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[Experimental development and rationale for a renal decellularization protocol with subsequent comprehensive assessment of the biological scaffold].

Wed, 06/21/2017 - 21:45

[Experimental development and rationale for a renal decellularization protocol with subsequent comprehensive assessment of the biological scaffold].

Urologiia. 2017 Jun;(2):5-13

Authors: Glybochko PV, Alekseenko SN, Gubareva EA, Kuevda EV, Basov AA, Sotnichenko AS, Dzhimak SS, Gumenyuk IS, Egiev IK, Chechelyan VN, Nakokhov RZ, Lyasota OM, Teterin YV

Abstract
Chronic renal failure (CRF) is one of the most challenging problems of contemporary medicine. Patients with chronic renal failure usually need renal replacement therapy as either hemodialysis, peritoneal dialysis or a kidney transplant. The latter is the most promising option for end-stage kidney disease. However, the shortage of donor organs, the complexity of their delivery, the difficulty in finding an immunologically compatible donor and the need for lifelong immunosuppression triggered advances in modern tissue engineering. In this field, the primary priority is focused on developing bioengineered scaffolds with subsequent recellularization with autologous cells. Using such constructs would allow for solving both ethical and immunological problems of transplantation. The aim of this pilot study was to develop a new method of renal decellularization using small laboratory animals.
MATERIALS AND METHODS: The study investigated the morphological structure of the obtained decellularized matrix and quantitatively tested DNA residues in the resulting scaffold. We proposed a new biophysical method for assessing the matrix quality using the EPR spectroscopy and conducted experiments on the matrix recellularization with mesenchymal multipotent stem cells to estimate cytotoxicity, cell viability and metabolic activity.
RESULTS: The obtained decellularized renal matrix retained the native tissue architecture after a complete removal of the cell material, had no cytotoxic properties and supported cell adhesion and proliferation.
CONCLUSION: All the above suggests that the proposed decellularization protocol is a promising method to produce tissue-engineered kidney constructs with possible clinical application in the foreseeable future.

PMID: 28631900 [PubMed - in process]

[Concurrence of acute graft rejection and polyomavirus nephropathy: A clinical case].

Wed, 06/21/2017 - 21:45

[Concurrence of acute graft rejection and polyomavirus nephropathy: A clinical case].

Arkh Patol. 2017;79(3):42-46

Authors: Motin YG, Omelchenko OV, Bukiy TP, Bgatova NP, Gryzlov AY

Abstract
The paper describes a case of diagnosing acute renal graft rejection concurrent with polyomavirus nephropathy. Histochemical and electron microscopic methods were used to examine biopsy specimens, which showed morphological changes occurring in the allograft, the ultrastructural characteristics of polyomavirus and the features of its spread in kidney tissue structures.

PMID: 28631715 [PubMed - in process]

Transesophageal echocardiography in orthotopic liver transplantation: a comprehensive intraoperative monitoring tool.

Wed, 06/21/2017 - 21:45
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Transesophageal echocardiography in orthotopic liver transplantation: a comprehensive intraoperative monitoring tool.

Crit Ultrasound J. 2017 Dec;9(1):15

Authors: Vetrugno L, Barbariol F, Baccarani U, Forfori F, Volpicelli G, Della Rocca G

Abstract
Intraoperative transesophageal echocardiography is a minimally invasive monitoring tool that can provide real-time visual information on ventricular function and hemodynamic volume status in patients undergoing liver transplantation. The American Association for the Study of Liver Diseases states that transesophageal echocardiography should be used in all liver transplant candidates in order to assess chamber sizes, hypertrophy, systolic and diastolic function, valvular function, and left ventricle outflow tract obstruction. However, intraoperative transesophageal echocardiography can be used to "visualize" other organs too; thanks to its proximity and access to multiple acoustic windows: liver, lung, spleen, and kidney. Although only limited scientific evidence exists promoting this comprehensive use, we describe the feasibility of TEE in the setting of liver transplantation: it is a highly valuable tool, not only as a cardiovascular monitoring, but also as a tool to evaluate lungs and pleural spaces, to assess hepatic vein blood flow and inferior vena cava anastomosis and patency, i.e., in cases of modified surgical techniques. The aim of this case series is to add our own experience of TEE as a comprehensive intraoperative monitoring tool in the field of orthotopic liver transplantation (and major liver resection) to the literature.

PMID: 28631103 [PubMed - in process]

Biomarkers to detect rejection after kidney transplantation.

