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Decision aids to increase living donor kidney transplantation.

Tue, 10/17/2017 - 12:45
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Decision aids to increase living donor kidney transplantation.

Curr Transplant Rep. 2017 Mar;4(1):1-12

Authors: Gander JC, Gordon EJ, Patzer RE

Abstract
PURPOSE OF REVIEW: For the more than 636,000 adults with end-stage renal disease (ESRD) in the U.S., kidney transplantation is the preferred treatment compared to dialysis. Living donor kidney transplantation (LDKT) comprised 31% of kidney transplantations in 2015, an 8% decrease since 2004. We aimed to summarize the current literature on decision aids that could be used to improve LDKT rates.
RECENT FINDINGS: Decision aids are evidence-based tools designed to help patients and their families make difficult treatment decisions. LDKT decision aids can help ESRD patients, patients' family and friends, and healthcare providers engage in treatment decisions and thereby overcome multifactorial LDKT barriers.
SUMMARY: We identified 12 LDKT decision aids designed to provide information about LDKT, and/or to help ESRD patients identify potential living donors, and/or to help healthcare providers make decisions about treatment for ESRD or living donation. Of these, 4 were shown to be effective in increasing LDKT, donor inquiries, LDKT knowledge, and willingness to discuss LDKT. Although each LDKT decision aid has limitations, adherence to decision aid development guidelines may improve decision aid utilization and access to LDKT.

PMID: 29034143 [PubMed]

Persistent Regional and Racial Disparities in Non-Directed Living Kidney Donation.

Tue, 10/17/2017 - 12:45
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Persistent Regional and Racial Disparities in Non-Directed Living Kidney Donation.

Clin Transplant. 2017 Oct 15;:

Authors: Kumar K, Holscher CM, Luo X, Garonzik Wang J, Anjum S, King EA, Massie AB, Tonascia JM, Purnell TS, Segev DL

Abstract
Non-directed living donors (NDLD) are an important and growing source of kidneys to help reduce the organ shortage. In its infancy, NDLD transplantation was clustered at a few transplant centers and rarely benefited African American recipients. However, NDLDs have increased 9.4-fold since 2000, and now are often used to initiate kidney paired donation (KPD) chains. Therefore, we hypothesized that the initial geographic clustering and racial disparities may have improved. We used SRTR data to compare NDLDs and their recipients between 2008-2015 and 2000-2007. We found that NDLD increased an average of 12% per year, from 20 in 2000 to 188 in 2015 (IRR: 1.12, 95% CI: 1.11-1.13, p<0.001). In 2000-2007, 18.3% of recipients of NDLD kidneys were African American; this decreased in 2008-2015 to 15.7%. NDLD transplants initially became more evenly distributed across centers (Gini 0.91 in 2000 to Gini 0.69 in 2011), but then became more clustered at fewer transplant centers (Gini 0.75 in 2015). Despite the increased number of NDLDs, racial disparities have worsened and the center-level distribution of NDLD transplants has narrowed in recent years. This article is protected by copyright. All rights reserved.

PMID: 29032601 [PubMed - as supplied by publisher]

[Outcome of living kidney donors for transplantation].

Tue, 10/17/2017 - 12:45
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[Outcome of living kidney donors for transplantation].

Nephrol Ther. 2017 Oct 11;:

Authors: Lanot A, Bouvier N, Chatelet V, Lecouf A, Tillou X, Ligny BH

Abstract
Nowadays, several treatments exist to treat terminal chronic renal failure. Best results for the recipients are obtained with kidney transplantation concerning mortality and quality of life. Transplantation is also the cheaper option for society. Living kidney donation raises the issue of the becoming of the donor, an absolutely healthy subject who gets to a surgical procedure. The becoming of living kidney donors has been compared with the one of controls subjects in several studies. The evaluations focused on the complications of nephrectomy in the short and long-term: kidney failure, hypertension, proteinuria, possibility of pregnancy, quality of life, and mortality. The first results did not show any risk linked to kidney donation, compared to general population. However, since 2013, kidney donors were found at higher risk for kidney failure and even for mortality, compared with controls selected like donor candidates. The risk of kidney donation is nevertheless acceptable and minimal, on the condition of rigorous selection of candidates and regular follow-up.

PMID: 29031488 [PubMed - as supplied by publisher]

Regulation of Potassium Homeostasis in CKD.

