Conversion to Mammalian Target of Rapamycin Inhibitors Increases Risk of de novo Donor-Specific Antibodies

Transplant International Conversion to Mammalian Target of Rapamycin Inhibitors Increases Risk of de novo Donor-Specific Antibodies

Abstract

In kidney transplantation, conversion to mammalian target of rapamycin (mTOR) inhibitors may avoid calcineurin-inhibitor (CNI) nephrotoxicity, but its impact on post-transplant allo-immunization remains largely unexplored. This retrospective cohort study analyzed the emergence of donor-specific antibodies (DSA) in kidney-transplant recipients relative to their immunosuppressive therapy. Among 270 recipients without pre-transplant immunization who were screened regularly for de novo DSA, 56 were converted to mTOR inhibitors after CNI withdrawal. DSA emergence was increased in patients who were converted to mTOR inhibitors (HR 2.4; 95% CI 1.06-5.41, p=0.036). DSA were mainly directed against donor HLA-DQB1 antigens. The presence of one or two DQ mismatches was a major risk factor for DQ DSA (HR 5.32; 95% CI 1.58-17.89 and HR 10.43; 95% CI 2.29-47.56 respectively; p<0.01). Rejection episodes were more likely in patients converted to mTOR inhibitors but this difference did not reach significance (16% versus 7.9%, p=0.185). Concerning graft function, no significant change was observed one year after conversion (p=0.31). In conclusion, conversion to mTOR inhibitors may increase the risk of developing class II DSA, especially in the presence of DQ mismatches: this strategy may favor chronic antibody-mediated rejection and thus reduce graft survival.

This article is protected by copyright. All rights reserved.

http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Ftri.12330

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Do Omega-3 Fatty Acids Reduce Cardiovascular Risk in Elderly Patients?

Information sourced from BMJ:

BMJ 2014;348:g2185

Research News

Omega 3 supplements do not reduce cardiovascular risk in elderly

Zosia Kmietowicz

Commentators have said that more trials on the effects of omega 3 fatty acid supplements "seem unjustified" after another study found that their use was not associated with a reduced risk of cardiovascular disease. Patients should be advised to eat fish rather than take the supplements, they said.

They were commenting on a study reported in JAMA Internal Medicine that looked at daily dietary supplementation with omega 3 polyunsaturated fatty acids (also found in fish) or lutein and zeaxanthin (nutrients found in green leafy vegetables) in 4203 people who had age related macular degeneration.¹ The participants, whose average age was 74 years, were part of the Age Related Eye Disease Study (AREDS2), a trial looking at the impact of the two supplements on progression to advanced macular degeneration. They had been randomised to take supplements containing the omega 3 fatty acids docosahexaenoic acid (350 mg) and eicosapentaenoic acid (650 mg); the macular xanthophylls lutein (10 mg) and zeaxanthin (2 mg); a combination of the two; or placebo.

To investigate the effects of the supplements on cardiovascular disease the AREDS2 Research Group obtained cardiovascular outcomes prospectively.

A total of 459 cardiovascular events met the study definitions over the course of 4.8 years, but there was no reduction in heart attack, stroke, and cardiovascular death or secondary cardiovascular disease outcomes (hospital admission for heart failure, revascularisation, or unstable angina) among patients taking the supplements.

The authors concluded that the results "are consistent with a growing body of evidence from clinical trials that have found little CVD [cardiovascular disease] benefit from moderate levels of dietary supplementation."

In a commentary on the study, doctors from the lipid disorders clinic at the Hospital of Ioannina in Greece and epidemiology unit at the University of Ioannina Medical School asked, how do the findings "fit into the (re)considerations about the design and conduct of future trials on omega 3 supplementation?"² They argue that with more than 2000 trials, almost 200 systematic reviews and meta-analyses, and more than 700 registered "closed" trials awaiting results indexed on PubMed "the omega 3 research agenda seems to be losing focus."

Evidence from trials, they say, showed that "omega 3 supplementation with daily doses close to 1 g in patients with or without established CVD shows no clear, considerable benefit. Continuing to conduct more RCTs [randomised controlled trials] seems unjustified."