Wed, 06/21/2017 - 21:45
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Biomarkers to detect rejection after kidney transplantation.

Pediatr Nephrol. 2017 Jun 19;:

Authors: Dharnidharka VR, Malone A

Abstract
Detecting acute rejection in kidney transplantation has been traditionally done using histological analysis of invasive allograft biopsies, but this method carries a risk and is not perfect. Transplant professionals have been working to develop more accurate or less invasive biomarkers that can predict acute rejection or subsequent worse allograft survival. These biomarkers can use tissue, blood or urine as a source. They can comprise individual molecules or panels, singly or in combination, across different components or pathways of the immune system. This review highlights the most recent evidence for biomarker efficacy, especially from multicenter trials.

PMID: 28631040 [PubMed - as supplied by publisher]

Graft nephrectomy in children.

Wed, 06/21/2017 - 21:45
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Graft nephrectomy in children.

Pediatr Nephrol. 2017 Jun 19;:

Authors: Phillips BL, Callaghan CJ

Abstract
Kidney transplantation is recognised as the gold standard treatment of end-stage renal disease in most children, with excellent graft survival rates. When graft failure occurs, renal transplant recipients (RTRs) have the option of removal of the transplant (graft nephrectomy [GN]), or leaving the failed transplant in situ. The aims of this review are to discuss the indications for GN, surgical techniques, outcomes after GN (including risks of allosensitisation and the impact on subsequent transplants), and the possible role of routine GN in the asymptomatic RTR with a failed renal allograft. Literature in both the pediatric and adult renal transplant fields is reviewed. We also discuss how future research in this area could advance our knowledge of which patients to select for GN, and the most appropriate surgical approach.

PMID: 28631039 [PubMed - as supplied by publisher]

Understanding Medication Nonadherence after Kidney Transplant.

Wed, 06/21/2017 - 21:45
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Understanding Medication Nonadherence after Kidney Transplant.

J Am Soc Nephrol. 2017 Jun 19;:

Authors: Nevins TE, Nickerson PW, Dew MA

Abstract
Alloimmunity remains a barrier to long-term graft survival that necessitates lifelong immunosuppressive therapy after renal transplant. Medication nonadherence has been increasingly recognized as a major impediment to achieving effective immunosuppression. Electronic medication monitoring further reveals that nonadherence manifests early after transplant, although the effect is delayed. The etiology of nonadherence is multifactorial, with the strongest risk factors including past nonadherence and being an adolescent or young adult. Other risk factors with smaller but consistently important effects include minority race/ethnicity, poor social supports, and poor perceived health. In children, risk factors related to parental and child psychologic and behavioral functioning and parental distress and burden are also important. Qualitative systematic reviews highlight the need to tailor interventions to each transplant recipient's unique needs, motivations, and barriers rather than offer a one size fits all approach. To date, relatively few interventions have been studied, and most studies conducted were underpowered to allow definitive conclusions. If the kidney transplant community's goal of "one transplant for life" is to become a reality, then solutions for medication nonadherence must be found and implemented.

PMID: 28630231 [PubMed - as supplied by publisher]

Immunogenicity of class i hla but not preformed low mfi donor specific antibodies correlates with outcomes after first renal transplantation.

Wed, 06/21/2017 - 21:45
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Immunogenicity of class i hla but not preformed low mfi donor specific antibodies correlates with outcomes after first renal transplantation.

Transpl Immunol. 2017 Jun 16;:

Authors: Lobashevsky A, Goggins W, Rosner K, Taber T

Abstract
BACKGROUND: The role of low levels of circulating donor specific antibodies (DSA) producing negative flow cytometry cross match is not completely defined. The purpose of this study was to examine the clinical significance of preexisting low levels of class I DSAs in flow cytometry cross match (FC CM) negative first kidney transplant recipients (KTRs).
METHODS: All of the KTRs (n=41) had low levels of anti-class I antibodies only. The kidney transplant outcome was evaluated by the development of a deleterious effect (DE) in recipients in the study cohort (Group 1: DE+, Group 2: DE-). Positivity for DE was determined based on the following criteria: biopsy proven transplant glomerulopathy (TG), de novo development of DSAs, increasing MFI values for preexisting DSAs, and the development of biopsy proven AMR. Anti-HLA antibodies were tested using single antigen Luminex technology. The HLAMatchmaker computer algorithm was used for the immunogenicity analysis of antibody verified (AbVer) mismatched eplets (MME) at the HLA-A and B loci.
RESULTS: The results of this study showed that the number of AbVer MME is larger (P=0.03) in the group of KTR who developed DE. We also demonstrated that the number of AbVer MME is a strong predictor of post-transplant DE. These results indicate that persistent weakly reactive DSA is not a significant risk factor for the development of post-transplant DE and that recipients with such antibodies can be successfully transplanted.
CONCLUSIONS: Immunogenicity of AbVer MME at HLA-A and B loci is strong predictor of post-transplant increases of the MFI values of preexisting or de novo developed DSA in the FC CM negative first KTR. Avoiding of transplants with more than eleven Class I AbVer MMEs may be the optimal approach to reduce the risk of kidney graft failure.

