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Continuous erythropoiesis receptor activator (CERA) for the anaemia of chronic kidney disease.

Mon, 08/07/2017 - 18:48
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Continuous erythropoiesis receptor activator (CERA) for the anaemia of chronic kidney disease.

Cochrane Database Syst Rev. 2017 Aug 07;8:CD009904

Authors: Saglimbene VM, Palmer SC, Ruospo M, Natale P, Craig JC, Strippoli GF

Abstract
BACKGROUND: Continuous erythropoiesis receptor activator (CERA) is a newer, longer acting ESA which might be preferred to other ESAs (epoetin or darbepoetin) based on its lower frequency of administration. Different dosing requirements and molecular characteristics of CERA compared with other ESAs may lead to different health outcomes (mortality, cardiovascular events, quality of life) in people with anaemia and chronic kidney disease (CKD).
OBJECTIVES: To assess benefits and harms of CERA compared with other epoetins (darbepoetin alfa and epoetin alfa or beta) or placebo/no treatment or CERA with differing strategy of administration for anaemia in individuals with CKD.
SEARCH METHODS: We searched the Cochrane Kidney and Transplant Specialised Register to 13 June 2017 through contact with the Information Specialist using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE, and EMBASE; handsearching conference proceedings; and searching the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA: We included randomised controlled trials (RCTs) of at least three months' duration, comparing CERA with a different ESA (darbepoetin alfa or epoetin alfa or beta) or placebo or standard care or versus CERA with different strategies for administration in people with any stage of CKD.
DATA COLLECTION AND ANALYSIS: Data were extracted by two independent investigators. We summarised patient-centred outcomes (all-cause and cardiovascular mortality, major adverse cardiovascular events, red cell blood transfusion, iron therapy, cancer, hypertension, seizures, dialysis vascular access thrombosis, drug injection-related events, hyperkalaemia and health-related quality of life and haemoglobin levels) using random effects meta-analysis. Treatment estimates were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean differences or standardized mean difference with 95% CI for continuous outcomes.
MAIN RESULTS: We included 27 studies involving 5410 adults with CKD. Seven studies (1273 participants) involved people not requiring dialysis, 19 studies (4209 participants) involved people treated with dialysis and one study (71 participants) evaluated treatment in recipients of a kidney transplant. Treatment was given for 24 weeks on average. No data were available for children with CKD. Studies were generally at high or unclear risk of bias from allocation concealment and blinding of outcomes. Only two studies masked participants and investigators to treatment allocation. One study compared CERA with placebo, nine studies CERA with epoetin alfa or beta, nine studies CERA with darbepoetin alfa, and two studies compared CERA with epoetin alfa or beta and darbepoetin alfa. Three studies assessed the effects of differing frequencies of CERA administration and five assessed differing CERA doses.There was low certainty evidence that CERA had little or no effects on mortality (RR 1.07, 95% CI 0.73 to 1.57; RR 1.11, 95% CI 0.75 to 1.65), major adverse cardiovascular events (RR 5.09, 95% CI 0.25 to 105.23; RR 5.56, 95% CI 0.99 to 31.30), hypertension (RR 1.01, 95% CI 0.75 to 1.37; RR 1.00, 95% CI 0.79 to 1.28), need for blood transfusion (RR 1.02, 95% CI 0.72 to 1.46; RR 0.94, 95% CI 0.55 to 1.61), or additional iron therapy (RR 1.03, 95% CI 0.91 to 1.15; RR 0.99, 95% CI 0.95 to 1.03) compared to epoetin alfa/beta or darbepoetin alfa respectively. There was insufficient evidence to compare the effect of CERA to placebo on clinical outcomes. Only one low quality study reported that CERA compared to placebo might lead to little or no difference in the risk of major cardiovascular events (RR 2.97, 95% CI 0.31 to 28.18) and hypertension ((RR 0.73, 95% CI 0.35 to 1.52). There was low certainty evidence that different doses (higher versus lower) or frequency (twice versus once monthly) of CERA administration had little or no different effect on all-cause mortality (RR 3.95, 95% CI 0.17 to 91.61; RR 0.97, 95% CI 0.56 to 1.66), hypertension (RR 0.45, 95% CI 0.08 to 2.52; RR 0.85, 95% CI 0.60 to 1.21), and blood cell transfusions (RR 4.16, 95% CI 0.89 to 19.53; RR 0.91, 95% CI 0.51 to 1.62). No studies reported comparative treatment effects of different ESAs on health-related quality of life.
AUTHORS' CONCLUSIONS: There is low certainty evidence that CERA has little or no effects on patient-centred outcomes compared with placebo, epoetin alfa or beta or darbepoetin alfa for adults with CKD. The effects of CERA among children who have CKD have not studied in RCTs.

