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Renal outcome after kidney-transplantation in Korean patients with lupus nephritis.

Sat, 08/12/2017 - 12:45
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Renal outcome after kidney-transplantation in Korean patients with lupus nephritis.

Lupus. 2017 Jan 01;:961203317725591

Authors: Park ES, Ahn SS, Jung SM, Song JJ, Park YB, Lee SW

Abstract
We investigated renal outcome of kidney-transplantation in 19 Korean recipients with biopsy-proven lupus nephritis and compared it with 18 Korean age- and gender-matched recipients without lupus nephritis who were diagnosed with end-stage renal disease caused by renal diseases other than lupus nephritis in a single centre. We reviewed histological findings of kidneys and calculated cumulative dose of immunosuppressive agents. We assessed renal flare of systemic lupus erythematosus, recurrence of lupus nephritis and graft failure as prognosis. The mean age of recipients with lupus nephritis was 43.5 years and all patients were female. Six patients had class III, 10 had class IV and three had class V. There were no meaningful differences in demographic data, renal replacement modality, cumulative doses of immunosuppressants and prognosis between recipients with and without lupus nephritis. Eight patients experienced renal flare of systemic lupus erythematosus, but there were no cases of recurrence of lupus nephritis or graft failure in recipients with lupus nephritis. Kidney-recipients with class IV lupus nephritis exhibited a lower cumulative renal flare of systemic lupus erythematosus free survival rate than those with class III lupus nephritis. In conclusion, renal outcome of kidney-transplantation in patients with lupus nephritis is similar to that in those without lupus nephritis, and class IV was associated with renal flare of systemic lupus erythematosus.

PMID: 28799839 [PubMed - as supplied by publisher]

Patient with a total artificial heart maintained on outpatient dialysis while listed for combined organ transplant, a single center experience.

Sat, 08/12/2017 - 12:45
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Patient with a total artificial heart maintained on outpatient dialysis while listed for combined organ transplant, a single center experience.

Hemodial Int. 2017 Aug 11;:

Authors: Hanna RM, Hasnain H, Kamgar M, Hanna M, Minasian R, Wilson J

Abstract
Advanced mechanical circulatory support is increasingly being used with more sophisticated devices that can deliver pulsatile rather than continuous flow. These devices are more portable as well, allowing patients to await cardiac transplantation in an outpatient setting. It is known that patients with renal failure are at increased risk for developing worsening acute kidney injury during implantation of a ventricular assist device (VAD) or more advanced modalities like a total artificial heart (TAH). Dealing with patients who have an implanted TAH who develop renal failure has been a challenge with the majority of such patients having to await a combined cardiac and renal transplant prior to transition to outpatient care. Protocols do exist for VAD implanted patients to be transitioned to outpatient dialysis care, but there are no reported cases of TAH patients with end stage renal disease (ESRD) being successfully transitioned to outpatient dialysis care. In this report, we identify a patient with a TAH and ESRD transitioned successfully to outpatient hemodialysis and maintained for more than 2 years, though he did not survive to transplant. It is hoped that this report will raise awareness of this possibility, and assist in the development of protocols for similar patients to be successfully transitioned to outpatient dialysis care.

PMID: 28799694 [PubMed - as supplied by publisher]

Monoclonal Antibodies: A Review.

Sat, 08/12/2017 - 12:45
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Monoclonal Antibodies: A Review.

Curr Clin Pharmacol. 2017 Aug 09;:

Authors: Singh S, Kumar N, Dwiwedi P, Charan J, Kaur R, Sidhu P, Chugh VK

Abstract
Over the last three decades, monoclonal antibodies (MAbs) have made a striking transformation from scientific tools to powerful human therapeutics. Muromonab CD3 a murine MAb, was first FDA approved therapeutic MAb for prevention of kidney transplant rejection. Since its approval in 1986, there has been decline in the further application and approvals until the late 1990s when the first chimeric Mab, Rituximab was approved for the treatment of low grade B cell lymphoma in 1997. With the approval by licensing authorities of chimeric, followed by humanized and then fully human monoclonal antibodies, rate of approval and monoclonal antibodies available in the market for the treatment of various diseases has increased dramatically. As of March 2017, FDA has approved approximately 60 therapeutic MAbs with much more currently under evaluation in various phases of clinical trials. MAbs are approved for the treatment of a diseases belonging to various system like cardiovascular, respiratory, hematology, kidney, immunology and oncology. Mab are approved for the treatment of orphan diseases or indications such as paroxysmal nocturnal hemoglobinuria as well as cancers and multiple sclerosis where hundreds of patients are treated and even diseases such as breast cancer, asthma and rheumatoid arthritis where millions are being treated. This review focuses briefly on types, molecular targets, mechanism of actions and therapeutic indications of FDA approved MAb products that are currently on the market.

PMID: 28799485 [PubMed - as supplied by publisher]

Ex-vivo ureteroscopy of deceased donor kidneys.

Sat, 08/12/2017 - 12:45
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Ex-vivo ureteroscopy of deceased donor kidneys.

Can Urol Assoc J. 2017 Aug;11(8):251-253

Authors: Machen GL, Milburn PA, Lowry PS, Lappin JA, Doherty DK, El Tayeb MM

Abstract
INTRODUCTION: When encountered, the ideal management of lithiasis in deceased donor kidneys is not well-defined. With advances in endourological techniques, minimally invasive treatments are becoming an increasingly viable option. We set out to describe our experience performing ex-vivo ureteroscopy on cadaveric donor kidneys, including one in which the procedure was completed on-pump.
METHODS: A retrospective chart review was undertaken to identify patients who had undergone ex-vivo ureteroscopy prior to cadaveric renal transplant. Four patients were identified, including one in which the procedure was done with the kidney remaining on-pump. The surgical technique and subsequent data were reviewed.
RESULTS: Ex-vivo ureteroscopy was successfully completed in all four instances without intraoperative complication. All kidneys were endoscopically stone-free. Creatinine nadirs ranged from 0.8-1.4. All four patients remained stone-free at a mean followup of 13 months.
CONCLUSIONS: Our series provides further evidence as to the safety and efficacy of ex-vivo ureteroscopy prior to transplantation in cadaveric renal transplants and describes a novel technique in the form of on-pump ex-vivo ureteroscopy.

PMID: 28798825 [PubMed]

NEDD4-family E3 ligase dysfunction due to PKHD1/Pkhd1 defects suggests a mechanistic model for ARPKD pathobiology.

Sat, 08/12/2017 - 12:45
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NEDD4-family E3 ligase dysfunction due to PKHD1/Pkhd1 defects suggests a mechanistic model for ARPKD pathobiology.

Sci Rep. 2017 Aug 10;7(1):7733

Authors: Kaimori JY, Lin CC, Outeda P, Garcia-Gonzalez MA, Menezes LF, Hartung EA, Li A, Wu G, Fujita H, Sato Y, Nakanuma Y, Yamamoto S, Ichimaru N, Takahara S, Isaka Y, Watnick T, Onuchic LF, Guay-Woodford LM, Germino GG

Abstract
Autosomal recessive polycystic kidney disease (ARPKD) is an important childhood nephropathy, occurring 1 in 20,000 live births. The major clinical phenotypes are expressed in the kidney with dilatation of the collecting ducts, systemic hypertension, and progressive renal insufficiency, and in the liver with biliary dysgenesis, portal tract fibrosis, and portal hypertension. The systemic hypertension has been attributed to enhanced distal sodium reabsorption in the kidney, the structural defects have been ascribed to altered cellular morphology, and fibrosis to increased TGF-β signaling in the kidney and biliary tract, respectively. The pathogenic mechanisms underlying these abnormalities have not been determined. In the current report, we find that disrupting PKHD1 results in altered sub-cellular localization and function of the C2-WWW-HECT domain E3 family of ligases regulating these processes. We also demonstrate altered activity of RhoA and increased TGF-β signaling and ENaC activity. Linking these phenomena, we found that vesicles containing the PKHD1/Pkhd1 gene product, FPC, also contain the NEDD4 ubiquitin ligase interacting protein, NDFIP2, which interacts with multiple members of the C2-WWW-HECT domain E3 family of ligases. Our results provide a mechanistic explanation for both the cellular effects and in vivo phenotypic abnormalities in mice and humans that result from Pkhd1/PKHD1 mutation.

