Thursday, August 29, 2013

Multicenter Validation of Urinary CXCL9 as a Risk-Stratifying Biomarker for Kidney Transplant Injury.

AJT Multicenter Validation of Urinary CXCL9 as a Risk-Stratifying Biomarker for Kidney Transplant Injury.

Noninvasive biomarkers are needed to assess immune risk and ultimately guide therapeutic decision-making following kidney transplantation. A requisite step toward these goals is validation of markers that diagnose and/or predict relevant transplant endpoints. The Clinical Trials in Organ Transplantation-01 protocol is a multicenter observational study of biomarkers in 280 adult and pediatric first kidney transplant recipients. We compared and validated urinary mRNAs and proteins as biomarkers to diagnose biopsy-proven acute rejection (AR) and stratify patients into groups based on risk for developing AR or progressive renal dysfunction. Among markers tested for diagnosing AR, urinary CXCL9 mRNA (odds ratio [OR] 2.77, positive predictive value [PPV] 61.5%, negative predictive value [NPV] 83%) and CXCL9 protein (OR 3.40, PPV 67.6%, NPV 92%) were the most robust. Low urinary CXCL9 protein in 6-month posttransplant urines obtained from stable allograft recipients classified individuals least likely to develop future AR or a decrement in estimated glomerular filtration rate between 6 and 24 months (92.5-99.3% NPV). Our results support using urinary CXCL9 for clinical decision-making following kidney transplantation. In the context of acute dysfunction, low values can rule out infectious/immunological causes of injury. Absent urinary CXCL9 at 6 months posttransplant defines a subgroup at low risk for incipient immune injury.



http://www.unboundmedicine.com/medline/citation/23968332/Multicenter_Validation_of_Urinary_CXCL9_as_a_Risk_Stratifying_Biomarker_for_Kidney_Transplant_Injury_


Medication Adherence Assessment: High Accuracy of the New Ingestible Sensor System in Kidney Transplants

Transplantation - Most Popular Articles Medication Adherence Assessment: High Accuracy of the New Ingestible Sensor System in Kidney Transplants

imageBackgroundThis open-label single-arm exploratory study evaluated the accuracy of the Ingestible Sensor System (ISS), a novel technology for directly assessing the ingestion of oral medications and treatment adherence. MethodsISS consists of an ingestible event marker (IEM), a microsensor that becomes activated in gastric fluid, and an adhesive personal monitor (APM) that detects IEM activation. In this study, the IEM was combined to enteric-coated mycophenolate sodium (ECMPS). Twenty stable adult kidney transplants received IEM-ECMPS for a mean of 9.2 weeks totaling 1227 cumulative days. ResultsEight patients prematurely discontinued treatment due to ECMPS gastrointestinal symptoms (n=2), skin intolerance to APM (n=2), and insufficient system usability (n=4). Rash or erythema due to APM was reported in 7 (37%) patients, all during the first month of use. No serious or severe adverse events and no rejection episode were reported. IEM detection accuracy was 100% over 34 directly observed ingestions; Taking Adherence was 99.4% over a total of 2824 prescribed IEM-ECMPS ingestions. ISS could detect accurately the ingestion of two IEM-ECMPS capsules taken at the same time (detection rate of 99.3%, n=2376). ConclusionsISS is a promising new technology that provides highly reliable measurements of intake and timing of intake of drugs that are combined with the IEM.


http://journals.lww.com/transplantjournal/Fulltext/2013/08150/Medication_Adherence_Assessment___High_Accuracy_of.6.aspx

Thursday, August 22, 2013

Outcomes of Simultaneous Liver and Kidney Transplantation in Relation to a High Level of Preformed Donor-Specific Antibodies

Transplantation - Published Ahead-of-Print Outcomes of Simultaneous Liver and Kidney Transplantation in Relation to a High Level of Preformed Donor-Specific Antibodies

