Skip directly to content

PubMed Kidney Transplant

Subscribe to PubMed Kidney Transplant feed PubMed Kidney Transplant
NCBI: db=pubmed; Term=kidney transplant
Updated: 1 hour 14 min ago

[Brain abscesses caused by Nocardia farcinica in a kidney transplanted man].

Wed, 06/14/2017 - 12:45

[Brain abscesses caused by Nocardia farcinica in a kidney transplanted man].

Ugeskr Laeger. 2017 Jun 05;179(23):

Authors: Tinggaard M, Bagge K

Abstract
Nocardiosis is primarily an opportunistic infection caused by aerobic Gram-positive bacteria of the genus Nocardia. In this case report we describe a male patient who previously received a kidney transplant and was admitted to hospital with chills, headache and pain in the neck and left eye, tremor and coordination problems. A magnetic resonance scan of the brain showed multiple abscesses, and blood culture was positive for Nocardia farcinica. Nocardiosis of the central nervous system is a rare, but serious differential diagnosis in immunosuppressed patients with signs of high intracranial pressure.

PMID: 28606302 [PubMed - in process]

Pharmacokinetics and safety of carfilzomib in patients with relapsed multiple myeloma and end-stage renal disease (ESRD): an open-label, single-arm, phase I study.

Wed, 06/14/2017 - 12:45
Related Articles

Pharmacokinetics and safety of carfilzomib in patients with relapsed multiple myeloma and end-stage renal disease (ESRD): an open-label, single-arm, phase I study.

Cancer Chemother Pharmacol. 2017 Jun;79(6):1067-1076

Authors: Quach H, White D, Spencer A, Ho PJ, Bhutani D, White M, Inamdar S, Morris C, Ou Y, Gyger M

Abstract
PURPOSE: The pharmacokinetics (PK) of carfilzomib have been previously studied in multiple myeloma patients with varying degrees of renal impairment (normal, mild, moderate, severe, and end-stage renal disease [ESRD]) at doses of 15 and 20 mg/m(2). This study evaluated carfilzomib PK at higher doses of 27 and 56 mg/m(2) in normal renal function and ESRD patients.
METHODS: Patients received carfilzomib on two consecutive days/week for 3 weeks every 28-day cycle: 20 mg/m(2) (cycle 1 day 1-2), escalated to 27 mg/m(2) on cycle 1 day 8; if tolerated, 56 mg/m(2) starting cycle 2 day 1. The primary objective was PK assessment with safety/tolerability and response rate as secondary and exploratory objectives, respectively.
RESULTS: 26 patients were enrolled (15 normal, 11 ESRD). There was a trend toward higher area under the concentration time curve (AUC) and maximum concentration in ESRD versus normal renal function patients; however, high interpatient PK variability was discerned. Relative to patients with normal renal function, ESRD patients showed 33% higher AUC. Overall response rate was 43% for the normal renal function and 60% for the ESRD groups. Safety findings were generally similar between the two groups and consistent with the known safety profile of carfilzomib in multiple myeloma patients.
CONCLUSION: There were no meaningful differences in PK between patients with normal renal function and ESRD in light of carfilzomib exposure-response relationships. These results continue to support dosing recommendation that no starting dose adjustment of carfilzomib appears warranted in patients with baseline renal impairment.

PMID: 28424963 [PubMed - indexed for MEDLINE]

Leucine-rich repeat-containing G-protein-coupled receptor 5-positive cells in the endometrial stem cell niche.

Wed, 06/14/2017 - 12:45
Related Articles

Leucine-rich repeat-containing G-protein-coupled receptor 5-positive cells in the endometrial stem cell niche.

Fertil Steril. 2017 Feb;107(2):510-519.e3

Authors: Cervelló I, Gil-Sanchis C, Santamaría X, Faus A, Vallvé-Juanico J, Díaz-Gimeno P, Genolet O, Pellicer A, Simón C

