Skip directly to content

PubMed Kidney Transplant

Subscribe to PubMed Kidney Transplant feed PubMed Kidney Transplant
NCBI: db=pubmed; Term=kidney transplant
Updated: 4 min 24 sec ago

Chronic kidney disease.

Fri, 11/24/2017 - 13:45

Chronic kidney disease.

Nat Rev Dis Primers. 2017 Nov 23;3:17088

Authors: Romagnani P, Remuzzi G, Glassock R, Levin A, Jager KJ, Tonelli M, Massy Z, Wanner C, Anders HJ

Abstract
Chronic kidney disease (CKD) is defined by persistent urine abnormalities, structural abnormalities or impaired excretory renal function suggestive of a loss of functional nephrons. The majority of patients with CKD are at risk of accelerated cardiovascular disease and death. For those who progress to end-stage renal disease, the limited accessibility to renal replacement therapy is a problem in many parts of the world. Risk factors for the development and progression of CKD include low nephron number at birth, nephron loss due to increasing age and acute or chronic kidney injuries caused by toxic exposures or diseases (for example, obesity and type 2 diabetes mellitus). The management of patients with CKD is focused on early detection or prevention, treatment of the underlying cause (if possible) to curb progression and attention to secondary processes that contribute to ongoing nephron loss. Blood pressure control, inhibition of the renin-angiotensin system and disease-specific interventions are the cornerstones of therapy. CKD complications such as anaemia, metabolic acidosis and secondary hyperparathyroidism affect cardiovascular health and quality of life, and require diagnosis and treatment.

PMID: 29168475 [PubMed - in process]

Effects of nutraceuticals on sexual satisfaction and lower urinary tract symptoms in a cohort of young-old men.

Fri, 11/24/2017 - 13:45

Effects of nutraceuticals on sexual satisfaction and lower urinary tract symptoms in a cohort of young-old men.

Phytother Res. 2017 Nov 23;:

Authors: Perri A, Ilacqua A, Valenti M, Aversa A

Abstract
The aim of this study was to evaluate the effects of nutraceuticals containing multiple supplemental facts (Virherbe®/Rekupros®) on sexual satisfaction and lower urinary tract symptoms (LUTS) in young-old men. In an open-label trial, 40 males (mean age 66 ± 13) with sexual disturbances and mild LUTS but without cognitive/motor impairment and clinical hypogonadism were enrolled. Sexual desire (SD; IIEF-SD domain) and satisfaction (Global Assessment Question; GAQ), the capacity to perform daily activities (evaluated by 6-min walking test [6MWT]), and International Prostate Symptoms Scores (IPSS) were evaluated before and after oral administration of 2 capsules/day of each supplement for 8 weeks. The difference from baseline for SD was +2.6 (p < .05) and -4.2 points for IPSS (p < .05), with significance in subscales of urinary streaming/nocturia (p < .01), respectively; 6MWT increased from 507 ± 44 versus 527 ± 58 meters (p < .001). GAQ scale-responses showed overall improvement in overall 75% population, with a significant improvement in QoL (p < .01). These changes returned to baseline at 1-month withdrawal follow-up. No adverse events were reported. These supplemental facts improved sexual desire, satisfaction with sex life, physical performance, and LUTS in young-old men, suggesting that they may be effective in patients in whom standard treatments are not suitable.

PMID: 29168235 [PubMed - as supplied by publisher]

Clinical potential of mesenchymal stem/stromal cell-derived extracellular vesicles.

Fri, 11/24/2017 - 13:45

Clinical potential of mesenchymal stem/stromal cell-derived extracellular vesicles.

Stem Cell Investig. 2017;4:84

Authors: Giebel B, Kordelas L, Börger V

Abstract
Within the last two decades mesenchymal stem/stromal cells (MSCs) emerged after hematopoietic stem cells as the second most investigated and applied somatic stem cell entity so far. MSCs mediate immunosuppressive as well as pro-regenerative activities. Against the initial assumption, MSCs may not primarily exert their therapeutic functions in a cellular but rather in a paracrine manner. Here, extracellular vesicles (EVs), such as exosomes and microvesicles, have been identified as major mediators of these paracrine effects. Meanwhile, MSC-EVs have been applied to an increasing amount of different animal models and were tested in a patient suffering from steroid-refractory acute graft-versus-host disease (acute GvHD) as well as in a patient cohort with chronic kidney disease. So far, the MSC-EV administration appears to be safe in humans and all tested animal models. Improvements were reported in all settings. Thus, MSC-EVs appear as promising novel therapeutic agents which might help to improve disease associated symptoms in millions of patients. Here, we review some of the milestones in the field, briefly discuss challenges and highlight clinical aspects of acute GvHD and its treatment with MSCs and MSC-EVs.