Tue, 10/17/2017 - 12:45
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Regulation of Potassium Homeostasis in CKD.

Adv Chronic Kidney Dis. 2017 Sep;24(5):305-314

Authors: DuBose TD

Abstract
Disturbances of potassium homeostasis can cause either hyperkalemia or hypokalemia and result in serious consequences. Although the consequences of acute and chronic hyperkalemia and treatment of these conditions in CKD have been widely appreciated by nephrologists, more recent information has focused attention on the consequences of chronic hypokalemia. Several recent studies have documented a "U-shaped" relationship between the serum [K(+)] and higher mortality in several clinical studies. The causes of dyskalemias are placed into the unique perspective of patients with CKD and its evolution with progression of CKD to later stages and focuses on the pathophysiology of these disorders. Emphasis is placed on the high mortality associated with both low and high levels of potassium that are unique to patients with CKD. Recent information regarding sensors of changes in the serum [K(+)] that evoke changes in NaCl transport in the DCT1 and subsequent efferent responses by aldosterone-responsive cells in the DCT2 and cortical collecting duct to adjust K(+) secretion by the renal outer medullary potassium channel is reviewed in detail. These sensing mechanisms can be interrupted by drugs, such as the calcineurin inhibitors to cause both hypertension and hyperkalemia in kidney transplant patients, or can be inherited as familial hypertensive hyperkalemia. The role and pathogenesis of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in causing hyperkalemia is a common stop point for cessation of these important drugs, but, and newer agents to lower the serum [K(+)] that might allow continuation of angiotensin-converting enzyme or angiotensin receptor blocker therapy are examined. Finally, the importance of emphasis on potassium-containing foods, such as fresh produce and fruit in the diets of patients with early-stage CKD, is examined as an under-appreciated area requiring more emphasis by nephrologists caring for these patients and may be unique to food-challenged patients with CKD.

PMID: 29031357 [PubMed - in process]

Transplant Tourism Following the Declaration of Istanbul: Poor Outcomes and Nephrologist Dilemma.

Tue, 10/17/2017 - 12:45
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Transplant Tourism Following the Declaration of Istanbul: Poor Outcomes and Nephrologist Dilemma.

Nephrology (Carlton). 2017 Oct 14;:

Authors: AlBugami MM, AlOtaibe FE, AlAbadi AM, Hamawi K, Bel'eed-Akkari K

Abstract
BACKGROUND: Transplant tourism (TT) violates many international laws and documents. Despite all efforts, TT seems to be increasing. The aim of this study is to review outcomes of recipients of commercially transplanted kidneys since the Declaration of Istanbul.
METHODS: All recipients of kidney transplantation done abroad and then returned to our center, from September 2008 to December 2015, were included (tourists). Demographics and outcomes were collected from patients' charts. All data were compared with all recipients of living donor kidney transplants done at our center (locals).
RESULTS: A total of 86 tourists and 365 locals were included. Both groups had similar age and gender. Re-grafting rates were the same, however, more preemptive transplants were done abroad. TT was increasing over time. Tourists presented early after TT, median 17.5 (IQR 7 - 30) days, and 47.7% were encountered initially in the emergency department. 1-year graft and patient survivals were significantly lower among tourists compared with locals (87.2% vs. 98.0%, P<0.001 and 90.7% vs. 98.0%, P<0.001, respectively). Tourists had a significantly higher rate of acute cellular rejection (19.8% vs. 7.1%, P<0.001), and they sustained significantly higher rates of serious viral, bacterial and fungal infections compared with the locals.
CONCLUSION: TT seems to be increasing despite international condemnation and efforts to stop it. Outcomes are significantly worse when compared to local transplant recipients. Concerted effort is needed to better inform patients about the ethical and physical harms related to TT, and to point them towards ethically sound and medically safer alternatives.

PMID: 29030994 [PubMed - as supplied by publisher]

Adenine-induced chronic kidney disease in rats.

Tue, 10/17/2017 - 12:45
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Adenine-induced chronic kidney disease in rats.

