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Refining the Policy for Timing of Kidney Transplant Waitlist Qualification.

Fri, 08/11/2017 - 12:45
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Refining the Policy for Timing of Kidney Transplant Waitlist Qualification.

Transplant Direct. 2017 Aug;3(8):e195

Authors: Lee BJ, McCulloch CE, Grimes BA, Chandran S, Allen IE, Delgado C, Hsu CY

Abstract
BACKGROUND: Earlier qualification for the kidney transplant waitlist expedites transplant and is therefore associated with improved outcomes. U.S. Organ Procurement and Transplantation Network policies state that "measured or calculated creatinine clearance or glomerular filtration rate less than or equal to 20 mL/min" triggers waitlist time accrual. The choice of qualification method is somewhat arbitrary, and the policy implies that decline in renal function is monotonic.
METHODS: (1) We used survival analysis to quantify temporal differences in waitlist qualification by applying 3 kidney-function-estimating equations (Cockcroft-Gault, Modification of Diet in Renal Disease study, Chronic Kidney Disease Epidemiology Collaboration) to serial creatinine measurements from 3 patient cohorts: 1 of waitlisted patients at a major U.S. academic center and 2 national, multicenter cohorts of chronic kidney disease patients (African American Study of Kidney Disease and Hypertension, Modification of Diet in Renal Disease). (2) Survival analysis assessed whether requiring patients to demonstrate persistently reduced renal function on 2 occasions at least 90 days apart would meaningfully change qualification order.
RESULTS: On average, time to waitlist qualification would be delayed on the order of 1 to 2 years by using calculated creatinine clearance (per the Cockcroft-Gault equation). Compared with current policy, requiring demonstration of persistently reduced renal function delayed qualification by 0.6 to 2.1 years and caused 40% to 50% of patients to switch the order in which they qualify by 6 months or more.
CONCLUSIONS: The kidney transplantation policies should be revised, such that timing of waitlist qualification is more standardized. We suggest that mention of using calculated creatinine clearance be dropped from the Organ Procurement and Transplantation Network policy wording and the units to quantify kidney function be changed to mL/min per 1.73 m(2). Some consideration should be given to whether requiring persistently reduced renal function would better identify patients most likely to benefit from earlier waitlist qualification.

PMID: 28795146 [PubMed]

Renal Outcomes in Patients With IgA Nephropathy Undergoing Liver Transplant: A Retrospective Cohort Study.

Fri, 08/11/2017 - 12:45
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Renal Outcomes in Patients With IgA Nephropathy Undergoing Liver Transplant: A Retrospective Cohort Study.

Transplant Direct. 2017 Aug;3(8):e193

Authors: Hommos MS, El-Zoghby ZM

Abstract
BACKGROUND: End-stage liver disease (ESLD) is the most common cause of secondary immunoglobulin A nephropathy (IgAN). Multiple mechanisms have been proposed to explain the association between liver disease and IgAN. Although some mechanisms are expected to reverse in patients after liver transplant, the long-term renal prognosis is unclear for these patients.
METHODS: This observational retrospective cohort study examined the renal outcomes of 14 patients who had IgAN with end-stage liver disease and subsequently underwent either liver transplant alone or combined liver and kidney transplant at a single tertiary care center.
RESULTS: Of the 7 patients who underwent liver transplant alone, hematuria persisted in 2, 4 had progressive loss of kidney function with worsening proteinuria in 3 but only 1 reached end-stage renal disease 5 years posttransplant. Among 7 combined liver and kidney transplant recipients, 1 had histologic and 1 had histologic and clinical recurrence of IgAN without kidney allograft loss.
CONCLUSIONS: IgAN in patients with advanced liver disease does not necessarily resolve after liver transplant but has overall favorable renal outcomes.

PMID: 28795144 [PubMed]

High Intrapatient Variability of Tacrolimus Levels and Outpatient Clinic Nonattendance Are Associated With Inferior Outcomes in Renal Transplant Patients.

Fri, 08/11/2017 - 12:45
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High Intrapatient Variability of Tacrolimus Levels and Outpatient Clinic Nonattendance Are Associated With Inferior Outcomes in Renal Transplant Patients.