PMID: 28798345 [PubMed - in process]

Prolonged Administration of Twice-Daily Bolus Intravenous Tacrolimus in the Early Phase After Lung Transplantation.

Sat, 08/12/2017 - 12:45
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Prolonged Administration of Twice-Daily Bolus Intravenous Tacrolimus in the Early Phase After Lung Transplantation.

Ann Transplant. 2017 Aug 11;22:484-492

Authors: Hirano Y, Sugimoto S, Mano T, Kurosaki T, Miyoshi K, Otani S, Yamane M, Kobayashi M, Miyoshi S, Oto T

Abstract
BACKGROUND Although administration of tacrolimus, whether by the enteric, sublingual, or continuous intravenous routes, has some limitations, twice-daily bolus intravenous tacrolimus administration has been shown to be beneficial in optimizing efficacy and safety after lung transplantation. However, at present, the duration of bolus intravenous tacrolimus administration is limited, and the effects of prolonged bolus intravenous tacrolimus administration remain unknown. Our study was aimed at assessing the safety and efficacy of prolonged twice-daily bolus intravenous tacrolimus administration in the early phase after lung transplantation. MATERIAL AND METHODS We retrospectively investigated the data of 62 recipients of lung transplantation who had received twice-daily bolus intravenous administration of tacrolimus, followed by oral tacrolimus, after lung transplantation at our institution between January 2011 and October 2015. RESULTS The median duration of bolus intravenous tacrolimus administration was 19 days (4-72 days). The target trough level was achieved in 89% of the patients by day 3. Acute kidney injury occurred in 27% of the patients during bolus intravenous tacrolimus. Two patients (3%) had neurotoxicity, necessitating discontinuation of tacrolimus. Suspected acute rejection requiring steroid pulse therapy occurred in 21% of patients during the follow-up period. Eight patients (13%) developed chronic lung allograft dysfunction during the follow-up period. The 1-year and 5-year survival rates after lung transplantation were 95% and 76%, respectively. CONCLUSIONS These results suggest that prolonged bolus intravenous tacrolimus administration in the early phase after lung transplantation is a safe and effective alternative to enteric, sublingual, or continuous intravenous administration.

PMID: 28798289 [PubMed - in process]

Biomarker research to improve clinical outcomes of peritoneal dialysis: consensus of the European Training and Research in Peritoneal Dialysis (EuTRiPD) network.

Sat, 08/12/2017 - 12:45
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Biomarker research to improve clinical outcomes of peritoneal dialysis: consensus of the European Training and Research in Peritoneal Dialysis (EuTRiPD) network.

Kidney Int. 2017 Aug 08;:

Authors: Aufricht C, Beelen R, Eberl M, Fischbach M, Fraser D, Jörres A, Kratochwill K, LópezCabrera M, Rutherford P, Schmitt CP, Topley N, Witowski J

Abstract
Peritoneal dialysis (PD) therapy substantially requires biomarkers as tools to identify patients who are at the highest risk for PD-related complications and to guide personalized interventions that may improve clinical outcome in the individual patient. In this consensus article, members of the European Training and Research in Peritoneal Dialysis Network (EuTRiPD) review the current status of biomarker research in PD and suggest a selection of biomarkers that can be relevant to the care of PD patients and that are directly accessible in PD effluents. Currently used biomarkers such as interleukin-6, interleukin-8, ex vivo-stimulated interleukin-6 release, cancer antigen-125, and advanced oxidation protein products that were collected through a Delphi procedure were first triaged for inclusion as surrogate endpoints in a clinical trial. Next, novel biomarkers were selected as promising candidates for proof-of-concept studies and were differentiated into inflammation signatures (including interleukin-17, M1/M2 macrophages, and regulatory T cell/T helper 17), mesothelial-to-mesenchymal transition signatures (including microRNA-21 and microRNA-31), and signatures for senescence and inadequate cellular stress responses. Finally, the need for defining pathogen-specific immune fingerprints and phenotype-associated molecular signatures utilizing effluents from the clinical cohorts of PD patients and "omics" technologies and bioinformatics-biostatistics in future joint-research efforts was expressed. Biomarker research in PD offers the potential to develop valuable tools for improving patient management. However, for all biomarkers discussed in this consensus article, the association of biological rationales with relevant clinical outcomes remains to be rigorously validated in adequately powered, prospective, independent clinical studies.