PMID: 28782299 [PubMed - as supplied by publisher]

Health Related Quality of life in bladder cancer. Current approach and future perspectives.

Mon, 08/07/2017 - 18:48
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Health Related Quality of life in bladder cancer. Current approach and future perspectives.

Clujul Med. 2017;90(3):262-267

Authors: Truta A, Popon TAH, Saraci G, Ghervan L, Pop IV

Abstract
Bladder cancer is a real health problem due to its increased incidence, high recurrence rate and the fact that usually it is detected in advanced stages with limited number of diagnostic tools and different therapy response rates to current therapeutic strategies. Because of these issues we must develop screening programs and sensitive diagnostic strategies capable of detecting the disease during its early stages but also for characterizing evolution, prognosis and therapeutic response. Issues of great importance are those related to health quality of life of patients from the moment of diagnosis till the use of existing therapeutic approaches. This paper reviews some facets of life quality in patients diagnosed with bladder cancer stressing upon some proposed questionnaires and some new cell and molecular biology and genomic acquisitions (molecular biomarkers) that may become indicators of prognosis, therapeutic response and life quality but also essential tools in guiding therapeutic strategies.

PMID: 28781521 [PubMed]

Anesthetic management in a patient of autosomal dominant polycystic kidney disease with end stage renal disease undergoing endovascular coiling for multiple intracranial aneurysms.

Mon, 08/07/2017 - 18:48
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Anesthetic management in a patient of autosomal dominant polycystic kidney disease with end stage renal disease undergoing endovascular coiling for multiple intracranial aneurysms.

J Anaesthesiol Clin Pharmacol. 2017 Apr-Jun;33(2):256-258

Authors: Mitra R, Rath GP, Dube SK, Hasija N

Abstract
A 27-year-old woman of autosomal dominant polycystic kidney disease presented with multiple intracranial aneurysms at anterior communicating artery and left middle cerebral artery bifurcation. She was undergoing hemodialysis every alternate day and was waiting for a renal transplantation. Endovascular coiling of both these aneurysms was performed under general endotracheal anesthesia. During the procedure special precaution was taken with regard to intra-procedural fluid management and maintenance of cerebral perfusion pressure. The procedure remained uneventful during which a stable hemodynamics was maintained. In this report, the implication of intraprocedural fluid infusion by the neuroradiologist its possible influence on overall anesthetic management has been described.

PMID: 28781456 [PubMed]

Epigenetics: a potential key mechanism involved in the pathogenesis of cardiorenal syndromes.

Mon, 08/07/2017 - 18:48
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Epigenetics: a potential key mechanism involved in the pathogenesis of cardiorenal syndromes.

J Nephrol. 2017 Aug 05;:

Authors: Virzì GM, Clementi A, Brocca A, de Cal M, Ronco C

Abstract
Epigenetics is defined as the heritable changes in gene expression patterns which are not directly encoded by modifications in the nucleotide DNA sequence of the genome, including higher order chromatin organization, DNA methylation, cytosine modifications, covalent histone tail modifications, and short non-coding RNA molecules. Recently, much attention has been paid to the role and the function of epigenetics and epimutations in the cellular and subcellular pathways and in the regulation of genes in the setting of both kidney and cardiovascular disease. Indeed, deregulation of histone alterations has been highlighted in a large spectrum of renal and cardiac disease, including chronic and acute renal injury, renal and cardiac fibrosis, cardiac hypertrophy and failure, kidney congenital anomalies, renal hypoxia, and diabetic renal complications. Nevertheless, the role of epigenetics in the pathogenesis and pathophysiology of cardiorenal syndromes is currently underexplored. Given the significant clinical relevance of heart-kidney crosstalk, efforts in the research for new action mechanisms concurrently operating in both pathologies are thus of maximum interest. This review focuses on epigenetic mechanisms involved in heart and kidney disease, and their possible role in the setting of cardiorenal syndromes.

PMID: 28780716 [PubMed - as supplied by publisher]

A policy model of cardiovascular disease in moderate-to-advanced chronic kidney disease.

Mon, 08/07/2017 - 18:48
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A policy model of cardiovascular disease in moderate-to-advanced chronic kidney disease.