PMID: 28629951 [PubMed - as supplied by publisher]

Comparative Analysis of Four Scores to Stratify Patients With Heart Failure and Reduced Ejection Fraction.

Wed, 06/21/2017 - 21:45
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Comparative Analysis of Four Scores to Stratify Patients With Heart Failure and Reduced Ejection Fraction.

Am J Cardiol. 2017 May 11;:

Authors: Freitas P, Aguiar C, Ferreira A, Tralhão A, Ventosa A, Mendes M

Abstract
There are several prognostic risk scores available for patients with heart failure with reduced ejection fraction (HFrEF) that can aid in the decision of listing candidates for heart transplant (HTx). A direct comparison between these scores has not been performed. Therefore, our objective was to evaluate the calibration and discriminative power of 4 contemporary HF scores. A retrospective analysis of 259 patients with HFrEF who underwent cardiopulmonary exercise test was conducted. The Heart Failure Survival Score (HFSS), Seattle Heart Failure Model (SHFM), Meta-analysis Global Group in Chronic Heart Failure (MAGGIC), and Metabolic Exercise Cardiac Kidney Index (MECKI) were compared. During the first year, 7 deaths occurred (6 cardiovascular) and 25 patients were submitted to HTx (8 urgent). Over a 2-year period, 14 deaths occurred (10 cardiovascular) and 34 patients received an HTx (8 urgent). Calibration analysis showed that SHFM and HFSS tended to underestimate event occurrence, whereas MAGGIC and MECKI tended to overestimate risk, especially in the highest risk subgroups. Interestingly, MECKI score at 1 year was well calibrated (expected similar to observed events). Overall, the MECKI score consistently showed better discrimination ability for all studied end points (areas under the curve between 0.8 and 0.9). In conclusion, along with HFSS and SHFM, the MECKI score can also be used to aid treatment decisions, such as HTx listing with the advantage of being very well calibrated at 1-year intervals, which might allow us to avoid the pitfalls of under/overestimation of risk.

PMID: 28629552 [PubMed - as supplied by publisher]

Screening for chronic kidney disease of uncertain aetiology in Sri Lanka: usability of surrogate biomarkers over dipstick proteinuria.

Wed, 06/21/2017 - 21:45
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Screening for chronic kidney disease of uncertain aetiology in Sri Lanka: usability of surrogate biomarkers over dipstick proteinuria.

BMC Nephrol. 2017 Jun 19;18(1):199

Authors: Ratnayake S, Badurdeen Z, Nanayakkara N, Abeysekara T, Ratnatunga N, Kumarasiri R

Abstract
BACKGROUND: The use of dipstick proteinuria to screen Chronic Kidney Disease of uncertain aetiology (CKDu) in Sri Lanka is a recently debated matter of dispute. The aim of this study was to assess the suitability of biomarkers: serum creatinine, cystatin C and urine albumin to creatinine ratio (ACR) for screening CKDu in Sri Lanka.
METHODS: Forty-four male CKDu patients and 49 healthy males from a CKDu-endemic region were selected. Meanwhile, 25 healthy males from a non-endemic region were selected as an absolute control. The diagnostic accuracy of each marker was compared using the above three study groups.
RESULTS: In receiver operating characteristics (ROC) plots for creatinine, cystatin C and ACR, values of area under the curve (AUC) were 0.926, 0.920 and 0.737 respectively when CKDu was compared to non-endemic control. When CKDu was compared to endemic control, AUCs of above three analytes were distinctly lower as 0.718, 0.808 and 0.678 respectively. Cystatin C exhibited the highest sensitivity for CKDu when analyzed against both control groups where respective sensitivities were 0.75 against endemic control and 0.89 against non-endemic control. ROC-optimal cutoff limits of creatinine, cystatin C and ACR in CKDu vs non-endemic control were 89.0 μmol/L, 1.01 mg/L and 6.06 mg/g-Cr respectively, whereas in CKDu vs endemic control the respective values were 111.5 μmol/L, 1.22 mg/L and 12.66 mg/g-Cr.
CONCLUSIONS: Amongst the three biomarkers evaluated in this study, our data suggest that Cystatin C is the most accurate functional marker in detecting CKDu in endemic regions, yet the high cost hinders its usability on general population. Creatinine is favorable over dipstick proteinuria owing to its apparent accuracy and cost efficiency, while having the ability to complement the kidney damage marker (ACR) in screening. ACR may not be favorable as a standalone screening marker in place of dipstick proteinuria due to its significant decline in sensitivity against the CKDu-endemic population. However, creatinine and ACR in a complementary manner could overcome current shortcomings of dipstick proteinuria and such a dual marker tool could be commodious in screening CKDu-type tubulointerstital diseases. Furthermore, use of ACR may also increase the ability to clinically discriminate CKDu from other glomerular nephropathies.