PMID: 29167805 [PubMed]

Disparities in Health Literacy and Healthcare Utilization among Adolescents and Young Adults with Chronic or End-stage Kidney Disease.

Fri, 11/24/2017 - 13:45

Disparities in Health Literacy and Healthcare Utilization among Adolescents and Young Adults with Chronic or End-stage Kidney Disease.

J Pediatr Nurs. 2017 Oct 31;38:57-61

Authors: Levine R, Javalkar K, Nazareth M, Faldowski RA, de Ferris MD, Cohen S, Cuttance J, Hooper SR, Rak E

Abstract
PURPOSE: Low health literacy adversely affects health outcomes in adults with chronic kidney disease. The current study examined associations between limited/inadequate health literacy and health services utilization among adolescents and young adults (AYA) with chronic or end-stage kidney disease (CKD or ESKD).
DESIGN AND METHODS: This was a retrospective cohort study that enrolled patients from both the pediatric- and adult-focused nephrology clinics of a major university hospital. Demographic information, patients' health literacy and numeracy skills (Newest Vital Sign), and health services utilization (emergency department visits, preventable hospitalizations, total hospitalizations, and length of stay in the hospital) were evaluated. A negative binomial regression model for counts tested the association between AYA patients' literacy/numeracy skills and health services utilization.
RESULTS: The study enrolled 142 participants, 66 (46.5%) patients from adult nephrology and 76 (53.5%) from pediatric nephrology clinics, with a mean age of 20.8±5.60years (range 12-31). Half of the sample (n=72, 51%) had limited health literacy skills. Health literacy/numeracy level was not significantly associated with total hospitalizations, preventable hospitalizations, emergency department (ED) visits, or length of hospital stay. However, public insurance/self-pay, minority race, and kidney transplant/dialysis diagnoses were associated with more preventable hospitalizations.
CONCLUSIONS: Among AYA with CKD/ESKD, there were no differences between the low and adequate health literacy groups on health care utilization outcomes when modeling clinical outcomes (total hospitalizations, preventable hospitalizations, ED visits, and length of hospital stay) after adjusting for demographics and disease type. This suggests that other factors warrant consideration in healthcare utilization rates.

PMID: 29167082 [PubMed - as supplied by publisher]

Multimodal imaging of retinal pigment epithelial detachments in patients with C3 glomerulopathy: case report and review of the literature.

Fri, 11/24/2017 - 13:45

Multimodal imaging of retinal pigment epithelial detachments in patients with C3 glomerulopathy: case report and review of the literature.

BMC Ophthalmol. 2017 Nov 22;17(1):207

Authors: Kheir V, Dirani A, Halfon M, Venetz JP, Halabi G, Guex-Crosier Y

Abstract
BACKGROUND: To describe the optical coherence tomography angiograhy (OCTA) of drusenoid pigment epithelial detachments (PEDs) in a woman affected by Complement 3 (C3) glomerulopathy, which represents a spectrum of glomerular diseases characterized on fluorescent microscopy by C3 accumulation with absent, or scanty, immunoglobulin deposits. It is due to acquired or genetically defective alternative pathway control and is generally associated with drusen-like deposits in Bruch's membrane, as well as choriocapillaris. These retinal lesions can be associated with choroidal neovascularization and central serous chorioretinopathy (CSCR). OCTA is useful to detect neovascularization without injecting a contrast product, particularly in these patients who may have renal insufficiency.
CASE PRESENTATION: A 28-year-old woman affected by C3 glomerulpathy was diagnosed with asymptomatic multiple bilateral PEDs during a routine ophthalmologic consultation. To better characterize the lesions, multimodal imaging was performed and included: optic coherence tomography (OCT), en-face OCT, OCTA, fluorescence and indocyanine angiography. The OCTA clearly identified vascular network rarefaction with decreased choriocapillary vascularization. It confirmed that PEDs associated with C3 glomerulonephritis are not vascularized, but rather of serous type.
CONCLUSIONS: Patients affected by C3 glomerulopathy can develop neovascular membranes as retinal complications of pigment epithelial detachments. Optical coherence angiography may be indicated to identify this complication, without injecting any contrast product that could produce further kidney damage.

PMID: 29166869 [PubMed - in process]

Improvement in Pancreas Transplant Evaluation and Surgical Volume Using a Multidisciplinary Approach.

