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Exposure to contrast media in the perioperative period confers no additional risk of acute kidney injury in surgical patients.

Thu, 12/14/2017 - 13:45

Exposure to contrast media in the perioperative period confers no additional risk of acute kidney injury in surgical patients.

Nephrol Dial Transplant. 2017 Dec 09;:

Authors: Zealley I, Wang H, Donnan PT, Bell S

Abstract
Background: Iodinated contrast media (CM) used in angiography and computed tomography (CT) scans is an important cause of acute kidney injury (AKI) in hospitalized patients undergoing surgery. Contrast-induced nephropathy leads to AKI soon after CM administration. The aim of the study was to determine whether the timing of contrast media exposure related to diagnostic imaging during the immediate perioperative period influences the risk of post-operative AKI.
Methods: All patients aged 18 years or above who underwent diagnostic imaging within 7 days of non-cardiac surgery between 1 January 2003 and 31 December 2013 in the Tayside region of Scotland, UK were included in the analysis. The primary outcome of AKI was defined using the Kidney Disease: Improving Global Outcomes creatinine-based criteria. Multiple logistic regressions were performed to identify predictors for AKI.
Results: Of 9300 patients, 6224 were exposed to CM in the immediate perioperative period and 3076 were not. Post-operative AKI occurred in 678 (10.9%) of the 6224 patients who were exposed to CM. On multiple logistic regression, independent predictors of post-operative AKI were increasing age, male gender, lower baseline renal function and treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Timing of CM exposure did not affect risk of developing AKI, odds ratio 0.972 (95% confidence interval 0.935-1.010), P = 0.146.
Conclusions: For patients who have either just had or are soon to undergo general surgical procedures there appears to be no need to limit CT scan quality by avoiding the administration of CM. These patients may benefit from the increased diagnostic utility of contrast-enhanced CT scans without increasing their risk of perioperative AKI.

PMID: 29237046 [PubMed - as supplied by publisher]

Strategies to manage cardiovascular risk in chronic kidney disease.

Thu, 12/14/2017 - 13:45

Strategies to manage cardiovascular risk in chronic kidney disease.

Nephrol Dial Transplant. 2017 Nov 09;:

Authors: Mark PB

PMID: 29237023 [PubMed - as supplied by publisher]

Abdominal aorta and pelvic artery calcifications on plain radiographs may predict mortality in chronic kidney disease, hemodialysis and renal transplantation.

Thu, 12/14/2017 - 13:45

Abdominal aorta and pelvic artery calcifications on plain radiographs may predict mortality in chronic kidney disease, hemodialysis and renal transplantation.

Int Urol Nephrol. 2017 Dec 13;:

Authors: Disthabanchong S, Vipattawat K, Phakdeekitcharoen B, Kitiyakara C, Sumethkul V

Abstract
PURPOSE: Vascular calcification is common in chronic kidney disease (CKD) and predicts poor patient outcomes. While computed tomography is the gold standard for evaluation of vascular calcification, plain radiograph offers a simpler and less costly alternative. The calcification of abdominal aorta, iliac and femoral arteries has been evaluated by plain radiograph, but the data on their outcome predictabilities are still limited. The present study investigated the role of abdominal aortic calcification (AAC) and pelvic arterial calcification (PAC) in predicting overall morality in non-dialysis CKD stages 2-5 (CKD 2-5), maintenance hemodialysis (HD) and long-term kidney transplant (KT) patients.
METHODS: Four hundred and nineteen patients were included. Lateral abdominal and pelvic radiographs were obtained. The degree of AAC and PAC was evaluated according to the methods described previously by Kaupplia et al. and Adragao et al. Patients were followed prospectively for 5 years.
RESULTS: AAC and PAC scores correlated well with the correlation coefficients of 0.442 for CKD 2-5, 0.438 for HD and 0.586 for KT (p < 0.001). Patients with AAC score > 6 or PAC score > 1 were older, showed higher prevalence of DM and had higher serum phosphate and PTH but lower serum albumin and eGFR. A more severe degree of AAC was associated with an increase in KT duration, whereas a more severe degree of PAC was associated with worsening kidney function and prolonged dialysis vintage. Kaplan-Meier survival curves revealed AAC score > 6 as a significant predictor of all-cause mortality in CKD 2-5 but not in HD or KT, whereas PAC score > 1 was a significant predictor of all-cause mortality in all three populations. After adjusting for age, the predictability of AAC was lost, whereas PAC remained an independent predictor of mortality in all three populations. Adjustments for cardiovascular and CKD risk factors including age, gender, BMI, DM, serum albumin, calcium and phosphate attenuated the predictability of PAC in HD but not in CKD 2-5 or KT patients.
CONCLUSION: PAC was better than AAC in predicting mortality in CKD, HD and KT patients.