Instead they said that a meta-analysis of individual participant data could "draw conclusions on the postulated omega 3 varying effects based on the participants' characteristics." Other trials could look at gaps in the research, such as high dose omega 3 supplementation (more than 1 g daily) in people with high triglyceride (TG) levels.

They conclude: "Until then, omega 3 should be considered only as TG-lowering agents for those with severe hypertriglyceridemia (an extreme minority of the general population). Patients raising the question of taking omega 3 supplements should be informed of the uncertainty surrounding their choice, and regular dietary consumption of (whole) fish should be preferentially encouraged as a source of omega 3 (not supplements) based on the wealth of the available epidemiological evidence."

References

01. Writing group of the ARDS2 Research Group. Effect of long-chain ω-3 fatty acids and lutein + zeaxanthin supplements on cardiovascular outcomes: results of the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA Intern Med 18 Mar 2014, doi:10.1001/jamainternmed.2014.328.
[PubMed® abstract]

02. Rizos EC, Ntzani EE. ω-3 fatty acids and lutein + zeaxanthin supplementation for the prevention of cardiovascular disease. JAMA Intern Med 18 Mar 2014, doi:10.1001/jamainternmed.2013.13734.
[JAMA Intern Med Editorial Preview | PubMed® abstract]

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Adverse Effects of Statins: A Systematic Review and Meta-analysis

Information sourced from BMJ:

BMJ 2014;348:g2151

Research News

Statins may have fewer side effects than is claimed, meta-analysis finds

Jacqui Wise

London

Only a few types of side effect reported from use of statins are genuinely due to the drug itself, as almost all side effects were reported just as often with a placebo, a systematic review of randomised controlled trials has concluded.¹

The findings are important, as the NHS in England is considering wider prescribing of statins. Draft guidance from the National Institute for Health and Care Excellence has recommended lowering the risk threshold for starting treatment with statins to prevent cardiovascular disease.²

Researchers from the National Heart and Lung Institute in London carried out a meta-analysis of 29 randomised controlled trials involving 83 880 patients. Overall, the study found serious adverse events among 14.6% of patients receiving statins and 14.9% given a placebo in the primary prevention trials and in 9.9% of those on statins and 11.2% of those on placebo in the secondary prevention trials.

The authors said that evaluation of the efficacy of statins was always based on evidence from randomised controlled trials of the drugs against placebo but that the evaluation of side effects was not. Adverse events listed for statins come from many sources, including observational studies.

Many side effects such as myopathy, fatigue, muscle aches, and rhabdomyolysis have been commonly attributed to statins, but the researchers found that these were no more common among patients taking statins than among those taking a placebo. The withdrawal rate from trials was also similar for statins and placebo, at around 12-15%.

The study, published in the European Journal of Preventive Cardiology, found that only the risk of developing new onset diabetes mellitus was significantly higher in patients taking statins than in those taking a placebo. Across primary and secondary prevention trials, the rate of developing diabetes was 3% with statins and 2.4% with placebo.

In 14 primary prevention trials that involved 46 262 participants, treatment with statins was associated with an increase in the absolute risk of diabetes of 0.5% (95% confidence interval 0.1% to 1%; P=0.012) and with a reduced risk of death by a similar amount (−0.5% (−0.9 to −0.2%); P=0.003). In the 15 secondary prevention randomised controlled trials (37 618 patients) statins reduced deaths by an absolute 1.4% (0.7% to 2.1%; P<0.001). But only one of these trials reported rates of development of diabetes, and it showed no significant effect.

The only significant adverse event recorded in both primary and secondary prevention was asymptomatic liver transaminase elevation, which was 0.4% more frequent with statins across all trials. However, the authors said it was unclear whether this elevation was harmful.

Judith Finegold, clinical research fellow at the National Heart and Lung Institute in London, said, "Most people in the general population, if you repeatedly ask them a detailed questionnaire, will not feel perfectly well in every way on every day. Why should they suddenly feel well when taking a tablet after being warned of possible adverse effects?"

