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Renal function reserve

Nina Kimer, Julie Steen Pedersen, Troels Malte Busk, Lise Lotte Gluud, Lise Hobolth, Aleksander Krag, Søren Møller, Flemming Bendtsen
BACKGROUND AND RATIONALE: Decompensated cirrhosis is characterized by disturbed systemic and splanchnic hemodynamics. Bacterial translocation from the gut is considered the key driver in this process. Intestinal decontamination with rifaximin may improve hemodynamics. This double-blind, randomized, controlled trial investigates the effects of rifaximin on hemodynamics, renal function and vasoactive hormones. METHODS: We randomized 54 stable out-patients with cirrhosis and ascites to rifaximin 550 mg BD (n=36) or placebo BD (n=18)...
October 24, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Saurabh Chaudhri, Alice A Thomas, Nasreen Samad, Stanley L Fan
AIM: To determine if patients with failing kidney transplants who opt to have peritoneal dialysis (PD) have poor short-term PD technique survival and increased rates of peritonitis. METHODS: We performed a retrospective analysis comparing 50 consecutive patients starting PD after a failed kidney transplant to 93 incident patients starting PD (matching for age, gender, diabetes causing renal failure, ethnicity and year of starting PD). RESULTS: The mean follow-up period was 26 months...
October 20, 2016: Nephrology
Oleg O Rummo, Mario Carmellini, Lionel Rostaing, Rainer Oberbauer, Maarten H L Christiaans, Christiane Mousson, Robert M Langer, Franco Citterio, Bernard Charpentier, Malcolm Brown, Gbenga Kazeem, Frank Lehner
ADHERE was a randomized, open-label, Phase IV study comparing renal function at Week 52 post-kidney transplant, in patients who received prolonged-release tacrolimus-based immunosuppressive regimens. On days 0-27, patients received prolonged-release tacrolimus (initially 0.2mg/kg/day), corticosteroids and mycophenolate mofetil (MMF). Patients were randomized on Day 28 to receive either prolonged-release tacrolimus plus MMF (Arm 1) or prolonged-release tacrolimus (≥25% dose-reduction on Day 42) plus sirolimus (Arm 2)...
October 18, 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
Huei-Fen Jheng, Motohiko Hirotsuka, Tsuyoshi Goto, Masayuki Shibata, Yasuki Matsumura, Teruo Kawada
SCOPE: Diabetic nephropathy (DN) is a major cause of end-stage renal disease. Here, we examined the effect of long-term consumption of a low-fat soy milk powder (LFSMP) on the diabetic kidney structure and function. METHODS AND RESULTS: KKAy mice were fed a casein- LFSMP-or high-fat soy mixture powder (HFSMP)-based diet for 4 months. Plasma and urine were subjected to a biochemical assay every 2-4 weeks. Renal morphology and protein expression were evaluated by histochemical staining and western blots...
October 17, 2016: Molecular Nutrition & Food Research
Sebastian Völz, Sara Svedlund, Bert Andersson, Gan Li-Ming, Bengt Rundqvist
Resistant hypertension is associated with increased risk for cardiovascular events. Coronary flow reserve (CFR) is impaired in patients with hypertension and an independent predictor of cardiac mortality. However, there are no published data on CFR in the subset of treatment-resistant hypertension. The aim of this study was to assess CFR in patients with resistant hypertension. Twenty-five consecutive patients with primary resistant hypertension, scheduled for renal denervation, 25 matched patients with controlled hypertension, and 25 healthy controls underwent transthoracic colour Doppler echocardiography at rest and during adenosine infusion...
October 17, 2016: Clinical Research in Cardiology: Official Journal of the German Cardiac Society
Mathijs van de Vrie, Jeroen K Deegens, Michael Eikmans, Johan van der Vlag, Luuk B Hilbrands
Urine represents a non-invasive source in which proteins and nucleic acids can be assessed. Such analytes may function as biomarkers to monitor kidney graft pathology at every desired frequency, thereby providing a time window to prevent graft damage by therapeutic intervention. Recently, several proteins have been measured in urine as markers of graft injury. However, the specificity is limited, and measuring urinary proteins generally lacks the potential to predict early kidney graft damage. Currently, urinary mRNA and microRNA are being investigated to evaluate the prognostic value of changes in gene expression during the initial stages of graft damage...
October 15, 2016: American Journal of Transplantation
I Lobb, J Jiang, D Lian, W Liu, A Haig, M N Saha, R Torregrossa, M E Wood, M Whiteman, A Sener
Ischemia-reperfusion injury (IRI) is unavoidably caused by loss and subsequent restoration of blood flow during organ procurement and prolonged IRI results in increased rates of delayed graft function and early graft loss. The endogenously produced gasotransmitter, hydrogen sulfide (H2 S), is a novel molecule that mitigates hypoxic tissue injury. The current study investigates the protective mitochondrial effects of H2 S during in vivo cold storage and subsequent renal transplantation (RTx) and in vitro cold hypoxic renal injury...