Transplant Direct. 2017 Aug;3(8):e192

Authors: Goodall DL, Willicombe M, McLean AG, Taube D

Abstract
BACKGROUND: Nonadherence to immunosuppressants is associated with rejection and allograft loss. Intrapatient variability (IPV) of immunosuppression levels is a marker of nonadherence. This study describes the impact of IPV of tacrolimus levels in patients receiving a tacrolimus monotherapy immunosuppression protocol.
METHODS: We retrospectively analyzed the outpatient tacrolimus levels of kidney-only transplant patients taken between 6 and 12 months posttransplant. IPV was determined using the coefficient of variance.
RESULTS: Six hundred twenty-eight patients with a mean number of 8.98 ± 3.81 tacrolimus levels and a mean follow-up of 4.72 ± 2.19 years were included. Multivariate analysis showed death was associated with increasing age (1.04 [1.01-1.07], P = 0.0055), diabetes at time of transplant (2.79 [1.44-5.41], P = 0.0024), and rejection (2.34 [1.06-5.19], P = 0.036). Variables associated with graft loss included the highest variability group (2.51 [1.01-6.27], P = 0.048), mean tacrolimus level less than 5 ng/mL (4.32 [1.94-9.63], P = 0.0003), a high clinic nonattendance rate (1.10 [1.01-1.20], P = 0.03), and rejection (9.83 [4.62-20.94], P < 0.0001). Independent risk factors for rejection were de novo donor-specific antibody (3.15 [1.84-5.39], P < 0.0001), mean tacrolimus level less than 5 ng/mL (2.57 [1.27-5.19], P = 0.00860, and a high clinic nonattendance rate (1.11 [1.05-1.18], P = 0.0005).
CONCLUSIONS: This study shows that high tacrolimus IPV and clinic nonattendance are associated with inferior allograft survival. Interventions to minimize the causes of high variability, particularly nonadherence are essential to improve long-term allograft outcomes.

PMID: 28795143 [PubMed]

Plasma Proenkephalin and Poor Long-Term Outcome in Renal Transplant Recipients.

Fri, 08/11/2017 - 12:45
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Plasma Proenkephalin and Poor Long-Term Outcome in Renal Transplant Recipients.

Transplant Direct. 2017 Aug;3(8):e190

Authors: Kieneker LM, Hartmann O, Struck J, Bergmann A, Gansevoort RT, Joosten MM, van den Berg E, de Boer RA, Bakker SJL

Abstract
BACKGROUND: Proenkephalin (pro-ENK), a stable and reliable surrogate marker for unstable enkephalins, was found to be associated with acute kidney injury and chronic renal failure in previous studies. We aimed to investigate whether pro-ENK is linked to chronic kidney injury and poor long-term outcome in renal transplant recipients (RTR).
METHODS: We included 664 stable RTR and 95 healthy kidney donors. Pro-ENK was measured in plasma with a double monoclonal sandwich immunoassay. Graft failure was defined as return to dialysis therapy or retransplantation.
RESULTS: Median pro-ENK was 110 pmol/L (interquartile range [IQR], 85-148 pmol/L) in RTR and 48 pmol/L (IQR, 42-55 pmol/L) in kidney donors. Pro-ENK was correlated with estimated glomerular filtration rate (GFR) (rs = -0.80, P < 0.001) in RTR and with measured GFR (rs = -0.74, P < 0.001) in kidney donors. During a median follow-up of 3.1 years (IQR, 2.7-3.9 years), 45 RTR developed graft failure and 76 died. Pro-ENK was positively associated with risk (hazard ratio [HR] per standard deviation increment of the logarithm of pro-ENK; 95% confidence interval [CI]) of graft failure (HR, 4.80; 95% CI, 3.55-6.48) and mortality (HR, 1.50; 95% CI, 1.22-1.85). After adjustment of age, sex, and estimated GFR, the association of pro-ENK with graft failure remained significant (HR, 2.36; 95% CI, 1.37-4.06), whereas no significant association of pro-ENK with risk of all-cause mortality was observed (HR, 1.34; 95% CI, 0.90-2.09).
CONCLUSIONS: Plasma pro-ENK is associated with kidney function as reflected by correlations with measured GFR in both RTR and kidney donors. In addition, pro-ENK was independently associated with increased risk of graft failure in RTR. Pro-ENK may aid in identification of RTR at risk for late graft failure.