Heart. 2017 Aug 05;:

Authors: Schlackow I, Kent S, Herrington W, Emberson J, Haynes R, Reith C, Wanner C, Fellström B, Gray A, Landray MJ, Baigent C, Mihaylova B, SHARP Collaborative Group

Abstract
OBJECTIVE: To present a long-term policy model of cardiovascular disease (CVD) in moderate-to-advanced chronic kidney disease (CKD).
METHODS: A Markov model with transitions between CKD stages (3B, 4, 5, on dialysis, with kidney transplant) and cardiovascular events (major atherosclerotic events, haemorrhagic stroke, vascular death) was developed with individualised CKD and CVD risks estimated using the 5 years' follow-up data of the 9270 patients with moderate-to-severe CKD in the Study of Heart and Renal Protection (SHARP) and multivariate parametric survival analysis. The model was assessed in three further CKD cohorts and compared with currently used risk scores.
RESULTS: Higher age, previous cardiovascular events and advanced CKD were the main contributors to increased individual disease risks. CKD and CVD risks predicted by the state-transition model corresponded well to risks observed in SHARP and external cohorts. The model's predictions of vascular risk and progression to end-stage renal disease were better than, or comparable to, those produced by other risk scores. As an illustration, at age 60-69 years, projected survival for SHARP participants in CKD stage 3B was 13.5 years (10.6 quality-adjusted life years (QALYs)) in men and 14.8 years (10.7 QALYs) in women. Corresponding projections for participants on dialysis were 7.5 (5.6 QALYs) and 7.8 years (5.4 QALYs). A non-fatal major atherosclerotic event reduced life expectancy by about 2 years in stage 3B and by 1 year in dialysis.
CONCLUSIONS: The SHARP CKD-CVD model is a novel resource for evaluating health outcomes and cost-effectiveness of interventions in CKD.
TRIAL REGISTRATION NUMBER: NCT00125593 and ISRCTN54137607; Post-results.

PMID: 28780579 [PubMed - as supplied by publisher]

Rescue effects of ginger extract on dose dependent radiation-induced histological and biochemical changes in the kidneys of male Wistar rats.

Mon, 08/07/2017 - 18:48
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Rescue effects of ginger extract on dose dependent radiation-induced histological and biochemical changes in the kidneys of male Wistar rats.

Biomed Pharmacother. 2017 Aug 03;94:569-576

Authors: Saberi H, Keshavarzi B, Shirpoor A, Gharalari FH, Rasmi Y

Abstract
Radiation is an essential modality in the management of cancer therapy, but its acute and chronic side effects on the normal organs limit the helpfulness of radiotherapy. The deleterious effects of radiation begin with oxidative stress and inflammatory reaction to radiolytic hydrolysis and formation of free radicals. The aim of the current study was to investigate the effect of dose dependent whole body radiation exposure on histological and biochemical alterations in rat kidney. It was also planned to find out whether ginger extract mitigated the deleterious effects of different doses of radiation in rat kidney. Male Wistar rats were exposed to three doses (2, 4, and 8Gy) of γ- ray with or without a 10day pretreatment with ginger extract. After 10days of whole body γ- ray exposure, the results revealed proliferation of glomerular and tubular cells, fibrosis in glomerular and peritubular and a significant increase in 8-OHdG, CRP, cystatin C (in 8Gy), plasma urea and creatinine levels, as well as a significant decrease in total antioxidant capacity of radiation groups compared to those of the control group. Ginger extract administration once daily for 10 consecutive days before exposure to 2-4-8Gy radiotherapy, which ameliorated histological and biochemical alterations in kidneys of the rats entirely or partially compared to those in the ethanol group rats. These findings indicate that whole body exposure to radiation induces kidney damage through oxidative DNA damage and inflammatory reactions, and that these effects can be alleviated using ginger pretreatment as an antioxidant and anti-inflammatory agent.

PMID: 28780473 [PubMed - as supplied by publisher]

Intra-hepatic Depletion of Mucosal Associated Invariant T cells in Hepatitis C Virus-induced Liver Inflammation.

Mon, 08/07/2017 - 18:48
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Intra-hepatic Depletion of Mucosal Associated Invariant T cells in Hepatitis C Virus-induced Liver Inflammation.