Background: The protective effect of the liver allograft when simultaneously transplanted with a kidney in the setting of allosensitization is unclear. Methods: We analyzed the significance of sensitization, defined based on positive cytotoxicity crossmatches, positive flow cytometry crossmatches, and/or the presence of high levels of donor-specific antibodies, on the outcomes of simultaneous liver and kidney (SLK) transplantation. We reviewed 56 SLK performed at our center through December 31, 2011 and identified 13 patients who met high sensitization criteria. Results: Median patient survival was not significantly different: 86 months (95% confidence interval [CI], 47-135) for nonsensitized patients versus 151 months (95% CI, 4 to [infinity]) for sensitized patients (P=0.5). The 5-year survival was 67% (95% CI, 0.5-0.8) in the nonsensitized group and 64% (95% CI, 0.3-0.9) in the sensitized group. There were six renal allograft failures in the nonsensitized group but none in the sensitized group. The adjusted hazard ratios associated with the risk of death or the combined risk of death or renal allograft failure were 0.7 (95% CI, 0.1-3.8) and 0.4 (95% CI, 0.1-2.2) for sensitized versus nonsensitized patients. There were significantly more renal allograft rejections in the sensitized group (5 vs. 1; P=0.002) in the first year after transplantation, only one showing C4d positivity. Creatinine levels at 1 year after transplantation were similar: 1.5 mg/dL in the nonsensitized group versus 1.36 mg/dL in the sensitized group (P=0.6). Conclusion: Sensitization does not appear to have a significant negative impact on the survival of SLK patients. (C) 2013 by Lippincott Williams & Wilkins


http://pdfs.journals.lww.com/transplantjournal/9000/00000/Outcomes_of_Simultaneous_Liver_and_Kidney.98487.pdf


Wednesday, August 21, 2013

Controlled-Dose Versus Fixed-Dose Mycophenolate Mofetil for Kidney Transplant Recipients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Transplantation - Current Issue Controlled-Dose Versus Fixed-Dose Mycophenolate Mofetil for Kidney Transplant Recipients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

imageBackgroundAlthough mycophenolate mofetil (MMF) is recommended at a fixed dose, there is increasing interest in controlled-dose (CD) MMF based on therapeutic drug monitoring. We systematically evaluated published randomized controlled trials (RCTs) on the efficacy and safety of CD versus fixed-dose MMF for kidney transplant recipients. MethodsThe electronic databases Medline, Embase, and Cochrane Library (up to June 2012) were searched to identify relevant RCTs. Two reviewers independently applied the study selection criteria, examined the study quality, and extracted the data. Dichotomous measures were expressed as relative risk (RR) and continuous outcomes were expressed as weighted mean difference, both with 95% confidence intervals (CIs). All statistical analyses were performed using Review Manager 5.1.6. ResultsFour RCTs met our selection criteria and included 1755 de novo recipients. The differences between CD and fixed-dose MMF in treatment failure (RR, 0.95; 95% CI, 0.82–1.10; P=0.52), serum creatinine clearance (weighted mean difference, 2.46; 95% CI, −1.15 to 6.07; P=0.18), total gastrointestinal adverse events (RR, 1.23; 95% CI, 0.65–2.35; P=0.53), diarrhea (RR, 1.08; 95% CI, 0.92–1.25; P=0.35), anemia (RR, 1.24; 95% CI, 0.95–1.64; P=0.12), leukopenia (RR, 1.12; 95% CI, 0.93–1.35; P=0.25), thrombocytopenia (RR, 0.80; 95% CI, 0.47–1.36; P=0.41), and malignancy (RR, 0.61; 95% CI, 0.27–1.38; P=0.23) were not statistically significant. Furthermore, total infections were more frequent in the CD group (36.0% vs. 30.9%; RR, 1.16; 95% CI, 1.03–1.30; P=0.01). ConclusionsBased on current evidence, CD MMF administration cannot be recommended as routine practice for kidney transplant recipients. Therapeutic drug monitoring for MMF may be targeted toward high-risk recipients, who should be identified in future studies.


http://journals.lww.com/transplantjournal/Fulltext/2013/08270/Controlled_Dose_Versus_Fixed_Dose_Mycophenolate.4.aspx

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Alberto Reino Buelvas
Médico Internista Nefrólogo
Hospital San Vicente de Paul
Grupo Trasplantes Renales
Director Médico Unidad Renal

Extrarenal Factors Influencing Resistance Index in Stable Kidney Transplant Recipients