PMID: 28795142 [PubMed]

Posttransplant Outcomes of Kidneys Donated After Brain Death Followed by Circulatory Death: A Cohort Study of 128 Chinese Patients.

Fri, 08/11/2017 - 12:45
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Posttransplant Outcomes of Kidneys Donated After Brain Death Followed by Circulatory Death: A Cohort Study of 128 Chinese Patients.

Transplant Direct. 2017 Aug;3(8):e189

Authors: Na N, Li K, Huang Z, Miao B, Hu C, Li H, Wang D, Qiu J

Abstract
BACKGROUND: Donation after brain death followed by circulatory death (DBCD) is a new class in the unique Chinese donor classification system. Currently, in China, the organ transplantation of DBCD is rising. However, there is a dearth of research on the characteristics and outcomes of DBCD kidney transplantation.
METHOD: We collected 128 DBCD renal transplant patients who underwent surgery between June 2013 and May 2016 at our center to analyze clinical outcomes and to share our experience to enhance perioperative management in DBCD kidney transplantation.
RESULTS: At the end of follow-up, no patients experienced primary nonfunction, but delayed graft function occurred in 25.8%. One- and 3-year graft survivals were 97.7% and 94.5%, respectively. The average length of stay was 20.88 ± 14.6 days, the incidence of posttransplant complications was 46.1% (59 patients), and 31 patients suffered more than 1 complication. In addition, the average length of stay of patients without complications and with at least 1 complication was 13.07 ± 2.01 days and 30.02 ± 17.4 days, respectively. There was a significantly higher incidence of complications associated with the postoperative hospital stay in DBCD patients.
CONCLUSIONS: Patients who received a DBCD kidney demonstrated a good outcome in terms of both graft survival and graft function. Hence, DBCD is suitable for national reality and conditions and offers a feasible option for deceased-donor kidney transplantation in China. To prevent complications and reduce the duration of hospital stay, we should strengthen preoperative and postoperative management.

PMID: 28795141 [PubMed]

Late Reoccurrence of Collapsing FSGS After Transplantation of a Living-Related Kidney Bearing APOL 1 Risk Variants Without Disease Evident in Donor Supports the Second Hit Hypothesis.

Fri, 08/11/2017 - 12:45
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Late Reoccurrence of Collapsing FSGS After Transplantation of a Living-Related Kidney Bearing APOL 1 Risk Variants Without Disease Evident in Donor Supports the Second Hit Hypothesis.

Transplant Direct. 2017 Aug;3(8):e185

Authors: Kalil RS, Smith RJ, Rastogi P, Katz DA, Thomas CP

PMID: 28795137 [PubMed]

Renal Autotransplantation and Extracorporeal Nephron-Sparing Surgery for De Novo Renal Cell Carcinoma in a Kidney Allograft.

Fri, 08/11/2017 - 12:45
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Renal Autotransplantation and Extracorporeal Nephron-Sparing Surgery for De Novo Renal Cell Carcinoma in a Kidney Allograft.

Transplant Direct. 2017 Aug;3(8):e122

Authors: Ono S, Kenmochi T, Ito T, Aida N, Otsuki K, Akutsu N, Maruyama M, Kusaka M, Shiroki R, Hoshinaga K

Abstract
De novo renal cell carcinoma (RCC) rarely occurs in kidney allografts; however, the risk of RCC in these patients is 100-fold that of the general healthy population. Although total nephrectomy has been the standard treatment for kidney allograft RCC, several authors have reported that early-stage RCC in kidney allografts was successfully treated with nephron-sparing surgery. We herein describe a new procedure involving renal autotransplantation and extracorporeal nephron-sparing surgery, which was performed to treat de novo RCC near the hilum of a transplanted kidney. In the 22 months since transplantation, the patient's renal function has been favorable, and no recurrence has been observed. In conclusion, renal autotransplantation is a feasible technique for the treatment of RCC in kidney allografts, especially RCC located near the hilum.

PMID: 28795136 [PubMed]

Safe and ethical living kidney donation in Qatar: A national health system's approach.

Fri, 08/11/2017 - 12:45
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Safe and ethical living kidney donation in Qatar: A national health system's approach.

