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Unravelling current sexual care in chronic kidney disease; perspective of social workers.

Wed, 12/13/2017 - 13:45
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Unravelling current sexual care in chronic kidney disease; perspective of social workers.

J Ren Care. 2017 Dec 12;:

Authors: van Ek GF, Keurhorst D, Krouwel EM, Nicolai MPJ, Den Ouden MEM, Elzevier HW, Putter H, Pelger RCM, Den Oudsten BL

Abstract
BACKGROUND: Fifty to eighty percent of patients suffering from chronic kidney disease (CKD) experience a form of sexual dysfunction (SD), even after renal transplantation. Despite this, inquiring about SD is often not included in the daily practice of renal care providers.
OBJECTIVES: This paper explores the perspectives of renal social workers regarding sexual care for patients and evaluates their practice, attitude towards responsibility and knowledge of SD.
DESIGN: A cross-sectional study was conducted using a 41-item online survey.
PARTICIPANTS: Seventy-nine members of the Dutch Federation of Social Workers Nephrology.
RESULTS: It was revealed that 60% of respondents discussed SD with a fifth of their patients. Frequency of discussion was associated with experience (p = 0.049), knowledge (p = 0.001), supplementary education (p = 0.006), and the availability of protocols on sexual care (p = 0.007). Main barriers towards discussing SD consisted of 'culture and religion' (51.9%), 'language and ethnicity' (49.4%), and 'presence of a third person' (45.6%). Sufficient knowledge of SD was present in 28% of respondents. The responsibility for discussion was 96% nephrologists and 81% social workers.
CONCLUSION: This study provides evidence that a part of Dutch nephrology social workers do not provide sexual care regularly, due to insufficient experience and sexual knowledge, absence of privacy and protocols and barriers based on cultural diversity. According to the respondents the responsibility for this aspect of care should be multidisciplinary. Recommendations include a need for further education on the topic, private opportunities to discuss SD and multidisciplinary guidelines on sexual care.

PMID: 29230963 [PubMed - as supplied by publisher]

Unusual Pathology in a Kidney from a Heart-Transplant Patient.

Wed, 12/13/2017 - 13:45
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Unusual Pathology in a Kidney from a Heart-Transplant Patient.

Case Rep Transplant. 2017;2017:1084718

Authors: Larcher M, Delas A, Delmas C, Cointault O, Dambrin C, Del Bello A, Kamar N

Abstract
Acute kidney injury (AKI) is often observed after heart transplantation. In this setting, acute tubular necrosis is the main histological finding on kidneys. We report the unusual pathology found in a kidney from a heart-transplant patient. The patient experienced several hemodynamic insults, massive transfusion, and implantation of a mechanical circulatory-support device before heart transplantation: there was prolonged AKI after transplantation. A kidney biopsy revealed acute tubular necrosis and renal hemosiderosis, which was probably related to the transfusion and to mechanical circulatory-support device-induced intravascular hemolysis. Assessment of iron during resuscitation could have prevented, at least partly, AKI.

PMID: 29230343 [PubMed]

Comparative clinical trial of the variability factors of the exposure indices used for the drug monitoring of two tacrolimus formulations in kidney transplant recipients.

Wed, 12/13/2017 - 13:45
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Comparative clinical trial of the variability factors of the exposure indices used for the drug monitoring of two tacrolimus formulations in kidney transplant recipients.

Pharmacol Res. 2017 Dec 08;:

Authors: Marquet P, Albano L, Woillard JB, Rostaing L, Kamar N, Sakarovitch C, Gatault P, Buchler M, Charpentier B, Thervet E, Cassuto E

Abstract
BACKGROUND: Several studies found differences in tacrolimus whole blood trough levels (C0) or area-under-the curve (AUC) between the twice-daily (Tac-BID) and once-daily (Tac-OD) formulations given to kidney transplant recipients at equal doses. As C0 is widely used as a surrogate of the AUC for individual dose adjustment, this study investigated the correlation and proportionality between C0 and the 24h-AUC, depending on the formulation, time post-transplantation, pharmacogenetics traits and other individual characteristics.
METHODS: 45 adult kidney transplant recipients were randomized to receive either Tac OD or Tac BID. On days 8±1 (D8) and 90±3 (month 3, M3), blood samples were collected over 24h in both groups. Tacrolimus concentrations were determined using HPLC-MS/MS and common CYP3A5, CYP3A4 and ABCB1 genotypes characterized using allelic discrimination assays. Tacrolimus population pharmacokinetics was studied in the two patient groups using the Iterative Two Stage (ITS) technique, considering a one-compartment model with two gamma laws to describe the absorption phase. Bayesian estimation based on the C0, C1h and C3h concentrations was employed to estimate individual Tac AUC0-12h and AUC12-24h (for Tac BID), or AUC0-24h (for Tac OD). Multiple linear regression was used to evaluate the influence of Tac formulation, post-transplantation period, recipient gender, existing glucose metabolism disorders, and CYP3A5, CYP3A4 and ABCB1 genotypes on C0, AUC0-24h and the AUC-to-trough concentration ratios.
RESULTS: The Full Analysis Set comprised 22 patients on Tac OD and 20 on Tac BID. Tac exposure indices as well as their time evolution were similar in the two groups. Multi-linear modeling analysis showed that the Tac dose was higher with Tac-OD than Tac-BID, on D8 than at M3 and in CYP3A5 expressors (p<0.0001 for all). No such influence was found on C0 or C24h, while the AUC0-24h was significantly higher on D8 than at M3. The AUC0-24h/C0 ratio was not affected by the drug formulation and the polymorphisms studied, but it was significantly lower on D8 than at M3 (p=7.8×10-5). In contrast, both the post-transplantation period (p=1.53×10-4), and CYP3A5 expression (p=0.003) had a significant influence on the AUC0-24h/C24h ratio, explaining 19% and 12% of its variability, respectively. Consistently, for both Tac formulations, the AUC0-24h was better correlated with C24h than C0, and for Tac-BID the AUC0-12h was better correlated with C12h than C0.
CONCLUSIONS: This study confirms that the precisely timed 12h- or 24h-post-dose blood concentration (as opposed to the vaguely defined 'trough level') is a convenient surrogate of the 24h-AUC of tacrolimus for the two TAC formulations over the first 3 months post-transplantation. Still, for a given C24h value, AUC0-24h was higher on D8 and in CYP3A5 expressors. Bayesian estimation of AUC0-12h for TAC BID and AUC0-24h for TAC OD is feasible using only 3 time points within the first 3hours, thus giving access to the actual overall exposure.