Nephrology (Carlton). 2017 Oct 14;:

Authors: Diwan V, Brown L, Gobe GC

Abstract
Many animal models have been developed to study the causes and treatments of chronic kidney disease (CKD) in humans, an insidious disease resulting from kidney injury and characterised by persistent functional decline for more than 3 months, with or without evidence of structural deficit. The eventual outcome of CKD may be end-stage kidney disease (ESKD), where patients need dialysis or transplantation to survive. Cardiovascular disease is accelerated in patients with CKD and contributes to increased mortality, with the relationship between CKD and cardiovascular disease being bi-directional. Most animal models do not mimic the complexity of the human disease as many do not develop CKD-associated cardiovascular disease. The adenine diet model of CKD in rodents is an exception. The original adenine diet model produced rapid-onset kidney disease with extensive tubulointerstitial fibrosis, tubular atrophy, crystal formation and marked vessel calcification. Since then, lower adenine intake in rats has been found to induce slowly progressive kidney damage and cardiovascular disease. These chronic adenine diet models allow the characterisation of relatively stable kidney and cardiovascular disease, similar to CKD in humans. In addition, interventions for reversal can be tested. Here the key features of the adenine diet model of CKD are noted, along with some limitations of other available models. In summary, the data presented here support use of chronic low-dose adenine diet in rats as an easy and effective model for understanding human CKD, especially the links with cardiovascular disease, and developing potential therapeutic interventions.

PMID: 29030945 [PubMed - as supplied by publisher]

Genetics of Acute Rejection after Kidney Transplantation.

Tue, 10/17/2017 - 12:45
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Genetics of Acute Rejection after Kidney Transplantation.

Transpl Int. 2017 Oct 14;:

Authors: Dorr CR, Oetting WS, Jacobson PA, Israni AK

Abstract
Treatment of acute rejection (AR) following kidney transplantation has improved in recent years, but there are still limitations to successful outcomes. This review article covers literature in regards to recipient and donor genetics of AR kidney and secondarily of liver allografts. Many candidate gene and some genome wide association studies (GWAS) have been conducted for AR in kidney transplantation. Genetic associations with AR in kidney and liver are mostly weak and in most cases the associations have not been reproducible. A limitation in the study of AR is the lack of sufficiently large populations, which are often not stratified, to study the AR phenotype which in this era occurs in <10% of transplants. Furthermore, the AR phenotype has been difficult to define and the definitions of classifications have evolved over time. Literature related to the pharmacogenomics of TAC is robust and has been validated in many studies. Associations between gene expression and AR are emerging as markers of outcomes and AR classification. In the future, combinations of pre-transplant genotype for AR risk prediction, genotype-based immune suppressant dosing, pharmacogenomic markers to select AR maintenance or treatment and expression markers from biopsies may provide valuable clinical tools for guiding treatment. This article is protected by copyright. All rights reserved.

PMID: 29030886 [PubMed - as supplied by publisher]

[10 years of external quality assurance in dialysis in Germany: Results and future prospects].

Tue, 10/17/2017 - 12:45
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[10 years of external quality assurance in dialysis in Germany: Results and future prospects].

Z Evid Fortbild Qual Gesundhwes. 2017 Oct 10;:

Authors: Büchtemann D, Meinhold S, Follert P

Abstract
BACKGROUND: In 2006, the Federal Joint Committee introduced a quality assurance programme for ambulatory dialysis treatment in Germany. Regarding the impact of chronic dialysis treatment on the quality of life of patients and on health care costs, quality assurance in dialysis is considered highly relevant. The directive on Quality Assurance in Dialysis (QSD-RL) established an external quality assurance programme based on the assessment of certain quality parameters combined with an internal quality management system based on benchmarking parameters in all dialysis practices and centres. Data on quality parameters are collected and analysed quarterly. Regional associations of statutory health insurance physicians take responsibility for quality improvement measures and sanctions. This article aims to provide an overview of the development of quality parameters from 2008 to 2015.
METHODS: We analysed the summarised annual quality reports published on the website of the Federal Joint Committee between 2009 and 2016. We present results on the so-called core quality parameters duration and frequency of dialysis sessions (both for haemodialysis patients), wKt/V for peritoneal dialysis patients, and percentage of haemodialysis patients with central venous catheters which has only been measured since 2014.
RESULTS AND CONCLUSIONS: In 2015, 92,000 patients received outpatient dialysis. Between 2008 and 2015, the results for the core quality parameters duration and frequency of haemodialysis improved while the results for wKt/V seemingly show an unfavourable trend. The percentage of patients with central venous catheters appears to be quite high, and thus indicates that there is potential for quality improvement.
FUTURE PERSPECTIVES: For the future, the Federal Joint Committee has resolved to merge the quality assurance programmes in dialysis and in kidney transplantation into a newly designed programme that has the potential to follow patients through all stages and kinds of renal replacement therapy and to focus on further aspects of treatment quality.