Qatar Med J. 2017;2017(2):3

Authors: Asim M, Al-Maslamani Y, Al-Malki H

Abstract
The increasing incidence of end-stage kidney disease in Qatar has led to growing demand for donor kidneys. The deceased donor kidney program has yet to achieve its full potential; hence, living kidney donation has been widely adopted as an appropriate alternative. The reliance on living kidney donors however, raises a number of social, ethical, and legal concerns surrounding informed consent, voluntarism, psychosocial evaluation, perioperative care, and long-term follow-up of living kidney donors. Many of these concerns become heightened in a multicultural, multilingual society within a Gulf country such as Qatar. This article provides an insight into the challenges that living kidney donation poses in a multiethnic society with significant socioeconomic divides. It also discusses the remedial measures that the Qatari government, healthcare authorities, and transplant community have adopted to address these issues.

PMID: 28795019 [PubMed]

Chronic kidney disease and sports participation by children and adolescents.

Fri, 08/11/2017 - 12:45
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Chronic kidney disease and sports participation by children and adolescents.

Transl Pediatr. 2017 Jul;6(3):207-214

Authors: Master Sankar Raj V, Patel DR, Ramachandran L

Abstract
Individuals suffering from chronic kidney disease (CKD) deal with major morbidity and mortality including poor exercise tolerance. A variety of factors including anemia, poor muscle mass, cardiovascular changes and limited physical activity contribute to exercise intolerance. Studies suggest that early initiation of aerobic and resistance training improves the muscle function, ability to tolerate exercise and quality of life in CKD patients. A thorough medical examination and exercise testing are recommended before initiating an exercise regimen in individuals with CKD. Though current recommendations suggest a qualified approval to contact sports in patients with solitary kidney, a proper risk assessment and counselling must be provided detailing all the risks involved. Special care must be taken to avoid infection or damage to the peritoneal dialysis catheter and hemodialysis vascular access sites. Collision sports should be avoided in individuals with kidney transplant, ectopic kidney or with other urological abnormalities (severe hydronephrosis or ureteropelvic junction obstruction) with high risk of injury.

PMID: 28795012 [PubMed]

A case series on simultaneous liver and kidney transplantation: do we need intraoperative renal replacement therapy?

Fri, 08/11/2017 - 12:45
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A case series on simultaneous liver and kidney transplantation: do we need intraoperative renal replacement therapy?

Korean J Anesthesiol. 2017 Aug;70(4):467-476

Authors: Wi W, Hahm TS, Kim GS

Abstract
Since the implementation of the model for end-stage liver disease (MELD) scoring system in 2002, the liver transplantation (LT) society has observed a substantial increase in the number of recipients with renal dysfunction. Intraoperative renal replacement therapy (ioRRT) has emerged as one of the solutions available to manage high-MELD score recipients; however, its usefulness has not yet been proven. To date, we have experienced five cases of simultaneous liver and kidney transplantation (SLKT). Recipients of SLKT tend to have a lower pre-transplant kidney function and the longer operation time mandates a larger amount of fluid than LT alone. Hence, anesthetic care is more prone to be challenged by hyperkalemia, metabolic acidosis, and volume overload, making ioRRT a theoretically valuable intervention. However, in all five cases, recipients were managed without ioRRT, resulting in excellent graft and patient survival. As such, in this case series, we discuss current issues about ioRRT and SLKT.

PMID: 28794844 [PubMed]

Recurrent AA Amyloidosis Combined With Chronic Active Antibody-mediated Rejection After Kidney Transplantation.

Fri, 08/11/2017 - 12:45
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Recurrent AA Amyloidosis Combined With Chronic Active Antibody-mediated Rejection After Kidney Transplantation.

Iran J Kidney Dis. 2017 Jul;11(4):322-325

Authors: Yeo MK, Ham YR, Choi SY, Lee YM, Park MH, Suh KS

Abstract
Kidney transplantation for amyloidosis remains a contentious issue. Recurrence of amyloidosis is one of the risks of transplantation. Chronic active antibody-mediated rejection is an important cause of chronic allograft dysfunction. A 47-year-old woman underwent kidney transplantation due to renal AA amyloidosis with unknown etiology. Six years posttransplantation, a kidney biopsy showed AA amyloidosis with chronic active antibody-mediated rejection. Donor-specific antibody class II was positive. The patient underwent intravenous plasmapheresis and treatment with rituximab and colchicine. The relationship between recurrence of amyloidosis and rejection was not obvious. Clinical characteristics of kidney transplantation for AA amyloidosis were subjected to literature review and 315 cases were identified. The incidence of amyloidosis recurrence and acute and chronic rejection rates were 15%, 15%, and 8%, respectively. Five-year patient and graft survival rates were 77% and 82%, respectively. Clinical courses of kidney transplantation in AA amyloidosis were, thus, identified.