PMID: 29229354 [PubMed - as supplied by publisher]

Immunoproteasome inhibition prevents chronic antibody-mediated allograft rejection in renal transplantation.

Wed, 12/13/2017 - 13:45
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Immunoproteasome inhibition prevents chronic antibody-mediated allograft rejection in renal transplantation.

Kidney Int. 2017 Dec 04;:

Authors: Li J, Basler M, Alvarez G, Brunner T, Kirk CJ, Groettrup M

Abstract
Chronic antibody-mediated rejection is the major cause of fading allograft function and loss after renal transplantation. Currently, pharmacological agents for the suppression of chronic antibody-mediated rejection are lacking. Non-selective proteasome inhibitors suppress antibody-mediated allograft rejection. However, extensive adverse side effects of these inhibitors severely limit their application. In contrast, immunoproteasome inhibition is effective in preclinical models of autoimmune diseases and was applied over weeks without obvious adverse side effects. ONX 0914, an immunoproteasome subunit LMP7 (β5i)-selective inhibitor, impeded the chronic rejection of kidneys transplanted from Fischer to allogeneic Lewis rats. ONX 0914 inhibited immunoproteasome induction both in immune organs and renal allografts. Selective immunoproteasome inhibition reduced the numbers of B and plasma cells, and suppressed donor-specific alloantibody production. The infiltration of T cells, B cells and macrophages as well as interferon-γ, interleukin-17, IgG and complement deposition were reduced in renal allografts of ONX 0914-treated recipients. Chronic nephropathy was ameliorated and renal allograft function preserved, enabling long-term survival of recipients. Thus, our studies define a critical role of the immunoproteasome in chronic kidney allograft rejection and suggest immunoproteasome inhibition as a promising therapeutic approach to suppress chronic antibody-mediated rejection.

PMID: 29229189 [PubMed - as supplied by publisher]

Special Considerations in Pediatric Kidney Transplantation.

Wed, 12/13/2017 - 13:45
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Special Considerations in Pediatric Kidney Transplantation.

Adv Chronic Kidney Dis. 2017 Nov;24(6):398-404

Authors: Hebert SA, Swinford RD, Hall DR, Au JK, Bynon JS

Abstract
Universally accepted as the treatment of choice for children needing renal replacement therapy, kidney transplantation affords children the opportunity for an improved quality of life over dialysis therapy. Immunologic and surgical advances over the last 15 years have improved the pediatric patient and kidney graft survival. Unique to pediatrics, congenital genitourinary anomalies are the most common primary diseases leading to kidney failure, many with urological issues. Early urological evaluation for post-transplant bladder dysfunction and emphasis on immunization adherence are the mainstays of pediatric pretransplant and post-transplant evaluations. A child's height can be challenging, sometimes requiring an intra-abdominally placed graft, particularly if the patient is <20 kg. Maintenance immunosuppression regimens are similar to adult kidney graft recipients, although distinctive pharmacokinetics may change dosing intervals in children from twice a day to thrice a day. Viral infections and secondary malignancies are problematic for children relative to adults. Current trends to reduce/remove corticosteroid therapy from post-transplant protocols have produced improved linear growth with less steroid toxicity; although these studies are still ongoing, graft function and survival are considered acceptable. Finally, all children with a kidney transplant need a smooth transition to adult clinics. Future research in pertinent psychosocial aspects and continued technological advances will only serve to optimize the transition process. Although some aspects of kidney transplantation are similar in children and adults, for instance immunosuppression and immunosuppressive regimens, and rejection mechanisms and their diagnosis using the Banff criteria, there are important differences this review will focus on and which continue to drive innovation.