PMID: 28797473 [PubMed - as supplied by publisher]

A 58-Year-Old Man With Position-Dependent Nocturnal Dyspnea.

Sat, 08/12/2017 - 12:45
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A 58-Year-Old Man With Position-Dependent Nocturnal Dyspnea.

Chest. 2017 Aug;152(2):e51-e55

Authors: Schertel A, Horvath CM, Pichler Hefti J, Aubert JD, Brill AK

Abstract
CASE PRESENTATION: A 58-year-old man with idiopathic pulmonary fibrosis, who had received a right-sided single-lung transplant 2 years earlier, was referred to the sleep clinic for the assessment of nocturnal position-dependent episodes of dyspnea and frequent arousals when lying on his right side. There was no subjective worsening of daytime respiratory symptoms, but he complained of fatigue and unrefreshing sleep. His Epworth Sleepiness Scale score was 12/24. After lung transplantation he had a favorable course while receiving immunosuppression with prednisolone, everolimus, and mycophenolate mofetil. In addition, he had received diagnoses of stable coronary artery disease and moderate chronic kidney failure.

PMID: 28797401 [PubMed - in process]

Transplantation of the Patient with Human Immunodeficiency Virus.

Sat, 08/12/2017 - 12:45
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Transplantation of the Patient with Human Immunodeficiency Virus.

Adv Surg. 2017 Sep;51(1):65-76

Authors: Jackson KR, Cameron A

PMID: 28797346 [PubMed - in process]

Ureteric re-implant for the strictured renal allograft: How I do it.

Sat, 08/12/2017 - 12:45
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Ureteric re-implant for the strictured renal allograft: How I do it.

Can J Urol. 2016 Jun;23(3):8296-300

Authors: McGregor T, Kroczak T, Huang C, Koulack J

Abstract
Ureteric stricture is the most common urologic complication following renal transplantation. Initial treatment should consist of endoscopic management, however patients that fail endoscopic management or strictures that are not amendable to endoscopic management are appropriate candidates for open surgical repair. In this manuscript we describe the steps and surgical technique we use to manage complicated ureteric strictures refractory to endoscopic management at our center. Ureteric re-implant with the use of a Boari flap is a safe, effective and definitive option for repair of ureteric strictures following renal transplantation. This approach provides excellent long term outcomes in terms of renal function preservation and negligible recurrence rates.

PMID: 27347624 [PubMed - indexed for MEDLINE]

Correspondence to: 'Pregnancy outcomes in simultaneous pancreas and kidney transplant recipients: a national French survey study'.

Fri, 08/11/2017 - 12:45
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Correspondence to: 'Pregnancy outcomes in simultaneous pancreas and kidney transplant recipients: a national French survey study'.

Transpl Int. 2017 Aug 10;:

Authors: Khalid U, Ilham MA, Awad M, Elker D

Abstract
We read with great interest this article (1). The authors have described outcomes of 26 pregnancies in 22 SPK patients. We were very impressed with the overall outcomes reported -fetal survival of 92.6%, and kidney and pancreas graft survival at 1 year post-conception of 96% and 100% respectively. Overall the conclusion that can be inferred broadly from this data is that pregnancy in SPK patients is safe. This article is protected by copyright. All rights reserved.

PMID: 28796928 [PubMed - as supplied by publisher]

Marginal organ allocation: old and new REALity.

Fri, 08/11/2017 - 12:45
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Marginal organ allocation: old and new REALity.