PMID: 28794296 [PubMed - in process]

Upregulated Expression of Circulating MicroRNAs in Kidney Transplant Recipients With Interstitial Fibrosis and Tubular Atrophy.

Fri, 08/11/2017 - 12:45
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Upregulated Expression of Circulating MicroRNAs in Kidney Transplant Recipients With Interstitial Fibrosis and Tubular Atrophy.

Iran J Kidney Dis. 2017 Jul;11(4):309-318

Authors: Zununi Vahed S, Poursadegh Zonouzi A, Ghanbarian H, Ghojazadeh M, Samadi N, Ardalan M

Abstract
INTRODUCTION: The discovery of circulating microRNAs (miRNAs), as potential noninvasive diagnostic biomarkers, has opened new avenues of research for identifying transplant patients with chronic allograft dysfunction. The present study aimed to investigate the expression levels of 4 immune-related miRNAs, miR-21, miR-31, miR-142-3p, and miR-155, in plasma samples of kidney allograft recipients.
MATERIALS AND METHODS: The plasma expression levels of the miRNAs were evaluated by quantitative real-time polymerase chain reaction in 53 kidney recipients with long-term stable allograft function (n = 27), biopsy-proven interstitial fibrosis and tubular atrophy (n = 26), and healthy controls (n = 15). The possible correlation between clinical parameters and the circulating miRNAs and the receiver-operating characteristic analysis were performed.
RESULTS: Significantly upregulated expressions of miR-21 (P = .02), miR-142-3p (P = .048), and miR-155 (P = .005) were observed in plasma samples of recipients with interstitial fibrosis and tubular atrophy in comparison to the stable allograft function and healthy control groups. Expression level of the miR-21 in plasma was correlated with creatinine (r = -0.432, P = .03) and estimated glomerular filtration rate (r = 0.423, P = .031). Multivariable analysis indicated that miR-21, miR-142-3p, and miR-155 in plasma samples could discriminate almost most of the patients with interstitial fibrosis and tubular atrophy (area under curve, 0.802; sensitivity, 81%; specificity, 92%).
CONCLUSIONS: Our data suggested that altered expression of miR-21, miR-142-3p, and miR-155 in plasma samples might be associated with kidney allograft dysfunction and could be used for graft monitoring in kidney transplantation.

PMID: 28794294 [PubMed - in process]

Antibiotic Prophylaxis for Urinary Tract Infection-Related Renal Scarring: A Systematic Review.

Fri, 08/11/2017 - 12:45
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Antibiotic Prophylaxis for Urinary Tract Infection-Related Renal Scarring: A Systematic Review.

Pediatrics. 2017 May;139(5):

Authors: Hewitt IK, Pennesi M, Morello W, Ronfani L, Montini G

Abstract
CONTEXT: Acute pyelonephritis may result in renal scarring. Recent prospective studies have shown a small benefit of antibiotic prophylaxis in preventing symptomatic and febrile urinary tract infections (UTIs), while being underpowered to detect any influence in prevention of renal damage.
OBJECTIVES: Review of the literature and a meta-analysis to evaluate the effect of antibiotic prophylaxis on UTI-related renal scarring.
DATA SOURCES: Medline, Embase, and Cochrane Controlled Trials Register electronic databases were searched for studies published in any language and bibliographies of identified prospective randomized controlled trials (RCTs) performed and published between 1946 and August 2016.
STUDY SELECTION: Subjects 18 years of age or younger with symptomatic or febrile UTIs, enrolled in prospective RCTs of antibiotic prophylaxis where (99m)Tc dimercaptosuccinic acid scans were performed at entry into the study and at late follow-up to detect new scar formation.
DATA EXTRACTION: The literature search, study characteristics, inclusion and exclusion criteria, and risk of bias assessment were independently evaluated by 2 authors.
RESULTS: Seven RCTs (1427 subjects) were included in the meta-analysis. Our results show no influence of antibiotic prophylaxis in preventing renal scarring (pooled risk ratio, 0.83; 95% confidence interval, 0.55-1.26) as did a subanalysis restricted to those subjects with vesicoureteral reflux (pooled risk ratio, 0.79; 95% confidence interval, 0.51-1.24).
LIMITATIONS: Limitations include the small number of studies, short duration of follow-up, and insufficient children with high-grade dilating reflux and/or renal dysplasia enrolled in the studies.
CONCLUSIONS: Antibiotic prophylaxis is not indicated for the prevention of renal scarring after a first or second symptomatic or febrile UTI in otherwise healthy children.