Transplantation - Current Issue Extrarenal Factors Influencing Resistance Index in Stable Kidney Transplant Recipients

imageBackgroundIncreased intrarenal resistance index (RI) has been associated with decreased long-term allograft and patient survival in kidney transplant recipients. Taking into account the potential role of endothelial dysfunction, systemic inflammation, arteriosclerotic lesions, and left ventricle remodeling, we performed a cross-sectional study that aimed to evaluate extrarenal factors that may have influence on kidney graft RI in a large cohort of stable kidney transplant recipients. MethodsOne hundred seventy-four kidney transplant recipients were enrolled into the study. Mean time after transplantation was 8.4±1.8 years. Echocardiography, carotid ultrasound (intima-media thickness), pulse wave velocity, and Doppler examination of kidney graft were performed. The inflammatory markers, adhesion molecules, and plasma N-terminal prohormone of brain natriuretic peptide concentrations were also measured. Patients were divided into quartile subgroups based on RI value (Q1: RI≤0.68, Q2: RI=0.69–0.72, Q3: RI=0.73–0.76, and Q4: RI≥0.77). ResultsThe analyzed subgroups were comparable with respect to demographics (except age) and anthropometric parameters as well as comorbidities. The values of age, serum phosphate, pulse wave velocity, left ventricular mass (LVM), and LVM index (LVMI) increased in subsequent RI quartile subgroups. The strongest correlation was found between RI and age, LVM, LVMI, and plasma parathormone concentration and was negative with estimated glomerular filtration rate. In backward stepwise multivariate regression analysis, the RI variability was explained by age, LVMI, and serum phosphate concentration. ConclusionArterial stiffness and left ventricular hypertrophy may significantly influence the intrarenal vascular resistance measured using Doppler sonography in stable kidney transplant recipients.


http://journals.lww.com/transplantjournal/Fulltext/2013/08270/Extrarenal_Factors_Influencing_Resistance_Index_in.12.aspx


Sunday, August 18, 2013

The Survival Benefit of Kidney Transplantation in Obese Patients.

AJT The Survival Benefit of Kidney Transplantation in Obese Patients.

Obese patients have a decreased risk of death on dialysis but an increased risk of death after transplantation, and may derive a lower survival benefit from transplantation. Using data from the United States between 1995 and 2007 and multivariate non-proportional hazards analyses we determined the relative risk of death in transplant recipients grouped by body mass index (BMI) compared to wait-listed candidates with the same BMI (n = 208 498). One year after transplantation the survival benefit of transplantation varied by BMI: Standard criteria donor transplantation was associated with a 48% reduction in the risk of death in patients with BMI ≥ 40 kg/m(2) but a ≥66% reduction in patients with BMI < 40 kg/m(2) . Living donor transplantation was associated with ≥66% reduction in the risk of death in all BMI groups. In sub-group analyses, transplantation from any donor source was associated with a survival benefit in obese patients ≥50 years, and diabetic patients, but a survival benefit was not demonstrated in Black patients with BMI ≥ 40 kg/m(2) . Although most obese patients selected for transplantation derive a survival benefit, the benefit is lower when BMI is ≥40 kg/m(2) , and uncertain in Black patients with BMI ≥ 40 kg/m(2) .



http://www.unboundmedicine.com/medline/citation/23890325/The_Survival_Benefit_of_Kidney_Transplantation_in_Obese_Patients_


Abdominal tuberculosis following kidney transplantation: clinicopathologic features and follow-up in a unique case series

Clinical Transplantation Abdominal tuberculosis following kidney transplantation: clinicopathologic features and follow-up in a unique case series

Background Kidney transplant recipients are at a high risk of opportunistic infection. The aims of this study were to describe the epidemiology, clinical features, and prognosis of abdominal tuberculosis (TB) in kidney transplant recipients. Methods All cases of abdominal TB that occurred in kidney transplant recipients at our center between 1998 and 2010 were retrospectively reviewed. Detailed demographic data, clinical profile information, and the treatment response were recorded. Results Among the 7833 kidney transplantations performed during the study period, eight patients (0.1%) developed abdominal TB. There were four men and four women in this group. The mean age of the patients was 44 ± 12 yr. The time from kidney transplantation to TB was 6.7 ± 3.4 yr. The symptoms were weight loss (87.5%), diarrhea (87.5%), fever (75%), abdominal pain (62.5%), and lower gastrointestinal bleeding (37.5%). The delay between the identification of the clinical symptoms and the diagnosis was an average of six months. The diagnosis was confirmed histopathologically for most patients. The cecum and ascending colon were the most common sites involved. Two patients required surgical intervention. Five patients received a 4-drug regimen, and three had hepatotoxicity. The median length of antituberculous therapy was nine (6–12) months. Five patients lost their graft. Overall, the hospital mortality was 12.5%. Conclusions Kidney transplantation increases the risk of TB, particularly as an extrapulmonary disease. The symptoms of infection are often attenuated, leading to delayed diagnosis. Therefore, a careful approach to the patient and supportive data are necessary to make the final and timely diagnosis.