PMID: 29236239 [PubMed - as supplied by publisher]

Association of Whole Blood Tacrolimus Concentrations with Kidney Injury in Heart Transplantation Patients.

Thu, 12/14/2017 - 13:45

Association of Whole Blood Tacrolimus Concentrations with Kidney Injury in Heart Transplantation Patients.

Eur J Drug Metab Pharmacokinet. 2017 Dec 13;:

Authors: Sikma MA, Hunault CC, Kirkels JH, Verhaar MC, Kesecioglu J, de Lange DW

Abstract
BACKGROUND AND OBJECTIVES: Acute kidney injury (AKI) is frequently observed after heart transplantation and is associated with morbidity and mortality. However, many confounding factors also contribute to the development of AKI in heart transplants. We hypothesized that supratherapeutic whole-blood tacrolimus trough concentrations are associated with AKI.
METHODS: In a retrospective observational cohort from April 2005 to December 2012, all adult heart transplantation patients were included. AKI was assessed in the first 2 weeks after transplantation as classified by the Kidney Disease Improving Global Outcomes Network (KDIGO). Whole-blood tacrolimus trough concentrations were determined from day 1 to day 14 and at 1, 3, 6 and 12 months post-transplantation. The therapeutic range was 9 to 15 ng/ml in the first 2 months and tapered to 5-8 ng/ml thereafter. The relationship between supratherapeutic tacrolimus trough concentrations and AKI was evaluated. The impact of various potentially confounding factors on tacrolimus concentrations and AKI was considered.
RESULTS: We included 110 patients. AKI occurred in 57% of patients in the first week. Recovery from AKI was seen in 24%. The occurrence of chronic kidney disease (CKD) was 19% at 1 year. Whole-blood tacrolimus trough concentrations were often supratherapeutic and, despite correction for confounding factors, independently associated with AKI (OR 1.66; 95% CI 1.20-2.31).
CONCLUSIONS: Supratherapeutic whole-blood tacrolimus trough concentrations are independently associated with the development of AKI in adult heart transplantation patients. More stringent dosing of tacrolimus early after transplantation may be critical in preserving the kidney function.

PMID: 29236211 [PubMed - as supplied by publisher]

Nutrition and Muscle in Cirrhosis.

Thu, 12/14/2017 - 13:45
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Nutrition and Muscle in Cirrhosis.

J Clin Exp Hepatol. 2017 Dec;7(4):340-357

Authors: Anand AC

Abstract
As the cirrhosis progresses, development of complication like ascites, hepatic encephalopathy, variceal bleeding, kidney dysfunction, and hepatocellular carcinoma signify increasing risk of short term mortality. Malnutrition and muscle wasting (sarcopenia) is yet other complications that negatively impact survival, quality of life, and response to stressors, such as infection and surgery in patients with cirrhosis. Conventionally, these are not routinely looked for, because nutritional assessment can be a difficult especially if there is associated fluid retention and/or obesity. Patients with cirrhosis may have a combination of loss of skeletal muscle and gain of adipose tissue, culminating in the condition of "sarcopenic obesity." Sarcopenia in cirrhotic patients has been associated with increased mortality, sepsis complications, hyperammonemia, overt hepatic encephalopathy, and increased length of stay after liver transplantation. Assessment of muscles with cross-sectional imaging studies has become an attractive index of nutritional status evaluation in cirrhosis, as sarcopenia, the major component of malnutrition, is primarily responsible for the adverse clinical consequences seen in patients with liver disease. Cirrhosis is a state of accelerated starvation, with increased gluconeogenesis that requires amino acid diversion from other metabolic functions. Protein homeostasis is disturbed in cirrhosis due to several factors such as hyperammonemia, hormonal, and cytokine abnormalities, physical inactivity and direct effects of ethanol and its metabolites. New approaches to manage sarcopenia are being evolved. Branched chain amino acid supplementation, Myostatin inhibitors, and mitochondrial protective agents are currently in various stages of evaluation in preclinical studies to prevent and reverse sarcopenia, in cirrhosis.

PMID: 29234200 [PubMed]

Echocardiographic and Electrocardiographic Predictors of Adverse Outcomes in Spontaneous Bacterial Peritonitis.

Thu, 12/14/2017 - 13:45
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Echocardiographic and Electrocardiographic Predictors of Adverse Outcomes in Spontaneous Bacterial Peritonitis.