PMID: 28557737 [PubMed - indexed for MEDLINE]

BK virus in solid organ transplantation: Pretransplant screening of recipients and risk factors for disease.

Fri, 08/11/2017 - 12:45
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BK virus in solid organ transplantation: Pretransplant screening of recipients and risk factors for disease.

Pediatr Transplant. 2017 08;21(5):

Authors: L'Huillier AG, Allen UD

PMID: 28419633 [PubMed - indexed for MEDLINE]

Controlled donation after circulatory death in the Netherlands: more organs, more efforts.

Fri, 08/11/2017 - 12:45
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Controlled donation after circulatory death in the Netherlands: more organs, more efforts.

Neth J Med. 2016 Aug;74(7):285-91

Authors: Leiden H, Haase-Kromwijk B, Hoitsma A, Jansen N

Abstract
BACKGROUND: The Netherlands was one of the first countries in Europe to stimulate controlled donation after circulatory death (cDCD) at a national level in addition to donation after brain death (DBD). With this program the number of organ transplants increased, but it also proved to have challenges as will be shown in this 15-year review.
METHODS: Data about deceased organ donation in the Netherlands, from 2000 until 2014, were analysed taking into account the whole donation process from donor referral to the number of organs transplanted.
RESULTS: Donor referral increased by 58%, from 213 to 336 donors per year, and the number of organs transplanted rose by 42%. Meanwhile the contribution of cDCD donors increased from 14% in 2000 to 54% in 2014 among all referrals. The organs were transplanted from 92-99% of referred DBD donors, but this percentage was significantly lower for cDCD donors and also decreased from 86% in 2000-2002 to 67% in 2012-2014. In 16% of all referred cDCD donors, organs were not recovered because donors did not die within the expected two-hour time limit after withdrawal of life- upporting treatment. Furthermore, cDCD is more often performed at a higher donor age, which is associated with a lower percentage of transplanted organs.
CONCLUSION: Although cDCD resulted in more transplants, the effort in donor recruitment is considerably higher. Important challenges in cDCD that need further attention are the time limit after withdrawal of life-supporting treatment and donor age, as well as the possibilities to stimulate non-renal transplants including the heart by machine preservation.

PMID: 27571943 [PubMed - indexed for MEDLINE]

3K3A-activated protein C stimulates postischemic neuronal repair by human neural stem cells in mice.

Fri, 08/11/2017 - 12:45
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3K3A-activated protein C stimulates postischemic neuronal repair by human neural stem cells in mice.

Nat Med. 2016 Sep;22(9):1050-5

Authors: Wang Y, Zhao Z, Rege SV, Wang M, Si G, Zhou Y, Wang S, Griffin JH, Goldman SA, Zlokovic BV