Abstract
OBJECTIVE: To study, isolate and characterize leucine-rich repeat-containing heterotrimeric guanine nucleotide-binding protein-coupled receptor 5 (LGR5)-positive cells from human endometrium to determine their functional relevance.
DESIGN: Prospective experimental animal study.
SETTING: University research laboratories.
ANIMAL(S): Nonobese diabetic mice (NOD-SCID) (strain code 394; NOD.CB17-Prkdc(scid)/NcrCrl).
INTERVENTION(S): Human LGR5(+) cells were labeled with superparamagnetic iron oxide nanoparticles (SPIOs) and injected under the kidney capsule in immunocompromised mice.
MAIN OUTCOME MEASURE(S): Epithelial and stromal LGR5(+) cells were isolated from human endometrium by means of fluorescence-activated cell sorting, and phenotypic characterization was performed by means of flow cytometry with the use of hematopoietic and mesenchymal markers. Engrafted SPIO-labeled LGR5(+) cells were localized with the use of Prussian blue staining and immunohistochemistry against CD9 and Vimentin. Deep transcriptomic profiling of LGR5(+) cells was performed with the use of microarrays and RNA sequencing.
RESULT(S): The percentage of LGR5(+) cells in human endometrium represented 1.08 ± 0.73% and 0.82 ± 0.76% of total cells in the epithelial and stromal compartments, respectively. LGR5(+) cells were phenotypically characterized by abundant expression of CD45 hematopoietic marker and no expression of surface markers CD31, CD34, CD133, CD73, and CD90. Coexpression with the macrophage marker CD163 was detected. Xenotransplantation of labeled LGR5(+) cells into the kidney capsules of immunocompromised mice resulted in a weak endometrial reconstitution from this cell of origin. Transcriptomic profiling revealed new attributes for LGR5(+) cells related to their putative hematopoietic origin.
CONCLUSION(S): These data suggest that endometrial LGR5 is not an endogenous stem cell marker. Instead, LGR5(+) cells appear to be recruited from blood to be part of the stem cell niche at the perivascular microenvironment to activate the endogenous niche.

PMID: 27887719 [PubMed - indexed for MEDLINE]

A randomized crossover study comparing membrane and centrifugal therapeutic plasma exchange procedures.

Wed, 06/14/2017 - 12:45
Related Articles

A randomized crossover study comparing membrane and centrifugal therapeutic plasma exchange procedures.

Transfusion. 2016 Dec;56(12):3065-3072

Authors: Kes P, Janssens ME, Bašić-Jukić N, Kljak M

Abstract
BACKGROUND: Therapeutic plasma exchange (TPE) can be performed either on a membrane-based system (mTPE) or on a device that separates blood components by centrifugation (cTPE). The number of studies in this field is limited. This randomized study is the first that offers data on the membrane-based Diapact device (B. Braun Medical, Inc.) for TPE procedures and compares it to the centrifuge-based Spectra Optia (Terumo BCT, Inc.).
STUDY DESIGN AND METHODS: Twenty-seven patients were enrolled in this randomized prospective head-to-head study comparing the mTPE and cTPE systems. Procedures on both devices were standardized and the plasma removal efficiency (PRE); total procedure time (including setup and priming time); and removal efficiencies of blood cells, immunoglobulin (Ig)G, and fibrinogen for all procedures were analyzed.
RESULTS: While both systems removed similar amounts of plasma, it took the cTPE device a mean of 101.5 ± 24.6 minutes to finalize a procedure that was one-third less than procedures on the mTPE device (157 ± 26.2 min; p < 0.0001), due to a difference in PRE between the Spectra Optia (83.0% ± 4.9%) and the Diapact (53.2% ± 6.6%; p < 0.0001). The difference in removal efficiencies of IgG and blood cells were not significantly different but the Spectra Optia was more efficient in removing the larger fibrinogen protein than the Diapact (72.3% ± 8.5% vs. 62.9% ± 16.1%, respectively; p < 0.02).
CONCLUSION: This study shows that, although both systems perform adequate and safe TPE procedures, those on the Spectra Optia in comparison to the Diapact are more efficient in terms of plasma removal and significantly shorter.

PMID: 27704559 [PubMed - indexed for MEDLINE]

Sofosbuvir-Based Antiviral Therapy Is Highly Effective In Recurrent Hepatitis C in Liver Transplant Recipients: Canadian Multicenter "Real-Life" Experience.

Wed, 06/14/2017 - 12:45
Related Articles

Sofosbuvir-Based Antiviral Therapy Is Highly Effective In Recurrent Hepatitis C in Liver Transplant Recipients: Canadian Multicenter "Real-Life" Experience.

Transplantation. 2016 May;100(5):1059-65

Authors: Faisal N, Bilodeau M, Aljudaibi B, Hirsch G, Yoshida EM, Hussaini T, Ghali MP, Congly SE, Ma MM, Leonard J, Cooper C, Peltekian K, Renner EL, Lilly LB

Abstract
BACKGROUND: This study evaluates the efficacy, safety, and tolerability of regimens containing sofosbuvir (SOF) in the treatment of hepatitis C virus (HCV) recurrence in all genotypes in patients outside of clinical trials in all Canadian transplant centers.
METHODS: One hundred twenty liver transplantation recipients from across Canada with HCV recurrence were started on SOF-based regimens (SOF + simeprevir ± ribavirin (RBV), n = 53; SOF + pegylated interferon + RBV, n = 25; SOF + RBV, n = 36; and SOF + ledipasvir, n = 6) between January and November 2014. Mean age 58 ± 6.85 years, majority (83%) were genotype 1, male (81%), and treatment experienced (82%). Twenty-seven percent had fibrosing cholestatic hepatitis/early aggressive HCV in the graft, and 48% had F3/4 fibrosis. The primary outcomes included patient and graft survival, on- and end-of-treatment response and sustained virological response at 12 weeks after treatment end (SVR12), and adverse events.
RESULTS: One hundred thirteen of 120 (94%) patients were HCV RNA undetectable at end of treatment, and SVR12 was achieved in 102/120 (85%) patients, with 7 relapses, 1 nonresponder, and 10 deaths (liver-related complications). Sixty-three percent had HCV RNA levels below the lower limit of quantification at week 4. Serum creatinine levels remained stable throughout the treatment. Severe anemia occurred in 13% of patients, primarily in RBV-based regimens.
CONCLUSIONS: Sofosbuvir-based antiviral therapy for HCV recurrence after liver transplantation was well tolerated, with an overall high SVR12 rate (85%) including patients with severe disease recurrence and F3-4 cirrhosis. The response rate was higher (91%) in mild HCV recurrence, suggesting earlier treatment might be beneficial.