Thu, 11/23/2017 - 13:45

Improvement in Pancreas Transplant Evaluation and Surgical Volume Using a Multidisciplinary Approach.

Am J Transplant. 2017 Nov 22;:

Authors: Scalea JR, Sultan S, Lamos E, Bartlett ST, Barth RN

Abstract
Pancreas numbers are down: Pancreas transplantation is the only long-term treatment for diabetes which restores glucose homeostasis, without the risks of hypoglycemia.(1-3) Further, receiving a simultaneous pancreas kidney (SPK) transplant improves life expectancy over kidney transplantation alone.(4,5) Despite this, the total number of pancreas transplants in the United States has decreased since 2006. Experts in the field recently reported that, while this drop in volume is multifactorial, the lack of a steady referral source is partly to blame.(1) This article is protected by copyright. All rights reserved.

PMID: 29166550 [PubMed - as supplied by publisher]

Neurological complications of solid organ transplantation.

Thu, 11/23/2017 - 13:45

Neurological complications of solid organ transplantation.

Arq Neuropsiquiatr. 2017 Oct;75(10):736-747

Authors: Pedroso JL, Dutra LA, Braga-Neto P, Abrahao A, Andrade JBC, Silva GLD, Viana LA, Pestana JOM, Barsottini OG

Abstract
Solid organ transplantation is a significant development in the treatment of chronic kidney, liver, heart and lung diseases. This therapeutic approach has increased patient survival and improved quality of life. New surgical techniques and immunosuppressive drugs have been developed to achieve better outcomes. However, the variety of neurological complications following solid organ transplantation is broad and carries prognostic significance. Patients may have involvement of the central or peripheral nervous system due to multiple causes that can vary depending on time of onset after the surgical procedure, the transplanted organ, and the intensity and type of immunosuppressive therapy. Neurological manifestations following solid organ transplantation pose a diagnostic challenge to medical specialists despite extensive investigation. This review aimed to provide a practical approach to help neurologists and clinicians assess and manage solid organ transplant patients presenting with acute or chronic neurological manifestations.

PMID: 29166466 [PubMed - in process]

Use of organs from hepatitis C virus positive donors for uninfected recipients: a potential cost-effective approach to save lives?

Thu, 11/23/2017 - 13:45

Use of organs from hepatitis C virus positive donors for uninfected recipients: a potential cost-effective approach to save lives?

Transplantation. 2017 Nov 22;:

Authors: Trotter PB, Summers DM, Ushiro-Lumb I, Robb M, Bradley JA, Powell J, Watson CJE, Neuberger J

Abstract
BACKGROUND: Organs from hepatitis C virus (HCV) seropositive (HCVpos) individuals are seldom used for transplantation because of the risk of disease transmission. Because transmitted HCV is now amenable to effective treatment we estimated the potential impact of using HCVpos deceased donor organs for transplantation.
METHODS: The Potential Donor Audit (PDA) of patients (<80years) dying in UK critical care units and the UK Transplant Registry (UKTR) was searched to identify HCVpos potential and proceeding deceased donors. Donor organ quality was assessed using validated donor organ quality indices. Cost analysis was performed by comparing the cumulative cost of direct acting antivirals with haemodialysis and renal transplantation.
RESULTS: Between 2009-2016, 120 patients identified from the PDA were not considered as potential donors because of the presence of HCV. Between 2000-2015, 244 HCVpos potential deceased donors were identified from the UKTR, and 76 (31%) proceeded to donation, resulting in 63 liver, 27 kidney and 2 heart transplants. Recipient and graft survival was not adversely impacted by donor HCVpos status. Most (69%) offered organs were declined because of positive virology although their quality was similar to that of other transplanted organs. The additional costs of treating recipients exposed to HCV by receiving a HCVpos kidney was cost-neutral with dialysis 5 years from transplantation.
CONCLUSIONS: HCVpos donors represent a potential source of organs for HCVneg recipients as many good quality HCVpos donor organs are not currently used for transplantation. This change in practice may increase access to transplantation without having an adverse effect on transplant outcome.

PMID: 29166338 [PubMed - as supplied by publisher]

Merging an Activity Tracker with SystemCHANGE™ to Improve Physical Activity in Older Kidney Transplant Recipients.

Thu, 11/23/2017 - 13:45

Merging an Activity Tracker with SystemCHANGE™ to Improve Physical Activity in Older Kidney Transplant Recipients.