Abstract
Activated protein C (APC) is a blood protease with anticoagulant activity and cell-signaling activities mediated by the activation of protease-activated receptor 1 (F2R, also known as PAR1) and F2RL1 (also known as PAR3) via noncanonical cleavage. Recombinant variants of APC, such as the 3K3A-APC (Lys191-193Ala) mutant in which three Lys residues (KKK191-193) were replaced with alanine, and/or its other mutants with reduced (>90%) anticoagulant activity, engineered to reduce APC-associated bleeding risk while retaining normal cell-signaling activity, have shown benefits in preclinical models of ischemic stroke, brain trauma, multiple sclerosis, amyotrophic lateral sclerosis, sepsis, ischemic and reperfusion injury of heart, kidney and liver, pulmonary, kidney and gastrointestinal inflammation, diabetes and lethal body radiation. On the basis of proof-of-concept studies and an excellent safety profile in humans, 3K3A-APC has advanced to clinical trials as a neuroprotectant in ischemic stroke. Recently, 3K3A-APC has been shown to stimulate neuronal production by human neural stem and progenitor cells (NSCs) in vitro via a PAR1-PAR3-sphingosine-1-phosphate-receptor 1-Akt pathway, which suggests the potential for APC-based treatment as a strategy for structural repair in the human central nervous (CNS) system. Here we report that late postischemic treatment of mice with 3K3A-APC stimulates neuronal production by transplanted human NSCs, promotes circuit restoration and improves functional recovery. Thus, 3K3A-APC-potentiated neuronal recruitment from engrafted NSCs might offer a new approach to the treatment of stroke and related neurological disorders.

PMID: 27548576 [PubMed - indexed for MEDLINE]

Hypovitaminosis D in patients undergoing kidney transplant: the importance of sunlight exposure.

Thu, 08/10/2017 - 12:45
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Hypovitaminosis D in patients undergoing kidney transplant: the importance of sunlight exposure.

Clinics (Sao Paulo). 2017 Jul;72(7):415-421

Authors: Vilarta CF, Unger MD, Dos Reis LM, Dominguez WV, David-Neto E, Moysés RM, Titan S, Custodio MR, Hernandez MJ, Jorgetti V

Abstract
OBJECTIVES:: Recent studies have shown a high prevalence of hypovitaminosis D, defined as a serum 25-hydroxyvitamin D level less than 30 ng/ml, in both healthy populations and patients with chronic kidney disease. Patients undergoing kidney transplant are at an increased risk of skin cancer and are advised to avoid sunlight exposure. Therefore, these patients might share two major risk factors for hypovitaminosis D: chronic kidney disease and low sunlight exposure. This paper describes the prevalence and clinical characteristics of hypovitaminosis D among patients undergoing kidney transplant.
METHODS:: We evaluated 25-hydroxyvitamin D serum levels in a representative sample of patients undergoing kidney transplant. We sought to determine the prevalence of hypovitaminosis D, compare these patients with a control group, and identify factors associated with hypovitaminosis D (e.g., sunlight exposure and dietary habits).
RESULTS:: Hypovitaminosis D was found in 79% of patients undergoing kidney transplant, and the major associated factor was low sunlight exposure. These patients had higher creatinine and intact parathyroid hormone serum levels, with 25-hydroxyvitamin D being inversely correlated with intact parathyroid hormone serum levels. Compared with the control group, patients undergoing kidney transplant presented a higher prevalence of 25-hydroxyvitamin D deficiency and lower serum calcium, phosphate and albumin but higher creatinine and intact parathyroid hormone levels.
CONCLUSIONS:: Our results confirmed the high prevalence of hypovitaminosis D in patients undergoing kidney transplant. Therapeutic strategies such as moderate sunlight exposure and vitamin D supplementation should be seriously considered for this population.

PMID: 28793001 [PubMed - in process]

Long- term outcome of renal transplantation from octogenarian donors: A multicenter controlled study.

Thu, 08/10/2017 - 12:45
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Long- term outcome of renal transplantation from octogenarian donors: A multicenter controlled study.

Am J Transplant. 2017 Aug 09;:

Authors: Ruggenenti P, Silvestre C, Boschiero L, Rota G, Furian L, Perna A, Rossini G, Remuzzi G, Rigotti P