PMID: 29029967 [PubMed - as supplied by publisher]

Comparative efficacy and safety of antibody induction therapy for the treatment of kidney: a network meta-analysis.

Tue, 10/17/2017 - 12:45
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Comparative efficacy and safety of antibody induction therapy for the treatment of kidney: a network meta-analysis.

Oncotarget. 2017 Sep 12;8(39):66426-66437

Authors: Shao M, Tian T, Zhu X, Ming Y, Iwakiri Y, Ye S, Ye Q

Abstract
To evaluate the efficacy and safety of antibody induction therapies in kidney transplantation. Systematic literature searches were undertaken using MEDLINE, Embase, and Cochrane Library database from 1980 to 2016. Randomized controlled trials (RCTs) comparing three antibody induction therapies (alemtuzumab, interleukin-2 receptor antibodies and antithymocyte globulin) between each other were identified. Bayesian network meta-analysis was used to combine both the direct and indirect evidence on treatment efficacy and its safety. Antibody induction therapy studies, comprising of 18 RCTs (3444 kidney transplant recipients), were included. Overall, alemtuzumab treatment was superior to the ATG group (OR: 0.49, 95% CI: 0.32 to 0.71) and IL-2RAs group (OR: 0.36, 95% CI: 0.25 to 0.52) for reducing the 1-year acute rejection in kidney transplant recipients. Although alemtuzumab treatment was nearly same with ATG group and IL-2RAs group in improving patient survival and renal function, it can reduce the adverse effects of cytomegalovirus infection more efficiently than ATG group (OR: 0.59, 95% CI: 0.32 to 0.95) and IL-2RAs group (OR: 1.08, 95% CI: 0.61 to 1.73). Alemtuzumab was not associated with increased other adverse effects. Alemtuzumab treatment is safe and effective for kidney transplant recipients. No serious adverse effects were observed in trials or in general populations.

PMID: 29029524 [PubMed]

Therapeutic potential of tonsil-derived mesenchymal stem cells in dextran sulfate sodium-induced experimental murine colitis.

Tue, 10/17/2017 - 12:45
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Therapeutic potential of tonsil-derived mesenchymal stem cells in dextran sulfate sodium-induced experimental murine colitis.

PLoS One. 2017;12(8):e0183141

Authors: Yu Y, Song EM, Lee KE, Joo YH, Kim SE, Moon CM, Kim HY, Jung SA, Jo I

Abstract
The therapeutic potential of tonsil-derived mesenchymal stem cells (TMSC) prepared from human tonsillar tissue has been studied in animal models for several diseases such as hepatic injury, hypoparathyroidism, diabetes and muscle dystrophy. In this study, we examined the therapeutic effects of TMSC in a dextran sulfate sodium (DSS)-induced colitis model. TMSC were injected in DSS-induced colitis mice via intraperitoneal injection twice (TMSC[x2]) or four times (TMSC[x4]). Control mice were injected with either phosphate-buffered saline or human embryonic kidney 293 cells. Body weight, stool condition and disease activity index (DAI) were examined daily. Colon length, histologic grading, and mRNA expression of pro-inflammatory cytokines, interleukin 1β (IL-1β), IL-6, IL-17 and tumor necrosis factor α, and anti-inflammatory cytokines, IL-10, IL-11 and IL-13, were also measured. Our results showed a significant improvement in survival rates and body weight gain in colitis mice injected with TMSC[x2] or TMSC[x4]. Injection with TMSC also significantly decreased DAI scores throughout the experimental period; at the end of experiment, almost complete reversal of DAI scores to normal was found in colitis mice treated with TMSC[x4]. Colon length was also significantly recovered in colitis mice treated with TMSC[x4]. However, histopathological alterations induced by DSS treatment were not apparently improved by injection with TMSC. Finally, treatment with TMSC[x4] significantly reversed the mRNA levels of IL-1β and IL-6, although expression of all pro-inflammatory cytokines tested was induced in colitis mice. Under our experimental conditions, however, no apparent alterations in the mRNA levels of all the anti-inflammatory cytokines tested were found. In conclusion, our findings demonstrate that multiple injections with TMSC produced a therapeutic effect in a mouse model of DSS-induced colitis.