PMID: 28629425 [PubMed - in process]

The Impact of Hospital/Surgeon Volume on Acute Renal Failure and Mortality in Liver Transplantation: A Nationwide Cohort Study.

Wed, 06/21/2017 - 21:45
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The Impact of Hospital/Surgeon Volume on Acute Renal Failure and Mortality in Liver Transplantation: A Nationwide Cohort Study.

PLoS One. 2016;11(10):e0162992

Authors: Cheng CW, Liu FC, Lin JR, Tsai YF, Chen HP, Yu HP

Abstract
The aim of this study was to assess whether the case volume of surgeons and hospitals affects the rates of postoperative complications and survival after liver transplantation. This population-based retrospective cohort study included 2938 recipients of liver transplantation performed between 1998 and 2012, enrolled from the Taiwan National Health Insurance Research Database. They were divided into two groups, according to the cumulative case volume of their operating surgeons and the case volume of their hospitals. The duration of intensive care unit stay and post-transplantation hospitalization, postoperative complications, and mortality were analyzed. The results showed that, in the low and high case volume surgeons groups, respectively, acute renal failure occurred at the rate of 14.11% and 5.86% (p<0.0001), and the overall mortality rates were 19.61% and 12.44% (p<0.0001). In the low and high case volume hospital groups, respectively, acute renal failure occurred in 11% and 7.11% of the recipients (p = 0.0004), and the overall mortality was 18.44% and 12.86% (p<0.0001). These findings suggest that liver transplantation recipients operated on higher case volume surgeons or in higher case volume hospitals have a lower rate of acute renal failure and mortality.

PMID: 27706183 [PubMed - indexed for MEDLINE]

A comparative analysis between proteasome and immunoproteasome inhibition in cellular and humoral alloimmunity.

Tue, 06/20/2017 - 12:45
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A comparative analysis between proteasome and immunoproteasome inhibition in cellular and humoral alloimmunity.

Int Immunopharmacol. 2017 Jun 16;50:48-54

Authors: Eleftheriadis T, Pissas G, Antoniadi G, Liakopoulos V, Stefanidis I

Abstract
Triggered by the successful administration of the proteasome inhibitor bortezomib in kidney transplant recipients with acute or chronic antibody-mediated rejection, we evaluated the effect of the proteasome inhibitor CEP-18770 and of the selective immunoproteasome inhibitor ONX-0914 on cellular and humoral alloimmunity. Cellular alloimmunity was assessed by cell proliferation in a two-way mixed lymphocyte reaction (MLR) with human peripheral blood mononuclear cells (PBMC). For assessing humoral alloimmunity we developed a method, where humoral alloimmunity was induced in one-way MLR. The de novo production of alloantibodies was measured with an antibody-mediated complement-dependent cytotoxicity assay, in which supernatants from the above MLRs were used against resting PBMC similar to the stimulator cells of the forementioned MLRs. In two-way MLRs ONX-0914 inhibited cell proliferation more than CEP-18770. In one-way MLRs CEP-18770 and ONX-0194 decreased alloantibody production to the same extent. Inhibition of the immunoproteasome is superior to inhibition of the proteasome in suppressing cellular alloimmunity, and equally effective as regards to humoral alloimmunity. Considering the selective expression of the immunoproteasome in immune cells and the expected restrictive toxicity of its inhibitors, these results render immunoproteasome an excellent target for the development of new immunosuppressive medications in the field of transplantation.