J Clin Exp Hepatol. 2017 Dec;7(4):321-327

Authors: Shah M, Patnaik S, Maludum O, Patil S, De Venecia TA, Figueredo VM

Abstract
Background: Patients with cirrhosis who develop Spontaneous Bacterial Peritonitis (SBP) suffer from cirrhotic cardiomyopathy which is characterized by impaired contractility in response to stress despite a relatively normal resting cardiac output. We hypothesized that electrocardiographic and echocardiographic information would help prognosticate patients developing SBP in addition to existing scoring systems.
Methods: Cirrhotic patients admitted to Einstein Medical Center from 01/01/2005 to 6/30/2012 for SBP, and did not receive a transplant within one year, were included. Patients were classified as QTc low vs. high, and E/E' low vs. high at cut points ≥480 ms for QTc and ≥10 for E/E' ratio. We estimated 1-year survival using Kaplan Meier curves. Regression analysis and Cox proportional hazards model were used for QTc and E/E' ratio, respectively, for assessing 1-year survival.
Results: Among 112 patients with electrocardiogam, 78 were classified as QTc low. Among 64 patients with echocardiograms, 23 were classified as E/E' low. Higher QTc was associated with increased in-hospital acute kidney injury. QTc and E/E' ratio predicted worse 1-year survival (HR = 2.16, 95% CI 1.29-3.49; HR 2.65, 95% CI 1.31-5.35, respectively) on univariate and multivariate analysis (OR = 1.02, 95% CI 1.01-1.03; HR = 3.26, 95% CI 1.22-9.82 respectively) after adjusting for both Child Pugh stage, MELD score among other risk factors.
Conclusion: In conclusion, cirrhotic patients with SBP who present with a prolonged QTc interval are at a greater risk for acute renal failure during hospitalization. High QTc duration and an E/E' ratio of ≥10 independently predict increased mortality at 1-year follow-up.

PMID: 29234197 [PubMed]

Acute kidney injury: Precision perioperative care protects the kidneys.

Thu, 12/14/2017 - 13:45
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Acute kidney injury: Precision perioperative care protects the kidneys.

Nat Rev Nephrol. 2017 Dec 13;14(1):8-10

Authors: Bihorac A, Hobson CE

PMID: 29234162 [PubMed - in process]

Extracellular vesicles from human-induced pluripotent stem cell-derived mesenchymal stromal cells (hiPSC-MSCs) protect against renal ischemia/reperfusion injury via delivering specificity protein (SP1) and transcriptional activating of sphingosine...

Thu, 12/14/2017 - 13:45
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Extracellular vesicles from human-induced pluripotent stem cell-derived mesenchymal stromal cells (hiPSC-MSCs) protect against renal ischemia/reperfusion injury via delivering specificity protein (SP1) and transcriptional activating of sphingosine kinase 1 and inhibiting necroptosis.

Cell Death Dis. 2017 Dec 11;8(12):3200

Authors: Yuan X, Li D, Chen X, Han C, Xu L, Huang T, Dong Z, Zhang M

Abstract
Renal ischemia-reperfusion is a main cause of acute kidney injury (AKI), which is associated with high mortality. Here we show that extracellular vesicles (EVs) secreted from hiPSC-MSCs play a critical role in protection against renal I/R injury. hiPSC-MSCs-EVs can fuse with renal cells and deliver SP1 into target cells, subsequently active SK1 expression and increase S1P formation. Chromatin immunoprecipitation (ChIP) analyses and luciferase assay were used to confirm SP1 binds directly to the SK1 promoter region and promote promoter activity. Moreover, SP1 inhibition (MIT) or SK1 inhibition (SKI-II) completely abolished the renal protective effect of hiPSC-MSCs-EVs in rat I/R injury mode. However, pre-treatment of necroptosis inhibitor Nec-1 showed no difference with the administration of hiPSC-MSCs-EVs only. We then generated an SP1 knockout hiPSC-MSC cell line by CRISPR/Cas9 system and found that SP1 knockout failed to show the protective effect of hiPSC-MSCs-EVs unless restoring the level of SP1 by Ad-SP1 in vitro and in vivo. In conclusion, this study describes an anti-necroptosis effect of hiPSC-MSCs-EVs against renal I/R injury via delivering SP1 into target renal cells and intracellular activating the expression of SK1 and the generation of S1P. These findings suggest a novel mechanism for renal protection against I/R injury, and indicate a potential therapeutic approach for a variety of renal diseases and renal transplantation.

PMID: 29233979 [PubMed - in process]

The utility of anti-Müllerian hormone in women with chronic kidney disease, on haemodialysis and after kidney transplantation.

Thu, 12/14/2017 - 13:45
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The utility of anti-Müllerian hormone in women with chronic kidney disease, on haemodialysis and after kidney transplantation.