Nephrol Nurs J. 2017 Mar-Apr;44(2):153-157

Authors: O'Brien T, Hathaway D, Russell CL, Moore SM

Abstract
Motivational strategies to increase adherence to a long-term physical activity regimen have been unsuccessful for kidney transplant recipients. We propose a theory-based SystemCHANGE™ + Activity Tracker framework. The SystemCHANGE™ + Activity Tracker approach combines small, individual-driven experiments for increasing physical activity with visual feedback from the wireless activity tracker, which enables clients to study their progress in increasing physical activity. The SystemCHANGE™ + Activity Tracker approach is designed to empower kidney transplant recipients to improve and maintain their physical activity behavior.

PMID: 29165966 [PubMed - in process]

Post-Transfer Predictors of Poor Outcomes in Pediatric Renal Transplant Recipients.

Thu, 11/23/2017 - 13:45

Post-Transfer Predictors of Poor Outcomes in Pediatric Renal Transplant Recipients.

Nephrol Nurs J. 2017 Mar-Apr;44(2):119-157

Authors: Coyne B, Hollen PJ, Yan G, Barcia J, Brayman K

Abstract
The aims of this study were twofold: 1) to describe the post-transfer (defined as from pediatric to adult providers) incidence of predictors (medication nonadherence, acute rejection, and change in kidney function), as well as outcomes (graft loss) for adolescent and young adult kidney transplant recipients during a three-year post-transfer follow-up period; and 2) to identify variables to monitor these predictors, in the form of a clinical profile, so providers can promote early intervention for these medically at-risk adolescents. National data were used to describe predictors and outcomes for 250 youth (16 to 25 years old) three years after transfer of care. These predictors were combined with previous literature to develop a preliminary clinical profile. Using an evidence-based clinical profile with predictors for graft loss by a dedicated healthcare professional as a transition coordinator will assist in identifying those at risk for poor outcomes after transfer.

PMID: 29165963 [PubMed - in process]

Shipping Living Donor Kidneys and Transplant Recipient Outcomes.

Thu, 11/23/2017 - 13:45

Shipping Living Donor Kidneys and Transplant Recipient Outcomes.

Am J Transplant. 2017 Nov 22;:

Authors: Treat E, Chow EKH, Peipert JD, Waterman A, Kwan L, Massie AB, Thomas AG, Bowring MG, Leeser D, Flechner S, Melcher ML, Kapur S, Segev DL, Veale J

Abstract
Kidney paired donation (KPD) is an important tool to facilitate living donor kidney transplantation (LDKT). Concerns remain over prolonged cold ischemia times (CIT) associated with shipping kidneys long distances through KPD. We examined the association between CIT and delayed graft function (DGF), allograft survival, and patient survival for 1,267 shipped and 205 non-shipped/internal KPD LDKTs facilitated by the National Kidney Registry in the United States from 2008-2015, compared to 4,800 unrelated, non-shipped, non-KPD LDKTs. Shipped KPD recipients had a median CIT of 9.3 hours (range = 0.25 to 23.9 hours), compared to 1.0 hour for internal KPD transplants and 0.93 hours for non-KPD LDKTs. Each hour of CIT was associated with a 5% increased odds of DGF (adjusted odds ratio: 1.05, 95% CI: 1.02-1.09, p<0.01). However, there was not a significant association between CIT and all-cause graft failure (aHR: 1.01, 95% CI: 0.98-1.04, p=0.4), death-censored graft failure (aHR: 1.02, 95% CI: 0.98-1.06, p=0.4), or mortality (aHR 1.00, 95% CI: 0.96-1.04, p>0.9). This study of KPD-facilitated LDKTs found no evidence that long CIT is a concern for reduced graft or patient survival. Studies with longer follow-up are needed to refine our understanding of the safety of shipping donor kidneys through KPD. This article is protected by copyright. All rights reserved.

PMID: 29165871 [PubMed - as supplied by publisher]

A controlled study of the effects of ferric carboxymaltose on bone and haematinic biomarkers in chronic kidney disease and pregnancy.

Thu, 11/23/2017 - 13:45

A controlled study of the effects of ferric carboxymaltose on bone and haematinic biomarkers in chronic kidney disease and pregnancy.