Finegold called on drug regulators to highlight in the long lists of reported side effects those few whose risk was greater than that experienced with placebo. "We believe that patients should be empowered to make their own decisions, but we must first make sure they have top quality, unbiased information," she said.

References

1. Finegold J, Manisty C, Goldacre B, Barron A, Francis D. What proportion of symptomatic side effects in patients taking statins are genuinely caused by the drug? Systematic review of randomized placebo-controlled trials to aid patient choice. Eur J Preventive Cardiol 12 Mar 2014 [PubMed® abstract]
2. Wise J. NICE recommends wider use of statins in draft guidelines. BMJ 2014;348:g1518. [Full-text PDF of BMJ News article]

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Peritonitis relacionada a diálisis peritoneal - Nuestra Experiencia

Peritoneal dialysis-related peritonitis: twenty-sevenyears of experience in a Colombian medical center
John F. Nieto-Ríos1, James S. Díaz-Betancur2, Mario Arbeláez-Gómez3, Álvaro García-García3, Joaquín Rodelo-Ceballos3, Alberto Reino-Buelvas4, Lina M. Serna-Higuita5, Jorge E. Henao-Sierra3
1 Servicio de Nefrología. Hospital Pablo Tobón Uribe. Medellín, Antioquia (Colombia)
2 Servicio de Medicina Interna. Hospital San Vicente de Paúl. Medellín, Antioquia (Colombia)
3 Servicio de Nefrología. Hospital San Vicente de Paúl. Docente Universidad de Antioquia, Medellín, Antioquia (Colombia) 4 Servicio de Nefrología. Hospital San Vicente de Paúl. Medellín, Antioquia (Colombia)
5 Servicio de Nefrología. Hospital Pablo Tobón Uribe. Docente Universidad de Antioquia, Medellín, Antioquia (Colombia) 

Nefrologia 2014;34(1):88-95
doi:10.3265/Nefrologia.pre2013.Nov.12002

originals

ABSTRACT
Peritonitis has been the most common complication of continues ambulatory peritoneal dialysis (CAPD) since it was first implemented, and it remains the leading cause of treatment failure and transfer to other renal replacement therapies. This study presents a Colombian series with a total of 2469 episodes of peritonitis in 914 patients from a cohort of 1,497 patients on PD, who were followed for almost three decades at a single center. This is the largest Latin American series of patients with PD-related peritonitis. Objective: To describe the CAPD-related peritonitis in a cohort of patients followed for 27 years at a single center, and compare the results with those observed elsewhere in the world. Study Design: Prospective study of incident patients on CAPD from March 1981 to December 2008. Results: In our center, the rate of peritonitis has been steady between 0.8 and 0.9 since 1981 and no significant changes have been noticed in the 27 years of follow up. The rate remains similar to that described nowadays by other large dialysis centers in the world, which have reported significant improvements in recent decades. No significant differences were found in the isolates of gram-positive and gram-negative microorganisms or fungi with respect to those reported by other large series, or in the frequency of culture-negative peritonitis. Conclusion: This study presents the largest Latin American series of patients with CAPD-related peritonitis with a total of 2,469 patients. In this study, the rate of CAPD-related peritonitis remained almost the same during the three decades of observation despite having used three different CAPD systems. Our hypothesis is that the socio-economic conditions of the patients admitted for peritoneal dialysis influences the rate of peritonitis. 