PMID: 29229171 [PubMed - in process]

Care of the Pediatric Patient on Chronic Dialysis.

Wed, 12/13/2017 - 13:45
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Care of the Pediatric Patient on Chronic Dialysis.

Adv Chronic Kidney Dis. 2017 Nov;24(6):388-397

Authors: Chua AN, Warady BA

Abstract
Optimal care of the pediatric end-stage renal disease (ESRD) patient on chronic dialysis is complex and requires multidisciplinary care as well as patient/caregiver involvement. The dialysis team, along with the family and patient, should all play a role in choosing the dialysis modality which best meets the patient's needs, taking into account special considerations and management issues that may be particularly pertinent to children who receive peritoneal dialysis or hemodialysis. Meticulous attention to dialysis adequacy in terms of solute and fluid removal, as well as to a variety of clinical manifestations of ESRD, including anemia, growth and nutrition, chronic kidney disease-mineral bone disorder, cardiovascular health, and neurocognitive development, is essential. This review highlights current recommendations and advances in the care of children on dialysis with a particular focus on preventive measures to minimize ESRD-associated morbidity and mortality. Advances in dialysis care and prevention of complications related to ESRD and dialysis have led to better survival for pediatric patients on dialysis.

PMID: 29229170 [PubMed - in process]

Successful Endovascular Management of a Transplant Renal Artery Pseudoaneurysm Complicated With Arterioureteral Fistula.

Wed, 12/13/2017 - 13:45
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Successful Endovascular Management of a Transplant Renal Artery Pseudoaneurysm Complicated With Arterioureteral Fistula.

Prog Transplant. 2017 Jan 01;:1526924817746913

Authors: Turunç V, Eroğlu A, Tabandeh B, Dheir H, Soylu Ö, Demir MK

Abstract
We report a case of renal artery pseudoaneurysm at the anastomosis site complicated with arterioureteral fistula (AUF) in a 57-year-old kidney transplant recipient who presented with intermittent massive hematuria at one month post-transplant. We successfully treated the pseudoaneurysm and AUF with endovascular covered stent implantation. The diagnosis of AUF is rare and it is a condition that occurs in patients with previous pelvic or vascular surgery, chronic ureteral catheterization and radiotherapy. This diagnosis requires the expertise of the urologist, vascular surgeon and interventional radiologist. The fistula most often occur in the iliac arteries and are often associated with pseudoaneurysms or abscesses. Angiography and ureteral contrast studies (antegrade or retrograde pyelography) are the most valuable diagnostic tools. Treatment of AUF via endovascular approach using covered stents is effective and safe, and is becoming the reference treatment in AUFs.

PMID: 29228871 [PubMed - as supplied by publisher]

Posttransplant lymphoproliferative disorders in kidney transplant recipients: a retrospective cohort analysis over two decades in Hong Kong.

Wed, 12/13/2017 - 13:45
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Posttransplant lymphoproliferative disorders in kidney transplant recipients: a retrospective cohort analysis over two decades in Hong Kong.

Oncotarget. 2017 Nov 14;8(57):96903-96912

Authors: Cheung CY, Ma MKM, Chau KF, Chak WL, Tang SCW

Abstract
Objective: To characterize the posttransplant lymphoproliferative disorders (PTLD) including the Epstein-Barr virus (EBV) status, histological subgroups, site of occurrence and the clinical outcome in the Chinese kidney transplant recipients.
Methods: A retrospective cohort study of 1, 227 adult kidney transplant recipients who were followed up in two transplant centers in Hong Kong over two decades.
Results: 23 (1.9%) patients developed PTLD. Median duration from transplant to PTLD was 104 (5-252) months. Six patients (26.1%) had early PTLD and 17 (73.9%) had late PTLD. Ten (43%) developed PTLD >10 years after transplant. All patients in early PTLD group were EBV-positive. In the late PTLD group, 60% were EBV-negative and 40% EBV-positive. More than 90% of cases were monomorphic PTLD with majority being diffuse large B cell lymphoma. Bone marrow was the most common extranodal site. The overall treatment response rate was 52.2 %. None of the patients developed rejection or relapse after PTLD. At a median follow-up of 9 (1-79) months after PTLD, 18 patients died. Patient survival was 48% at 1 year and 30% at 3 years and death-censored allograft survival was 82% at 1year and 73% at 3 years.
Conclusion: Late PTLD is common. Careful adjustment of immunosuppression, close monitoring of patients, increased awareness and early detection of the disease are essential.

PMID: 29228580 [PubMed]

Crizotinib achieves long-lasting disease control in advanced papillary renal-cell carcinoma type 1 patients with MET mutations or amplification. EORTC 90101 CREATE trial.

Wed, 12/13/2017 - 13:45
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Crizotinib achieves long-lasting disease control in advanced papillary renal-cell carcinoma type 1 patients with MET mutations or amplification. EORTC 90101 CREATE trial.