Gastroenterology. 2017 Aug 02;:

Authors: Bolte FJ, O'Keefe AC, Webb LM, Serti E, Rivera E, Liang TJ, Ghany M, Rehermann B

Abstract
BACKGROUND & AIMS: Chronic hepatitis affects phenotypes of innate and adaptive immune cells. Mucosal associated invariant T (MAIT) cells are enriched in the liver as compared to the blood, respond to intra-hepatic cytokines, and (via the semi-invariant T-cell receptor) to bacteria translocated from the gut. Little is known about the role of MAIT cells in livers of patients with chronic hepatitis C virus (HCV) infection and their fate after antiviral therapy.
METHODS: We collected blood samples from 42 patients with chronic HCV infection who achieved a sustained virologic response after 12 weeks of treatment with sofosbuvir and velpatasvir. Mononuclear cells were isolated from blood before treatment, at weeks 4 and 12 during treatment, and 24 weeks after the end of treatment. Liver biopsies were collected from 37 of the patients prior to and at week 4 of treatment. Mononuclear cells from 56 blood donors and 10 livers that were not suitable for transplantation were used as controls. Liver samples were assessed histologically for inflammation and fibrosis. Mononuclear cells from liver and blood were studied by flow cytometry and analyzed for responses to cytokine and bacterial stimulation.
RESULTS: The frequency of MAIT cells among T cells was significantly lower in blood and liver samples of patients with HCV infection than of controls (median 1.31% vs 2.32% for blood samples, P=.0048 and median 4.34% vs 13.40% for liver samples, P=.001). There was an inverse correlation between the frequency of MAIT cells in the liver and histologically determined levels of liver inflammation (r=-.5437, P=.0006) and fibrosis (r=-.5829, P=.0002). MAIT cells from the liver had higher levels of activation and cytotoxicity than MAIT cells from blood (P<.0001). Production of interferon gamma (IFNG) by MAIT cells was dependent on monocyte-derived interleukin 18 (IL18), and was reduced in patients with HCV infection in response to T-cell receptor-mediated but not cytokine-mediated stimulation, as compared to controls. Anti-viral therapy rapidly decreased liver inflammation and MAIT cell activation and cytotoxicity, and increased the MAIT cell frequency among intra-hepatic but not blood T cells. The MAIT cell response to T-cell receptor-mediated stimulation did not change during the 12 weeks of antiviral therapy.
CONCLUSIONS: In analyses of paired blood and liver samples from patients with chronic HCV infection before, during and after antiviral therapy with sofosbuvir and velpatasvir, we found that intrahepatic MAIT cells are activated by monocyte-derived cytokines and depleted in HCV-induced liver inflammation.

PMID: 28780074 [PubMed - as supplied by publisher]

Neurological Complications of Renal Disease.

Mon, 08/07/2017 - 18:48
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Neurological Complications of Renal Disease.

Semin Pediatr Neurol. 2017 Feb;24(1):25-32

Authors: Baluarte JH

Abstract
Neurological manifestations related to electrolyte disorders, drug toxicity, and uremia are common in chronic kidney disease (CKD). Seizures and coma are frequent complications of acute renal insufficiency (uremia), whereas peripheral neuropathy and encephalopathy, observed in progressive uremia, are terminal events. Failure to excrete metabolic products causes their accumulation and can lead to severe intoxication. Clinically, the signs and symptoms of uremia can vary widely, depending on the biological characteristics of the patient, the specific type of renal disease, and the time of the uremic intoxication. CKD is an increasing problem worldwide and is now being recognized as a global health burden particularly for cardiovascular and cerebrovascular ischemic events. Despite improvements in the medical management of advanced CKD, including dialysis and transplantation, patients manifest a number of symptoms that neurologists are often confronted with. Appropriate drug dosing, awareness of potential side effects of medications, prompt diagnosis, and treatment are essential in preventing neurological long-term morbidity and mortality.

PMID: 28779862 [PubMed - in process]

Management of renal dysfunction in patients with liver cirrhosis: role of pretransplantation hemodialysis and outcomes after liver transplantation.

Mon, 08/07/2017 - 18:48
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Management of renal dysfunction in patients with liver cirrhosis: role of pretransplantation hemodialysis and outcomes after liver transplantation.