PMID: 26950722 [PubMed - indexed for MEDLINE]

Everolimus with cyclosporine withdrawal or low-exposure cyclosporine in kidney transplantation from Month 3: a multicentre, randomized trial.

Tue, 06/13/2017 - 12:45

Everolimus with cyclosporine withdrawal or low-exposure cyclosporine in kidney transplantation from Month 3: a multicentre, randomized trial.

Nephrol Dial Transplant. 2017 Jun 01;32(6):1060-1070

Authors: Budde K, Zeier M, Witzke O, Arns W, Lehner F, Guba M, Jacobi J, Kliem V, Reinke P, Hauser IA, Vogt B, Stahl R, Rath T, Duerr M, Paulus EM, May C, Porstner M, Sommerer C, HERAKLES Study Group

Abstract
Background.: Randomized trials have shown that early adoption of everolimus-based immunosuppressive regimens without a calcineurin inhibitor (CNI) improves long-term kidney graft function, but the optimal strategy for CNI minimization remains uncertain.
Methods.: In a prospective, randomized, multicentre, 12-month trial, 499 de novo kidney transplant patients were randomized at Month 3 to (i) remain on standard CNI (cyclosporine) therapy with mycophenolic acid, (ii) convert to everolimus with mycophenolic acid or (iii) start everolimus with reduced CNI and no mycophenolic acid (clinical trials registry: ClinicalTrials.gov-NCT00514514).
Results.: The primary endpoint, change in estimated glomerular filtration rate (eGFR) (Nankivell) from randomization to Month 12, was significantly greater in the CNI-free arm versus standard CNI therapy: mean difference 5.6 mL/min/1.73 m 2 [95% confidence interval (CI) 2.8-8.3 mL/min/1.73 m 2 , P < 0.001]. The improvement in eGFR in the CNI-free arm was also higher than in the low-CNI group (mean difference 5.5 mL/min/1.73 m 2 , 95% CI 2.8-8.2 mL/min/1.73 m 2 , P < 0.001), while results were similar in the low-CNI and standard CNI arms. The post-randomization incidence of biopsy-proven acute rejection was 11.7%, 8.1% and 7.9% in the CNI-free, low-CNI and standard CNI groups, respectively (CNI-free versus standard CNI, P = 0.27; low-CNI versus standard CNI, P = 1.00). Adverse events led to study drug discontinuation in 28.7%, 15.5% and 15.2% of CNI-free, low-CNI and standard CNI patients, respectively.
Conclusions.: Everolimus initiation with CNI withdrawal at Month 3 after kidney transplantation achieves a significant improvement in renal function at 12 months, with a similar rate of acute rejection.

PMID: 28605781 [PubMed - in process]

Uremia induces adipose tissue inflammation and muscle mitochondrial dysfunction.

Tue, 06/13/2017 - 12:45

Uremia induces adipose tissue inflammation and muscle mitochondrial dysfunction.