Eur J Cancer. 2017 Dec;87:147-163

Authors: Schöffski P, Wozniak A, Escudier B, Rutkowski P, Anthoney A, Bauer S, Sufliarsky J, van Herpen C, Lindner LH, Grünwald V, Zakotnik B, Lerut E, Debiec-Rychter M, Marréaud S, Lia M, Raveloarivahy T, Collette S, Albiges L

Abstract
PURPOSE: Papillary renal-cell carcinoma type 1 (PRCC1) is associated with MET gene alterations. Our phase II trial prospectively assessed the efficacy and safety of crizotinib in patients with advanced/metastatic PRCC1 with or without MET mutations (MET+ and MET-).
EXPERIMENTAL DESIGN: Eligible patients with reference pathology-confirmed PRCC1 received 250 mg oral crizotinib twice daily. Patients were attributed to MET+/MET- sub-cohorts by the sequencing of exons 16-19 of the MET gene in tumour tissue. The primary end-point was objective response rate (ORR). If at least two of the first 12 eligible and evaluable MET+ patients achieved a confirmed partial response (PR) or complete response (CR) (in accordance with the Response Evaluation Criteria in Solid Tumours, version 1.1), a maximum of 35 patients were enrolled. Secondary end-points included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), PFS rate (PFSR), overall survival (OS) and safety.
RESULTS: Forty-one patients provided consent, of whom 23 were eligible, treated and evaluable. In four MET+ patients, two achieved PR and one had stable disease (SD) (ORR 50%; 95% confidence interval [CI]: 6.8-93.2), DOR was 21.8 and 37.3 months, 1-year PFSR: 75.0% (95% CI: 12.8-96.1) and 1-year OS: 75.0% (95% CI: 12.8-96.1). Among 16 MET- patients, one achieved a PR lasting more than 9.9 months and 11 had SD (ORR: 6.3%; 95% CI: 0.2-30.2), 1-year PFSR: 27.3% (95% CI: 8.5-50.4) and 1-year OS: 71.8% (95% CI: 41.1-88.4). Among three patients with unknown MET status (MET?) due to technical failure, one achieved PR lasting more than 6.9 months, and one had SD (ORR 33.3%, 95% CI: 0.8-90.6), 1-year PFSR: 66.7% (95% CI: 5.4-94.5) and 1-year OS: 100%. MET amplification was found post hoc in one MET+ patient (PR, DOR: 37.3 months), and one MET- case who had SD. Common treatment-related adverse events were oedema (47.8%), fatigue (47.8%), nausea (39.1%), diarrhoea (39.1%) and blurred vision (34.8%).
CONCLUSION: Crizotinib is active and well tolerated in advanced, metastatic PRCC1, achieving objective responses and long-lasting disease control in patients with MET mutations or amplification. Sporadic, durable responses are also seen in MET- and MET? cases, suggesting the presence of other alterations of MET or alternative pathways.

PMID: 29149761 [PubMed - indexed for MEDLINE]

Putative role of KIR3DL1/3DS1 alleles and HLA-Bw4 ligands with end stage renal disease and long term renal allograft survival.

Wed, 12/13/2017 - 13:45
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Putative role of KIR3DL1/3DS1 alleles and HLA-Bw4 ligands with end stage renal disease and long term renal allograft survival.

Gene. 2017 Dec 30;637:219-229

Authors: Prakash S, Sarangi AN, Alam S, Sonawane A, Sharma RK, Agrawal S

Abstract
BACKGROUND: Killer immunoglobulin receptors (KIR) are highly polymorphic in nature. KIR3DL1/3DS1 genes are known to affect HLA-B antigen binding affinity causing natural killer (NK) cell inhibition, which results into successful renal transplantation. In this study we have examined whether alleles of KIR3DL1/3DS1 play any role in changing the binding affinity with HLA-Bw4 antigen and if so then how are they associated with long term renal allograft survival. We have also evaluated plausible association of KIR3DL1 with HLA-A23/A24/A32 with renal pathophysiology.
MATERIALS AND METHODS: KIR3DL1/3DS1 allelic diversity was examined in 501 renal transplant cases and 507 controls. PCR-SSP was used to determine the incidence of KIR3DL1/3DS1 genes and HLA class-I antigens. KIR3DL1/3DS1 alleles were determined by sequencing. Expression at transcription level for KIR3DL1/3DS1 genes was evaluated in the presence of HLA-Bw4. Different statistical analyses were performed using SPSS v 22.0. p≤0.05 was considered significant. Sequence based variant effect was predicted using Variant Effect Predictor. To evaluate whether variation in KIR3DL1 and HLA interaction changes the binding affinity structure based effect prediction was carried out using MutaBind and BindProf software.
RESULTS: For KIR3DL1*0010101, no-risk and low mRNA expression was seen among antibody mediated acute rejection (ABMR) and chronic rejection (CR) cases. Whereas, 3DS1*01301, 3DL1*00401, and 3DL1*00402 showed susceptibility and elevated mRNA expression with ABMR and CR. Two mutations c.320C>T (rs143159382) and c.911G>T (rs35974949), present in alleles 3DL1*00402 and 3DL1*00401 were predicted to be deleterious. Reduced renal allograft survival was observed for individuals possessing KIR3DL1*00401-HLA-Bw4+. In relation to HLA-A locus no significance was observed with ESRD, ABMR, and CR.
DISCUSSION: The experimental and computational data corroborated with each other suggesting susceptibility for renal allograft in presence of 3DL1*00402 and 3DL1*00401 alleles.

