scholarly journals An Exosomal Urinary miRNA Signature for Early Diagnosis of Renal Fibrosis in Lupus Nephritis

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 773 ◽  
Author(s):  
Solé ◽  
Moliné ◽  
Vidal ◽  
Ordi-Ros ◽  
Cortés-Hernández
Keyword(s):  
Lupus Nephritis ◽  
Renal Fibrosis ◽  
Target Genes ◽  
Early Stage ◽  
High Sensitivity ◽  
Increased Risk ◽  
Chronicity Index ◽  
Stage Renal Disease ◽  
End Stage

For lupus nephritis (LN) management, it is very important to detect fibrosis at an early stage. Urinary exosomal miRNAs profiling can be used as a potential multi-marker phenotyping tool to identify early fibrosis. We isolated and characterised urinary exosomes and cellular pellets from patients with biopsy-proven LN (n = 45) and healthy controls (n = 20). LN chronicity index (CI) correlated with urinary exosomal miR-21, miR-150, and miR-29c (r = 0.565, 0.840, −0.559, respectively). This miRNA profile distinguished low CI from moderate-high CI in LN patients with a high sensitivity and specificity (94.4% and 99.8%). Furthermore, this multimarker panel predicted an increased risk of progression to end-stage renal disease (ESRD). Pathway analysis identified VEGFA and SP1 as common target genes for the three miRNAs. Immunohistochemistry in LN renal biopsies revealed a significant increase of COL1A1 and COL4A1 correlated with renal chronicity. SP1 decreased significantly in the high-CI group (p = 0.002). VEGFA levels showed no differences. In vitro experiments suggest that these miRNA combinations promote renal fibrosis by increasing profibrotic molecules through SP1 and Smad3/TGFβ pathways. In conclusion, a urinary exosomal multimarker panel composed of miR-21, miR-150, and miR-29c provides a non-invasive method to detect early renal fibrosis and predict disease progression in LN.

scholarly journals Uremic Toxins and Their Relation with Oxidative Stress Induced in Patients with CKD

2021 ◽  
Vol 22 (12) ◽  
pp. 6196
Author(s):  
Anna Pieniazek ◽  
Joanna Bernasinska-Slomczewska ◽  
Lukasz Gwozdzinski
Keyword(s):  
Oxidative Stress ◽  
Uremic Toxins ◽  
Water Medium ◽  
Induce Insulin Resistance ◽  
Risk Of Mortality ◽  
Increased Risk ◽  
Stage Renal Disease ◽  
End Stage

The presence of toxins is believed to be a major factor in the development of uremia in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Uremic toxins have been divided into 3 groups: small substances dissolved in water, medium molecules: peptides and low molecular weight proteins, and protein-bound toxins. One of the earliest known toxins is urea, the concentration of which was considered negligible in CKD patients. However, subsequent studies have shown that it can lead to increased production of reactive oxygen species (ROS), and induce insulin resistance in vitro and in vivo, as well as cause carbamylation of proteins, peptides, and amino acids. Other uremic toxins and their participation in the damage caused by oxidative stress to biological material are also presented. Macromolecules and molecules modified as a result of carbamylation, oxidative stress, and their adducts with uremic toxins, may lead to cardiovascular diseases, and increased risk of mortality in patients with CKD.

scholarly journals Pentraxin 3 Activates JNK Signaling and Regulates the Epithelial-To-Mesenchymal Transition in Renal Fibrosis

2016 ◽  
Vol 40 (5) ◽  
pp. 1029-1038 ◽  
Author(s):  
Tung-Wei Hung ◽  
Jen-Pi Tsai ◽  
Shin-Huey Lin ◽  
Chien-Hsing Lee ◽  
Yi-Hsien Hsieh ◽  
...  
Keyword(s):  
Cell Migration ◽  
Renal Fibrosis ◽  
Epithelial To Mesenchymal Transition ◽  
Pentraxin 3 ◽  
Mesenchymal Transition ◽  
Affect Cell Viability ◽  
Stage Renal Disease ◽  
End Stage ◽  
E Cadherin

Background/Aims: Tubulointerstitial fibrosis can lead to end-stage renal disease. Pentraxin 3 (PTX3) is an acute phase protein produced by resident and innate immunity cells. We investigated the effect of PTX3 on cultured human proximal tubular epithelial (HK-2) cells and a rat unilateral ureteral obstruction (UUO) model of renal fibrosis. Methods: Gain-of-function experiments were used to examine the effect of recombinant human PTX3 (Rh-PTX3) on HK-2 cells. Cell proliferation (MTT assay) and in vitro cell migration were measured. The levels of PTX3, p-JNK, and EMT markers were measured using immunohistochemistry, RT-PCR, and western blotting in UUO rats and HK-2 cells. Results: HK-2 cells treated with Rh PTX3 did not affect cell viability, but significantly increased cell migration. Moreover, Rh-PTX3 increased the expression of snail, slug, N-cadherin, and vimentin, decreased the expression of E-cadherin, and increased the phosphorylation of JNK. SP600126 (a specific JNK inhibitor) enhanced the effects of Rh-PTX3. Rats with UUO exhibited time-dependent increased levels of PTX3, p-JNK, and vimentin, and decreased expression of E-cadherin. Conclusions: Our results suggest that PTX3 induces cell migration via upregulation of EMT in a JNK-dependent mechanism, and highlight the role of PTX3 in the pathogenesis renal fibrosis.

