology has been gradually recognized. Objective: We updated and described the current status of circRNAs in kidney diseases in nephrology. We particularly focused on the roles and mechanisms of circRNAs in systemic lupus erythematosus and lupus nephritis. Methods: We summarized recent reports published on PubMed, Web of Science, Scopus, Scielo databases using key words circRNAs, kidney diseases or renal diseases, or systemic lupus erythematosus. Results: Studies of circRNAs in certain kidney diseases such as acute kidney injury, focal segmental glomerulosclerosis, idiopathic membranous nephropathy, IgA nephropathy, diabetic nephropathy, hypertensive renal damage and particular lupus nephritis address the function and pathogenesis of circRNAs in these diseases. Mechanisms of circRNAs in the above human kidney diseases so far have focused on the role of sponging microRNAs and regulating the expression of target genes. Moreover, circRNAs have been detected in blood, urine, and kidney tissue samples. These results suggest that circRNAs can serve as biomarkers for the diagnosis and monitoring the progression of kidney diseases. Conclusion: CircRNAs play important roles in the pathogenesis, diagnosis, and treatment of kidney diseases emphasizing lupus nephritis in nephrology.

2021 ◽  
Vol 48 (1) ◽  
Author(s):  
Mervat E. Abdelazeem ◽  
Marwa I. Abdelhaleem ◽  
Rabab A. Mohamed ◽  
Enas A. Abdelaleem

Abstract Background Systemic lupus erythematosus (SLE) is a chronic disease which is mainly attributed to autoantibodies, cytokines, and immune complex deposition. Studies have demonstrated that cytokines and autoantibodies were strongly associated with renal diseases and can be used for the prediction of patients with lupus nephritis (LN). However, antibodies to dsDNA and the reduction of complements were also detected in non-LN patients as well as clinically non-active SLE patients. The current study was performed to detect the role of serum DKK-1 as a biomarker for the identification of SLE patients and patients with LN and its relation to disease activity and severity. The study was conducted on fifty clinically diagnosed SLE patients who were diagnosed according to Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE, in addition to thirty healthy control volunteers matched for age and sex. Assessment of SLE disease activity was done using Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Assessment of SLE disease severity was done using the Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) damage index. Serum levels of DKK-1 were measured for all participants by ELISA using commercially available kits. Results DKK-1 serum levels were significantly higher among active lupus nephritis cases as compared with SLE cases with no LN and with healthy controls (9197.60 μg/uL ± 2939.2 μg/uL vs. 6405.15 μg/uL ± 2018.91 μg/uL vs. 2790.33 μg/uL ± 833.49 μg/uL) respectively (p-values < 0.001). DKK-1 concentration was significantly higher among SLE patients with positive as compared with negative anti-double-stranded DNA (dsDNA) antibodies (p-value < 0.001). According to receiver operating characteristic (ROC) curve analysis, serum DKK-1 level diagnosed the SLE at a statistically significant level with a 98% sensitivity and 70% specificity and serum DKK-1 level also diagnosed active lupus nephritis at a 90% sensitivity and 63% specificity. Conclusion DKK-1 could diagnose SLE and lupus nephritis with high sensitivity and specificity. Serum DKK-1 is a reliable biomarker for the identification of SLE and patients with LN and could be used as a key molecule for the diagnosis of SLE and as a prognostic indicator of LN.


2003 ◽  
Vol 12 (2) ◽  
pp. 101-105 ◽  
Author(s):  
Yves Denizot ◽  
Eric Liozon ◽  
Laurence Guglielmi ◽  
Kim Ly ◽  
Pascale Soria ◽  
...  

Background:Platelet-activating factor (PAF) seems to be implicated in systemic lupus erythematosus (SLE) patients with associated renal diseases.Aims:In this study, we ensured the role of PAF in SLE patients without renal complications.Methods:Blood PAF and acetylhydrolase activity, plasma soluble phospholipase A2, and the presence of antibodies against PAF were investigated in 17 SLE patients without active nephritis and in 17 healthy controls.Results:Blood PAF levels were not different(P=0.45)between SLE patients (6.7±2.8 pg/ml) and healthy subjects (9.6±3.1 pg/ml). Plasma acetylhydrolase activity (the PAF-degrading enzyme) was significantly(P=0.03)elevated in SLE patients (57.8±6.4 nmol/min/ml) as compared with controls (37.9±2.6 nmol/min/ml). Plasma soluble phospholipase A2(the key enzyme for PAF formation) was not different(P=0.6)between SLE patients (59.1±5.1 U/ml) and controls (54.7±2.4 U/ml). Antibodies against PAF were detected only in 3/17 SLE patients. Flow cytometry analysis did not highlight PAF receptors on circulating leukocytes of SLE patients.Conclusion:This clinical study highlights no evidence for a putative important role of PAF in SLE patients without active nephritis.