PMID: 28942035 [PubMed - indexed for MEDLINE]

Favourable long-term outcome after coronary artery bypass grafting in a nationwide cohort.

Wed, 12/13/2017 - 13:45
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Favourable long-term outcome after coronary artery bypass grafting in a nationwide cohort.

Scand Cardiovasc J. 2017 Dec;51(6):327-333

Authors: Johannesdottir H, Arnadottir LO, Adalsteinsson JA, Axelsson TA, Sigurdsson MI, Helgadottir S, Helgason D, Gardarsdottir HR, Marteinsson SA, Geirsson A, Thorgeirsson G, Gudbjartsson T

Abstract
OBJECTIVES: In a nationwide cohort, we analyzed long-term outcome following coronary artery bypass grafting, using the combined strategy of left internal mammary artery to the left anterior descending artery and saphenous vein as secondary graft to other coronary targets.
METHODS: 1,507 consecutive patients that underwent myocardial revascularization during 2001-2012 in Iceland. Mean follow-up was 6.8 years. Major adverse cardiac and cerebrovascular events were depicted using the Kaplan-Meier method. Cox-regression was used to define risk factors. Relative survival was estimated by comparing overall survival to the survival of Icelanders of the same age and gender.
RESULTS: Mean age was 66 years, 83% were males, mean EuroSCOREst was 4.5, and 23% of the procedures were performed off-pump. At 5 years, 19.7% had suffered a major adverse cardiac or cerebrovascular event, 4.5% a stroke, 2.2% myocardial infarction, and 6.2% needed repeat revascularization. Overall 5-year survival was 89.9%, with a relative survival of 0.990. Independent predictors of major adverse cardiac and cerebrovascular events were left ventricular ejection fraction ≤30%, a previous history of percutaneous coronary intervention, chronic obstructive lung disease, chronic kidney disease, diabetes, and old age. The same variables and an earlier year of operation were predictors of long-term mortality.
CONCLUSIONS: The long-term outcome following myocardial revascularization, using the left internal mammary artery and the great saphenous vein as conduits, is favourable and improving. This is reflected by the 5-year survival of 89.9%, deviating minimally from the survival rate of the general Icelandic population, together with a freedom from major adverse cardiac and cerebrovascular events of 80.3%.

PMID: 28805102 [PubMed - indexed for MEDLINE]

Bariatric Surgery to Target Obesity in the Renal Transplant Population: Preliminary Experience in a Single Center.

Wed, 12/13/2017 - 13:45
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Bariatric Surgery to Target Obesity in the Renal Transplant Population: Preliminary Experience in a Single Center.

Transplant Proc. 2017 May;49(4):646-649

Authors: Gazzetta PG, Bissolati M, Saibene A, Ghidini CGA, Guarneri G, Giannone F, Adamenko O, Secchi A, Rosati R, Socci C

Abstract
During the last century, obesity has become a global epidemic. The effect of obesity on renal transplantation may occur in perioperative complications and impairment of organ function. Obese patients have metabolic derangements that can be exacerbated after transplantation and obesity directly impacts most transplantation outcomes. These recipients are more likely to develop adverse graft events, such as delayed graft function and early graft loss. Furthermore, obesity is synergic to some immunosuppressive agents in triggering diabetes and hypertension. As behavioral weight loss programs show disappointing results in these patients, bariatric surgery has been considered as a means to achieve rapid and long-term weight loss. Up-to-date literature shows laparoscopic bariatric surgery is feasible and safe in transplantation candidates and increases the rate of transplantation eligibility in obese patients with end-stage organ disease. There is no evidence that restrictive procedures modify the absorption of immunosuppressive medications. From 2013 to 2016 we performed six bariatric procedures (sleeve gastrectomy) on obese patients with renal transplantation; mean preoperative body mass index (BMI) was 39.8 kg/m2. No postoperative complication was observed and no change in the immunosuppressive medications regimen was needed. Mean observed estimated weight loss was 27.6%, 44.1%, 74.2%, and 75.9% at 1, 3, 6, and 12 months follow-up, respectively. Our recommendation is to consider patients with BMI >30 kg/m2 as temporarily ineligible for transplantation and as candidates to bariatric surgery if BMI >35 kg/m2. We consider laparoscopic sleeve gastrectomy as a feasible, first-choice procedure in this specific population.

PMID: 28457364 [PubMed - indexed for MEDLINE]

Characteristics, Management, and Outcomes of Surgically Treated Arteriovenous Fistula Aneurysm in Patients on Regular Hemodialysis.

Wed, 12/13/2017 - 13:45
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Characteristics, Management, and Outcomes of Surgically Treated Arteriovenous Fistula Aneurysm in Patients on Regular Hemodialysis.