October 15, 2016: American Journal of Transplantation
Simon R Knight, Samia Hussain
Early measures of graft function are increasingly used to assess efficacy in clinical trials of kidney transplant immunosuppression. This study aimed to assess the variability and quality of reporting of these endpoints in contemporary trials. Data regarding renal function endpoints were extracted from 213 reports from randomised controlled trials comparing immunosuppressive interventions in renal transplant recipients published between 2010 and 2014. 174 (81.7%) reports included a measure of renal function; in 44 (20...
October 14, 2016: Clinical Transplantation
Marcus Weitz, Onur Sazpinar, Maria Schmidt, Thomas J Neuhaus, Elisabeth Maurer, Claudia Kuehni, Paloma Parvex, Hassib Chehade, Sibylle Tschumi, Franz Immer, Guido F Laube
INTRODUCTION: Children often merit priority in access to deceased donor kidneys by organ-sharing organizations. We report the impact of the new Swiss Organ Allocation System (SOAS) introduced in 2007, offering all kidney allografts from deceased donors<60 years preferentially to children. METHODS: The retrospective cohort study included all paediatric transplant patients (< 20 years of age) before (n=19) and after (n=32) the new SOAS (from 2001-2014). Estimated glomerular filtration rate (eGFR), urine protein to creatinine ratio (UPC), need for antihypertensive medication, waiting times to kidney transplantation (KTX), number of pre-emptive transplantations and rejections, and the proportion of living donor transplants were considered as outcome parameters...
October 12, 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
Thomas Minor, Katja Sutschet, Oliver Witzke, Andreas Paul, Anja Gallinat
BACKGROUND: Post-transplant function of suboptimal kidney grafts can be improved but not accurately predicted by hypothermic machine perfusion. Therefore, a new concept of ex situ pre-implantation machine perfusion with controlled rewarming up to subnormothermic temperatures was developed and evaluated. METHODS: Porcine kidneys (n= 6/ group) were retrieved before or 30 min after cardiac arrest of the donor and subjected to 18 hours of static cold storage. In some cases 90 min of machine controlled oxygenated rewarming (COR) was added thereafter...
October 8, 2016: European Journal of Clinical Investigation
Aurore Barthélemy, Nicolas Bouvier, Renaud Verdon, Valérie Chatelet, Bruno Hurault de Ligny
We report the case of a human immunodeficiency virus-seropositive patient whose initial kidney transplant failed because of BK polyomavirus-induced nephropathy, and who underwent a second transplantation 3 years later. BK viruria was detected 1 day after transplantation. After 1 month, BK viremia developed along with a donor-specific antibody. After decreasing tacrolimus and mycophenolic acid and 2 courses of intravenous immunoglobulins, BK viremia and donor-specific antibody permanently disappeared, with stable renal function...
September 26, 2016: Transplant Infectious Disease: An Official Journal of the Transplantation Society
Shiromani Janki, Leonienke F C Dols, Reinier Timman, Evalyn E A P Mulder, Ine M M Dooper, Jacqueline van de Wetering, Jan N M IJzermans
To establish the outcome of live kidney donors five years after donation we investigated the risk for progressive renal function decline and quality of life (QoL). Data on estimated glomerular filtration rate (eGFR), creatinine, hypertension, QoL, and survival were assessed in a prospective cohort of 190 donors, who donated between 2008-2010.Data was available for >90%. The mean age pre-donation was 52.8±11.5years, 30 donors having pre-existent hypertension. The mean follow-up was 5.1±0.9 years. Eight donors had died due to non-donation related causes...
October 7, 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
Premraj Rajkumar, Jennifer L Pluznick
Recent studies have shown that orphan GPCRs of the GPR family are utilized as specialized chemosensors in various tissues to detect metabolites, and in turn to activate downstream pathways which regulate systemic homeostasis. These studies often find that such metabolites are generated by well-known metabolic pathways, implying that known metabolites and chemicals may perform novel functions. In this review, we summarize recent findings highlighting the role of deorphanized GPRs in renal development and function...
October 3, 2016: Acta Physiologica
Nicoline Valentina Krogstrup, Mihai Oltean, Gertrude J Nieuwenhuijs-Moeke, Frank J M F Dor, Ulla Møldrup, Søren Palmelund Krag, Bo Martin Bibby, Henrik Birn, Bente Jespersen
Delayed graft function is a frequent complication following deceased donor renal transplantation, and is closely related to ischaemia-reperfusion injury. Experimental and clinical studies have shown protection by remote ischaemic conditioning (RIC). We hypothesised that recipient RIC before kidney graft reperfusion reduces the time to graft recovery. This multicentre, blinded, randomised, controlled clinical trial included 225 adult recipients of renal transplants from deceased donors at four transplantation centres in Denmark, Sweden and the Netherlands...