http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Fctr.12210


Thursday, August 15, 2013

Overall and Cause-Specific Mortality in Transplant Recipients with a Pretransplantation Cancer History

Transplantation - Current Issue Overall and Cause-Specific Mortality in Transplant Recipients with a Pretransplantation Cancer History

imageBackground: It is unclear to what extent cancer history affects posttransplantation mortality in solid organ transplant recipients. Methods: We identified a Swedish population-based cohort of solid organ transplant recipients in the National Patient Register 1970 to 2008 and linked it to the Cancer and Cause-of-Death Register. Overall and cause-specific mortality was estimated using Cox regression. Results: Of 10,448 eligible recipients, 416 (4%) had a prior malignancy unrelated to the indication for transplantation diagnosed 2 months or more before surgery (median, 5.7 years). Mortality among cancer history recipients was 30% increased after transplantation, compared with other recipients (adjusted hazard ratio [HR], 1.3; 95% confidence interval [CI], 1.1–1.5; P<0.001), driven by cancer-specific death with no increase in cardiovascular, infectious, or other noncancer mortality. An increased rate of death due to cancer history was primarily observed among nonkidney recipients (adjusted HRnonkidney, 1.8; 95% CI, 1.3–2.5; HRkidney, 1.2; 95% CI, 1.0–1.4). Rates were greatest for patients with waiting times of 5 years or less but persisted with waiting times more than 10 years among kidney and nonkidney recipients with prior aggressive cancer types (gastrointestinal, breast, kidney/urothelial, and hematologic malignancies). Conclusion: We conclude that organ transplant recipients with cancer history are at a moderately increased rate of death after transplantation, driven primarily by death due to cancer recurrence.


http://journals.lww.com/transplantjournal/Fulltext/2013/08150/Overall_and_Cause_Specific_Mortality_in_Transplant.13.aspx


Comparison of Kidney Function Between Donation After Cardiac Death and Donation After Brain Death Kidney Transplantation

Transplantation - Current Issue Comparison of Kidney Function Between Donation After Cardiac Death and Donation After Brain Death Kidney Transplantation

imageBackgroud: Kidney graft survival is comparable between donation after cardiac death (DCD) and donation after brain death (DBD) kidney transplantation. However, data concerning kidney function after DCD kidney transplantation are lacking. Methods: We retrospectively compared kidney function between 64 DCD and 248 DBD kidney transplant recipients. Graft function was assessed using iothalamate glomerular filtration rate at 1, 4, and 12 months, then annually. The primary endpoint was the composite of death-censored graft loss or two consecutive iothalamate glomerular filtration rates less than 50 mL/min/1.73 m2 occurring within 5 years from transplantation. Secondary endpoints included death and graft loss or death. Results: Of the 312 patients, 102 (33%) experienced the primary endpoint, 78 (25%) experienced graft loss or death, and 44 (14%) died. In multivariable Cox regression analysis, there was no difference between DCD and DBD recipients regarding the primary endpoint (relative risk [RR], 1.16; P=0.59), death (RR, 0.97; P=0.94), or graft loss or death (RR, 1.09; P=0.79). In the subgroup of 64 DCD recipients, each 10-year increase in donor age was associated with increased risk of the primary endpoint (RR, 1.51; P=0.027) with the highest risk observed for donors older than 45 years (RR, 4.81; P=0.001). Delayed graft function affected 45% of the DCD recipients but had no impact on kidney function, graft survival, or patient survival. Conclusions: Posttransplantation kidney function is comparable between DCD and DBD kidney transplantations. In the subgroup of DCD recipients, kidneys from donors older than 45 years may be associated with a higher risk of poor kidney function; however, this finding requires validation in a larger patient group.


http://journals.lww.com/transplantjournal/Fulltext/2013/08150/Comparison_of_Kidney_Function_Between_Donation.10.aspx


Saturday, August 10, 2013

How Many Patients With History of Penicillin Allergy Are Truly Allergic?

Information sourced from NEJM Journal Watch:

Very Few Patients with Penicillin Allergy Histories Are Truly Allergic

David J. Amrol, MD reviewing Macy E and Ngor EW. J Allergy Clin Immunol Prac 2013 May.

Penicillin allergy testing can safely exclude IgE-mediated penicillin allergy.