Semin Vasc Surg. 2016 Dec;29(4):227-235

Authors: Thorat A, Jeng LB

Abstract
Patients with end-stage liver disease (ESLD) who develop hepatorenal syndrome (HRS) have very high mortality rates. For patients with HRS type I, median survival without specific therapy is only 2 weeks. Due to worsening clinical condition in such patients secondary to uremia and hepatic disease, some form of renal replacement therapy (RRT), either intermittent hemodialysis IHD or continuous veno-venous hemodialysis (CVVHD), must be instituted. However, the literature regarding the survival benefits of the hemodialysis for the worsening renal failure in liver cirrhotic patients remains limited. In this review, we performed a meta-analysis of nine different studies done in the last 2 decades that included 464 patients with end-stage liver disease with renal failure who received either pretransplantation or post-transplantation CVVHD. Survival of the patients was then analyzed with respect to patients with end-stage liver disease without renal failure that underwent liver transplantation (LT). Outcomes for the patients with pre-LT CVVHD were comparable with those of liver transplant recipients without renal failure. However, patients requiring post-LT hemodialysis for prolonged periods showed poor outcomes and a tendency to progress to chronic kidney disease. In all selected studies, patients with post-transplantation CVVHD for a prolonged period had a 3-year survival rate of ≤40%. This review highlights the role of pretransplantation CVVHD in selected patients with HRS who could achieve significantly better survival rates compared with patients without any renal replacement therapy or patients with post-transplantation CVVHD.

PMID: 28779790 [PubMed - in process]

Vascular access should be tailored to the patient.

Mon, 08/07/2017 - 18:48
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Vascular access should be tailored to the patient.

Semin Vasc Surg. 2016 Dec;29(4):146-152

Authors: Letachowicz K, Szyber P, Gołębiowski T, Kusztal M, Letachowicz W, Weyde W, Garcarek J, Klinger M

Abstract
A cornerstone of hemodialysis treatment is the creation of a functional and durable dialysis vascular access. Every patient with chronic kidney disease should have a plan of renal replacement therapy and access site protection. Factors having a crucial impact on vascular access selection include age, comorbidity, vessel quality, prognosis, dialysis urgency, and surgeon's preferences. Our medical group have reviewed these factors in our patients and, based on recently published data, developed a clinical decision tree for dialysis access in the chronic kidney disease patient. Vascular access care should be patient-centered with the aim to maximize patient survival without loss of vascular access options; and not focused only the primary patency rates of dialysis access procedures.

PMID: 28779781 [PubMed - in process]

Development of Severe Hyperparathyroidism Despite Short-Term Renal Replacement Therapy.

Sun, 08/06/2017 - 12:45
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Development of Severe Hyperparathyroidism Despite Short-Term Renal Replacement Therapy.

World J Surg. 2017 Aug 04;:

Authors: Okada M, Tominaga Y, Hiramitsu T, Ichimori T

Abstract
BACKGROUND: We occasionally experience cases of severe secondary hyperparathyroidism (SHPT) that require parathyroidectomy (PTX) despite undergoing short-term renal replacement therapy (RRT). Because the characteristics of such cases have never been discussed, we aimed to elucidate the pathophysiology of severe SHPT after short-term RRT by retrospectively analyzing clinical data.
METHODS: A total of 1013 patients with severe SHPT underwent PTX between January 2007 and April 2016 at Nagoya Daini Red Cross Hospital. Of these patients, 570 underwent RRT for ≥10 years (long RRT group) and 23 for ≤1 year (short RRT group). We retrospectively investigated and compared patient characteristics, preoperative data, subjective symptoms, and bone lesion incidence between the two groups.
RESULTS: A higher proportion of subjects with congenital or hereditary diseases as primary disease for chronic kidney disease (CKD) (21.7% (5/23) vs. 6.3% (36/570); P = 0.016) and longer predialysis period (21.2 ± 14.0 vs. 10.1 ± 9.2 years; P < 0.001) were observed in the short RRT group than in the long RRT group. Furthermore, lower serum calcium and phosphate levels, heavier parathyroid glands, and severe bone lesions were observed in the short RRT group than in the long RRT group.
CONCLUSION: Severe SHPT after short-term RRT appeared to occur because of long-term CKD before initiating RRT. Therefore, treating mineral and bone disorders during the early CKD stage might prevent severe SHPT development before initiating RRT.

PMID: 28779382 [PubMed - as supplied by publisher]

Outcomes of renal replacement therapy in boys with prune belly syndrome: findings from the ESPN/ERA-EDTA Registry.

Sun, 08/06/2017 - 12:45
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Outcomes of renal replacement therapy in boys with prune belly syndrome: findings from the ESPN/ERA-EDTA Registry.