PMID: 28628770 [PubMed - as supplied by publisher]

[Renal transplantations in the Centre for Nephrology in Szombathely, 1976-2016].

Tue, 06/20/2017 - 12:45
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[Renal transplantations in the Centre for Nephrology in Szombathely, 1976-2016].

Orv Hetil. 2017 Jun;158(25):984-991

Authors: Dobos A, Ruzsa E, Molnár E, Szakács G, Kulcsár I

Abstract
INTRODUCTION: The organized nephrological care in Szombathely commenced its activities in 1976.
AIM: Follow-up of our patients who has undergone a kidney transplantation.
METHOD: We used the local and national databases.
RESULTS: 213 patients (7 preemptive, 206 dialyzed) had 240 renal transplantations. Only 11 of them were living organ donation. Between 69 transplantations (Tx) were carried out between 1976-1995, and 163 Tx were done in the second 20 years. 122 patients (57%) are still alive (the average survival of these patients in renal replacement therapy - RRT - are 11.4 years), and 7 of them had transplantation between 1976-1995. The longest survival time was 35.1 years. Prevalence of patients on RRT at the end of 2016 was 1367 pmp in our county (32.5% living with functioning graft).
CONCLUSIONS: Number of transplanted patients has grown in the last decade. Proportion of living organ donation was minimal. Orv Hetil. 2017; 158(25): 984-991.

PMID: 28627948 [PubMed - in process]

Macrophages Regulate Unilateral Ureteral Obstruction-Induced Renal Lymphangiogenesis through C-C Motif Chemokine Receptor 2-Dependent Phosphatidylinositol 3-Kinase-AKT-Mechanistic Target of Rapamycin Signaling and Hypoxia-Inducible Factor-1α/Vascular...

Tue, 06/20/2017 - 12:45
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Macrophages Regulate Unilateral Ureteral Obstruction-Induced Renal Lymphangiogenesis through C-C Motif Chemokine Receptor 2-Dependent Phosphatidylinositol 3-Kinase-AKT-Mechanistic Target of Rapamycin Signaling and Hypoxia-Inducible Factor-1α/Vascular Endothelial Growth Factor-C Expression.

Am J Pathol. 2017 Jun 13;:

Authors: Guo YC, Zhang M, Wang FX, Pei GC, Sun F, Zhang Y, He X, Wang Y, Song J, Zhu FM, Pandupuspitasari NS, Liu J, Huang K, Yang P, Xiong F, Zhang S, Yu Q, Yao Y, Wang CY

Abstract
Lymphangiogenesis occurs during renal fibrosis in patients with chronic kidney diseases and vascular endothelial growth factor (VEGF)-C is required for the formation of lymphatic vessels; however, the underlying mechanisms remain unclear. We demonstrate that macrophages can regulate unilateral ureteral obstruction (UUO)-induced renal lymphangiogenesis by expressing high levels of VEGF-C by C-C motif chemokine receptor 2 (CCR2)-mediated signaling. Mice deficient in Ccr2 manifested repressed lymphangiogenesis along with attenuated renal injury and fibrosis after UUO induction. The infiltrated macrophages after UUO induction generated a microenvironment in favor of lymphangiogenesis, which likely depended on Ccr2 expression. Mechanistic studies revealed that CCR2 is required for macrophages to activate phosphatidylinositol 3-kinase (PI3K)-AKT-mechanistic target of rapamycin (mTOR) signaling in response to its ligand monocyte chemoattractant protein 1 stimulation, whereas hypoxia-inducible factor (HIF)-1α is downstream of PI3K-AKT-mTOR signaling. HIF-1α directly bound to the VEGF-C promoter to drive its expression to enhance lymphangiogenesis. Collectively, we characterized a novel regulatory network in macrophages, in which CCR2 activates PI3K-AKT-mTOR signaling to mediate HIF-1α expression, which then drives VEGF-C expression to promote lymphangiogenesis.

PMID: 28627412 [PubMed - as supplied by publisher]

"Spectrum of hepatitis B and renal involvement".

Tue, 06/20/2017 - 12:45
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"Spectrum of hepatitis B and renal involvement".