scholarly journals Huidouba Improved Podocyte Injury by Down-Regulating Nox4 Expression in Rats With Diabetic Nephropathy

2020 ◽  
Vol 11 ◽  
Author(s):  
KunBao Yang ◽  
YingHui Bai ◽  
Ning Yu ◽  
BiNan Lu ◽  
GuiYan Han ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Early Stage ◽  
Fasting Blood Glucose ◽  
Folk Medicine ◽  
Scientific Basis ◽  
Transmission Electron ◽  
Podocyte Loss ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy (DN), as the most common microvascular complication of diabetes mellitus (DM), has become one of the leading causes of end-stage renal disease (ESRD). Numerous studies have indicated that podocyte loss plays an important role in the development of DN and can even cause proteinuria in the early stage of DN. In the study, we found that Huidouba (HDB) significantly decreased the level of fasting blood glucose (FBG), the ratio of microalbumin to urine creatine (mAlb/Ucr), serum creatine (Scr), serum urea nitrogen (BUN), and malondialdehyde (MDA) in the kidney and downregulated the expression of Nox4 predominantly located in glomerular tissue while upregulating nephrin and WT1 expression in DN rats. In addition, HDB could also reduce podocyte damage and glomerular basement membrane (GBM) pathologic changes, as shown by transmission electron microscopy (TEM). In vitro study showed that HDB could inhibit high glucose (HG)-induced Reactive Oxygen Species (ROS) production and protect against podocyte apoptosis by downregulated Nox4 expression in podocytes. These results may provide a scientific basis for developing HDB as a potential folk medicine for the treatment of DN.

Clinical outcomes of lupus nephritis patients with different proportions of crescents

Lupus ◽  
2016 ◽  
Vol 25 (14) ◽  
pp. 1532-1541 ◽  
Author(s):  
W Zhang ◽  
M Yuan ◽  
L Hong ◽  
Q Zhou ◽  
W Chen ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Patient Survival ◽  
Activity Index ◽  
Prognostic Significance ◽  
Adverse Outcomes ◽  
Baseline Serum ◽  
Chronicity Index ◽  
Stage Renal Disease ◽  
End Stage

Background The prognostic significance of different proportions of crescents in lupus nephritis (LN) remains unclear. We assessed the long-term prognosis of LN patients with different proportions of crescents. Methods In this single-center, retrospective cohort study, 788 eligible LN patients were enrolled. The primary endpoint was doubling of baseline serum creatinine and end-stage renal disease; the secondary endpoint was death. Results There were 406 (51.5%) patients demonstrating crescents at biopsy, and they had more severe baseline status: lower estimated glomerular filtration rate (eGFR), more proteinuria, more severe microscopic hematuria, and higher pathological scores for both activity index (AI) and chronicity index (CIn) (all p < 0.001, respectively). After a median follow-up period of 56 months (range: 3–172 months), no significant differences were observed in terms of renal or patient survival in these two groups ( p = 0.188). In LN patients with crescents, patient survival was poorer along with the increase in the proportion of crescents; for crescentic LN, patient survival was 78.9% at five years and 52.6% at 10 years (vs. subgroups of crescent proportion <10%, 10%–19%, 20%–49%: 95.5%, 92.3%, 91.7% at five years; 86.1%, 80.1%, 66.5% at 10 years, respectively, p = 0.008). Furthermore, there were higher proportions of crescents independently predicted for adverse outcomes of renal progression and mortality ( p = 0.049) after adjusting for age, sex, baseline eGFR, proteinuria, AI, and CIn in the multivariate Cox proportional hazard model. Conclusion The overall long-term renal survival of LN patients with and without crescents was comparable. However, a higher proportion of crescents increased the risk for unfavorable outcomes. Therefore, more attention should be paid to the lesions of crescents, and more prospective studies are needed to explore the optimal regimens for LN patients with different proportions of crescents.

Could Antioxidant Supplementation Delay Progression of Cardiovascular Disease in End-Stage Renal Disease Patients?

