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Kiev, Ukraine

ABSTRACT: To investigate whether myofibrillogenesis regulator 1 (MR-1) attenuates renal ischemia/reperfusion (I/R) injury via inhibiting phosphorylated Akt (p-Akt) mitochondrial translocation-mediated opening of the mitochondrial permeability transition pore (mPTP), we injected adenovirus containing MR-1 gene or its siRNAs to the left kidney subcapsular areas of Sprague-Dawley rats, which subsequently underwent experimental renal I/R injury. Renal functions and the severity of the tubular injury were evaluated by the serum creatinine and blood urea nitrogen levels and the pathological scores. We also examined the mitochondrial morphology and functions. Total/p-Akt were assessed by western blot using the mitochondrial and the cytosolic fractions of cortex of renal tissue, respectively. We found that mitochondrial and cytosolic MR-1 levels and mitochondrial p-Akt decreased, and cytosolic p-Akt increased after reperfusion. Subcapsular injection of adenovirus led to higher MR-1 expression in the mitochondria/cytosol, inhibited mPTP opening, and alleviated renal I/R injury; adenovirus injection also up-regulated mitochondrial total and p-Akt levels more prominently compared to the normal saline (NS) group. Subcapsular injection of MR-1 siRNAs significantly lowered MR-1 expression and induced renal injury, with increased mPTP opening and mitochondrial damage, similar to I/R injury. MR-1 interacted with Akt in renal cortex homogenate. Wortmannin, a phosphatidylinositol 3 kinase (PI3K) inhibitor, abolished both mitochondrial p-Akt recruitment and the protective effect of MR-1 overexpression on I/R injury. To conclude, MR-1 protects kidney against I/R injury through inhibiting mPTP opening and maintaining mitochondrial integrity, through the recruitment of PI3K-dependent p-Akt to the mitochondria. MR-1 could be a new therapeutic strategy for renal I/R injury. © 2016 by the Shock Society

Xu X.,Nanjing Southeast University | Zheng M.,Institute of Nephrology | Liu B.,Nanjing Southeast University
International Journal of Clinical and Experimental Medicine | Year: 2016

This study aims to explore the clinical value of urine TWEAK/Fn14 mRNA in lupus nephritis (LN) patients. Thirty one SLE (Systemic Lupus Erythematosus) patients with or without active LN and another 10 healthy controls were recruited. LN activity was assessed by SLE Disease Activity Index. Urinary expression of TWEAK, Fn14 and MCP-1 at the mRNA level was measured by RT-PCR. Urinary expression of TWEAK, Fn14 and MCP-1 mRNA was significantly increased in LN patients (P<0.05). TWEAK, Fn14, and MCP-1 mRNA expression was positively correlated with 24-h urinary proteins, SLEDAI and serum anti-double stranded DNA antibodies (r=0.632, P=0.0001; r=0.651, P=0.001; r=0.417, P=0.02). TWEAK mRNA was positively associated with Fn14 and MCP-1 mRNA (r=0.871, P<0.0001; r=0.561, P<0.0001). In summary, TWEAK, Fn14 and MCP-1 mRNA are potential biomarkers of LN activity. © 2016, E-Century Publishing Corporation. All rights reserved.

Xie P.,Institute of Nuclear Medicine | Huang J.-M.,Institute of Nuclear Medicine | Lin H.-Y.,Institute of Nephrology | Wu W.-J.,Institute of Nuclear Medicine | Pan L.-P.,Institute of Nuclear Medicine
International Urology and Nephrology | Year: 2013