Nephrol Dial Transplant. 2017 Jun 01;32(6):943-951

Authors: Martinez Cantarin MP, Whitaker-Menezes D, Lin Z, Falkner B

Abstract
Background.: End-stage renal disease (ESRD) is associated with inflammation and increased reactive oxygen species (ROS). Inflammation and oxidative stress are associated with several complications of ESRD. The aim of this study was to determine histological characteristics of adipose tissue and muscle mitochondrial function in uremia and its relationship with inflammation.
Methods.: ESRD patients ( n  = 18) and controls ( n  = 6) were enrolled for studies of adipose and muscle tissue by immunohistochemistry and western blot. In a uremic muscle cell model, C2C12 cells were exposed to uremic serum and inflammatory cytokines. Mitochondrial function was studied by MitoTracker Orange, translocase of the mitochondrial outer membrane 20 (TOMM20) and mitochondrial oxidative phosphorylation complex subunit expression.
Results.: ESRD patients had increased macrophage infiltration in subcutaneous and visceral adipose tissue compared with controls, even in nonobese ESRD patients (P < 0.05). Compared with controls, TOMM20 expression in muscle tissue was lower in ESRD, consistent with reduced mitochondrial function (P < 0.05). C2C12 exposed to uremia had decreased mitotracker intensity (P < 0.05) and the reduced mitochondrial function was rescued by N-acetyl cysteine (P < 0.01). Similarly, C2C12 cells exposed to tumor necrosis factor α (TNF-α)/interleukin-6 (IL-6) have decreased mitotracker intensity (P < 0.01) that was rescued with adiponectin (P < 0.05). C2C12 exposed to TNF-α, IL-6 and buthionine sulfoximine had decreased TOMM20 expression and cells exposed to TNF-α showed a decrease in subunits of mitochondrial complexes I and III.
Conclusion.: Our data indicate that uremia is associated with increased adipose tissue macrophage infiltration and concurrent muscle tissue mitochondrial dysfunction induced by inflammation/ROS. Adipose tissue is a potential source of inflammation in ESRD that is not due to increased adiposity and may contribute to mitochondrial dysfunction in uremia.

PMID: 28605780 [PubMed - in process]

A novel homozygous UMOD mutation reveals gene dosage effects on uromodulin processing and urinary excretion.

Tue, 06/13/2017 - 12:45

A novel homozygous UMOD mutation reveals gene dosage effects on uromodulin processing and urinary excretion.

Nephrol Dial Transplant. 2017 Jun 10;:

Authors: Edwards N, Olinger E, Adam J, Kelly M, Schiano G, Ramsbottom SA, Sandford R, Devuyst O, Sayer JA

Abstract
Heterozygous mutations in UMOD encoding the urinary protein uromodulin are the most common genetic cause of autosomal dominant tubulointerstitial kidney disease (ADTKD). We describe the exceptional case of a patient from a consanguineous family carrying a novel homozygous UMOD mutation (p.C120Y) affecting a conserved cysteine residue within the EGF-like domain III of uromodulin. Comparison of heterozygote and homozygote mutation carriers revealed a gene dosage effect with unprecedented low levels of uromodulin and aberrant uromodulin fragments in the urine of the homozygote proband. Despite an amplified biological effect of the homozygote mutation, the proband did not show a strikingly more severe clinical evolution nor was the near absence of urinary uromodulin associated with urinary tract infections or kidney stones.

PMID: 28605509 [PubMed - as supplied by publisher]

Illness Cognition among Kidney Transplant Recipients: A Preliminary Longitudinal Study.

Tue, 06/13/2017 - 12:45

Illness Cognition among Kidney Transplant Recipients: A Preliminary Longitudinal Study.

Health Soc Work. 2017 Jun 09;:1-2

Authors: Hamama-Raz Y, Ben-Ezra M, Tirosh Y, Baruch R, Nakache R

PMID: 28605438 [PubMed - as supplied by publisher]

Prevalence of CYP3A5 Genomic Variances and Their Impact on Tacrolimus Dosing Requirements among Kidney Transplant Recipients in Eastern North Carolina.

Tue, 06/13/2017 - 12:45

Prevalence of CYP3A5 Genomic Variances and Their Impact on Tacrolimus Dosing Requirements among Kidney Transplant Recipients in Eastern North Carolina.

Pharmacotherapy. 2017 Jun 12;:

Authors: Maldonado AQ, Asempa T, Hudson S, Rebellato LM

Abstract
STUDY OBJECTIVE: To assess the prevalence of CYP3A5 genomic variances and their impact on tacrolimus dosing requirements among kidney transplant recipients in eastern North Carolina.
DESIGN: Single-center, retrospective cohort study.
SETTING: Large tertiary care medical center.
PATIENTS: A total of 162 adults who received a kidney transplant between March 1, 2013, and February 28, 2015, and received oral tacrolimus as part of their maintenance immunosuppression; of these patients, 85 patients expressed a genotype with a CYP3A5*1 variant (CYP3A5*1 group), and 77 patients expressed genotypes with other CYP3A5 variants (nonexpressor group).
MEASUREMENTS AND MAIN RESULTS: All patients were followed for 1 year posttransplantation. The primary endpoint was the tacrolimus total daily dose (TDD) required to achieve the first therapeutic trough level based on the presence or absence of the CYP3A5*1 variant. The prevalence of different CYP3A5 variants across race-ethnicities in the study cohort was determined by CYP3A5 genotyping for each patient. The CYP3A5*1 and nonexpressor groups did not differ significantly with respect to sex, mean age, or mean weight. The CYP3A5*1 group was largely African-American (93%, p<0.0005) compared with other race-ethnicities. Among the CYP3A5*1 expressors compared with nonexpressors, the mean tacrolimus TDD in milligrams at the first therapeutic tacrolimus level was significantly higher (12 vs 8 mg/day, p≤0.001). Similarly, the mean tacrolimus TDD in milligrams/kilogram was 50% greater among CYP3A5*1 expressors (0.15 vs. 0.1 mg/kg/day, p≤0.0005). The predominant genotypic variants were CYP3A5*3/*3 (33%), CYP3A5*1/*3 (20%), and CYP3A5*1/*1 (19%).
CONCLUSION: This study illustrates the prevalence of the CYP3A5*1 variant among African-American kidney transplant recipients and the effect of this gene expression on the tacrolimus TDD. Patients with the CYP3A5*1 variant require higher tacrolimus doses, on average, to achieve desirable drug levels. In addition, this study provides transplant clinicians with insight and support to dose tacrolimus more aggressively in African-American kidney transplant recipients who may be at higher risk for both toxicities as well as poor clinical outcomes related to inadequate immunosuppression. This article is protected by copyright. All rights reserved.