Ann Vasc Surg. 2017 May;41:46-55

Authors: Al-Thani H, El-Menyar A, Al-Thani N, Asim M, Hussein A, Sadek A, Sharaf A, Fares A

Abstract
BACKGROUND: To investigate the clinical characteristics, surgical interventions, and outcomes of arteriovenous fistula (AVF) aneurysms, we retrospectively analyzed patients on regular hemodialysis (HD).
METHODS: We conducted a cohort study of all patients with HD access who presented with AVF aneurysms and underwent operative procedures over a 11-year period. Patients' demographics, comorbidities, vascular access characteristics, management of aneurysms, complications, and outcomes were analyzed.
RESULTS: Of the 700 end-stage renal failure patients, 530 patients were maintained on HD (130 through PermCath and 400 through AV access in terms of AVF and arteriovenous graft). We identified 129 patients who developed AV aneurysms, and 40 of them required surgical interventions (24 men and 16 women) with a mean age of 58 ± 14.6 years. The 40 patients who developed AVF aneurysms underwent 43 surgical interventions. The majority of aneurysms were presented with thinning and ulceration (82.5%) of the overlying skin. Thirty-four patients had true aneurysms and 6 had pseudoaneurysms. The aneurysmal AVF comprised 26 brachiocephalic fistulas, 9 radiocephalic fistulas, 3 brachial artery grafts, 1 ulnar-basilic fistula, and 1 Fem-Fem graft at presentation. Patients were treated mainly with ligation (13; 32.5%), excision and repair with graft interposition (15; 37.5%) or vein interposition (11; 27.5%), and end-to-end AVF (1; 2.5%). The median follow-up postsurgery duration was 53 months (range 1-192) and the median duration from fistula creation to the surgical intervention was 52 months (range 4-182). On follow-up, 34 patients continued on HD, while 5 underwent renal transplantation and 1 shifted to peritoneal dialysis. The overall all-cause mortality rate was 37.5% and the leading causes of mortality were sepsis/pneumonia (60%), myocardial infarction, and heart failure (40%).
CONCLUSIONS: In HD patients, the rate of AVF aneurysmal formation is high with a significant rate of morbidity and mortality. Therefore, timely and appropriate evaluation and surgical intervention are crucial.

PMID: 28238919 [PubMed - indexed for MEDLINE]

Native T1 mapping: inter-study, inter-observer and inter-center reproducibility in hemodialysis patients.

Wed, 12/13/2017 - 13:45
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Native T1 mapping: inter-study, inter-observer and inter-center reproducibility in hemodialysis patients.

J Cardiovasc Magn Reson. 2017 Feb 27;19(1):21

Authors: Graham-Brown MP, Rutherford E, Levelt E, March DS, Churchward DR, Stensel DJ, McComb C, Mangion K, Cockburn S, Berry C, Moon JC, Mark PB, Burton JO, McCann GP

Abstract
BACKGROUND: Native T1 mapping is a cardiovascular magnetic resonance (CMR) technique that associates with markers of fibrosis and strain in hemodialysis patients. The reproducibility of T1 mapping in hemodialysis patients, prone to changes in fluid status, is unknown. Accurate quantification of myocardial fibrosis in this population has prognostic potential.
METHODS: Using 3 Tesla CMR, we report the results of 1) the inter-study, inter-observer and intra-observer reproducibility of native T1 mapping in 10 hemodialysis patients; 2) inter-study reproducibility of left ventricular (LV) structure and function in 10 hemodialysis patients; 3) the agreement of native T1 map and native T1 phantom analyses between two centres in 20 hemodialysis patients; 4) the effect of changes in markers of fluid status on native T1 values in 10 hemodialysis patients.
RESULTS: Inter-study, inter-observer and intra-observer variability of native T1 mapping were excellent with co-efficients of variation (CoV) of 0.7, 0.3 and 0.4% respectively. Inter-study CoV for LV structure and function were: LV mass = 1%; ejection fraction = 1.1%; LV end-diastolic volume = 5.2%; LV end-systolic volume = 5.6%. Inter-centre variability of analysis techniques were excellent with CoV for basal and mid-native T1 slices between 0.8-1.2%. Phantom analyses showed comparable native T1 times between centres, despite different scanners and acquisition sequences (centre 1: 1192.7 ± 7.5 ms, centre 2: 1205.5 ± 5 ms). For the 10 patients who underwent inter-study testing, change in body weight (Δweight) between scans correlated with change in LV end-diastolic volume (ΔLVEDV) (r = 0.682;P = 0.03) representing altered fluid status between scans. There were no correlations between change in native T1 between scans (ΔT1) and ΔLVEDV or Δweight (P > 0.6). Linear regression confirmed ΔT1 was unaffected by ΔLVEDV or Δweight (P > 0.59).
CONCLUSIONS: Myocardial native T1 is reproducible in HD patients and unaffected by changes in fluid status at the levels we observed. Native T1 mapping is a potential imaging biomarker for myocardial fibrosis in patients with end-stage renal disease.

PMID: 28238284 [PubMed - indexed for MEDLINE]

Iron Therapy Challenges for the Treatment of Nondialysis CKD Patients.

Wed, 12/13/2017 - 13:45
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Iron Therapy Challenges for the Treatment of Nondialysis CKD Patients.