PMID: 28854223 [PubMed - indexed for MEDLINE]

Prevention of lupus nephritis development in NZB/NZW mice by selective blockade of CD28.

Tue, 10/17/2017 - 12:45
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Prevention of lupus nephritis development in NZB/NZW mice by selective blockade of CD28.

Eur J Immunol. 2017 Aug;47(8):1368-1376

Authors: Laurent L, Le Fur A, Bloas RL, Néel M, Mary C, Moreau A, Poirier N, Vanhove B, Fakhouri F

Abstract
Systemic lupus erythematosus (SLE) is a chronic systemic inflammatory disease. Autoantibodies (autoAbs) against double-stranded DNA (ds DNA), the hallmark of lupus, are produced and maintained by the interaction between auto-reactive B cells and CD4(+) T cells. This interplay is controlled by the CD28/CD80-86/CTLA-4 axis. Here we investigated whether selective blockade of CD28-CD80/86 co-stimulatory interactions abrogates lupus nephritis development in a murine model of SLE. To this aim, NZB/NZW F1 mice were treated for 3 months, either with an anti-CD28 Fab' fragment or a control Fab'-IgG. The effect of CD28 blockade on lupus nephritis onset, survival, production of anti-ds DNA antibodies and costimulatory molecules was evaluated. CD28 blockade prevented the development of lupus nephritis and prolonged survival during the 3-month treatment and 12 weeks after. Furthermore, the production of anti-ds DNA autoAbs was decreased. Lastly, the protective effect of CD28 blockade was associated with increased intrarenal expression of the immunoregulatory molecule, Indoleamine 2, 3-dioxygenase, of the co-inhibitory receptor programmed cell-Death - 1 (PD-1) and of its ligand programmed death ligand - 1 (PDL-1).In conclusion, CD28 blockade prevented the development of lupus nephritis in NZB/NZW F1 mice. This immunomodulatory strategy is a promising candidate for SLE therapy in humans.

PMID: 28631301 [PubMed - indexed for MEDLINE]

CMV drives the expansion of highly functional memory T cells expressing NK-cell receptors in renal transplant recipients.

Tue, 10/17/2017 - 12:45
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CMV drives the expansion of highly functional memory T cells expressing NK-cell receptors in renal transplant recipients.

Eur J Immunol. 2017 Aug;47(8):1324-1334

Authors: Makwana N, Foley B, Fernandez S, Lee S, Irish A, Pircher H, Price P

Abstract
Cytomegalovirus (CMV) is a common opportunistic infection encountered in renal transplant recipients (RTRs) and may be reactivated without symptoms at any time post-transplant. We describe how active and latent CMV affect T-cell subsets in RTRs who are stable on maintenance therapy. T-cell responses to CMV were assessed in RTRs (n = 54) >2 years post-transplant, and healthy controls (n = 38). Seven RTRs had CMV DNA detectable in plasma. CMV antibody and DNA aligned with increased proportions of CD8(+) T cells and reduced CD4/CD8 ratios. This paralleled an expansion of effector memory T-cell (TEM ), terminally differentiated T-cell (TEMRA ) and CD57(+) TEMRA cell populations. Expression of NK-cell receptors, LIR-1 and KLRG1 on CD4(+) and CD8(+) CD57(+) TEM and TEMRA cells correlated with elevated interferon-γ and cytotoxic responses to anti-CD3 and increased cytotoxic responses to CMV phosphoprotein (pp) 65 in RTRs who carried CMV DNA. CD8(+) T cells from all CMV seropositive RTRs responded efficiently to CMV immediate early (IE) -1 peptides. The data show that latent and active CMV infection can alter T-cell subsets in RTRs many years after transplantation, and up-regulate T-cell expression of NK-cell receptors. This may enhance effector responses of CD4(+) and CD8(+) T cells against CMV.

PMID: 28586095 [PubMed - indexed for MEDLINE]

Number of patients on dialysis increases 30.

Tue, 10/17/2017 - 12:45
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Number of patients on dialysis increases 30.

CMAJ. 2017 02 21;189(7):E292

Authors: Collier R

PMID: 28246250 [PubMed - indexed for MEDLINE]

Haemagglutinin and neuraminidase sequencing delineate nosocomial influenza outbreaks with accuracy equivalent to whole genome sequencing.