PMID: 28605053 [PubMed - as supplied by publisher]

Iatrogenic lymphocutaneous fistula secondary to right-sided pheresis catheter placement and its percutaneous treatment: a case report.

Tue, 06/13/2017 - 12:45

Iatrogenic lymphocutaneous fistula secondary to right-sided pheresis catheter placement and its percutaneous treatment: a case report.

J Vasc Access. 2017 Jun 06;:0

Authors: Quencer KB, Ayyagari RR, Friedman T

Abstract
We present a case of an iatrogenic lymphocutaneous fistula secondary to placement of a tunneled, large bore (14.5 Fr) right-sided internal jugular vein for plasmapheresis to treat antibody-mediated kidney transplant rejection. While iatrogenic lymphatic leaks caused by neck and thoracic surgeries are well described in the literature, lymphatic leak or lymphocutaneous fistula resulting from image-guided placement of a central venous catheter through the right internal jugular vein has yet to be described. We also describe the successful percutaneous treatment of this lymphocutaneous fistula using a combination of n-butyl cyanoacrylate glue and embolization coils.

PMID: 28604987 [PubMed - as supplied by publisher]

Developing a neonatal acute kidney injury research definition: A report from the NIDDK neonatal AKI workshop.

Tue, 06/13/2017 - 12:45

Developing a neonatal acute kidney injury research definition: A report from the NIDDK neonatal AKI workshop.

Pediatr Res. 2017 Jun 12;:

Authors: Zappitelli M, Ambalavanan N, Askenazi DJ, Moxey-Mims MM, Kimmel PL, Star RA, Abitbol CL, Brophy PD, Hidalgo G, Hanna M, Morgan CM, Raju TNK, Ray P, Reyes-Bou Z, Roushdi A, Goldstein SL

Abstract
Normal developmental changes during postnatal life hinder the development of an AKI definition and advancement of neonatal AKI research. This report summarizes the expert discussion at a National Institute of Diabetes and Digestive and Kidney Diseases sponsored neonatal AKI workshop, on knowledge gaps in defining neonatal AKI. The most important knowledge gaps and neonatal AKI definition research recommendations were agreed upon and defined. Several challenges were identified in defining neonatal AKI using serum creatinine (SCr) and urine output criteria applied in adults and children. Neonate-tailored AKI definitions incorporating neonatal physiology should be developed and tested, with a focus on applicability across gestational and postnatal age groups. Studies evaluating associations of AKI with short and long-term outcomes and validating new AKI biomarkers are research priorities.Pediatric Research accepted article preview online, 12 June 2017. doi:10.1038/pr.2017.136.

PMID: 28604760 [PubMed - as supplied by publisher]

Severe Sarcopenia and Increased Fat Stores in Pediatric Patients With Liver, Kidney, or Intestine Failure.

Tue, 06/13/2017 - 12:45

Severe Sarcopenia and Increased Fat Stores in Pediatric Patients With Liver, Kidney, or Intestine Failure.

J Pediatr Gastroenterol Nutr. 2017 Jun 09;:

Authors: Mangus RS, Bush WJ, Kubal CA, Miller C

Abstract
OBJECTIVES: Malnutrition and wasting predict clinical outcomes in children with severe chronic illness. Objectively calculated malnutrition in children with end-stage organ failure has not been well studied. This analysis compares children with kidney, liver or intestine failure to healthy controls to quantitate the disparity in muscle and fat stores.
METHODS: Children younger than age 19 with end stage liver, kidney or intestine failure and with pre-transplant computed tomography (CT) imaging were selected from the transplant database. Age and gender-matched healthy controls were selected from the trauma database. Measures of nutrition status included a scaled scoring of core muscle mass, and visceral and subcutaneous fat stores. Analysis was conducted using the pooled and individually matched subject-control differences.
RESULTS: There were 81 subjects included in the final analysis (liver (n = 35), kidney (n = 20) and intestine (n = 26)). Children with end-stage liver disease had a 23% reduction in muscle mass, a 69% increase in visceral fat and a 29% increase in subcutaneous fat. End-stage renal disease patients had a 19% reduction in muscle mass and a 258% increase in subcutaneous fat. Intestine failure patients had a 24% reduction in muscle mass, a 30% increase in visceral fat and a 46% increase in subcutaneous fat.
CONCLUSIONS: These results demonstrate significant sarcopenia and increased fat stores in end-stage organ failure patients which supports the idea of an active physiologic mechanism to store fat while losing muscle mass. Sarcopenia may be related to total protein loss from a catabolic state, or from decreased synthesis (liver), wasting (kidney) or malabsorption (intestine).