Clin J Am Soc Nephrol. 2016 Jul 07;11(7):1269-80

Authors: Locatelli F, Mazzaferro S, Yee J

Abstract
The clinical consequences of untreated, severe anemia in patients with nondialysis CKD can be significant, but disparities exist in the anemia treatment guidelines and position papers issued from working groups and associations across the world. These differ in hemoglobin target and iron levels and their emphasis on various iron markers and other clinical outcomes. Not surprisingly, disparities are observed in anemia treatment strategies among patients with nondialysis CKD across different areas of the world. Over the past decade, the prescription and dosage of both iron therapies and erythropoiesis-stimulating agents have shifted, with notable regional differences observed. Moreover, there is ongoing debate regarding oral versus intravenous administration of iron. Compared with oral iron therapy, which often leads to gastrointestinal adverse events, low patient adherence, and low efficacy, intravenous iron administration has been associated with potential serious adverse events, such as anaphylaxis. New iron-based compounds and drugs currently under development are reviewed to describe their potential benefits in the treatment of anemia in patients with CKD. New oral compounds, including iron-based phosphate binders, heme iron polypeptide, and liposomal iron, show different rates of absorption with possibly different efficacy and improved tolerability. These new potential therapies offer health care providers additional anemia treatment options for their patients with CKD; however, the management of anemia in the CKD population continues to present challenges that require prospective studies to identify the optimal iron therapy for patients.

PMID: 27185524 [PubMed - indexed for MEDLINE]

Effect of severe hypoalbuminemia on toxicity of high-dose melphalan and autologous stem cell transplantation in patients with AL amyloidosis.

Wed, 12/13/2017 - 13:45
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Effect of severe hypoalbuminemia on toxicity of high-dose melphalan and autologous stem cell transplantation in patients with AL amyloidosis.

Bone Marrow Transplant. 2016 Oct;51(10):1318-1322

Authors: Lee SY, Meehan RS, Seldin DC, Sloan JM, Quillen K, Shelton A, Brauneis D, Sanchorawala V

Abstract
High-dose melphalan with stem cell transplantation (HDM/SCT) extends survival and induces hematologic and clinical responses in patients with light chain (AL) amyloidosis. Eighty percent of melphalan is bound to plasma proteins (60% albumin-bound). We hypothesized that patients with profound hypoalbuminemia have a greater free melphalan fraction and more toxicity. Patients with AL amyloidosis treated with HDM/SCT between 2011 and 2014 with severe hypoalbuminemia (SH), defined as serum albumin ⩽2 g/dL were studied retrospectively. Sixteen patients with SH were identified. Forty-one patients without severe hypoalbuminemia (WSH) treated between 2011 and 2012 served as control. The incidence of acute renal failure requiring hemodialysis was 25% among patients with SH, compared with 5% among patients WSH (P=0.05). Not all patients who needed dialysis required it long term; 6.25% for SH and 2.44% for WSH (P=0.49). The rates of grade 3 or 4 febrile neutropenia and gastrointestinal toxicities were not significantly different between the groups. Engraftment kinetics were similar for both groups. Grade 4 renal toxicity and grade 3 lightheadedness were more frequent in patients with SH undergoing HDM/SCT for AL amyloidosis. Further studies into the mechanism of increased renal toxicity in patients with SH are warranted.

PMID: 27183092 [PubMed - indexed for MEDLINE]

Frequency Of Different Risk Factors Associated With Recurrent Urinary Tract Infection Among Postmenopausal Women.

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

Frequency Of Different Risk Factors Associated With Recurrent Urinary Tract Infection Among Postmenopausal Women.

J Ayub Med Coll Abbottabad. 2016 Apr-Jun;28(2):353-356

Authors: Jameel S, Mahmud SN

Abstract
BACKGROUND: Urinary Tract Infection is one of the most common infections encountered by women. These infections have the tendency to recur. In order to identify women at risk of recurrence there is a need to identify risk factors associated with it. Among women, factors predisposing to recurrent infections are not much explored. The study was done with an objective to determine different risk factors associated with recurrent UTI among postmenopausal women.
METHODS: This was a cross sectional study conducted at the Out Patient Department of Nephrology in Shifa International Hospital Islamabad over a period of six months, June 6th to December 5th 2012. Information regarding demographics and risk factors were recorded on a predesigned pro forma. A descriptive analysis was done for quantitative variables like age and qualitative variables like marital status and frequency of different risk factors. Stratification of risk factors according to age was also done.
RESULTS: Hundred females were enrolled into the study after informed consent. The mean age of the study population was 64.4±9.48. 97% of the population was married. Out of 100 patients, 42 had high post-void volume, 35 had urinary incontinence and 17 patients were having cystocele. According to age stratification, most frequently affected age group was between 51-60 years (38%), followed by 61-70 years (36%), then 25% in more than 70 years, whereas only 1% was between 41-50 years.
CONCLUSIONS: Recurrent UTI in postmenopausal females is most frequently associated with high post void volume and most frequently affected age group is between 51-60 years.

PMID: 28718537 [PubMed - indexed for MEDLINE]

Mechanisms and mediators of hypertension induced by erythropoietin and related molecules.