Reprod Biomed Online. 2017 Nov 28;:

Authors: Stoumpos S, Lees J, Welsh P, Hund M, Geddes CC, Nelson SM, Mark PB

Abstract
Women with renal disease have menstrual and gonadal dysfunction manifesting as hormonal imbalance. Anti-Müllerian hormone (AMH) is a potential measure of ovarian reserve. We examined circulating AMH concentrations in young women with renal failure, determined associations with clinical characteristics, and compared AMH with age-matched healthy individuals. AMH was measured in 77 women: 26 had chronic kidney disease (CKD), 26 were on haemodialysis (HD), and 25 had a kidney transplant. Random AMH levels were highest in women on HD [HD 2.9 (1.1-5.2), CKD 1.6 (0.7-2.2), transplant 1.5 (1.0-4.2) ng/ml]. On multiple linear regression, AMH was 53% higher [95% CI 0.20-0.98, P = 0.002] in women on HD and decreased by 20% per 5-year increase in age (P < 0.001). AMH was 43% lower in women with renal failure compared with 600 age-matched controls [1.7 (0.9-3.8) versus 3.0 (1.9-5.0) ng/ml, P < 0.001]; however, we found no difference in AMH between those on HD and healthy individuals [2.9 (1.1-5.2) versus 3.0 (1.9-5.0) ng/ml]. AMH may be a useful biomarker in female renal patients with non-dialysis dependent renal disease pursuing pregnancy. In contrast, AMH levels are higher in HD but unlikely to reflect ovarian reserve.

PMID: 29233504 [PubMed - as supplied by publisher]

Intractable ascites associated with mycophenolate in a simultaneous kidney-pancreas transplant patient: a case report.

Thu, 12/14/2017 - 13:45
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Intractable ascites associated with mycophenolate in a simultaneous kidney-pancreas transplant patient: a case report.

BMC Nephrol. 2017 Dec 12;18(1):360

Authors: Weber NT, Sigaroudi A, Ritter A, Boss A, Lehmann K, Goodman D, Farese S, Weiler S, Mueller TF

Abstract
BACKGROUND: Mycophenolic acid (MPA), either given as an ester pro-drug or as an enteric-coated sodium salt, is the most commonly prescribed anti-proliferative immunosuppressive agent used following organ transplantation and widely applied in immune-mediated diseases. Clinicians are well aware of common adverse reactions related to MPA treatment, in particular diarrhea, leukopenia and infections. Here we report a case of severe, persistent ascites associated with MPA treatment. The otherwise unexplained and intractable ascites, requiring repeated paracenteses for more than 8 months, rapidly ceased with stopping the MPA treatment. To our knowledge this is the first case of severe ascites associated with MPA treatment reported in the scientific literature.
CASE PRESENTATION: A 45-year old female with type 1 diabetes mellitus received a simultaneous kidney-pancreas transplant. The surgery was uneventful. However, post-operatively she developed severe transudative ascites requiring in total more than 40 paracenteses treatments draining in the average 2.8 l of ascites fluid. The ascites formation persisted despite exclusion of a surgical complication, fully functioning kidney and pancreas allografts, lack of any significant proteinuria, normalization of circulating albumin levels, intensive use of diuretics and deliberate attempts to increase the intervals between the paracentesis treatments. Various differential diagnoses, including infectious, hepatic, vascular and cardiac causes were ruled out. Nine months after surgery enteric-coated mycophenolate sodium was switched to azathioprine after which ascites completely resolved. When mycophenolate was recommenced abdominal fullness and weight gain reoccurred. The patient had to be switched to long-term azathioprine treatment. More than 1 year post-conversion the patient remains free of ascites.
CONCLUSION: MPA is the most widely used antimetabolite immunosuppressive agent. We suggest to consider MPA treatment in the differential diagnosis of severe and unexplained ascites in transplant and non-transplant patients.

PMID: 29233098 [PubMed - in process]

Type 1 diabetic patients have better endothelial function after simultaneous pancreas-kidney transplantation than after kidney transplantation with continued insulin therapy.

Thu, 12/14/2017 - 13:45
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Type 1 diabetic patients have better endothelial function after simultaneous pancreas-kidney transplantation than after kidney transplantation with continued insulin therapy.

Diab Vasc Dis Res. 2017 Dec 01;:1479164117744423

Authors: Ziaja J, Kowalik AP, Kolonko A, Kamińska D, Owczarek AJ, Kujawa-Szewieczek A, Kusztal MA, Badura J, Bożek-Pająk D, Choręza P, Zakrzewska A, Król R, Chłopicki S, Klinger M, Więcek A, Chudek J, Cierpka L