Pediatr Nephrol. 2017 Aug 04;:

Authors: Yalcinkaya F, Bonthuis M, Erdogan BD, van Stralen KJ, Baiko S, Chehade H, Maxwell H, Montini G, Rönnholm K, Sørensen SS, Ulinski T, Verrina E, Weber S, Harambat J, Schaefer F, Jager KJ, Groothoff JW

Abstract
BACKGROUND: As outcome data for prune belly syndrome (PBS) complicated by end-stage renal disease are scarce, we analyzed characteristics and outcomes of children with PBS using the European Society for Pediatric Nephrology/European Renal Association-European Dialysis and Transplant Association (ESPN/ERA-EDTA) Registry data.
METHODS: Data were available for 88 male PBS patients aged <20 years who started renal replacement therapy (RRT) between 1990 and 2013 in 35 European countries. Patient characteristics, survival, and transplantation outcomes were compared with those of male patients requiring RRT due to congenital obstructive uropathy (COU) and renal hypoplasia or dysplasia (RHD).
RESULTS: Median age at onset of RRT in PBS was lower [7.0; interquartile range (IQR) 0.9-12.2 years] than in COU (9.6; IQR: 3.0-14.1 years) and RHD (9.4; IQR: 2.7-14.2 years). Unadjusted 10-year patient survival was 85% for PBS, 94% for COU, and 91% for RHD. After adjustment for country, period, and age, PBS mortality was similar to that of RHD but higher compared with COU [hazard ratio (HR) 1.96, 95% confidence interval (CI) 1.03-3.74]. Seventy-four PBS patients (84%) received a first kidney transplant after a median time on dialysis of 8.4 (IQR 0.0-21.1) months. Outcomes with respect to time on dialysis before transplantation, chance of receiving a first transplant within 2 years after commencing RRT, and death-censored, adjusted risk of graft loss were similar for all groups.
CONCLUSIONS: This study in the largest cohort of male patients with PBS receiving RRT to date demonstrates that outcomes are comparable with other congenital anomalies of the kidney and urinary tract, except for a slightly higher mortality risk compared with patients with COU.

PMID: 28779237 [PubMed - as supplied by publisher]

Acute Kidney Injury in Transplant Setting: Differential Diagnosis and Impact on Health and Health Care.

Sun, 08/06/2017 - 12:45
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Acute Kidney Injury in Transplant Setting: Differential Diagnosis and Impact on Health and Health Care.

Adv Chronic Kidney Dis. 2017 Jul;24(4):228-232

Authors: Abu Jawdeh BG, Govil A

Abstract
Acute kidney injury (AKI) is common in kidney transplant recipients. In addition to the usual causes of AKI in native kidneys, certain features and risk factors are unique to kidney allografts. In this article, we will present an overview of the common transplant-specific AKI etiologies that include increased susceptibility to hemodynamic-mediated AKI, acute rejection, medication-induced AKI, recurrence of native kidney disease, infections, urinary tract obstruction, vascular thrombosis and post-transplant lymphoproliferative disorder. AKI is independently associated with allograft loss and patient mortality. It is, therefore, prudent for transplant centers to address it as a major quality measure.

PMID: 28778362 [PubMed - in process]

Mesenchymal Stem Cells in Fibrotic Disease.

Sat, 08/05/2017 - 12:45
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Mesenchymal Stem Cells in Fibrotic Disease.

Cell Stem Cell. 2017 Aug 03;21(2):166-177

Authors: El Agha E, Kramann R, Schneider RK, Li X, Seeger W, Humphreys BD, Bellusci S

Abstract
Fibrosis is associated with organ failure and high mortality and is commonly characterized by aberrant myofibroblast accumulation. Investigating the cellular origin of myofibroblasts in various diseases is thus a promising strategy for developing targeted anti-fibrotic treatments. Recent studies using genetic lineage tracing technology have implicated diverse organ-resident perivascular mesenchymal stem cell (MSC)-like cells and bone marrow-MSCs in myofibroblast generation during fibrosis development. In this Review, we give an overview of the emerging role of MSCs and MSC-like cells in myofibroblast-mediated fibrotic disease in the kidney, lung, heart, liver, skin, and bone marrow.

PMID: 28777943 [PubMed - in process]

Refinement of Humoral Immune-monitoring in Kidney Transplantation: the role of "hidden" Alloreactive Memory B cells.

Sat, 08/05/2017 - 12:45
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Refinement of Humoral Immune-monitoring in Kidney Transplantation: the role of "hidden" Alloreactive Memory B cells.