Transpl Int. 2017 Aug 10;:

Authors: Fehr T, Immer F

Abstract
Since the first kidney transplantation in 1954 and introduction of systemic immunosuppression one decade later, kidney transplantation has been incredibly successful in reducing morbidity and mortality of patients suffering from end-stage kidney disease. Despite the fact that transplant procedures have increased every decade and all around the world, they were outpaced by the number of patients entered on transplant waiting lists about 20 years ago. This article is protected by copyright. All rights reserved.

PMID: 28796924 [PubMed - as supplied by publisher]

Low renal but high extrarenal phenotype variability in Schimke immuno-osseous dysplasia.

Fri, 08/11/2017 - 12:45
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Low renal but high extrarenal phenotype variability in Schimke immuno-osseous dysplasia.

PLoS One. 2017;12(8):e0180926

Authors: Lipska-Ziętkiewicz BS, Gellermann J, Boyer O, Gribouval O, Ziętkiewicz S, Kari JA, Shalaby MA, Ozaltin F, Dusek J, Melk A, Bayazit AK, Massella L, Hyla-Klekot L, Habbig S, Godron A, Szczepańska M, Bieniaś B, Drożdż D, Odeh R, Jarmużek W, Zachwieja K, Trautmann A, Antignac C, Schaefer F, PodoNet Consortium

Abstract
Schimke immuno-osseous dysplasia (SIOD) is a rare multisystem disorder with early mortality and steroid-resistant nephrotic syndrome (SRNS) progressing to end-stage kidney disease. We hypothesized that next-generation gene panel sequencing may unsurface oligosymptomatic cases of SIOD with potentially milder disease courses. We analyzed the renal and extrarenal phenotypic spectrum and genotype-phenotype associations in 34 patients from 28 families, the largest SMARCAL1-associated nephropathy cohort to date. In 11 patients the diagnosis was made unsuspectedly through SRNS gene panel testing. Renal disease first manifested at median age 4.5 yrs, with focal segmental glmerulosclerosis or minimal change nephropathy on biopsy and rapid progression to end-stage kidney disease (ESKD) at median age 8.7 yrs. Whereas patients diagnosed by phenotype more frequently developed severe extrarenal complications (cerebral ischemic events, septicemia) and were more likely to die before age 10 years than patients identified by SRNS-gene panel screening (88 vs. 40%), the subgroups did not differ with respect to age at proteinuria onset and progression to ESKD. Also, 10 of 11 children diagnosed unsuspectedly by Next Generation Sequencing were small at diagnosis and all showed progressive growth failure. Severe phenotypes were usually associated with biallelic truncating mutations and milder phenotypes with biallelic missense mutations. However, no genotype-phenotype correlation was observed for the renal disease course. In conclusion, while short stature is a reliable clue to SIOD in children with SRNS, other systemic features are highly variable. Our findings support routine SMARCAL1 testing also in non-syndromic SRNS.

PMID: 28796785 [PubMed - in process]

Comparison of stroke volume measurements during hemodialysis using bioimpedance cardiography and echocardiography.

Fri, 08/11/2017 - 12:45
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Comparison of stroke volume measurements during hemodialysis using bioimpedance cardiography and echocardiography.

Hemodial Int. 2017 Aug 10;:

Authors: Germain MJ, Joubert J, O'Grady D, Nathanson BH, Chait Y, Levin NW

Abstract
BACKGROUND: Fluid management remains a major challenge of hemodialysis (HD) care, with serious implications for morbidity and mortality. Intradialytic fluid management is typically guided by blood pressure, an indirect resultant of hemodynamics status. Direct measurements of hemodynamic parameters may improve cardiovascular outcomes by providing rational bases for intervention. We compare stroke volume (SV) measurements using a noninvasive, regional biompedance cardiography device (NiCaS) with Doppler echocardiography (Echo) in HD setting.
METHODS: Stroke volumes were simultaneously measured using the devices in 17 patients receiving maintenance HD. Measurements were made during 2 weekly HD treatments, and twice within each HD treatment during the first and last hour of each treatment, for a total of 64 SV measurements. Agreement between devices was assessed using linear regression, a Pearson's correlation coefficient, and a Bland-Altman plot all adjusted for repeated measures within patients.
RESULTS: Echo and NiCaS SV mean and 95% CIs were 58.0 (50.1, 65.8) and 56.7 (49.4, 64.0) mL, respectively. NiCaS SV correlated strongly with Echo SV during the first and last hours of treatments (r = 0.93, P < 0.001 and r = 0.92, P < 0.001, respectively). Linear regression of NiCaS on Echo showed a slope of 0.97, 95% CI (0.91, 1.02) which did not differ from 1, P = 0.20. A Bland-Altman plot and 4-Quadrant plot confirmed that the 2 methods produced comparable measurements.
CONCLUSION: NiCaS SV measurements are similar to and strongly correlated with Echo SV measurements. This suggests that noninvasive NiCaS technology may be a practical method for measuring SV during HD.

PMID: 28796425 [PubMed - as supplied by publisher]

Impact of carbapenem-resistant Klebsiella pneumoniae (CR-KP) infections in kidney transplantation.

Fri, 08/11/2017 - 12:45
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Impact of carbapenem-resistant Klebsiella pneumoniae (CR-KP) infections in kidney transplantation.

Transpl Infect Dis. 2017 Aug 10;:

Authors: Varotti G, Dodi F, Terulla A, Santori G, Mariottini G, Bertocchi M, Marchese A, Fontana I

Abstract
BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CR-KP) infections in solid organ transplant patients are progressively increasing and are associated with worse outcomes, although potential risk factors and therapeutic strategies are still not well defined.
METHODS: We conducted a retrospective matched-pair analysis in which we compared 26 recipients CR-KP-positive after kidney transplantation (KT) with 52 CR-KP-negative patients transplanted in the same period, during a CR-KP outbreak occurred in our hospital. Twenty-one patients (80%) received a combined antibiotic treatment. At the end of the follow-up, of the 26 CR-KP infected patients, 11 (42.3%) experienced at least one episode of re-infection, 9 (34.6%) remained colonized, and 6 (23.0%) had a symptomatic infection. Two of the 11 patients with re-infection died, while 9 were colonized at the end of the study.
RESULTS: A significantly better patient (P=.043) and graft (P <.001) survival was observed in CR-KP-negative patients. Univariate analysis identified the following variables as potential risk factors associated with CR-KP infection after KT: lower body mass index (P=.020); higher creatinine levels at post-transplant days 7 (P=.009), 15 (P=.026), and 30 (P=.019); longer hospital stay (P=.007); longer cold ischemia time (P=.004); delayed graft function (P=.020); and higher Clavien-Dindo score (P=.006).
CONCLUSION: The study confirmed that a CR-KP positivity may affect the outcome of a kidney transplant population. In severe CR-KP infections with sepsis, a combined antibiotic treatment seems to be advisable. This article is protected by copyright. All rights reserved.

PMID: 28796391 [PubMed - as supplied by publisher]

Posttransplantation anemia in kidney transplant recipients: A retrospective cohort study.

Fri, 08/11/2017 - 12:45
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Posttransplantation anemia in kidney transplant recipients: A retrospective cohort study.

Medicine (Baltimore). 2017 Aug;96(32):e7735

Authors: Gafter-Gvili A, Ayalon-Dangur I, Cooper L, Shochat T, Rahamimov R, Gafter U, Mor E, Grossman A