Tue, 12/12/2017 - 16:48

Mechanisms and mediators of hypertension induced by erythropoietin and related molecules.

Nephrol Dial Transplant. 2017 Dec 08;:

Authors: Agarwal R

Abstract
Hypertension is a common but frequently overlooked adverse effect of erythropoietin (EPO) therapy. Underreporting of hypertension with EPO is likely due to either more aggressively managing hypertension through the prescription of antihypertensive drugs or closer attention to dry weight. The purpose and focus of this review is to critically evaluate the mechanisms of EPO-induced hypertension. Preclinical data are considered first, followed by clinical data where available. Mediated by a variety of molecules, there is an imbalance in the vascular tone favoring net vasoconstriction that mediates EPO-induced hypertension. Animal studies show the primary importance of chronic kidney disease in the genesis of EPO-induced hypertension. Preclinical studies show deranged regulation of the nitric oxide, endothelins and porstanoids and the sympathoadrenal and renin-angiotensin pathways as causes of EPO-induced hypertension. Human studies suggest that EPO administration is also associated with increased responsiveness to catecholamines and angiotensin II on vascular tissue; in addition, hypoxia-induced vasodilation may be impaired in those with EPO-induced hypertension. There is little evidence for EPO as a direct vasoconstrictor or its effect on blood viscosity as a mechanism of EPO-induced hypertension. EPO-induced hypertension, at least in part, appears to be independent of an increase in hemoglobin, because experiments show that hemoglobin may be increased by EPO without an increase in blood pressure (BP) by simply treating the animals with EPO-binding protein and that treatment with EPO in the setting of iron deficiency may not increase hemoglobin but may still increase BP. However, experimental data are not consistent across studies and better mechanistic designs are needed, especially in patients with chronic kidney disease, to dissect the precise mechanism of EPO-induced hypertension. Animal studies suggest that hypoxia-inducible factor stablizers may induce hypertension by provoking calcification and augmenting chronic intermittent hypoxia as occurs in sleep apnea. Others show that there may be an antihypertensive effect via kidney repair. Whether these drugs will alter the risk of hypertension compared with EPO remains to be seen.

PMID: 29228345 [PubMed - as supplied by publisher]

Susceptibility of HLA-E*01:03 allele carriers to develop Cytomegalovirus replication after living-donor kidney transplantation.

Tue, 12/12/2017 - 16:48

Susceptibility of HLA-E*01:03 allele carriers to develop Cytomegalovirus replication after living-donor kidney transplantation.

J Infect Dis. 2017 Dec 08;:

Authors: Guberina H, da Silva Nardi F, Tomoya Michita R, Dolff S, Bienholz A, Heinemann FM, Wilde B, Trilling M, Horn PA, Kribben A, Witzke O, Rebmann V

Abstract
Cytomegalovirus (CMV) causes serious complications among solid-organ transplant recipients. We report the positive correlation between the presence of the Human Leukocyte Antigen (HLA)-E*01:03 allele in living-donor kidney recipients and CMV reactivation during the first year after transplantation. Thus, the HLA-E recipient genotyping may help to identify CMV-prone patients who require individualized patient-based CMV management.

PMID: 29228302 [PubMed - as supplied by publisher]

Myeloid Neoplasms Following Solid Organ Transplantation: Clinicopathologic Studies of 23 Cases.

Tue, 12/12/2017 - 16:48

Myeloid Neoplasms Following Solid Organ Transplantation: Clinicopathologic Studies of 23 Cases.

Am J Clin Pathol. 2017 Dec 07;:

Authors: Wu B, Ingersoll K, Jug R, Yang LH, Luedke C, Lo A, Su P, Liu X, Rehder C, Gong J, Lu CM, Wang E

Abstract
Objectives: Myeloid neoplasms (MNs) after solid organ transplant are rare, and their clinicopathologic features have not been well characterized.
Methods: We retrospectively analyzed 23 such cases.
Results: The ages ranged from 2 to 76 years, with a median of 59 years at the diagnosis. The median interval between the transplant and diagnosis was 56 months (range, 8-384 months). The transplanted organs included liver in five, kidney in six, lung in five, heart in six, and heart/lung in one case(s). The types of MN included acute myeloid leukemia (AML) in 12, myelodysplastic syndrome (MDS) in five, chronic myelogenous leukemia (CML) in four, and myeloproliferative neoplasms (MPNs) in two cases. Cytogenetics demonstrated clonal abnormalities in 18 (78.3%) cases, including unbalanced changes in 10 (55.6%), Philadelphia chromosome in four (22.2%), and other balanced aberrations in four (22.2%) cases. Thirteen (56.5%) patients died, with an estimated median survival of 9 months. With disease stratification, AML and MDS have short median survivals (3.5 and 7 months, respectively), with an initial precipitous decline of the survival curve.
Conclusions: Posttransplant MNs have a latency period between that seen in AML/MDS related to alkylators and that associated with topoisomerase II inhibitors. The cytogenetic profile suggests a mutagenic effect on leukemogenesis. The clinical outcome for AML/MDS is dismal, with death occurring at an early phase of treatment.

PMID: 29228125 [PubMed - as supplied by publisher]

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