Proton pump inhibitors do not increase the risk of acute rejection

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Netherlands Journal of Medicine 2014 Feb; 72 (2) : 86-90. Proton pump inhibitors do not increase the risk of acute rejection. G A J van Boekel, C H H Kerkhofs, F van de Logt, L B Hilbrands PMID: 24659591

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Long-Term Follow-Up of a Phase III Clinical Trial Comparing Tacrolimus Extended-Release/MMF, Tacrolimus/MMF, and Cyclosporine/MMF in De Novo Kidney Transplant Recipients

Transplantation - Current Issue Long-Term Follow-Up of a Phase III Clinical Trial Comparing Tacrolimus Extended-Release/MMF, Tacrolimus/MMF, and Cyclosporine/MMF in De Novo Kidney Transplant Recipients

BackgroundIn a phase III, open-label, comparative, noninferiority study, 638 subjects receiving de novo kidney transplants were randomized to one of three treatment arms: tacrolimus extended-release (Astagraf XL) qd, tacrolimus (Prograf) bid, or cyclosporine (CsA) bid. All subjects received basiliximab induction, mycophenolate mofetil, and corticosteroids. Safety and efficacy follow-up data through 4 years are reported. MethodsEvaluations included patient and graft survival, study drug discontinuations, laboratory values including renal function and development of new-onset diabetes after transplantation, concomitant medications, and adverse events. ResultsAt study termination, 129 Astagraf XL, 113 Prograf, and 79 CsA patients had continued follow-up. Demographic and baseline characteristics were similar in all arms. Four-year Kaplan-Meier estimates of patient survival in the Astagraf XL, Prograf, and CsA groups were 93.2, 91.2, and 91.7%, respectively, while graft survival was 84.7, 82.7, and 83.9%, respectively. At least one serious adverse event was reported in the majority of patients in each group during the study (65.9% Astagraf XL, 69.8% Prograf, and 65.6% CsA). Renal function was not significantly different between Astagraf XL and Prograf. HgbA1c levels were collected every 6 months; the 4-year Kaplan-Meier estimate for incidence of HgbA1c levels ≥6.5% was significantly higher for both tacrolimus formulations compared to CsA; 41.1% (Astagraf XL), 33.6% (Prograf), and 21.3% (CsA). ConclusionsIn this 4-year follow-up report, patients receiving Astagraf XL and Prograf showed comparable efficacy and safety profiles, with a higher incidence of new-onset diabetes after transplantation but superior renal function compared to patients receiving CsA.


http://journals.lww.com/transplantjournal/Fulltext/2014/03270/Long_Term_Follow_Up_of_a_Phase_III_Clinical_Trial.7.aspx

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The incidence, management and evolution of rapamycin-related side effects in kidney transplant recipients

Clinical Transplantation The incidence, management and evolution of rapamycin-related side effects in kidney transplant recipients

Abstract

Conversion from a calcineurin-inhibitor-based to a rapamycin-based immunosuppression may preserve kidney graft function. The side effects of rapamycin can limit its usefulness, but their management and evolution are rarely reported in clinical trials. We performed a retrospective cohort study in patients transplanted before December 31st, 2008 and who received rapamycin in order to replace calcineurin-inhibitors. In 219 patients studied, 98% presented >1 side effects after starting rapamycin. Side effects occurring in ≥ 10% of patients were dyslipidemia (52%, 95% confidence interval (CI): 45-59%), peripheral edema (37%, 95%CI: 31-43%), cytopenia (36%, 95% CI: 30-42%), acne (29%, 95% CI: 23-35%), proteinuria (23%, 95% CI: 17-29%) and oral ulcers 14% (95% CI: 10-18%). Proteinuria, ulcers and edema were difficult to manage and were more likely to cause cessation of rapamycin. Rapamycin was discontinued in 46% of patients (95% CI: 40-52%). Age (odds ratio (OR) per 10-year increase: 1.29, 95% CI: 1.05-1.59) and obesity (OR: 2.57, 95% CI: 1.10-6.01) were independently associated with cessation of rapamycin. We conclude that successful control of dyslipidemia and cytopenia can be achieved without discontinuing rapamycin. Most other side effects are harder to manage. Leaner, and younger patients are less likely to discontinue rapamycin due to side effects.