October 3, 2016: American Journal of Transplantation
M Fähling, S Mathia, J Scheidl, R Abramovitch, Z Milman, A Paliege, H Peters, P B Persson, S N Heyman, C Rosenberger
AIM: Cyclosporin A (CsA) causes renal toxicity. The underlying mechanisms are incompletely understood, but may involve renal hypoxia and hypoxia-inducible factors (Hifs). We sought for hypoxia and Hif in mouse kidneys with CsA-induced toxicity, assessed their time course, Hif-mediated responses and the impact of interventional Hif upregulation. METHODS: Mice received CsA or its solvent cremophore for up to 6 weeks. Low salt diet (Na(+) ↓) was given in combination with CsA to enhance toxicity...
September 30, 2016: Acta Physiologica
Raktim K Ghosh, Somedeb Ball, Avash Das, Dhrubajyoti Bandyopadhyay, Samhati Mondal, Debjit Saha, Anjan Gupta
Pulmonary arterial hypertension (PAH) is a relatively rare disease which due to its chronic nature has always been difficult to treat effectively. Selexipag is an oral prostacyclin (PGI2) agonist, which was approved by US Food and Drug Administration (US FDA) in December 2015 for the treatment of PAH. After its success in Phase 1 and Phase 2 clinical trials regarding the convenient oral twice daily dosing and low side-effect profile, selexipag raised the hope of controlling the disease progression in PAH patients...
September 27, 2016: Journal of Clinical Pharmacology
A Rossidis, M A Lim, M Palmer, M H Levine, A Naji, R D Bloom, P L Abt
In the United States, >100 000 patients are waiting for a kidney transplant. Given the paucity of organs available for transplant, expansion of eligibility criteria for deceased donation is of substantial interest. Sickle cell disease (SCD) is viewed as a contraindication to kidney donation, perhaps because SCD substantially alters renal structure and function and thus has the potential to adversely affect multiple physiological processes of the kidney. To our knowledge, transplantation from a donor with SCD has never been described in the literature...
September 24, 2016: American Journal of Transplantation
Laura Rivoli, A D Bastiaan Vliegenthart, Carmelita M J de Potter, Job J M H van Bragt, Nikolaos Tzoumas, Peter Gallacher, Tariq E Farrah, Neeraj Dhaun, James W Dear
AIM: microRNA-122 (miR-122) is a hepatotoxicity biomarker with utility in the management of paracetamol overdose and in drug development. Renal dysfunction and haemodialysis have been associated with a reduction in circulating microRNA. The objective of this study was to determine their effect on miR-122. METHODS: Blood samples were collected from 17 patients with end-stage renal disease (ESRD) on haemodialysis, 22 healthy controls, 30 patients with chronic kidney disease (CKD) and 15 patients post-kidney transplantation...
September 21, 2016: British Journal of Clinical Pharmacology
J Moritz Kaths, Jun Yu Cen, Yi Min Chun, Juan Echeverri, Ivan Linares, Sujani Ganesh, Paul Yip, Rohan John, Darius Bagli, Istvan Mucsi, Anand Ghanekar, David Grant, Lisa A Robinson, Markus Selzner
Hypothermic preservation is known to cause renal graft injury, especially in donation after circulatory death (DCD) kidney transplantation. We investigated the impact of cold storage (SCS) vs. short periods of normothermic ex vivo kidney perfusion (NEVKP) after SCS vs. prolonged, continuous NEVKP with near avoidance of SCS on kidney function after transplantation. Following 30 minutes of warm ischemia, kidneys were removed from 30kg Yorkshire pigs and preserved for 16h with: A) 16h SCS, B) 15h SCS + 1h NEVKP, C) 8h SCS + 8h NEVKP, D) 16h NEVKP...
September 20, 2016: American Journal of Transplantation
Tinus du Toit, Lisa Kaestner, Elmi Muller, Delawir Kahn
We report the first documented case of an inguinal hernia containing bladder, resulting in contralateral allograft hydroureteronephrosis. A 39 year old male patient presented with allograft dysfunction, a contralateral inguino-scrotal hernia and marked hydroureteronephrosis on ultrasound. Percutaneous nephrostogram and a retrograde cystogram suggested bladder herniation with incorporation of the contralateral ureteroneocystostomy into the hernia. Paraperitoneal bladder herniation was confirmed at surgery and hernioplasty was performed...
September 19, 2016: American Journal of Transplantation
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