Abstract
To assess whether biopsy-guided selection of kidneys from very old brain-death donors enables more successful transplantations, this multicenter, observational study compared graft survival between 37 Recipients of one or two histologically evaluated kidneys from >80-years-old donors and 198 Reference-Recipients of non-histologically evaluated single grafts from ≤60-year-old donors (transplant period: 2006-2013 at three Italian Centers). Over a median (IQR) of 25 (13-42) months, two Recipients (5.4%) and 10 Reference-Recipients (5.1%) required dialysis [crude and donor age- and sex-adjusted HRs (95% CI): 1.55 (0.34-7.12), p=0.576 and 1.41 (0.10-19.54), p=0.798, respectively]. Shared frailty analyses confirmed similar outcomes in a 1:2 propensity score study comparing Recipients with 74 Reference-Recipients matched by center, year, donor and recipient sex and age. Serum creatinine was similar across groups over 84-month follow-up. Recipients had remarkably shorter waiting times than Reference-Recipients and Matched-Reference-Recipients [7.5 (4.0-19.5) vs 36 (19-56) and 40 (24-56) months, respectively, p<0.0001 for both comparisons]. KDRI was 2.57±0.32 in Recipients versus 1.09±0.24 and 1.14±0.24 in Reference-Recipients and Matched-Reference-Recipients (p<0.0001 for both comparisons). Adverse events were similar across groups. Biopsy-guided allocation of kidneys from octogenarian donors permits further expansion of the donor-organ pool and faster access to a kidney transplant, without increasing the risk of premature graft failure. This article is protected by copyright. All rights reserved.

PMID: 28792681 [PubMed - as supplied by publisher]

Favorable Results in ABO-Incompatible Renal Transplantation without B-Cell-Targeted Therapy: Advantages and Disadvantages of Rituximab Pretreatment.

Thu, 08/10/2017 - 12:45
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Favorable Results in ABO-Incompatible Renal Transplantation without B-Cell-Targeted Therapy: Advantages and Disadvantages of Rituximab Pretreatment.

Clin Transplant. 2017 Aug 09;:

Authors: Okada M, Watarai Y, Iwasaki K, Murotani K, Futamura K, Yamamoto T, Hiramitsu T, Tsujita M, Goto N, Narumi S, Takeda A, Morozumi K, Uchida K, Kobayashi T

Abstract
The effectiveness of desensitization with rituximab in ABO-incompatible renal transplantation (ABO-I) has been widely reported. However, ABO-I outcomes are still worse than those of ABO-identical or ABO-compatible renal transplantation (ABO-Id/C). We retrospectively examined the outcomes in consecutive living donor ABO-Id/C (n = 412) and ABO-I (n = 205) cases to elucidate the causes of inferiority in ABO-I. ABO-I cases included recipients treated with rituximab (RIT, n = 131), splenectomy (SPX, n = 21), or neither because of low anti-A/B antibody titers (NoR/S, n = 53). Graft survival, infection, and de novo HLA antibody production were compared for ABO-I and ABO-Id/C, followed by stratification into RIT and NoR/S groups. Propensity score-based methods were employed to limit selection bias and potential confounders. Overall graft survival for ABO-I was significantly lower than that for ABO-Id/C (92.8% vs 97.2% after five years, P = 0.0037). Graft loss due to infection with ABO-I was significantly more frequent than that with ABO-Id/C, whereas acute antibody-mediated rejection (AMR) caused no graft failure in ABO-I recipients. Stratified analysis demonstrated significantly higher infection risk with RIT than with NoR/S. Safe reduction or avoidance of rituximab in desensitization protocols might contribute to further improvement of ABO-I outcome. This article is protected by copyright. All rights reserved.

PMID: 28792635 [PubMed - as supplied by publisher]

The Role of Bariatric Surgery in Abdominal Organ Transplantation-the Next Big Challenge?

Thu, 08/10/2017 - 12:45
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The Role of Bariatric Surgery in Abdominal Organ Transplantation-the Next Big Challenge?

Obes Surg. 2017 Aug 08;:

Authors: Dziodzio T, Biebl M, Öllinger R, Pratschke J, Denecke C

Abstract
Obesity is linked to inferior transplant outcome. Bariatric surgery (BS) is an established treatment of morbid obesity. We provide an overview on BS in the field of kidney (KT) and liver transplantation (LT). In end-stage renal disease (ESRD) and KT patients, BS seems safe and feasible. Complication rates were slightly higher compared to the non-transplant population, whereas weight loss and improvement of comorbidities were comparable. Sleeve gastrectomy (SG) was the preferred procedure before KT and superior to gastric bypass (GB) in regard to mortality and morbidity. If conducted after KT, both procedures showed comparable results. BS before LT was associated with high complication rates, in particular after GB. Albeit distinct complications, SG conducted after LT showed the best results. Immunosuppression (IS) changes after BS were rare.

PMID: 28791580 [PubMed - as supplied by publisher]

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