Abstract
The purpose of this study was to analyse the influence of simultaneous pancreas-kidney or kidney transplantation on endothelial function and systemic inflammation in type 1 diabetic patients with end-stage renal disease. In 39 simultaneous pancreas-kidney, 39 type 1 diabetic kidney and 52 non-diabetic kidney recipients, flow-mediated dilatation was measured. Additionally, blood glycated haemoglobin, serum creatinine and lipids, plasma nitrites [Formula: see text] and nitrates, asymmetric dimethylarginine, soluble vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and E-selectin, high-sensitivity C-reactive protein, tumour necrosis factor-α, interleukin 1β and interleukin 6 concentrations were assessed. During 58 ± 31 months follow-up period, flow-mediated dilatation and [Formula: see text] were greater in simultaneous pancreas-kidney than in type 1 diabetic kidney recipients [10.4% ± 4.7% vs 7.7% ± 4.2%, p < 0.05 and 0.94 (0.74-1.34) vs 0.24 (0.20-0.43) μmol/L, p < 0.01, respectively]. In type 1 diabetic patients after simultaneous pancreas-kidney or kidney transplantation, [Formula: see text] correlated with flow-mediated dilatation (r = 0.306, p < 0.05) and with blood glycated haemoglobin (r = -0.570, p < 0.001). The difference in [Formula: see text] was linked to blood glycated haemoglobin and estimated glomerular filtration rate, whereas the difference in flow-mediated dilatation was linked to [Formula: see text]. The levels of inflammatory markers (except soluble vascular cell adhesion molecule-1) were similar in simultaneous pancreas-kidney and type 1 diabetic kidney recipients. Improved endothelial function in type 1 diabetic patients with end-stage renal disease after simultaneous pancreas-kidney compared to kidney transplantation is associated with normalisation of glucose metabolism but not with improvement in plasma pro-inflammatory cytokines.

PMID: 29233018 [PubMed - as supplied by publisher]

Archetype JC Polyomavirus (JCPyV) Prevails in a Rare Case of JCPyV Nephropathy and in Stable Renal Transplant Recipients With JCPyV Viruria.

Thu, 12/14/2017 - 13:45
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Archetype JC Polyomavirus (JCPyV) Prevails in a Rare Case of JCPyV Nephropathy and in Stable Renal Transplant Recipients With JCPyV Viruria.

J Infect Dis. 2017 Nov 15;216(8):981-989

Authors: Seppälä HM, Helanterä IT, Laine PKS, Lautenschlager IT, Paulín LG, Jahnukainen TJ, Auvinen POV, Auvinen E

Abstract
Background: JC polyomavirus (JCPyV) is reactivated in approximately 20% of renal transplant recipients, and it may rarely cause JCPyV-associated nephropathy (JCPyVAN). Whereas progressive multifocal leukoencephalopathy of the brain is caused by rearranged neurotropic JCPyV, little is known about viral sequence variation in JCPyVAN owing to the rarity of this condition.
Methods: Using single-molecule real-time sequencing, characterization of full-length JCPyV genomes in urine and plasma samples from 1 patient with JCPyVAN and 20 stable renal transplant recipients with JCPyV viruria was attempted. Sequence analysis of JCPyV strains was performed, with emphasis on the noncoding control region, the major capsid protein gene VP1, and the large T antigen gene.
Results: Exclusively archetype strains were identified in urine from the patient with JCPyVAN. Full-length JCPyV sequences were not retrieved from plasma. Archetype strains were found in urine samples from 19 stable renal transplant recipients, with JCPyV quasispecies detected in 5 samples. In a patient with minor graft dysfunction, a strain with an archetype-like noncoding cont rol region was discovered. Individual point mutations were detected in both VP1 and large T antigen genes.
Conclusions: Archetype JCPyV was dominant in the patient with JCPyVAN and in stable renal transplant recipients. Archetype rather than rearranged JCPyV seems to drive the pathogenesis of JCPyVAN.

PMID: 28968776 [PubMed - indexed for MEDLINE]

Evaluation of intraarterial and intravenous cisplatin chemotherapy in the treatment of metastatic osteosarcoma using an orthotopic xenograft mouse model.

Thu, 12/14/2017 - 13:45
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Evaluation of intraarterial and intravenous cisplatin chemotherapy in the treatment of metastatic osteosarcoma using an orthotopic xenograft mouse model.