Transpl Int. 2017 Aug 04;:

Authors: Luque S, Lúcia M, Bestard O

Abstract
The advent of novel sensitive assays assessing circulating anti-HLA antibodies has allowed recognizing humoral alloimmunity as the main immune-mediated mechanism responsible of allograft rejection and graft loss in kidney transplantation. However, current immune-monitoring techniques, exclusively focusing on circulating anti-HLA antibodies, may underestimate the magnitude of humoral immune response as they exclude the memory B-cell (mBC) pool. Different biological compartments are involved in the intricate mechanisms triggering humoral alloimmune responses even in absence of detectable circulating alloantbodies. Recent studies in animal models as well as in clinical kidney transplantation have shown the key role of this B-cell subset triggering allograft rejection thus, emphasizing the value of recognizing anti-donor mBC both as a biomarker of allosensitization and as therapeutic targets. Therefore, considerable efforts are being made among the transplant research community to better understand the role, hierarchy and impact of mBC in the context of organ transplantation. In this review article, we provide a deep insight on the biology of mBC as well as main evidence of their role orchestrating allograft rejection. Also, we provide a thorough description of main immune-monitoring tools aiming at tracking mBC and a rational for their potential use to refine current humoral immune-risk assessment in kidney transplantation. This article is protected by copyright. All rights reserved.

PMID: 28777489 [PubMed - as supplied by publisher]

Discordant rejection in simultaneous pancreas and kidney transplantation: true discordance or analysis artefact ?

Sat, 08/05/2017 - 12:45
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Discordant rejection in simultaneous pancreas and kidney transplantation: true discordance or analysis artefact ?

Transpl Int. 2017 Aug 04;:

Authors: Assalino M, Hadaya K, Andres A, Berney T

Abstract
The article by Parajuli et al published in this issue of Transplant International is the latest, and perhaps the most convincing in a relatively small body of literature, to suggest that in a situation of simultaneous pancreas-kidney transplantation (SPK), in which both organs are from the same donor, one organ may be undergoing acute rejection independently from the other (1). The organ hierarchy in immunogeneicity and susceptibility to rejection is a long known biological phenomenon, with the liver at one end of the spectrum and the intestine the other. It was originally thought that such a hierarchy between kidney and pancreas was in disfavor of the latter (2). This article is protected by copyright. All rights reserved.

PMID: 28777488 [PubMed - as supplied by publisher]

Towards a conditional approach to anonymity? An explorative multi-center longitudinal study among anonymous living kidney donors and recipients.

Sat, 08/05/2017 - 12:45
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Towards a conditional approach to anonymity? An explorative multi-center longitudinal study among anonymous living kidney donors and recipients.

Transpl Int. 2017 Aug 04;:

Authors: Pronk MC, Slaats D, van der Pant KAMI, Vervelde J, Dooper IMM, Dor FJMF, Weimar W, van de Wetering J, Zuidema WC, Massey EK

Abstract
Anonymity between living donors and recipients is a topic of discussion among transplant professionals. This longitudinal study explored living kidney donors' and patients' perspectives on anonymity. Prior to surgery (T0) and 3 months afterwards (T1) participants in unspecified or specified indirect donation programs completed a questionnaire on their experiences with and attitudes towards anonymity as well as demographic and medical characteristics. Non-parametric tests were used to assess group differences and associations. Participants were content with anonymity at T0 and T1. Fourteen and 23% wanted to meet at T0 and T1 respectively. If the other party expressed the wish to meet, 50% (T0) and 55% (T1) would be willing to meet. Most participants agreed that meeting should be allowed if both parties agree. Attitude towards anonymity did not differ between donors/recipients, nor between T0/T1 and unspecified/specified indirect donation programs. This study showed that most donors and recipients who participated in anonymous donation schemes are in favor of a conditional approach to anonymity. Guidelines on how to revoke anonymity if both parties agree are needed and should include education about pros and cons of (non-) anonymity and a logistical plan on how, when, where and by whom anonymity should be revoked. This article is protected by copyright. All rights reserved.

PMID: 28777487 [PubMed - as supplied by publisher]

A simplified method of calculating cPRA for kidney allocation application in Hong Kong.

Sat, 08/05/2017 - 12:45
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A simplified method of calculating cPRA for kidney allocation application in Hong Kong.