Liver Int. 2017 Jun 19;:

Authors: Shah AS, Amarapurkar DN

Abstract
Renal involvement in hepatitis B occurs in various spectrums and its knowledge is important for clinicians in management of patients. The renal diseases most commonly associated with hepatitis B virus (HBV) infection include membranous nephropathy, membranoproliferative glomerulonephritis, and Polyarteritis nodosa. The widespread use of hepatitis B vaccination has decreased the incidence of HBV-related renal diseases. The incidence of HBV infection in dialysis patients has significantly decreased over the past few decades due to screening of blood products for hepatitis B surface antigen (HBsAg) and hepatitis B core antibody, implementation of infection control measures and hepatitis B vaccination. The definition of acute kidney injury has been recently modified in cirrhotic population, helping in prognosis and prediction of mortality. The most common etiologies of acute kidney injury in this cirrhotic population, which account for 80% to 90% of all cases, include volume depletion, acute tubular necrosis, and hepatorenal syndrome. Treatment with oral nucleoside/tide analogues (NA) brought a new paradigm in the management of HBsAg positive glomerulonephritis, kidney transplant recipients and dialysis patients, resulting in effective viral suppression, reduced hepatic complications, and improved patient survival, without compromising renal allograft outcome. NAs are cleared by the kidneys and therefore their dosage has to be adjusted in all patients with impaired renal function. This article reviews the recent knowledge of the pathogenesis and treatment of HBV-related glomerulonephritis and discusses the management of hepatitis B in patients on dialysis, kidney transplant recipients and cirrhotics, which is continuously evolving. This article is protected by copyright. All rights reserved.

PMID: 28627094 [PubMed - as supplied by publisher]

Invasive Trichophyton rubrum Mimicking Blastomycosis in a Patient with Solid Organ transplant.

Tue, 06/20/2017 - 12:45
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Invasive Trichophyton rubrum Mimicking Blastomycosis in a Patient with Solid Organ transplant.

J Cutan Pathol. 2017 Jun 19;:

Authors: Talebi-Liasi F, Shinohara MM

Abstract
We present a case of tissue invasive Trichophyton rubrum (T. rubrum) histologically mimicking blastomycosis in a patient with kidney transplant on chronic immunosuppression. Invasive dermatophyte infections are rare, and present a diagnostic challenge to the dermatopathologist due to atypical clinical and histopathological presentations.

PMID: 28627008 [PubMed - as supplied by publisher]

Discussion on the risk factors of developing cardiovascular diseases (CVD) after the kidney transplantation.

Tue, 06/20/2017 - 12:45
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Discussion on the risk factors of developing cardiovascular diseases (CVD) after the kidney transplantation.

Pak J Pharm Sci. 2017 Jan;30(1 Suppl):241-246

Authors: Wang K, Qu QS, Miao SZ, Zhang Y, Jing X

Abstract
To discuss the risk factors of developing cardiovascular disease (CVD) after the kidney transplantation. Retrospective analysis on the data of 1106 patients who had been underwent kidney allotransplantation in People's Hospital of Zhengzhou from July, 2010 to Dec, 2014 and conformed to the inclusion criteria was taken. Cox proportional hazard model was used to analyze the risk factors of developing CVD after the kidney transplantation. 7 days, 1 month, 3 months, 6 months and 12 months before and after the operation, the data collection and following-up visits were respectively arranged. 12 months after the operation, the following-up visits were arranged once a half year until the end of March, 2014. 216 (19.5%) patients developed CVD after the kidney transplantation. Among them, 47 (4.2%) patients developed CVD within the first three months after the operation, which accounted for 26.8% in the CVD patients; 125 (11.3%) patients developed CVD within the first one year after the operation, which accounted for 47.9% in the CVD patients. 51 (4.6%) patients died after the operation. Among them, 19 (2.7%) patients died of CVD, which accounted for 37.3% in the whole died patients. Multiple factors analysis revealed that the following were the risk factors to develop CVD after the kidney transplantation: The age of receptors was greater than 50 (OR=2.39, 95%CI 1.15-3.60); The receptors had diabetes before the surgery (OR=3.18, 95%CI 1.56-6.42); The receptors had CVD medical history before the surgery (OR=3.85, 95%CI 2.15-7.54); The primary diseases of receptors were diabetic nephropathy (DN) (OR=2.12, 95%CI 1.14-3.98); The preoperative dialysis time was greater than 12 months(OR=1.27, 95%CI 0.98-1.38); The postoperative serum creatinine of the receptors was greater than 200 μmol/L (OR=2.78, 95%CI 1.35~4.53); The delayed graft failure (DGF) occurred (OR=1.24, 95%CI 1.02~1.42); Acute rejection appeared(AR)(OR=2.98, 95%CI 1.56~5.72); Renal allograft dysfunction appeared (OR=4.86, 95%CI 3.15~7.78). The morbidity of CVD is high after the kidney transplantation and the risk factors are diversified. That revising or excluding relevant risk factors may lower the morbidity of developing CVD and is in favor of the long-term survival for the transplanted kidney.