Nephrol Dial Transplant. 2017 Nov 17;:

Authors: Huang LL, Lee D, Troster SM, Kent AB, Roberts MA, Macdougall IC, McMahon LP

Abstract
Background: Intravenous (IV) iron can modulate fibroblast growth factor 23 (FGF23) concentrations and cause transient but significant hypophosphataemia. However, it is unknown what other markers might be involved, especially in different patient groups. This study aimed to determine changes in bone and haematinic biomarkers following IV ferric carboxymaltose (FCM) and to identify risk factors for hypophosphataemia in pregnant subjects and those with chronic kidney disease (CKD).
Methods: Changes in bone [serum FGF23, fractional excretion of phosphate urinary fractional excretion of phosphate (FEPi), serum phosphate and serum vitamin D derivatives] and haematinic [plasma hepcidin, serum ferritin and transferrin saturation (TSAT)] biomarkers after 1 g of IV FCM were followed in iron-deficient pregnant and CKD patients and compared with controls (estimated glomerular filtration rate > 60 mL/min/1.73 m2). Data were collected at baseline and up to 42 days after infusion. Risk factors for post-FCM hypophosphataemia were also assessed.
Results: Sixty-five subjects completed the study (control, n = 20; pregnant, n = 20; CKD, n = 25). A uniform but variable increase across groups was seen in intact FGF23 (peak Day 2), whereas c-terminal FGF23 varied markedly. Trough serum phosphate timed with the peak FEPi at Day 7, recovering by Day 21 in the pregnant group and Day 42 in other groups. Independent predictors of a low phosphate nadir included baseline phosphate, FEPi and weight-adjusted FCM dose. All groups showed an early and marked increase in plasma hepcidin (peak Day 2), serum ferritin and TSAT (peak Day 7 for both).
Conclusions: Changes in bone and haematinic biomarkers differ between patient groups following IV FCM. For patients with lower serum phosphate concentrations, limiting the dose and measuring levels 7 days after administration may mitigate clinically significant hypophosphataemia.

PMID: 29165637 [PubMed - as supplied by publisher]

Health literacy and patient outcomes in chronic kidney disease: a systematic review.

Thu, 11/23/2017 - 13:45

Health literacy and patient outcomes in chronic kidney disease: a systematic review.

Nephrol Dial Transplant. 2017 Nov 20;:

Authors: Taylor DM, Fraser S, Dudley C, Oniscu GC, Tomson C, Ravanan R, Roderick P

Abstract
Background: Limited health literacy affects 25% of people with chronic kidney disease (CKD), and may reduce self-management skills resulting in poorer clinical outcomes. By disproportionately affecting people with low socio-economic status and non-white ethnicity, limited health literacy may promote health inequity.
Methods: We performed a systematic review of quantitative studies of health literacy and clinical outcomes among adults with CKD.
Results: A total of 29 studies (13 articles; 16 conference abstracts) were included. One included non-USA patients. Of the 29 studies, 5 were cohort studies and 24 were cross-sectional. In all, 18 300 patients were studied: 4367 non-dialysis CKD; 13 202 dialysis; 390 transplant; 341 unspecified. Median study size was 127 [interquartile range (IQR) 92-238)], but 480 (IQR 260-2392) for cohort studies. Median proportion of non-white participants was 48% (IQR 17-70%). Six health literacy measures were used. Outcomes included patient attributes, care processes, clinical/laboratory parameters and 'hard' clinical outcomes. Limited health literacy was significantly, independently associated with hospitalizations, emergency department use, missed dialysis sessions, cardiovascular events and mortality (in cohort studies). Study quality was high (1 study), moderate (3 studies) and poor (25 studies), limited by sampling methods, variable adjustment for confounders and reduced methodological detail given in conference abstracts.
Conclusions: There is limited robust evidence of the causal effects of health literacy on patient outcomes in CKD. Available evidence suggests associations with adverse clinical events, increased healthcare use and mortality. Prospective studies are required to determine the causal effects of health literacy on outcomes in CKD patients, and examine the relationships between socio-economic status, comorbidity, health literacy and CKD outcomes. Intervention development and evaluation will determine whether health literacy is a modifiable determinant of poor outcomes in CKD.

PMID: 29165627 [PubMed - as supplied by publisher]

Comparative effectiveness of allopurinol, febuxostat and benzbromarone on renal function in chronic kidney disease patients with hyperuricemia: a 13-year inception cohort study.

Thu, 11/23/2017 - 13:45

Comparative effectiveness of allopurinol, febuxostat and benzbromarone on renal function in chronic kidney disease patients with hyperuricemia: a 13-year inception cohort study.