PMID: 28604513 [PubMed - as supplied by publisher]

Pretransplant 4β-hydroxycholesterol does not predict tacrolimus exposure or dose requirements during the first days after kidney transplantation.

Tue, 06/13/2017 - 12:45
Related Articles

Pretransplant 4β-hydroxycholesterol does not predict tacrolimus exposure or dose requirements during the first days after kidney transplantation.

Br J Clin Pharmacol. 2017 Jun 11;:

Authors: Vanhove T, Hasan M, Annaert P, Oswald S, Kuypers DRJ

Abstract
AIMS: The CYP3A metric 4β-hydroxycholesterol (4βOHC) has been shown to correlate with tacrolimus steady-state apparent oral clearance (CL/F). Recently, pretransplant 4βOHC was shown not to predict tacrolimus CL/F after transplantation in a cohort of renal recipients (n=79). The goal of the current study was determine whether these findings could be validated in a substantially larger cohort.
METHODS: In a retrospective analysis of 279 renal recipients, tacrolimus trough concentrations (C0), daily dose, haematocrit and other relevant covariates were registered every day for the first 14 days after transplantation. 4βOHC and cholesterol were quantified on plasma collected immediately pretransplant using liquid chromatography tandem-mass spectrometry. Patients were genotyped for CYP3A5*1 and CYP3A4*22.
RESULTS: A total of 3551 tacrolimus C0 concentrations were registered. In a linear mixed model for the 14-day period, determinants of tacrolimus C0 were CYP3A5 genotype, haematocrit, age and weight (overall R(2) =0.179). Determinants of daily dose were CYP3A5 genotype, age, methylprednisolone dose, tacrolimus formulation, ALT and estimated glomerular filtration rate (overall R(2) =0.242). Considering each of the first 5 days separately, 4βOHC had a limited effect on tacrolimus C0 on day 3 only (-1.00 ng/ml per Ln, P=0.035) but not on any other day, and no effect on dose or C0/dose. During the first 5 days haematocrit and age, previously established as determinants of tacrolimus disposition under steady-state conditions, never explained more than 17.7% of between-subject variability in tacrolimus C0/dose.
CONCLUSIONS: The CYP3A metric 4βOHC cannot be used to predict tacrolimus dose requirements in the first days after transplantation.

PMID: 28603840 [PubMed - as supplied by publisher]

Contrast-Induced Nephropathy in Renal Transplant Recipients: A Single Center Experience.

Tue, 06/13/2017 - 12:45
Related Articles

Contrast-Induced Nephropathy in Renal Transplant Recipients: A Single Center Experience.

Front Med (Lausanne). 2017;4:64

Authors: Abu Jawdeh BG, Leonard AC, Sharma Y, Katipally S, Shields AR, Alloway RR, Woodle ES, Thakar CV

Abstract
BACKGROUND: Contrast-induced nephropathy (CIN) in native kidneys is associated with a significant increase in mortality and morbidity. Data regarding CIN in renal allografts are limited, however. We retrospectively studied CIN in renal allografts at our institution: its incidence, risk factors, and effect on long-term outcomes including allograft loss and death.
METHODS: One hundred thirty-five renal transplant recipients undergoing 161 contrast-enhanced computed tomography (CT) scans or coronary angiograms (Cath) between years 2000 and 2014 were identified. Contrast agents were iso- or low osmolar. CIN was defined as a rise in serum creatinine (SCr) by >0.3 mg/dl or 25% from baseline within 4 days of contrast exposure. After excluding 85 contrast exposures where patients had no SCr within 4 days of contrast administration, 76 exposures (CT: n = 45; Cath: n = 31) in 50 eligible patients were analyzed. Risk factors assessed included demographics, comorbid conditions, type/volume of contrast agent used, IV fluids, N-acetylcysteine administration, and calcineurin inhibitor use. Bivariate and multivariable analyses were used to assess the risk of CIN.
RESULTS: Incidence of CIN was 13% following both, CT (6 out of 45) and Cath (4 out of 31). Significant bivariate predictors of CIN were IV fluid administration (p = 0.05), lower hemoglobin (p = 0.03), and lower albumin (p = 0.02). In a multivariable model, CIN was predicted by N-acetylcysteine (p = 0.03) and lower hemoglobin (p = 0.01). Calcineurin inhibitor use was not associated with CIN. At last follow-up, CIN did not affect allograft or patient survival.
CONCLUSION: CIN is common in kidney transplant recipients, and there is room for quality improvement with regards to careful renal function monitoring post-contrast exposure. In our study, N-acetylcysteine exposure and lower hemoglobin were associated with CIN. Calcineurin inhibitor use was not associated with CIN. Our sample size is small, however, and larger prospective studies of CIN in renal allografts are needed.