J Exp Clin Cancer Res. 2016 Jul 16;35(1):113

Authors: Robl B, Botter SM, Pellegrini G, Neklyudova O, Fuchs B

Abstract
BACKGROUND: Osteosarcoma is the most common primary malignancy of bone. Its treatment relies on the administration of neoadjuvant and adjuvant chemotherapy combined with surgery. Alternative to common intravenous (i.v.) administration of chemotherapeutic drugs, clinical studies also evaluated the benefit of intraarterial (i.a.) administrations. However, conflicting results were obtained when both routes of administration of cisplatin (CDDP), a gold standard drug in osteosarcoma treatment, were compared. In order to overcome clinical confounding factors, we evaluated both routes of drug administration in a mouse model of experimental osteosarcoma.
METHODS: We directly compared i.v. versus i.a. drug infusions of cisplatin (CDDP), in an orthotopic xenograft mouse model of metastatic osteosarcoma. We performed tumor monitoring using caliper and micro computed tomography and measured tumor perfusion using laser speckle contrast imaging. Histopathological changes were evaluated using hematoxylin and eosin staining as well as immunohistochemistry (cleaved PARP-1, CD31, HIF-1α).
RESULTS: First, an effective concentration of 4 mg/kg i.a. CDDP was determined that significantly reduced primary tumor volume. We used this concentration of i.a. CDDP and compared it to infusions of i.v. CDDP. Systemic (i.v.) CDDP only showed minor suppression of tumor growth whereas local (i.a.) CDDP strongly inhibited tumor growth and destruction of cortical bone in the tumor-bearing hind limb. Inhibition of tumor growth was linked to a reduced blood perfusion and resulted in increased amounts of tumor necrosis after i.a. CDDP. After treatment with i.a. CDDP, remaining viable tumor tissue responded by increasing expression of HIF-1α. Side effects due to administration of CDDP were minor, showing no differences in kidney damage between i.v. and i.a. CDDP. However, increased epidermal apoptosis in the foot was an indirect marker for locally increased concentrations of CDDP.
CONCLUSIONS: Our findings demonstrate the great potential of local administration of cytotoxic chemotherapeutics, such as CDDP. Consequently, we provide a preclinical basis for a renewed interest in the clinical use of i.a. chemotherapy in osteosarcoma therapy.

PMID: 27421768 [PubMed - indexed for MEDLINE]

ATF2 predicts poor prognosis and promotes malignant phenotypes in renal cell carcinoma.

Thu, 12/14/2017 - 13:45
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ATF2 predicts poor prognosis and promotes malignant phenotypes in renal cell carcinoma.

J Exp Clin Cancer Res. 2016 Jul 04;35(1):108

Authors: Wu DS, Chen C, Wu ZJ, Liu B, Gao L, Yang Q, Chen W, Chen JM, Bao Y, Qu L, Wang LH

Abstract
BACKGROUND: Activating transcription factor 2 (ATF2) is a basic helix-loop-helix transcription factor, which has been shown to participate in the pathobiology of numerous cancers. However, the role of ATF2 in renal cell carcinoma (RCC) remains unclear.
METHODS: ATF2 knockdown and overexpression studies were performed in RCC cells to evaluate changes in cell viability, cell cycle, apoptosis, migration and invasion. Xenograft models were used to examine the tumorigenic and metastatic capability of RCC cells upon ATF2 suppression. The expression of ATF2 in human RCC samples was determined using immunohistochemistry on a tissue microarray.
RESULTS: ATF2 knockdown in RCC cells reduced their proliferative and metastatic potentials, whereas ATF2 overexpression enhanced these properties. Mechanistic studies revealed that the transcription of CyclinB1, CyclinD1, Snail and Vimentin was directly regulated by ATF2 in RCC cells. Moreover, ATF2 was shown to be highly expressed in RCC tissues, especially in tumors with metastases. High expression of ATF2 correlated with aggressive clinico-pathological characteristics and predicted poor prognosis of RCC patients.
CONCLUSIONS: ATF2 exerts an oncogenic role in RCC and could serve as an important prognostic biomarker.

PMID: 27377902 [PubMed - indexed for MEDLINE]

Mesenchymal Stem Cells in Kidney Repair.

Thu, 12/14/2017 - 13:45
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Mesenchymal Stem Cells in Kidney Repair.

Methods Mol Biol. 2016;1416:89-107

Authors: Morigi M, Rota C, Remuzzi G

Abstract
Every year 13.3 million people suffer acute kidney injury (AKI), which is associated with a high risk of death or development of long-term chronic kidney disease (CKD) in a substantial percentage of patients besides other organ dysfunctions. To date, the mortality rate per year for AKI exceeds 50 % at least in patients requiring early renal replacement therapy and is higher than the mortality for breast and prostate cancer, heart failure and diabetes combined.Until now, no effective treatments able to accelerate renal recovery and improve survival post AKI have been developed. In search of innovative and effective strategies to foster the limited regeneration capacity of the kidney, several studies have evaluated the ability of mesenchymal stem cells (MSCs) of different origin as an attractive therapeutic tool. The results obtained in several models of AKI and CKD document that MSCs have therapeutic potential in repair of renal injury, preserving renal function and structure thus prolonging animal survival through differentiation-independent pathways. In this chapter, we have summarized the mechanisms underlying the regenerative processes triggered by MSC treatment, essentially due to their paracrine activity. The capacity of MSC to migrate to the site of injury and to secrete a pool of growth factors and cytokines with anti-inflammatory, mitogenic, and immunomodulatory effects is described. New modalities of cell-to-cell communication via the release of microvesicles and exosomes by MSCs to injured renal cells will also be discussed. The translation of basic experimental data on MSC biology into effective care is still limited to preliminary phase I clinical trials and further studies are needed to definitively assess the efficacy of MSC-based therapy in humans.