This article is protected by copyright. All rights reserved.

http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Fctr.12361

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Predictive factors for adverse pregnancy outcomes after renal transplantation

Clinical Transplantation Predictive factors for adverse pregnancy outcomes after renal transplantation

Abstract

Several predictive factors associated with adverse pregnancy outcomes in female renal recipients have been suggested. Our study aimed to determine the most important factor for prediction of adverse pregnancy outcomes in female renal recipients. We studied 41 pregnancies in 29 female renal recipients retrospectively. We reviewed pregnancy outcomes and possible predictive factors including pre-pregnancy serum creatinine (SCr), pre-pregnancy glomerular filtration rate(GFR), pre-pregnancy hypertension, pre-pregnancy proteinuria, transplantation-pregnancy interval and type of immunosuppressants. We defined an adverse pregnancy-related outcomes index (APOI) that included the following conditions: (1) preeclampsia; (2) Fetal growth restriction (FGR); (3) prematurity before 34 weeks of gestation; (4) fetal loss (5) graft dysfunction during pregnancy or within 3 months from delivery. The cutoff of pre-pregnancy serum creatinine and GFR was determined by Receiver Operating Characteristics curves for the prediction of each adverse outcome and APOI. Only pre-pregnancy serum creatinine was associated with adverse pregnancy outcome and 1mg/dL was determined to be a useful cutoff for the prediction of each adverse outcomes. Pre-pregnancy SCr ≥1 mg/dL was associated with 7.7 times increased risk of preeclampsia and 6.9 times increased risk of APOI. Pre-pregnancy serum creatinine is the most powerful predictive factor for adverse pregnancy outcomes and < 1 mg/dL may be used as a screen for successful pregnancy outcome.

This article is protected by copyright. All rights reserved.

http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Fctr.12367

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Pulsatile Perfusion Reduces the Risk of Delayed Graft Function in Deceased Donor Kidney Transplants, Irrespective of Donor Type and Cold Ischemic Time

Transplantation - Current Issue Pulsatile Perfusion Reduces the Risk of Delayed Graft Function in Deceased Donor Kidney Transplants, Irrespective of Donor Type and Cold Ischemic Time

BackgroundThe role of pulsatile perfusion (PP) across different cold ischemic times (CIT) within different donor groups is unclear. This study examined the association of PP with delayed graft function (DGF) in all (n=94,709) deceased donor kidney transplants in the US between 2000 and 2011, as a function of CIT and donor type. MethodsUsing the Scientific Registry of Transplant Recipients data, all adult standard criteria donors (SCD, n=71,192), expanded criteria donors (ECD, n=15,122), and donors after circulatory death (DCD, n=8,395) kidney transplant recipients were identified. Within each donor group, transplants were stratified based on duration of CIT: 0 to 6 hours, 6.1 to 12 hours, 12.1 to 18 hours, 18.1 to 24 hours, 24.1 to 30 hours, 30.1 to 36 hours, and greater than 36 hours. Within each group, the odds of DGF with and without PP was determined after adjusting for donor, recipient, and transplant factors, including a propensity score for the likelihood of PP use, and clustering on transplant center using multivariable logistic regression. ResultsWhen stratified by donor type and CIT, the adjusted odds of DGF were lower with PP across all CIT in SCD transplants, when CIT was greater than 6 hours in ECD transplants, and when CIT was between 6 and 24 hours in DCD transplants. CIT was independently associated with a greater risk of DGF irrespective of storage method, but this effect was substantially modified by PP. ConclusionPP is associated with a reduced risk of DGF irrespective of donor type and CIT. Although PP modifies the impact of CIT on the risk of DGF, it does not eliminate its association with DGF, suggesting the optimal strategy to reduce DGF is to minimize CIT and utilize PP in all deceased donor transplants.


http://journals.lww.com/transplantjournal/Fulltext/2014/03270/Pulsatile_Perfusion_Reduces_the_Risk_of_Delayed.12.aspx

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Autoimmune Neutropenia After Kidney Transplantation: A Disregarded Entity of Posttransplant Neutropenia

Transplantation - Published Ahead-of-Print Autoimmune Neutropenia After Kidney Transplantation: A Disregarded Entity of Posttransplant Neutropenia