Abstract
We sought to assess the frequency and predictors of early and late posttransplantation anemia (PTA). In addition, we aimed to assess the outcomes of patients with anemia and to assess the impact of anemia on mortality, graft function, and graft failure.Patients who underwent kidney transplantation in a single center during a 4-year period were included. Predictors associated with the development of anemia at 6 months (early PTA) or 2 years (late PTA) were evaluated in a univariate and multivariate analyses. The effects of anemia and other variables on mortality and graft function were assessed.A total of 266 kidney transplant recipients were included. The prevalence of PTA at 6 months (early PTA) was 51.3% and at 2 years (late PTA) was 36.6%. Female sex was significantly associated with early PTA. Patients with early PTA proceeded to late PTA. Patients with both early and late PTA had a higher mortality rate at 4 years compared to patients without anemia. On multivariable analysis, lower Hb at 2 years posttransplantation (hazard ratio [HR] 0.716, 95% confidence intervals [CI] 0.541-0.948, for every increment of 1 g/dL) was significantly associated with mortality. Patients with late PTA suffered a decline in eGFR compared to patients without anemia (P = .026). Furthermore, a lower Hb at 2 years posttransplantation was also associated with graft failure (HR 0.775, 95% CI 0.619-0.969, for every increment of 1 g/dL).Post-transplantation anemia is significantly associated with late mortality, with a decline in graft function and with an increased incidence of graft failure.

PMID: 28796058 [PubMed - in process]

The FGF23-Klotho axis and cardiac tissue Doppler imaging in pediatric chronic kidney disease-a prospective cohort study.

Fri, 08/11/2017 - 12:45
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The FGF23-Klotho axis and cardiac tissue Doppler imaging in pediatric chronic kidney disease-a prospective cohort study.

Pediatr Nephrol. 2017 Aug 09;:

Authors: Tranæus Lindblad Y, Olauson H, Vavilis G, Hammar U, Herthelius M, Axelsson J, Bárány P

Abstract
BACKGROUND: Chronic kidney disease-associated mineral bone disorder (CKD-MBD) is common in pediatric kidney disease patients and a risk factor for future cardiovascular disease (CVD). Fibroblast growth factor-23 (FGF23) and Klotho are novel key players in CKD-MBD, and has been suggested to be involved in the development of CVD.
METHODS: This prospective cohort study included 74 pediatric patients; 31 with CKD (age range 0.8-18.8 years, glomerular filtration rate (GFR) range 9-68 mL/min/1.73 m(2)) and 43 transplanted patients (CKD-T; age range 3.3-17.7 years, GFR range 10-99 mL/min/1.73 m(2)) examined annually for 3 years. We assessed longitudinal patterns and predictors of FGF23 and soluble Klotho, as well as associations to cardiac remodeling and function using echocardiographic pulse wave Doppler (PWD) and color-coded tissue Doppler imaging (cc-TDI).
RESULTS: The prevalence of high FGF23 levels (≥95th percentile) was 60% in CKD and 42% in CKD-T patients, despite a low prevalence of hyperphosphatemia and normal Klotho levels. Low GFR at baseline was a predictor for high mean log FGF23 during follow-up in CKD and CKD-T patients (β = -0.2, p < 0.001). A high log FGF23 z-score longitudinally was borderline significantly associated with elevated left ventricular mass index (LVMI) in CKD patients (β = 1.8, p = 0.06). In addition, high log FGF23 (β = -0.43, p = 0.01) and low log Klotho (β = 0.44, p = 0.006) over time were associated with a worse left ventricular diastolic function (cc-TDI e'/a') in CKD-T patients.
CONCLUSIONS: In pediatric CKD and CKD-T patients, the FGF23 level increase and Klotho level decrease with progressing renal failure, despite well-controlled phosphate levels. Following adjustments, both high FGF23 and low Klotho levels were strongly associated with a worse left ventricular diastolic function longitudinally. The potential role of FGF23 and Klotho in cardiac morbidity in pediatric CKD requires further investigation.

PMID: 28795324 [PubMed - as supplied by publisher]

An efficient method for kidney allocation problem: a credibility-based fuzzy common weights data envelopment analysis approach.

Fri, 08/11/2017 - 12:45
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An efficient method for kidney allocation problem: a credibility-based fuzzy common weights data envelopment analysis approach.