PMID: 27236667 [PubMed - indexed for MEDLINE]

Height at First RRT and Mortality in Children.

Thu, 12/14/2017 - 13:45
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Height at First RRT and Mortality in Children.

Clin J Am Soc Nephrol. 2016 May 06;11(5):832-9

Authors: Ku E, Fine RN, Hsu CY, McCulloch C, Glidden DV, Grimes B, Johansen KL

Abstract
BACKGROUND AND OBJECTIVES: Poor linear growth is common in children with CKD and has been associated with higher mortality. However, recent data in adult dialysis patients have suggested a higher risk of death in persons of tall stature. In this study, we aimed to examine the risk of all-cause and cause-specific mortality in children at both extremes of height at the time of first RRT.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using the US Renal Data System, we performed a retrospective analysis of 13,218 children aged 2-19 years, who received their first RRT (dialysis or transplant) during 1995-2011. We used adjusted Cox models to examine the association between short (<3rd percentile) and tall (>3rd percentile) stature and risk of death, compared with less extreme heights.
RESULTS: Over a median follow-up of 7.1 years, there were 1721 deaths. Risk of death was higher in children with short (hazard ratio, 1.49; 95% confidence interval, 1.33 to 1.66) and tall stature (hazard ratio, 1.32; 95% confidence interval, 1.03 to 1.69) in adjusted analysis. In secondary analyses, there was a statistically significant interaction between height and body mass index categories (P=0.04), such that the association of tall stature with higher mortality was limited to children with elevated body mass index (defined as ≥95th percentile for age and sex). Children with short stature had a higher risk of cardiac- and infection-related death, whereas children with tall stature had a higher risk of cancer-related death.
CONCLUSIONS: Children with short and tall stature are at higher mortality risk, although this association was modified by body mass index at time of first RRT. Studies to further explore the reasons behind the higher risk of mortality in children with extremes of height at the time of first RRT are warranted.

PMID: 26933189 [PubMed - indexed for MEDLINE]

Effects of removal of the ischemic kidney in rabbits with unilateral renal hypertension, as compared to unilateral nephrectomy in normal rabbits.

Thu, 12/14/2017 - 13:45
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Effects of removal of the ischemic kidney in rabbits with unilateral renal hypertension, as compared to unilateral nephrectomy in normal rabbits.

Am J Physiol. 1949 Sep;158(3):438-43

Authors: FLASHER J, DRURY DR

PMID: 18137921 [PubMed - indexed for MEDLINE]

Cytomegalovirus (CMV) immune monitoring with ELISPOT and QuantiFERON-CMV assay in seropositive kidney transplant recipients.

Wed, 12/13/2017 - 13:45
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Cytomegalovirus (CMV) immune monitoring with ELISPOT and QuantiFERON-CMV assay in seropositive kidney transplant recipients.

PLoS One. 2017;12(12):e0189488

Authors: Lee H, Park KH, Ryu JH, Choi AR, Yu JH, Lim J, Han K, Kim SI, Yang CW, Chung BH, Oh EJ

Abstract
Although cytomegalovirus (CMV) specific cell-mediated immunity (CMI) has been suggested as a predictive marker for CMV infection, proper CMI monitoring strategy in CMV-seropositive recipients and optimal method are not defined. The aim of this study was to evaluate two interferon gamma release assays during early post-transplant period as a predictor of the development of CMV infection in CMV-seropositive patients. A total of 124 CMV-seropositive recipients who received kidney transplantation from CMV-seropositive donor were prospectively examined. At pre-transplant and post-transplant 1 and 3 months, CMV-CMIs were tested using QuantiFERON-CMV assay (QF-CMV) and CMV specific T cell ELISPOT against CMV pp65 and IE-1 antigens (pp65-ELISPOT, IE-1-ELISPOT). CMV DNAemia occurred in 16 (12.9%) patients within 3 months after transplant. Post-transplant pp65 or IE-1 ELISPOT response, but not QF-CMV, was significantly associated with CMV DNAemia. The pp65 ELISPOT (cut-off; 30 spots/200,000 cells) and IE-1 ELISPOT (10 spots/200,000 cells) at post-transplant 1 month predicted the risk of post-transplant CMV DNAemia (P = 0.019). Negative predictive values (NPV) for protection from CMV DNAemia in case of positive ELISPOT results were 94.5% (95% CI: 86.9-97.8%) and 97.6% (95% CI: 86.3-99.6%) in pp65-ELISPOT and IE-1-ELISPOT assays, respectively. These results suggest that the variability may exist between CMV ELISPOT assays and QF-CMV, and CMV ELISPOT at post-transplant 1 month can identify the risk of CMV DNAemia in seropositive kidney transplant recipients.