2020 ◽  
Vol 19 (1) ◽  
pp. 41-54 ◽  
Author(s):  
Stefanos Roumeliotis ◽  
Athanasios Roumeliotis ◽  
Xenia Gorny ◽  
Peter R. Mertens
Keyword(s):  
Oxidative Stress ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Close Association ◽  
Omega 3 ◽  
Endstage Renal Disease ◽  
Increased Risk ◽  
Underlying Mechanisms ◽  
Stage Renal Disease ◽  
End Stage

In end-stage renal disease patients, the leading causes of mortality are of cardiovascular (CV) origin. The underlying mechanisms are complex, given that sudden heart failure is more common than acute myocardial infarction. A contributing role of oxidative stress is postulated, which is increased even at early stages of chronic kidney disease, is gradually augmented in parallel to progression to endstage renal disease and is further accelerated by renal replacement therapy. Oxidative stress ensues when there is an imbalance between reactive pro-oxidants and physiologically occurring electron donating antioxidant defence systems. During the last decade, a close association of oxidative stress with accelerated atherosclerosis and increased risk for CV and all-cause mortality has been established. Lipid peroxidation has been identified as a trigger for endothelial dysfunction, the first step towards atherogenesis. In order to counteract the deleterious effects of free radicals and thereby ameliorate, or delay, CV disease, exogenous administration of antioxidants has been proposed. Here, we attempt to summarize existing data from studies that test antioxidants for CV protection, such as vitamins E and C, statins, omega-3 fatty acids and N-acetylcysteine.

scholarly journals A therapeutic vascular conduit to support in vivo cell-secreted therapy

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Edward X. Han ◽  
Hong Qian ◽  
Bo Jiang ◽  
Maria Figetakis ◽  
Natalia Kosyakova ◽  
...  
Keyword(s):  
Vascular Graft ◽  
Large Scale ◽  
Biological Effects ◽  
Therapeutic Protein ◽  
Close Proximity ◽  
Delivery Platform ◽  
Stage Renal Disease ◽  
End Stage

AbstractA significant barrier to implementation of cell-based therapies is providing adequate vascularization to provide oxygen and nutrients. Here we describe an approach for cell transplantation termed the Therapeutic Vascular Conduit (TVC), which uses an acellular vessel as a scaffold for a hydrogel sheath containing cells designed to secrete a therapeutic protein. The TVC can be directly anastomosed as a vascular graft. Modeling supports the concept that the TVC allows oxygenated blood to flow in close proximity to the transplanted cells to prevent hypoxia. As a proof-of-principle study, we used erythropoietin (EPO) as a model therapeutic protein. If implanted as an arteriovenous vascular graft, such a construct could serve a dual role as an EPO delivery platform and hemodialysis access for patients with end-stage renal disease. When implanted into nude rats, TVCs containing EPO-secreting fibroblasts were able to increase serum EPO and hemoglobin levels for up to 4 weeks. However, constitutive EPO expression resulted in macrophage infiltration and luminal obstruction of the TVC, thus limiting longer-term efficacy. Follow-up in vitro studies support the hypothesis that EPO also functions to recruit macrophages. The TVC is a promising approach to cell-based therapeutic delivery that has the potential to overcome the oxygenation barrier to large-scale cellular implantation and could thus be used for a myriad of clinical disorders. However, a complete understanding of the biological effects of the selected therapeutic is absolutely essential.

scholarly journals Identification of Novel Biomarker for Early Detection of Diabetic Nephropathy

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 457
Author(s):  
Kyeong-Seok Kim ◽  
Jin-Sol Lee ◽  
Jae-Hyeon Park ◽  
Eun-Young Lee ◽  
Jong-Seok Moon ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Early Stage ◽  
Kidney Injury ◽  
Diabetic Patients ◽  
High Morbidity ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Zucker Diabetic Fatty Rats ◽  
Kidney Injury Molecule 1 ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus. After development of DN, patients will progress to end-stage renal disease, which is associated with high morbidity and mortality. Here, we developed early-stage diagnostic biomarkers to detect DN as a strategy for DN intervention. For the DN model, Zucker diabetic fatty rats were used for DN phenotyping. The results revealed that DN rats showed significantly increased blood glucose, blood urea nitrogen (BUN), and serum creatinine levels, accompanied by severe kidney injury, fibrosis and microstructural changes. In addition, DN rats showed significantly increased urinary excretion of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Transcriptome analysis revealed that new DN biomarkers, such as complementary component 4b (C4b), complementary factor D (CFD), C-X-C motif chemokine receptor 6 (CXCR6), and leukemia inhibitory factor (LIF) were identified. Furthermore, they were found in the urine of patients with DN. Since these biomarkers were detected in the urine and kidney of DN rats and urine of diabetic patients, the selected markers could be used as early diagnosis biomarkers for chronic diabetic nephropathy.

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