Health Care Manag Sci. 2017 Aug 09;:

Authors: Ahmadvand S, Pishvaee MS

Abstract
Given the perennial imbalance and chronic scarcity between the demand for and supply of available organs, organ allocation is one of the most critical decisions in the management of organ transplantation networks. Organ allocation systems undergo rapid revisions for the sake of improved outcomes in terms of both equity and medical efficiency. This paper presents a Data Envelopment Analysis (DEA)-based model to evaluate the efficiency of possible patient-organ pairs for kidney allocation in order to enhance the fitness of organ allocation under inherent uncertainty in such problem. Eligible patient-kidney pairs are regarded as decision making units (DMUs) in a Credibility-based Fuzzy Common Weights DEA (CFCWDEA) approach and are ranked based on efficiency scores. Using a common set of weights for all DMUs ensures a high degree of fairness in the assessment and ranking of DMUs. The proposed model is also the first allocation method capable of coping with the vague and intervallic medical and nonmedical allocation factors by the aid of fuzzy programming. Verification and validation of the proposed approach are performed in two steps using a real case study from the Iranian kidney allocation system. First, the superiority of the proposed deterministic model in enhancing allocation outcomes is demonstrated and analyzed. Second, the applicability of the proposed fuzzy DEA method is demonstrated using a series of data realizations for different credibility levels.

PMID: 28795254 [PubMed - as supplied by publisher]

Kidney Transplantation in Patients With Active Multiple Myeloma: Case Reports.

Fri, 08/11/2017 - 12:45
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Kidney Transplantation in Patients With Active Multiple Myeloma: Case Reports.

Transplant Direct. 2017 Aug;3(8):e200

Authors: Lum EL, Kogut N, Pham T, Danovitch GM, Bunnapradist S

Abstract
Kidney disease is a common complication in patients with multiple myeloma. Traditionally, patients with active multiple myeloma and end-stage renal disease have been excluded from kidney transplantation due to the risk of malignancy progression. The introduction of bortezomib-based therapy for patients with multiple myeloma and renal impairment has significantly improved survival in this population. In this report, we present 2 cases of patients with active and controlled multiple myeloma who underwent successful kidney transplantation without progression of their underlying malignancy. In patients with active multiple myeloma controlled with bortezomib, kidney transplantation should be considered a valid option for patients with end-stage kidney disease.

PMID: 28795151 [PubMed]

The Effects of Tacrolimus on T-Cell Proliferation Are Short-Lived: A Pilot Analysis of Immune Function Testing.

Fri, 08/11/2017 - 12:45
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The Effects of Tacrolimus on T-Cell Proliferation Are Short-Lived: A Pilot Analysis of Immune Function Testing.

Transplant Direct. 2017 Aug;3(8):e199

Authors: Laskin BL, Jiao J, Baluarte HJ, Amaral S, Furth SL, Akimova T, Hancock WW, Levine MH, Reese PP, Beier UH

Abstract
BACKGROUND: Optimal immunosuppression after organ transplant should balance the risks of rejection, infection, and malignancy while minimizing barriers to adherence including frequent or time-sensitive dosing. There is currently no reliable immune function assay to directly measure the degree of immunosuppression after transplantation.
METHODS: We developed an immune function assay to mea//sure T-cell proliferation after exposure to immunosuppression in vivo. We tested the assay in mice, and then piloted the approach using single time point samples, 11 pediatric kidney transplant recipients prescribed tacrolimus, mycophenolate, and prednisone 6 months to 5 years posttransplant, with no history of rejection, opportunistic infection, or cancer. Twelve healthy adults were controls.
RESULTS: We demonstrated that our assay can quantify suppression of murine T-cell proliferation after tacrolimus treatment in vivo. In humans, we found a mean 25% reduction in CD4 and CD8 T-cell proliferation in pediatric renal transplant recipients on triple immunosuppression compared with adult healthy controls, but the pilot results were not statistically significant nor correlated with serum tacrolimus levels. We observed that cell processing and washing reduced the effects of tacrolimus on T-cell proliferation, as did discontinuation of tacrolimus treatment shortly before sampling.
CONCLUSIONS: T-cell proliferation is currently not suitable to measure immunosuppression because sample processing diminishes observable effects. Future immune function testing should focus on fresh samples with minimal washing steps. Our results also emphasize the importance of adherence to immunosuppressive treatment, because T-cell proliferation recovered substantially after even brief discontinuation of tacrolimus.

PMID: 28795150 [PubMed]

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