Almost 8% of the U.S. population claims to be allergic to penicillin, but only a small proportion of these patients are truly allergic. Penicillin skin testing is the only way to identify IgE-mediated allergy (an immediate hypersensitivity reaction mediated by preformed IgE bound to the surface of mast cells and basophils). Penicilloyl-poly-lysine (Pre-Pen), the major determinant of penicillin allergy, has been available commercially since 2009, but clinicians rarely order skin testing. Some physicians are concerned that Pre-Pen testing is inadequate without also testing for minor determinants (penicilloate and penilloate), which are not readily available.

From 2010 to 2012, 500 patients with histories of penicillin allergy (based on diagnoses recorded in their records) were skin tested in a California allergy department using penicilloyl-poly-lysine and fresh penicillin G. Negative tests were followed by 1-hour observed oral challenges with amoxicillin. Four patients reacted to one of the two skin-test agents, and another four exhibited positive objective symptoms after oral challenges. None of these reactions [were] life threatening or required epinephrine.

COMMENT

In this study, fewer than 1 in 50 patients with penicillin allergy histories were truly allergic. We should stop accepting penicillin allergy history as a reason for lifelong avoidance. All drug reactions should be documented carefully. Patients with severe delayed reactions such as Stevens Johnson syndrome, drug reaction with eosinophilia and systemic symptoms (DRESS), or hemolytic anemia should never be challenged or tested; those with mild delayed reactions probably can undergo oral challenges. For those with potential IgE-mediated reactions (i.e., hives, edema, or other symptoms of anaphylaxis occurring within 1–2 hours), penicillin testing followed by oral challenge is safe and effective. Penicillin is the only antibiotic for which such testing is available.

Dr. Amrol is an Associate Professor of Clinical Internal Medicine and Director of the Division of Allergy and Immunology at the University of South Carolina School of Medicine in Columbia.

CITATION:

Macy E and Ngor EW. Safely diagnosing clinically significant penicillin allergy using only penicilloyl-poly-lysine, penicillin, and oral amoxicillin. J Allergy Clin Immunol Prac 2013 May; 1:258. [J Allergy Clin Immunol Prac article abstract]

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Thursday, August 8, 2013

Independent Risk Factors for Urinary Tract Infection and for Subsequent Bacteremia or Acute Cellular Rejection: A Single-Center Report of 1166 Kidney Allograft Recipients

Transplantation - Published Ahead-of-Print Independent Risk Factors for Urinary Tract Infection and for Subsequent Bacteremia or Acute Cellular Rejection: A Single-Center Report of 1166 Kidney Allograft Recipients

Background: Urinary tract infection (UTI) is a frequent, serious complication in kidney allograft recipients. Methods: We reviewed the records of 1166 kidney allograft recipients who received their allografts at our institution between January 2005 and December 2010 and determined the incidence of UTI during the first 3 months after transplantation (early UTI). We used Cox proportional hazards models to determine the risk factors for early UTI and whether early UTI was an independent risk factor for subsequent bacteremia or acute cellular rejection (ACR). Results: UTI, defined as 105 or more bacterial colony-forming units/mL urine, developed in 247 (21%) of the 1166 recipients. Independent risk factors for the first episode of UTI were female gender (hazard ratio [HR], 2.9; 95% confidence intervals [CI], 2.2-3.7; P<0.001), prolonged use of Foley catheter (HR, 3.9; 95% CI, 2.8-5.4; P <0.001), ureteral stent (HR, 1.4; 95% CI, 1.1-1.8; P=0.01), age (HR, 1.1; 95% CI, 1.0-1.2; P=0.03), and delayed graft function (HR, 1.4; 95% CI, 1.0-1.9; P=0.06). Trimethoprim/sulfamethoxazole prophylaxis was associated with a reduced risk of UTI (HR, 0.6; 95% CI, 0.3-0.9; P=0.02). UTI was an independent risk factor for subsequent bacteremia (HR, 2.4; 95% CI, 1.2-4.8; P=0.01). Untreated UTI, but not treated UTI, was associated with an increased risk of ACR (HR, 2.8; 95% CI, 1.3-6.2; P=0.01). Conclusions: Female gender, prolonged use of Foley catheter, ureteral stent, age, and delayed graft function are independent risk factors for early UTI. UTI is independently associated with the development of bacteremia, and untreated UTI is associated with subsequent ACR. (C) 2013 by Lippincott Williams & Wilkins


http://pdfs.journals.lww.com/transplantjournal/9000/00000/Independent_Risk_Factors_for_Urinary_Tract.98474.pdf