Tue, 10/17/2017 - 12:45
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Haemagglutinin and neuraminidase sequencing delineate nosocomial influenza outbreaks with accuracy equivalent to whole genome sequencing.

J Infect. 2017 Apr;74(4):377-384

Authors: Houghton R, Ellis J, Galiano M, Clark TW, Wyllie S

Abstract
OBJECTIVES: We describe haemagglutinin (HA) and neuraminidase (NA) sequencing in an apparent cross-site influenza A(H1N1) outbreak in renal transplant and haemodialysis patients, confirmed with whole genome sequencing (WGS).
METHODS: Isolates were sequenced from influenza positive individuals. Phylogenetic trees were constructed using HA and NA sequencing and subsequently WGS. Sequence data was analysed to determine genetic relatedness of viruses obtained from inpatient and outpatient cohorts and compared with epidemiological outbreak information.
RESULTS: There were 6 patient cases of influenza in the inpatient renal ward cohort (associated with 3 deaths) and 9 patient cases in the outpatient haemodialysis unit cohort (no deaths). WGS confirmed clustered transmission of two genetically different influenza A(H1N1)pdm09 strains initially identified by analysis of HA and NA genes. WGS took longer, and in this case was not required to determine whether or not the two seemingly linked outbreaks were related.
CONCLUSION: Rapid sequencing of HA and NA genes may be sufficient to aid early influenza outbreak investigation making it appealing for future outbreak investigation. However, as next generation sequencing becomes cheaper and more widely available and bioinformatics software is now freely accessible next generation whole genome analysis may increasingly become a valuable tool for real-time Influenza outbreak investigation.

PMID: 28104386 [PubMed - indexed for MEDLINE]

[Not Available].

Tue, 10/17/2017 - 12:45
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[Not Available].

Nutr Hosp. 2016 Jul 19;33(4):394

Authors: Fernández Castillo R, Cañadas de la Fuente GR, Cañadas de la Fuente GA, De la Fuente Solana EI, Esteban de la Rosa RJ, Bravo Soto J

Abstract
Introducción: la obesidad y el sobrepeso presentan efectos adversos sobre la salud, lo que contribuye a la aparición de enfermedades metabólicas y cardiovasculares que ponen en peligro la integridad del injerto.Objetivo: investigar la influencia del IMC pretrasplante renal sobre el funcionamiento del injerto renal al año de trasplante mediante el estudio de cuatro métodos distintos de medir la filtración glomerular.Material y métodos: en este trabajo se ha seguido a 1.336 pacientes de ambos sexos trasplantados renales; se les realizaron mediciones pretrasplante y postrasplante de parámetros bioquímicos, mediciones antropométricas y función renal mediante medidas de filtrado glomerular.Resultados: a mayor índice de masa corporal pretrasplante se produce una disminución del filtrado glomerular medido por cuatro métodos distintos, así como mayor porcentaje de rechazos.Conclusiones: un IMC elevado pretrasplante contribuye a la disfunción del injerto, a una disminución del filtrado glomerular y a complicaciones del injerto en el primer año postrasplante.

PMID: 27571669 [PubMed - indexed for MEDLINE]

Outcomes in Patients With Metastatic Renal Cell Carcinoma Who Develop Everolimus-Related Hyperglycemia and Hypercholesterolemia: Combined Subgroup Analyses of the RECORD-1 and REACT Trials.

Tue, 10/17/2017 - 12:45
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Outcomes in Patients With Metastatic Renal Cell Carcinoma Who Develop Everolimus-Related Hyperglycemia and Hypercholesterolemia: Combined Subgroup Analyses of the RECORD-1 and REACT Trials.

Clin Genitourin Cancer. 2016 Oct;14(5):406-414

Authors: Bono P, Oudard S, Bodrogi I, Hutson TE, Escudier B, Machiels JP, Thompson JA, Figlin RA, Ravaud A, Basaran M, Porta C, Bracarda S, Brechenmacher T, Lin C, Voi M, Grunwald V, Motzer RJ