PMID: 28603715 [PubMed - in process]

Transplantation: Survival benefit of accepting a diabetic deceased donor kidney.

Tue, 06/13/2017 - 12:45
Related Articles

Transplantation: Survival benefit of accepting a diabetic deceased donor kidney.

Nat Rev Nephrol. 2017 Jun 12;:

Authors: Carney EF

PMID: 28603273 [PubMed - as supplied by publisher]

Anatomical and Radiological Analyses of L-shaped Kidney with Vascular Anomalies.

Tue, 06/13/2017 - 12:45
Related Articles

Anatomical and Radiological Analyses of L-shaped Kidney with Vascular Anomalies.

Kurume Med J. 2017 Jun 12;:

Authors: Iwanaga J, Watanabe K, Saga T, Tahara N, Tabira Y, Sakuragi A, Kaji K, Takahashi K, Yamaki KI

Abstract
L-shaped kidney is a congenital anomaly. The disorder results in the kidney appearing very similar in shape to horseshoe kidney (also a congenital anomaly), but either the right or left kidney is located at a position lower than the other kidney. In this report, we describe a woman with L-shaped kidney, identified during anatomical dissection, and compare the findings with clinical data obtained before her death. We discuss the embryology of L-shaped kidney based on detailed anatomical data on the kidney and its vascular system obtained by means of gross anatomical, radiological, and histological examinations. Our findings indicate the importance of detailed anatomical information when planning surgical procedures in patients with fused kidneys, as well as kidney transplantation, resection of renal carcinoma, or surgical treatment of abdominal aortic aneurysm.

PMID: 28603157 [PubMed - as supplied by publisher]

New Developments in Hepatorenal Syndrome.

Tue, 06/13/2017 - 12:45
Related Articles

New Developments in Hepatorenal Syndrome.

Clin Gastroenterol Hepatol. 2017 Jun 07;:

Authors: Mindikoglu AL, Pappas SC

Abstract
Hepatorenal Syndrome (HRS) continues to be one of the major complications of decompensated cirrhosis leading to death in the absence of liver transplantation. Challenges in precisely evaluating renal function in the patient with cirrhosis remain due to the limitations of serum creatinine (Cr) alone in estimating glomerular filtration rate (GFR); current GFR estimating models appear to underestimate renal function. Newer models incorporating renal biomarkers, such as the Cr-Cystatin C GFR Equation for Cirrhosis appear to more accurately estimate true GFR. A major change in the diagnostic criteria for HRS based on dynamic serial changes in serum Cr which regard HRS type 1 as a special form of acute kidney injury (AKI) promises the possibility of earlier identification of renal dysfunction in patients with cirrhosis. The diagnostic criteria of HRS still include the exclusion of other causes of kidney injury. Renal biomarkers have been disappointing in assisting with the differentiation of HRS from pre-renal azotemia and other kidney disorders. Serum metabolomic profiling may be a more powerful tool to assess renal dysfunction although the practical clinical significance of this remains unclear. As a result of the difficulties of assessing renal function in cirrhosis and the varying HRS diagnostic criteria and the rigor with which they are applied, the precise incidence and prevalence of HRS is unknown but it is likely that HRS occurs more commonly than expected. The pathophysiology of HRS is firmly rooted in the setting of progressive reduction in renal blood flow (RBF) as a result of portal hypertension and splanchnic vasodilation. Progressive, marked renal cortical ischemia in patients with cirrhosis parallels the evolution of diuretic-sensitive ascites to diuretic-refractory ascites and HRS, a recognized continuum of renal dysfunction in cirrhosis. Alterations in nitrous oxide (NO) production, both increased and decreased may play a major role in the pathophysiology of this evolution. The inflammatory cascade triggered by bacterial translocation and endotoxemia, increasingly recognized as important in the manifestations of acute on chronic liver failure, may also play a significant role in the pathophysiology of HRS. The mainstay of treatment remains vasopressor therapy with albumin in an attempt to reverse splanchnic vasodilation and improve RBF. Several meta-analyses confirm the value of vasopressors, chiefly terlipressin and norepinephrine, in improving renal function and reversing HRS type 1. Other interventions such as renal replacement therapy, transjugular intrahepatic porto-systemic shunt (TIPS), and artificial liver support systems have a very limited role to improve outcomes in HRS. Liver transplantation remains the definitive treatment for HRS. The frequency of simultaneous liver-kidney transplantation (SLKT) has increased dramatically in the Model for End-Stage Liver Disease (MELD) era, with changes is organ allocation policies. This has resulted in a more urgent need to accurately predict native kidney recovery from HRS after liver transplantation alone, to avoid unnecessary SLKT.