Nephrol Dial Transplant. 2017 Nov 17;:

Authors: Chou HW, Chiu HT, Tsai CW, Ting IW, Yeh HC, Huang HC, Kuo CC, CMUH Kidney Research Group

Abstract
Background: Direct comparisons of the effectiveness of allopurinol with that of other urate-lowering agents in chronic kidney disease (CKD) populations, as well as guideline recommendations for clinical practice, are lacking.
Methods: We constructed a pharmacoepidemiology cohort study by including patients from Taiwan's long-term integrated CKD care program to compare the effectiveness among allopurinol, febuxostat and benzbromarone in reducing the risk of progression to dialysis. A total of 874 patients with hyperuricemia who were newly treated with allopurinol, febuxostat or benzbromarone were included. The primary and secondary outcomes were incident end-stage renal disease (ESRD) and the serum uric acid (SUA) changes from baseline, respectively. The results were analyzed using multiple Cox proportional models adjusted for multinomial propensity scores. For subgroup analyses, we further stratified patients according to whether their latest SUA level reached the therapeutic target.
Results: Compared with allopurinol, benzbromarone therapy was associated with a reduced risk of progression to dialysis, the adjusted hazard ratio was 0.50 (95% confidence interval, 0.25-0.99). Patients who received allopurinol or febuxostat exhibited a comparable risk of ESRD [adjusted hazard ratio, 0.99 (0.40-2.44)]. Febuxostat was significantly more potent than allopurinol or benzbromarone in lowering SUA levels in the fully adjusted model. Among patients who reached the therapeutic target, those with febuxostat and benzbromarone initiation had a significantly lower risk of ESRD.
Conclusions: In conclusion, compared with conventional allopurinol, febuxostat and benzbromarone may be more effective in reducing the risk of progression to dialysis and in lowering SUA levels in CKD populations.

PMID: 29165620 [PubMed - as supplied by publisher]

Deletion of connective tissue growth factor ameliorates peritoneal fibrosis by inhibiting angiogenesis and inflammation.

Thu, 11/23/2017 - 13:45

Deletion of connective tissue growth factor ameliorates peritoneal fibrosis by inhibiting angiogenesis and inflammation.

Nephrol Dial Transplant. 2017 Nov 17;:

Authors: Toda N, Mori K, Kasahara M, Koga K, Ishii A, Mori KP, Osaki K, Mukoyama M, Yanagita M, Yokoi H

Abstract
Background: Connective tissue growth factor (CTGF/CCN2) regulates the signalling of other growth factors and promotes fibrosis. CTGF is increased in mice and humans with peritoneal fibrosis. Inhibition of CTGF has not been examined as a potential therapeutic target for peritoneal fibrosis because systemic CTGF knockout mice die at the perinatal stage.
Methods: To study the role of CTGF in peritoneal fibrosis of adult mice, we generated CTGF conditional knockout (cKO) mice by crossing CTGF floxed mice with RosaCreERT2 mice. We administered tamoxifen to Rosa-CTGF cKO mice to delete the CTGF gene throughout the body. We induced peritoneal fibrosis by intraperitoneal injection of chlorhexidine gluconate (CG) in wild-type and Rosa-CTGF cKO mice.
Results: Induction of peritoneal fibrosis in wild-type mice increased CTGF expression and produced severe thickening of the peritoneum. In contrast, CG-treated Rosa-CTGF cKO mice exhibited reduced thickening of the peritoneum. Peritoneal equilibration test revealed that the excessive peritoneal small-solute transport in CG-treated wild-type mice was normalized by CTGF deletion. CG-treated Rosa-CTGF cKO mice exhibited a reduced number of αSMA-, Ki67-, CD31- and MAC-2-positive cells in the peritoneum. Analyses of peritoneal mRNA showed that CG-treated Rosa-CTGF cKO mice exhibited reduced expression of Cd68, Acta2 (αSMA), Pecam1 (CD31) and Vegfa.
Conclusions: These results indicate that a deficiency of CTGF can reduce peritoneal thickening and help to maintain peritoneal function by reducing angiogenesis and inflammation in peritoneal fibrosis. These results suggest that CTGF plays an important role in the progression of peritoneal fibrosis.

PMID: 29165602 [PubMed - as supplied by publisher]

Con: The role of diet for people with advanced Stage 5 CKD.

Thu, 11/23/2017 - 13:45

Con: The role of diet for people with advanced Stage 5 CKD.