PMID: 29232714 [PubMed - in process]

Vaccination Practices in Pediatric Dialysis Patients Across Europe. A European Pediatric Dialysis Working Group and European Society for Pediatric Nephrology Dialysis Working Group Study.

Wed, 12/13/2017 - 13:45
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Vaccination Practices in Pediatric Dialysis Patients Across Europe. A European Pediatric Dialysis Working Group and European Society for Pediatric Nephrology Dialysis Working Group Study.

Nephron. 2017 Dec 12;:

Authors: Bakkaloğlu SA, Özdemir Atikel Y, Paglialonga F, Stefanidis CJ, Askiti V, Vidal E, Ariceta G, Melek E, Verrina E, Printza N, Vondrak K, Zurowska A, Zagozdzon I, Ekim M, Özmert EN, Dufek S, Jankauskiene A, Schmitt CP, Lévai E, Vande Walle J, Canpolat N, Holtta T, Fischbach M, Klaus G, Aufricht C, Shroff R, Edefonti A

Abstract
BACKGROUND: Data on the immunization practices in pediatric chronic kidney disease (CKD) patients are scarce. The purpose of this study was to evaluate current vaccination practices for children on dialysis across European pediatric nephrology centers.
METHODS: A total of 18 tertiary pediatric nephrology centers from 12 European countries were included in the study. The data on universal national immunization programs and immunization practices for children with chronic disease or risk were recorded from European Center for Disease Prevention and Control and the World Health Organization. The immunization practices and center protocols for monitoring antibody titers after vaccination in dialysis patients were obtained through a questionnaire.
RESULTS: All centers included in the study recommended immunization against hepatitis B virus (HBV), diphtheria, tetanus, pertussis, Hemophilus influenzae type b (Hib), poliomyelitis, measles, mumps, rubella (MMR), and streptococcus pneumonia in dialysis patients. In 16 centers, dialysis patients were vaccinated against influenza virus annually. HBV protective antibody titers were measured in 17 centers (during dialysis period in 14 centers, during pre-renal transplantation preparations in 14 centers or in both times in 11 centers). Hepatitis A virus (HAV) was reported to be followed in 13 centers, in 8 centers during dialysis period, and in 11 centers during pre-RTx preparations. MMR and varicella-zoster virus (VZV) protective antibody titers were measured during the dialysis period or before renal transplantation (RTx) in 12 and 15 centers, respectively, and in 6 centers both titers were checked both times.
CONCLUSION: There are variations in vaccination practice across Europe. Children with CKD, those undergoing dialysis, and transplant candidates should receive age-appropriate vaccinations before RTx as well as before the transition to adult nephrology clinics and antibody levels should be monitored to evaluate the immunization status before and after RTx.

PMID: 29232664 [PubMed - as supplied by publisher]

Geographic Disparity in Kidney Transplantation under KAS.

Wed, 12/13/2017 - 13:45
Related Articles

Geographic Disparity in Kidney Transplantation under KAS.

Am J Transplant. 2017 Dec 12;:

Authors: Zhou S, Massie AB, Luo X, Ruck JM, Chow EKH, Bowring MG, Bae S, Segev DL, Gentry SE

Abstract
The Kidney Allocation System fundamentally altered kidney allocation, causing a substantial increase in regional and national sharing that we hypothesized might impact geographic disparities. We measured geographic disparity in deceased donor kidney transplant (DDKT) rate under KAS (6/1/2015-12/1/2016), and compared that with pre-KAS (6/1/2013-12/3/2014). We modeled DSA-level DDKT rates with multilevel Poisson regression, adjusting for allocation factors under KAS. Using the model we calculated a novel, improved metric of geographic disparity: the median incidence rate ratio (MIRR) of transplant rate, a measure of DSA-level variation that accounts for patient casemix and is robust to outlier values. Under KAS, MIRR was 1.75 1.811.86 for adults, meaning that similar candidates across different DSAs have a median 1.81-fold difference in DDKT rate. The impact of geography was greater than the impact of factors emphasized by KAS: having an EPTS score ≤20% was associated with a 1.40-fold increase (IRR=1.35 1.401.45 , p<0.01) and a 3-year dialysis vintage was associated with a 1.57-fold increase (IRR=1.56 1.571.59 , p<0.001) in transplant rate. For pediatric candidates, MIRR was even more pronounced, at 1.66 1.922.27 . There was no change in geographic disparities with KAS (p=0.3). Despite extensive changes to kidney allocation under KAS, geography remains a primary determinant of access to DDKT. This article is protected by copyright. All rights reserved.

PMID: 29232040 [PubMed - as supplied by publisher]

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