Abstract
BACKGROUND: Hyperglycemia and hypercholesterolemia are class effects of mammalian target of rapamycin inhibitors. The purpose of this study was to characterize safety and efficacy of patients with metastatic renal cell carcinoma (mRCC) treated with everolimus in RECORD-1 (REnal Cell cancer treatment with Oral RAD001 given Daily) and REACT (RAD001 Expanded Access Clinical Trial in RCC) who developed these events.
PATIENTS AND METHODS: Adults with vascular endothelial growth factor-refractory mRCC received everolimus 10 mg/d in the randomized RECORD-1 (n = 277) and open-label REACT (n = 1367) studies. Outcomes included safety, treatment duration, overall response, and progression-free survival for patients who developed hypercholesterolemia or hyperglycemia.
RESULTS: In RECORD-1, 12% (33 of 277) and 20% (55 of 277) of patients developed any grade hyperglycemia or hypercholesterolemia, respectively, with only 6% (78 of 1367) and 1% (14 of 1367) of the same events, respectively, in REACT. Median everolimus treatment duration was similar for patients with hyperglycemia or hypercholesterolemia (RECORD-1, 6.2 and 6.2 months, respectively; REACT, 4.4 and 4.5 months, respectively), but longer than the overall populations (RECORD-1, 4.6 months; REACT, 3.2 months). In RECORD-1/REACT, 82%/68% of patients with hyperglycemia and 75%/71% of patients with hypercholesterolemia achieved partial response or stable disease. The incidence of clinically notable Grade 3 or 4 adverse events, other than anemia and lymphopenia, appeared to be similar across trials and subgroups. Although there was a trend for improved progression-free survival with development of hyperglycemia or hypercholesterolemia, the association was not statistically significant.
CONCLUSION: Hyperglycemia and hypercholesterolemia were observed in low numbers of patients, and although these events might be associated with improved response to everolimus, the differences were not significant. These findings should be validated with prospective biomarker studies.

PMID: 27287020 [PubMed - indexed for MEDLINE]

Safe Administration of An Anti-PD-1 Antibody to Kidney-transplant Patients: 2 Clinical Cases and Review of the Literature.

Sun, 10/15/2017 - 18:48

Safe Administration of An Anti-PD-1 Antibody to Kidney-transplant Patients: 2 Clinical Cases and Review of the Literature.

J Immunother. 2017 Nov/Dec;40(9):341-344

Authors: Winkler JK, Gutzmer R, Bender C, Lang N, Zeier M, Enk AH, Hassel JC

Abstract
Antiprogrammed cell-death protein 1 (PD-1) antibodies have revolutionized therapy of metastatic melanoma and other tumors, but some subgroups of patients such as immunosuppressed patients after solid-organ transplantation, have regularly been excluded from clinical studies. We report 2 cases of kidney-transplant patients who received an anti-PD-1 antibody to treat metastatic melanoma. Treatment was tolerated well with no relevant adverse events and stable kidney functions, but the melanoma progressed in both patients. Factors potentially affecting risk of allograft rejection and response to treatment, for example, immunosuppressive regimen and therapeutic sequence, are discussed on the basis of current literature. Further studies are necessary to determine the risk of allograft rejection and the therapeutic benefit of anti-PD-1 antibodies for organ-transplanted patients, in particular as these checkpoint inhibitors have become therapeutic standard in a variety of tumors other than melanoma.

PMID: 29028789 [PubMed - in process]

Co-inhibitory profile and cytotoxicity of CD57(+) PD-1(-) T-cells in end stage renal disease patients.

Sun, 10/15/2017 - 18:48

Co-inhibitory profile and cytotoxicity of CD57(+) PD-1(-) T-cells in end stage renal disease patients.

Clin Exp Immunol. 2017 Oct 13;:

Authors: Kraaijeveld R, de Graav GN, Dieterich M, Litjens NHR, Hesselink DA, Baan CC