Nephrol Dial Transplant. 2017 Nov 17;:

Authors: Woodrow G

Abstract
Restriction of dietary protein intake has been used in the management of chronic kidney disease (CKD) for many decades, yet remains controversial, with marked variations in its application in clinical practice. There is extensive literature on the subject, with some expert opinion advocating the use of protein restriction based on the balance of the available evidence. The largest randomized trial of low-protein diets is the Modification of Diet in Renal Disease study. Despite multiple secondary analyses, the essential intention-to-treat analysis failed to demonstrate a benefit in the primary outcome of rate of decline of glomerular filtration rate. There are criticisms of many published studies and meta-analyses, including the likelihood of publication bias and unsuitable biochemical endpoints that may be affected by dietary restriction in the absence of effects on kidney function, leading to false positive findings. It is also uncertain whether any benefits observed in these often older studies would be derived in patients undergoing modern standards of CKD management, including blood pressure control and renin-angiotensin blockade. Thus it is unclear whether, even in the strictly controlled environment of a clinical study, low-protein diets significantly slow CKD progression. Important questions exist regarding the applicability of these diets in routine clinical practice. Even in carefully selected study populations with intensive dietetic input, adherence to low-protein diets is poor. It is likely that only a small minority of CKD patients in routine practice could adhere to these diets, and although risks of malnutrition arising from protein restriction are uncertain, they will be greater in less supervised care outside of studies.

PMID: 29165595 [PubMed - as supplied by publisher]

Factors Associated with the Need for, and the Impact of, Extracorporeal Membrane Oxygenation in Children with Congenital Heart Disease during Admissions for Cardiac Surgery.

Thu, 11/23/2017 - 13:45

Factors Associated with the Need for, and the Impact of, Extracorporeal Membrane Oxygenation in Children with Congenital Heart Disease during Admissions for Cardiac Surgery.

Children (Basel). 2017 Nov 22;4(11):

Authors: Aiello S, Loomba RS

Abstract
INTRODUCTION: This study aimed to determine factors associated with the need for extracorporeal membrane oxygenation (ECMO) in children with congenital heart disease (CHD) during admission for cardiac surgery (CS). A secondary aim was to determine how ECMO impacted length, cost, and mortality of the admission.
METHODS: Data from the Kids' Inpatient Database (KIDS) were utilized. Admissions with CHD under 18 years of age with cardiac surgery were included. Need for ECMO in these admissions was then identified. Univariate analysis was conducted to compare characteristics between admissions with and without ECMO. Regression analyses were conducted to determine what factors were independently associated with ECMO and whether ECMO independently impacted admission characteristics.
RESULTS: A total of 46,176 admissions with CHD and CS were included in the final analysis. Of these, 798 (1.7%) required ECMO. Median age of ECMO admissions was 0.5 years. The following were associated with ECMO: decreased age, heart failure, acute kidney injury, arrhythmia, double outlet right ventricle, atrioventricular septal defect, transposition, Ebstein anomaly, hypoplastic left heart syndrome, common arterial trunk, tetralogy of Fallot, coronary anomaly, valvuloplasty, repair of total anomalous pulmonary venous connection, arterial switch, RV to PA conduit placement, and heart transplant (p < 0.01). ECMO independently increased length of stay by 17.8 days, cost of stay by approximately $415,917, and inpatient mortality 22-fold.
CONCLUSION: Only a small proportion of CHD patients undergoing CS require ECMO, although these patients require increased resource utilization and have high mortality. Specific cardiac lesions, cardiac surgeries, and comorbidities are associated with increased need for ECMO.

PMID: 29165381 [PubMed]

Bortezomib in Kidney Transplant: Current use and Perspectives.

Thu, 11/23/2017 - 13:45

Bortezomib in Kidney Transplant: Current use and Perspectives.

Curr Drug Metab. 2017 Nov 20;:

Authors: Rangel EB, Requião-Moura LR, de Sandes-Freitas TV, Marcelo-Gomes G

Abstract
BACKGROUND: Despite major advances in transplant medicine, antibody-mediated rejection (AMR) continues to have severe clinical implications and adversely affect graft survival. Therefore, the search for alternative drugs to treat AMR is widely pursued. The first-in-class proteasome inhibitor bortezomib (BZ) is a selective inhibitor of the 26S proteasome, which was initially approved for the treatment of malignant plasma cell disorders.
METHODS: This review encompasses how our understanding of inhibiting proteasome pathway created the basis of BZ research and important milestones accomplished in AMR treatment in the transplant setting. It further discusses at length the results of clinical studies, the tolerability profile, drug-drug interactions and the perspectives of BZ use in desensitization protocols.
RESULTS: Proteasome inhibition can downregulate NF-ĸB activity; decrease cell proliferation/differentiation; induce apoptosis via cell cycle arrest, endoplasmic reticulum stress and caspase induction due the accumulation of unfolded or misfolded proteins; and downregulate antigen presentation, cell-cell interaction, and cell migration. Proteasome inhibition is more evident in cells with high rate of protein synthesis and secretion, like plasma cells. These cells play a critical role in the production of antibodies during AMR.
CONCLUSIONS: There is accumulating evidence that the proteasome inhibitor BZ may substantially affect the function and integrity of alloantibody-secreting plasma cells in AMR after organ solid transplant, as well as the activation, proliferation and differentiation of T- and B-lymphocytes. Recent clinical studies have provided evidence that BZ has the capability to downregulate circulating antibodies and treat AMR episodes. Additional randomized-controlled studies are required to assess the impact of BZ during short and long follow-ups.