Transpl Int. 2017 Aug 04;:

Authors: Chan YP, Wong MWK, Tang LWM, Guo M, Yang W, Ip P, Li PKT, Leung CB, Chau KF, Lam JCK, Yeung NKM, Kwok JSY

Abstract
Calculated panel reactive antibody (cPRA) represents possibility of encountering an incompatible donor for organ transplant candidates, and has gradually replaced traditional PRA as a measurement of sensitization level. We tested two cPRA calculation methods on a cohort of renal candidate (n=613). HLA typing of 563 Chinese deceased renal donors were used to estimate allele and haplotype frequencies of Hong Kong donor pool. The OPTN formula was adopted to generate cPRA (cPRA(freq)). We also incorporated a computer script to compare unacceptable antigens of patients against HLA phenotype of donors. The cPRA based on historical donor filtering was the percentage of filter out count over total number of donors (cPRA(filter)). Values of cPRA(freq) and cPRA(filter) showed almost perfect agreement with Lin's correlation coefficient equal to 1.000. SD of bias was 0.6 cPRA point. Limit of agreement was 0.9 to -1.5 points difference. Furthermore, the poor agreement between our in-house cPRA and values from other online calculators indicated the necessity to use local population data for accurate cPRA calculation. Built-in donor filtering method was more practicable for Hong Kong due to factors such as cost and flexibility. An on-going donor pool can reflect population allele frequencies and permits efficient periodic update of cPRA. This article is protected by copyright. All rights reserved.

PMID: 28777478 [PubMed - as supplied by publisher]

Clinical depression as an unfavorable prognostic factor following kidney transplantation - How can we explain it?

Sat, 08/05/2017 - 12:45
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Clinical depression as an unfavorable prognostic factor following kidney transplantation - How can we explain it?

Transpl Int. 2017 Aug 04;:

Authors: Gaynor JJ, Ciancio G

Abstract
In this issue Lentine et al(1) provide a well thought-out analysis of the prognostic value of antidepressant medication use (as a surrogate measure of clinical depression) on post-transplant outcome. Specifically, they show that among 72,054 SRTR patients receiving a kidney transplant during 2008-2015, anti-depressant use (obtained from pharmaceutical fill records) within one year of transplant and during the first year post-transplant (12.6% and 18.0% of patients, respectively) correlated with a significantly higher death rate during the first and 2(nd) year post-transplant (P<.0001 each, aHR=1.39 and 1.94, respectively). This article is protected by copyright. All rights reserved.

PMID: 28777476 [PubMed - as supplied by publisher]

The sleeve method for creation of radiocephalic arteriovenous fistulas in patients with calcified vessels.

Sat, 08/05/2017 - 12:45
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The sleeve method for creation of radiocephalic arteriovenous fistulas in patients with calcified vessels.

J Vasc Access. 2017 Jul 26;:0

Authors: Gołębiowski T, Weyde W, Letachowicz K, Kusztal M, Augustyniak-Bartosik H, Penar J, Madziarska K, Zmonarski S, Krajewska M, Klinger M

Abstract
INTRODUCTION: Creation of an arteriovenous fistula (AVF) in patients with advanced atherosclerotic changes of the artery is often a challenge for the physician due to difficulties in suturing the vein to the side of the frangible artery. The sleeve technique relies on advancing the end of the artery into the lumen of the vein and protecting the anastomosis by adventitial sutures.
MATERIAL AND METHODS: The sleeve technique was performed in 23 patients with chronic kidney disease stage IV and V and included hemodialysis patients. Their mean age was 60.8 ± 14.8 years and hemodialysis treatment time 49.8 ± 40.2 months. The most frequent causes of chronic kidney disease are ischemic nephropathy (43%, n = 10) and type l diabetes (21%, n = 5). Only patients with extremely advanced atherosclerotic were recruited and analyzed.
RESULTS: The primary patency rate was 67%, 59%, 44% and 28% at 6, 12, 24, and 36 months, respectively. The secondary patency rate was 67%, 61%, 50% and 37% at 6, 12, 24, and 36 months, respectively. In three patients the AVF failed directly after the operation. Delayed fistula failure occurred in seven patients. The overall success in the creation of a functioning fistula was achieved in 15 of the 23 patients (65%). No serious complications were observed.
CONCLUSIONS: In patients with calcified atherosclerotic plaques, which constitute a barrier or make it difficult to suture the vein to the side of the artery, the sleeve method may be considered as an alternative before abandoning the creation of a fistula on the forearm. The technique is much simpler than the standard end-to-side or side-to-side anastomosis.

PMID: 28777423 [PubMed - as supplied by publisher]

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