PMID: 28625949 [PubMed - in process]

Mesenchymal Stem Cell-based Therapy as a New Horizon for Kidney Injuries.

Tue, 06/20/2017 - 12:45
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Mesenchymal Stem Cell-based Therapy as a New Horizon for Kidney Injuries.

Arch Med Res. 2017 Feb;48(2):133-146

Authors: Roushandeh AM, Bahadori M, Roudkenar MH

Abstract
Today, the prevalence of kidney diseases is increasing around the world, but there has still been no effective medical treatment. The therapeutic choices are confined to supportive cares and preventive strategies. Currently, mesenchymal stem cells (MSCs)-based cell therapy was proposed for the treatment of kidney injuries. However, after the transplantation of MSCs, they are exposed to masses of cytotoxic factors involving an inflammatory cytokine storm, a nutritionally-poor hypoxic environment and oxidative stresses that finally lead to minimize the efficacy of MSCs based cell therapy. Therefore, several innovative strategies were developed in order to potentiate MSCs to withstand the unfavorable microenvironments of the injured kidney tissues and improve their therapeutic potentials. This review aims to introduce MSCs as a new modality in the treatment of renal failure. Here, we discuss the clinical trials of MSCs-based therapy in kidney diseases as well as the in vivo studies dealing with MSCs application in kidney injuries mainly from the proliferation, differentiation, migration and survival points of view. The obstacles and challenges of this new modality in kidney injuries are also discussed.

PMID: 28625316 [PubMed - in process]

Methods to increase reproducibility in differential gene expression via meta-analysis.

Tue, 06/20/2017 - 12:45
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Methods to increase reproducibility in differential gene expression via meta-analysis.

Nucleic Acids Res. 2017 Jan 09;45(1):e1

Authors: Sweeney TE, Haynes WA, Vallania F, Ioannidis JP, Khatri P

Abstract
Findings from clinical and biological studies are often not reproducible when tested in independent cohorts. Due to the testing of a large number of hypotheses and relatively small sample sizes, results from whole-genome expression studies in particular are often not reproducible. Compared to single-study analysis, gene expression meta-analysis can improve reproducibility by integrating data from multiple studies. However, there are multiple choices in designing and carrying out a meta-analysis. Yet, clear guidelines on best practices are scarce. Here, we hypothesized that studying subsets of very large meta-analyses would allow for systematic identification of best practices to improve reproducibility. We therefore constructed three very large gene expression meta-analyses from clinical samples, and then examined meta-analyses of subsets of the datasets (all combinations of datasets with up to N/2 samples and K/2 datasets) compared to a 'silver standard' of differentially expressed genes found in the entire cohort. We tested three random-effects meta-analysis models using this procedure. We showed relatively greater reproducibility with more-stringent effect size thresholds with relaxed significance thresholds; relatively lower reproducibility when imposing extraneous constraints on residual heterogeneity; and an underestimation of actual false positive rate by Benjamini-Hochberg correction. In addition, multivariate regression showed that the accuracy of a meta-analysis increased significantly with more included datasets even when controlling for sample size.

PMID: 27634930 [PubMed - indexed for MEDLINE]

MicroRNA-146b, a Sensitive Indicator of Mesenchymal Stem Cell Repair of Acute Renal Injury.

Tue, 06/20/2017 - 12:45
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MicroRNA-146b, a Sensitive Indicator of Mesenchymal Stem Cell Repair of Acute Renal Injury.