PMID: 28602971 [PubMed - as supplied by publisher]

Renal Allograft Outcome After Simultaneous Heart and Kidney Transplantation.

Tue, 06/13/2017 - 12:45
Related Articles

Renal Allograft Outcome After Simultaneous Heart and Kidney Transplantation.

Am J Cardiol. 2017 May 11;:

Authors: Grupper A, Grupper A, Daly RC, Pereira NL, Hathcock MA, Kremers WK, Cosio FG, Edwards BS, Kushwaha SS

Abstract
Chronic kidney disease frequently accompanies end-stage heart failure and may result in consideration of simultaneous heart and kidney transplantation (SHKT). In recent years, there has been a significant increase in SHKT. This single-center cohort consisted of 35 patients who underwent SHKT during 1996 to 2015. The aim of this study was to review factors that may predict better long-term outcome after SKHT. Thirteen patients (37%) had delayed graft function (DGF) after transplant (defined as the need for dialysis during the first 7 days after transplant), which was significantly associated with mechanical circulatory support device therapy and high right ventricular systolic pressure before transplant. Most of the recipients had glomerular filtration rate (GFR) ≥50 ml/min/1.73 m(2) at 1 and 3 years after transplant (21 of 26 [81%] and 20 of 21 [95%], respectively). Higher donor age was associated with reduced 1-year GFR (p = 0.017), and higher recipient pretransplant body mass index was associated with reduced 3-year GFR (p = 0.008). There was a significant association between DGF and reduced median GFR at 1 and 3 years after transplant (p <0.005). Patient survival rates at 6 months, 1, and 3 years after transplant were 97%, 91%, and 86% respectively. In conclusions, our data support good outcomes after SHKT. Mechanical circulatory support device therapy and pulmonary hypertension before transplant are associated with DGF, which is a risk factor for poor long-term renal allograft function.

PMID: 28602210 [PubMed - as supplied by publisher]

Molecular appraisal of intestinal parasitic infection in transplant recipients.

Tue, 06/13/2017 - 12:45
Related Articles

Molecular appraisal of intestinal parasitic infection in transplant recipients.

Indian J Med Res. 2016 Aug;144(2):258-263

Authors: Yadav P, Khalil S, Mirdha BR

Abstract
BACKGROUND & OBJECTIVES: Diarrhoea is the main clinical manifestation caused by intestinal parasitic infections in patients, with special reference to transplant recipients who require careful consideration to reduce morbidity and mortality. Further, molecular characterization of some important parasites is necessary to delineate the different modes of transmission to consider appropriate management strategies. We undertook this study to investigate the intestinal parasitic infections in transplant recipients with or without diarrhoea, and the genotypes of the isolated parasites were also determined.
METHODS: Stool samples from 38 transplant recipients comprising 29 post-renal, two liver and seven bone marrow transplant (BMT) recipients presenting with diarrhoea and 50 transplant recipients (42 post-renal transplant, eight BMT) without diarrhoea were examined for the presence of intestinal parasites by light microscopy using wet mount, modified Ziehl-Neelsen staining for intestinal coccidia and modified trichrome staining for microsporidia. Genotypes of Cryptosporidium species were determined by multilocus genotyping using small subunit ribosomal (SSUrRNA), Cryptosporidium oocyst wall protein (COWP) and dihydrofolate reductase (DHFR) as the target genes. Assemblage study for Giardia lamblia was performed using triose phosphate isomerase (TPI) as the target gene. Samples were also screened for bacterial, fungal and viral pathogens.
RESULTS: The parasites that were detected included Cryptosporidium species (21%, 8/38), Cystoisospora (Isospora) belli (8%, 3), Cyclospora cayetanensis (5%, 2), G. lamblia (11%, 4), Hymenolepis nana (11%, 4), Strongyloides stercoralis (3%, 1) and Blastocystis hominis (3%, 1). Multilocus genotyping of Cryptosporidium species at SSUrRNA, COWP and DHFR loci could detect four isolates of C. hominis; two of C. parvum, one of mixed genotype and one could not be genotyped. All the C. hominis isolates were detected in adult post-renal transplant (PRT) recipients, whereas the C. parvum isolates included a child with BMT and an adult with PRT. Clostridium difficle, cytomegalovirus and Candida albicans were found in 2, 3 and 2 patients, respectively.
INTERPRETATION & CONCLUSIONS: In the present study, C. hominis was observed as an important parasite causing intestinal infections in transplant recipients. Multilocus genotyping of Cryptosporidium species could detect four isolates of C. hominis; two of C. parvum, one of mixed genotype and one could not be genotyped. Genotyping of G. lamblia revealed that assemblage B was most common.

PMID: 27934806 [PubMed - indexed for MEDLINE]

Pages