Lupus ◽  
2021 ◽  
pp. 096120332110279
Author(s):  
Ruth Fernandez-Ruiz ◽  
Rebecca B Blank ◽  
Ming Wu ◽  
H Michael Belmont

Introduction Activation of the complement pathway by immune complexes is a key feature of systemic lupus erythematosus (SLE) and SLE glomerulonephritis, which translates into low levels of C3 and C4 during active disease. C3 glomerulonephritis (C3GN) is part of a broader group of rare renal diseases, the C3 glomerulopathies, characterized by prominent C3 accumulation in the glomeruli with minimal to no immunoglobulin (Ig) deposition secondary to dysregulation of the alternative pathway of the complement system. Distinguishing lupus nephritis from other complement-mediated kidney disorders, including C3GN, represents a diagnostic challenge with potential therapeutic implications. Methods We report an unusual case of a 55-year-old woman with SLE and previous biopsy-proven class IV lupus nephritis, subsequently diagnosed with C3GN. Furthermore, we review the available literature published from January 2010—March 2021 on the clinical features and management of C3GN in the setting of SLE. Results In addition to our case, very few reports exist in the literature regarding C3GN in association with SLE. The underlying pathogenic mechanism of C3GN consists of dysregulation of the alternative pathway of the complement system, either due to genetic variation in complement-related genes or to acquired autoantibodies targeting C3 or C5 convertases; the latter mechanism could explain the occurrence of C3GN in the setting of autoimmune diseases, although it was not definitively identified in our patient or others with SLE. Similar to some of the previous reports, after suboptimal renal response on mycophenolate mofetil and rituximab, our patient has been successfully treated with eculizumab, thus far with >50% improvement in proteinuria. Conclusions C3GN represents an additional mechanism of renal injury in SLE mediated by alternative complement pathway dysregulation. Although rare, patients with SLE and persistent proteinuria with very low C3 would benefit from expedited renal biopsy to evaluate for C3GN as well as genetic testing, since this entity could require a different therapeutic approach.


2020 ◽  
Vol 19 (11) ◽  
pp. 102668
Author(s):  
Meera Ramanujam ◽  
Jürgen Steffgen ◽  
Sudha Visvanathan ◽  
Chandra Mohan ◽  
Jay S. Fine ◽  
...  

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Amol M. Patel ◽  
Lily Anne Romero Karam ◽  
Stephanie C. Fuentes Rojas ◽  
Warren E. Redfearn ◽  
Luan D. Truong ◽  
...  

Lupus nephritis is a common manifestation of systemic lupus erythematosus (SLE). IgA nephropathy is a common type of primary glomerulonephritis. Renal manifestations in SLE patients are often due to lupus nephritis; however, renal diseases unrelated to lupus nephritis are rarely reported. While crescentic IgA nephropathy with rapid clinical progression is rare, its development in patients with SLE in the absence of lupus nephritis is even more unusual. A 74-year-old woman with a history of SLE without known renal involvement, chronic kidney disease stage IIIa, congestive heart failure, hypertension, and type 2 diabetes mellitus presented with acute kidney injury. Her creatinine continued to rise rapidly. Renal biopsy revealed mesangial proliferative glomerulonephritis with crescent formation. Immunofluorescent staining showed IgA and C3 mesangial deposition and absence of C4 and C1q, consistent with IgA nephropathy. She received a course of methylprednisolone and plasmapheresis. Unfortunately, her renal function continued to deteriorate, and she was started on hemodialysis which was continued after hospital discharge. This case illustrates crescentic IgA nephropathy without lupus nephritis as the cause of acute kidney injury in a patient with SLE. It highlights the observation that renal diseases other than lupus nephritis can develop in SLE patients.


2019 ◽  
Vol 133 (9) ◽  
pp. 1049-1052 ◽  
Author(s):  
Raquel Cortes ◽  
Maria J. Forner

Abstract Circular RNAs (circRNAs) are a class of non-coding RNAs that regulate gene expression by acting as competitive endogenous RNAs (ceRNAs) and modulating gene transcription. Several studies support the implication of circRNAs in a variety of human diseases, but research on the role of circRNAs in systemic lupus erythematosus (SLE) is lacking. In a study recently published in Clinical Science (2018), Zhang et al. identified hsa_circ_0012919 as a potential biomarker of disease activity in SLE patients. The authors observed different circRNA expression between SLE patients and healthy controls, an association with clinical variables and with the abnormal DNA methylation present in SLE CD4+ T cells. Finally, Zhang et al. demonstrated that hsa_circ_0012919 acts as a miRNA sponge for miR-125a-3p, regulating the gene expression of targets RANTES and KLF13 that are involved in the physiology and pathophysiology of acute and chronic inflammatory processes. These findings support the role of circRNAs in the pathophysiology of SLE.


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