Purpose: To compare the performance of the Chronic Kidney Disease Epidemiology Collaboration (CDK-EPI) equation, the 24-h creatinine clearance rate (24hCCr), Cockroft-Gault (C-G) formula, the abbreviated Modification of Diet in Renal Disease (aMDRD) equation, the modified Modification of Diet in Renal Disease (mMDRD) equation in determining glomerular filtration rate (GFR) in Chinese patients with chronic kidney disease (CKD) and detect the most proper method to measure GFR in clinical practice. Methods: One hundred and fifty-four patients with CKD were enrolled in the present study. 99mTc- diethylene triamine pentaacetic acid (99mTc-DTPA) plasma clearance method measured by dual plasma sampling method (rGFR) was considered as the reference standard. GFR was estimated simultaneously using five methods: (1) CDK-EPI equation (eGFR1); (2) 24hCCr (eGFR2); (3) C-G formula (eGFR3); (4) abbreviated MDRD equation (eGFR4); (5) mMDRD equation (eGFR5). The comparison of correlation, regression, bias, precision, accuracy, limit of agreement, and receiver-operating characteristics (ROC) for detecting CKD (with a GFR cutoff of 60 mL min-1 1.73 m-2) among the methods was analyzed to identify the most suitable method. Results: All the equations correlated well with rGFR, and the correlation coefficient of CDK-EPI equation was the highest (reGFR1 = 0.922, P < 0.001). The Bland-Altman analysis showed that the limit of agreement for CDK-EPI equation was -25.5 to 30.3 mL min -1 1.73 m-2, which was the least range among the tested equations. The CDK-EPI equation represented the best capability in precision (14.24 mL min-1 1.73 m-2). The ROC curve showed the best performance in detecting CKD. The accuracy within ±30 % of CDK-EPI equation, 24hCCr, and mMDRD equation was 72.08, 69.48, and 70.13 %, respectively, and no statistical significant difference was found (P > 0.05). However, CDK-EPI equation had the highest accuracy when compared with the other two equations (P < 0.05). And its performance on bias showed no statistically significant difference compared with other four equations. Conclusions: Although its bias and accuracy did not overmatch the other four equations in our patient group, the CDK-EPI equation outperformed the other equations based on creatinine in correlation, precision, limit of agreement, and detecting CKD, and it is very simple, time-saving, and cost-effective. So we recommend intensely that the CDK-EPI equation is the most suitable method in determining GFR in Chinese patients with CKD and can be applied generally in clinical practice. © 2012 Springer Science+Business Media Dordrecht.

Stefanovic V.,Institute of Nephrology | Polenakovic M.,Macedonian Academy of science and Arts | Toncheva D.,Medical University-Sofia
Pathologie Biologie | Year: 2011

Balkan endemic nephropathy (BEN), a familial chronic tubulo-interstitial disease with a slow progression to terminal renal failure, affects people living in the alluvial plains along the tributaries of the Danube River. One of its most peculiar characteristics is a strong association with upper urothelial cancer. An increased incidence of upper urinary tract (UUT) transitional cell cancer (TCC) was discovered among the inhabitants of endemic settlements and in families affected by BEN. In areas where BEN is endemic, the incidence of upper tract TCC is significantly higher, even 100 times, than in non-endemic regions. A high incidence of urothelial cancer in end-stage BEN patients strongly suggests preventive nephro-ureterectomy in all end-stage patients with BEN treated with either transplantation or dialysis. Better understanding of the molecular mechanisms involved in carcinogenesis and tumor progression, has provided a large number of molecular markers of TCC, with a potential diagnostic and prognostic value. Markers that distinguish among TCC, normal urothelium, and benign urothelial conditions are potentially diagnostic, prognostic, and therapeutic targets. The geographic correlation and presence of AA-DNA adducts in both BEN and associated urothelial cancer, support the speculation that these diseases share a common etiology. Dietary exposure to AA is a significant risk factor for BEN and its attendant transitional cell cancer. These are cases of well-known AA induced urothelial carcinoma, and could be detected worldwide. The presence of more than one risk factors is possible and it is important to test etiological hypotheses in different endemic foci, preferably as a multicentric research. © 2009 Elsevier Masson SAS.

Yamamoto T.,Institute of Nephrology
Advances in Chronic Kidney Disease | Year: 2010

Databases which are useful for proteomic analysis of human kidney tissue and urine have been discussed in this article. Integration of the gene-centric and protein-centric general databases with those of human kidney tissue and urine proteomes may open a new window for research in nephrology. Proteins present in the kidney and urine provide basic tools for investigation of kidney function and disease. By comparing such databases between the healthy and diseased populations, we may be able to identify the following: proteins involved in the development of renal disease, proteins involved in progression of CKD, or new biomarker candidate proteins for either the development of renal disease or the progression of CKD. © 2010 National Kidney Foundation, Inc.

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