PMID: 29165070 [PubMed - as supplied by publisher]

Prevalence of left ventricular systolic dysfunction in pre-dialysis and dialysis patients with preserved left ventricular ejection fraction.

Thu, 11/23/2017 - 13:45

Prevalence of left ventricular systolic dysfunction in pre-dialysis and dialysis patients with preserved left ventricular ejection fraction.

Eur J Heart Fail. 2017 Nov 21;:

Authors: Hensen LCR, Goossens K, Delgado V, Abou R, Rotmans JI, Jukema JW, Bax JJ

Abstract
AIMS: Patients with chronic kidney disease (CKD) have an excess of cardiovascular morbidity and mortality, with heart failure (HF) being particularly frequent. Reduced left ventricular ejection fraction (LVEF) defines left ventricular (LV) systolic dysfunction and is associated with poor prognosis. However, CKD patients may have HF symptoms with preserved LVEF. In this subgroup of patients, two-dimensional speckle tracking echocardiography can detect LV systolic dysfunction by analysing LV myocardial deformation. The present study evaluated the prevalence of impaired LV global longitudinal strain (GLS) in CKD patients with preserved LVEF and its prognostic consequences.
METHODS AND RESULTS: Overall, 200 pre-dialysis and dialysis patients (65% men, mean age 60 ± 14 years) with CKD stage 3b-5 and preserved LVEF (≥50%) were evaluated. Left ventricular systolic dysfunction despite preserved LVEF was defined by LV GLS ≤15.2% (cut-off value derived from two standard deviations below the mean value of individuals without structural heart disease). Impaired LV GLS (≤15.2%) despite preserved LVEF was observed in 32% of patients. During a median follow-up of 33 months (interquartile range 17-62 months), 47% of patients underwent renal transplantation, 9% were admitted with HF, and 28% died. Patients with LV GLS ≤15.2% showed significantly worse cumulative event-free survival rates of the combined endpoint of HF hospitalization and all-cause mortality compared to patients with LV GLS >15.2% (log-rank P = 0.018).
CONCLUSION: The prevalence of impaired LV GLS despite preserved LVEF in pre-dialysis and dialysis patients is relatively high. Patients with preserved LVEF but impaired LV GLS have an increased risk of HF hospitalization and all-cause mortality.

PMID: 29164753 [PubMed - as supplied by publisher]

Expression of Mitochondrial-Encoded Genes in Blood Differentiate Acute Renal Allograft Rejection.

Thu, 11/23/2017 - 13:45

Expression of Mitochondrial-Encoded Genes in Blood Differentiate Acute Renal Allograft Rejection.

Front Med (Lausanne). 2017;4:185

Authors: Roedder S, Sigdel T, Hsieh SC, Cheeseman J, Metes D, Macedo C, Reed EF, Gritsch HA, Zeevi A, Shapiro R, Kirk AD, Sarwal MM

Abstract
Despite potent immunosuppression, clinical and biopsy confirmed acute renal allograft rejection (AR) still occurs in 10-15% of recipients, ~30% of patients demonstrate subclinical rejection on biopsy, and ~50% of them can show molecular inflammation, all which increase the risk of chronic dysfunction and worsened allograft outcomes. Mitochondria represent intracellular endogenous triggers of inflammation, which can regulate immune cell differentiation, and expansion and cause antigen-independent graft injury, potentially enhancing the development of acute rejection. In the present study, we investigated the role of mitochondrial DNA encoded gene expression in biopsy matched peripheral blood (PB) samples from kidney transplant recipients. Quantitative PCR was performed in 155 PB samples from 115 unique pediatric (<21 years) and adult (>21 years) renal allograft recipients at the point of AR (n = 61) and absence of rejection (n = 94) for the expression of 11 mitochondrial DNA encoded genes. We observed increased expression of all genes in adult recipients compared to pediatric recipients; separate analyses in both cohorts demonstrated increased expression during rejection, which also differentiated borderline rejection and showed an increasing pattern in serially collected samples (0-3 months prior to and post rejection). Our results provide new insights on the role of mitochondria during rejection and potentially indicate mitochondria as targets for novel immunosuppression.

PMID: 29164120 [PubMed]

Pages