Stem Cells Transl Med. 2016 10;5(10):1406-1415

Authors: Zhu Y, Yu J, Yin L, Zhou Y, Sun Z, Jia H, Tao Y, Liu W, Zhang B, Zhang J, Wang M, Zhang X, Yan Y, Xue J, Gu H, Mao F, Xu W, Qian H

Abstract
: The role of mesenchymal stem cells (MSCs) in kidney injury repair has been studied widely. However, the underlying molecular mechanism remains unclear. We profiled the altered microRNAs in renal tissues from cisplatin-induced acute kidney injury (AKI) rats treated with or without rat bone marrow MSCs (rMSCs). We observed that microRNA-146b (miR-146b) expression was considerably upregulated in renal tissues from AKI rats compared with that in healthy rats, and the expression decreased following MSC treatment after cisplatin administration. At the early stage of AKI, serum miR-146b levels exhibited a rapid increase that was even faster than that of two conventional renal function indexes: serum creatinine and blood urea nitrogen levels. Furthermore, the serum miR-146b levels in AKI patients were higher than those in healthy people. In vitro exposure to cisplatin also increased miR-146b expression in renal tubular epithelial cells (TECs). miR-146b knockdown protected renal TECs from cisplatin-induced apoptosis and promoted their proliferation. Moreover, ErbB4 was identified as a direct target of miR-146b, and miR-146b inhibition induced ErbB4 expression, resulting in enhanced proliferation of injured renal TECs. In addition, restoration by rMSCs could be controlled through ErbB4 downregulation. In conclusion, elevated miR-146b expression contributes to cisplatin-induced AKI, partly through ErbB4 downregulation. miR-146b might be an early biomarker for AKI, and miR-146b inhibition could be a novel strategy for AKI treatment.
SIGNIFICANCE: The present study found that microRNA-146b (miR-146b) might be a novel biomarker for acute kidney injury and an indicator for its recovery after treatment with mesenchymal stem cells (MSCs). The results showed that in acute kidney injury induced by cisplatin, miR-146b in serum increased more quickly than did the usual indexes of kidney injury and decreased with restoration of MSCs. In addition, inhibition of miR-146b could ameliorate the apoptosis induced by cisplatin and potentially improve the proliferation by freeing ErbB4 and its downstream proteins.

PMID: 27400799 [PubMed - indexed for MEDLINE]

Leukocyte Calpain Deficiency Reduces Angiotensin II-Induced Inflammation and Atherosclerosis But Not Abdominal Aortic Aneurysms in Mice.

Tue, 06/20/2017 - 12:45
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Leukocyte Calpain Deficiency Reduces Angiotensin II-Induced Inflammation and Atherosclerosis But Not Abdominal Aortic Aneurysms in Mice.

Arterioscler Thromb Vasc Biol. 2016 May;36(5):835-45

Authors: Howatt DA, Balakrishnan A, Moorleghen JJ, Muniappan L, Rateri DL, Uchida HA, Takano J, Saido TC, Chishti AH, Baud L, Subramanian V

Abstract
OBJECTIVE: Angiotensin II (AngII) infusion profoundly increases activity of calpains, calcium-dependent neutral cysteine proteases, in mice. Pharmacological inhibition of calpains attenuates AngII-induced aortic medial macrophage accumulation, atherosclerosis, and abdominal aortic aneurysm in mice. However, the precise functional contribution of leukocyte-derived calpains in AngII-induced vascular pathologies has not been determined. The purpose of this study was to determine whether calpains expressed in bone marrow (BM)-derived cells contribute to AngII-induced atherosclerosis and aortic aneurysms in hypercholesterolemic mice.
APPROACH AND RESULTS: To study whether leukocyte calpains contributed to AngII-induced aortic pathologies, irradiated male low-density lipoprotein receptor(-/-) mice were repopulated with BM-derived cells that were either wild-type or overexpressed calpastatin, the endogenous inhibitor of calpains. Mice were fed a fat-enriched diet and infused with AngII (1000 ng/kg per minute) for 4 weeks. Overexpression of calpastatin in BM-derived cells significantly attenuated AngII-induced atherosclerotic lesion formation in aortic arches, but had no effect on aneurysm formation. Using either BM-derived cells from calpain-1-deficient mice or mice with leukocyte-specific calpain-2 deficiency generated using cre-loxP recombination technology, further studies demonstrated that independent deficiency of either calpain-1 or -2 in leukocytes modestly attenuated AngII-induced atherosclerosis. Calpastatin overexpression significantly attenuated AngII-induced inflammatory responses in macrophages and spleen. Furthermore, calpain inhibition suppressed migration and adhesion of macrophages to endothelial cells in vitro. Calpain inhibition also significantly decreased hypercholesterolemia-induced atherosclerosis in the absence of AngII.
CONCLUSIONS: The present study demonstrates a pivotal role for BM-derived calpains in mediating AngII-induced atherosclerosis by influencing macrophage function.

PMID: 26966280 [PubMed - indexed for MEDLINE]

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