Abstract
Blockade of the CD80/86-CD28 pathway by belatacept after kidney transplantation is associated with an increased risk of rejection as compared with standard, calcineurin inhibitor (CNI)-based therapy. CD28(-) T-cells, which express CD57, are not susceptible to belatacept treatment. High number of CD4(+) CD57(+) PD-1(-) T-cells pre transplantation have been associated with a higher chance of rejection, although conflicting data have been reported. To investigate the working mechanism behind this possible higher chance of rejection, we studied the expression of co-inhibitory molecules (CD223, CD244 and PD-1), proliferative capacity and cytotoxic potential of FACS-sorted CD4(+) CD57(+) PD-1(-) and CD8(+) CD57(+) PD-1(-) T-cells, and their CD57(-) control populations, after allo antigen stimulation. The effect of belatacept on the cytotoxic capacity of pre-transplantation peripheral blood mononuclear cells from 20 patients who received belatacept post-transplantation was also tested. Expression of co-inhibitory molecule CD223 increased by approximately 10-fold after allogeneic stimulation in all four T-cell subsets. Proliferation and upregulation of CD244 and PD-1 was observed for CD4(+) CD57(-) PD-1(-) T-cells after allogeneic stimulation, but no upregulation of these markers occurred on CD8(+) T-cells or CD4(+) CD57(+) PD-1(-) T-cells. However, CD4(+) CD57(+) PD-1(-) T-cells and, to a lesser extent, CD8(+) CD57(+) PD-1(-) T-cells displayed higher cytotoxicity as indicated by granzyme B expression. Belatacept inhibited the cytotoxic potential of CD4(+) CD57(+) PD-1(-) T-cells (median of inhibition 31%, p<0.01) and CD8(+) CD57(+) PD-1(-) T-cells (median of inhibition 10%, p<0.05). In conclusion, alloantigen activated CD4(+) CD57(+) PD-1(-) T-cells exhibited a less proliferative but more cytotoxic profile than their CD57(-) counterparts. Their cytotoxic capacity can be partly inhibited by belatacept and was not associated with development of rejection after kidney transplantation. This article is protected by copyright. All rights reserved.

PMID: 29027667 [PubMed - as supplied by publisher]

Impact of spontaneous donor hypothermia on graft outcomes after kidney transplantation.

Sun, 10/15/2017 - 18:48
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Impact of spontaneous donor hypothermia on graft outcomes after kidney transplantation.

Am J Transplant. 2017 Oct 12;:

Authors: Schnuelle P, Mundt HM, Drüschler F, Schmitt WH, Yard BA, Krämer BK, Benck U

Abstract
A previous donor intervention trial found that therapeutic hypothermia reduced delayed graft function (DGF) after kidney transplantation. This retrospective cohort study nested in the randomized dopamine trial (ClinicalTrials. gov identifier: NCT000115115) investigates the effects of spontaneous donor hypothermia (core body temperature <36°C) on initial kidney graft function, and evaluates five-year graft survival. Hypothermia assessed by a singular measurement in the ICU 4-20 hours before procurement was associated with less DGF after kidney transplantation (OR 0.56, 95%CI 0.34 - 0.91). The benefit was greater when need for more than a single post-transplant dialysis session was analyzed (OR 0.48, 95%CI 0.28 - 0.82). Donor dopamine ameliorated dialysis requirement independent from hypothermia in a temporal relationship with exposure (OR 0.93, 95%CI 0.87 - 0.98, per hour). A lower core body temperature in the donor was associated with lower serum-creatinine levels before procurement, which may reflect lower systemic inflammation and attenuated renal injury from brain death. Despite a considerable effect on DGF, our study failed to demonstrate a graft survival advantage (HR 0.83, 95%CI 0.54 - 1.27), whereas dopamine treatment was associated with improved long-term outcome (HR 0.95, 95%CI 0.91 - 0.99 per hour). This article is protected by copyright. All rights reserved.

PMID: 29027352 [PubMed - as supplied by publisher]

Preoperative management of arteriovenous fistula (AVF) for hemodialysis.

Sun, 10/15/2017 - 18:48
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Preoperative management of arteriovenous fistula (AVF) for hemodialysis.

J Vasc Access. 2017 Oct 11;:0

Authors: Alfano G, Fontana F, Iannaccone M, Noussan P, Cappelli G

Abstract
Native arteriovenous fistula (AVF) is the favorite access for hemodialysis (HD). The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) recommends its creation in most patients with renal failure. Unfortunately, intensive efforts to promote native AVF in patients with marginal vessels have increased the rate of primary fistula failure. A non-functioning fistula prompts the use of central venous catheter (CVC) that, unlike AVF, has been associated with an increased risk of morbidity and mortality among patients receiving HD. We believe that successful and timely AVF placement relies on the development of a multidisciplinary integrated preoperative program divided into five stages: (i) management of patients with advanced chronic kidney disease (CKD), (ii) management of preoperative risk factors for AVF failure, (iii) planning of native AVF, (iv) assessment of patient eligibility and (v) preoperative vascular mapping. Focusing specifically on native AVF, we review scientific evidence regarding preoperative management of this vascular access in order to favor construction of long-term functioning fistula minimizing development of severe complications.

PMID: 29027182 [PubMed - as supplied by publisher]

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