Background: Neutropenia is common after kidney transplantation and is associated with an increased incidence of infections. Drug toxicities are the main causes of posttransplant neutropenia (PTN), mainly related to immunosuppressive drugs as mycophenolic acid (MPA) and anti-infectious agents, but some PTN remain unexplained. Methods: Between January 2012 and January 2013, cultures of autologous granulocytic progenitors from bone marrow aspirate were performed in two patients with unexplained severe neutropenia. Results: Both patients' serum inhibited granulocytic differentiation while granulocytic differentiation was normal with the control serum. Similar inhibition of differentiation of granulocytic progenitors from a control marrow was observed with the patients' serum as compared with the control serum. Moreover, in both cases intravenous immunoglobulins allowed full neutrophil count recovery. Other usual etiologies of acquired neutropenia including systemic drug toxicity, infection, and autoimmune disease were excluded. As frequently observed in adult immune neutropenia, granulocyte autoantibodies were absent in both cases. Owing to biological and clinical results, we concluded that an autoimmune mechanism was responsible for neutropenia. The levels of MPA, which is known to interact with tacrolimus, were not measured in our patients. However, the persistence of neutropenia more than 70 days after withdrawal of MPA did not support this hypothesis. Conclusion: Autoimmune neutropenia should be considered in kidney transplant recipients in case of persistent unexplained neutropenia as it allows effective treatment and avoids the withdrawal of important immunosuppressive and anti-infectious treatments. (C) 2014 by Lippincott Williams & Wilkins


http://pdfs.journals.lww.com/transplantjournal/9000/00000/Autoimmune_Neutropenia_After_Kidney.98282.pdf

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Three-Year Outcomes in Kidney Transplant Patients Randomized to Steroid-Free Immunosuppression or Steroid Withdrawal, with Enteric-Coated Mycophenolate Sodium and Cyclosporine: The Infinity Study

Journal of Transplantation - XXX Three-Year Outcomes in Kidney Transplant Patients Randomized to Steroid-Free Immunosuppression or Steroid Withdrawal, with Enteric-Coated Mycophenolate Sodium and Cyclosporine: The Infinity Study

In a six-month, multicenter, open-label trial, de novo kidney transplant recipients at low immunological risk were randomized to steroid avoidance or steroid withdrawal with IL-2 receptor antibody (IL-2RA) induction, enteric-coated mycophenolate sodium (EC-MPS: 2160 mg/day to week 6, 1440 mg/day thereafter), and cyclosporine. Results from a 30-month observational follow-up study are presented. Of 166 patients who completed the core study on treatment, 131 entered the follow-up study (70 steroid avoidance, 61 steroid withdrawal). The primary efficacy endpoint of treatment failure (clinical biopsy-proven acute rejection (BPAR) graft loss, death, or loss to follow-up) occurred in 21.4% (95% CI 11.8–31.0%) of steroid avoidance patients and 16.4% (95% CI 7.1–25.7%) of steroid withdrawal patients by month 36 (). BPAR had occurred in 20.0% and 11.5%, respectively (). The incidence of adverse events with a suspected relation to steroids during months 6–36 was 22.9% versus 37.1% (). By month 36, 32.4% and 51.7% of patients in the steroid avoidance and steroid withdrawal groups, respectively, were receiving oral steroids. In conclusion, IL-2RA induction with early intensified EC-MPS dosing and CNI therapy in de novo kidney transplant patients at low immunological risk may achieve similar three-year efficacy regardless of whether oral steroids are withheld for at least three months.


http://www.hindawi.com/journals/jtrans/2014/171898/

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Red Blood Cell Transfusions and the Risk of Allosensitization in Patients Awaiting Primary Kidney Transplantation

Transplantation - Current Issue Red Blood Cell Transfusions and the Risk of Allosensitization in Patients Awaiting Primary Kidney Transplantation

BackgroundMost studies of HLA sensitization after red blood cell transfusion in transplant candidates were done before widespread use of leukoreduced blood and based on relatively insensitive, nonspecific antibody assays. We evaluated the effect of transfusion on the breadth and magnitude of HLA antibody formation using current, sensitive, HLA-specific immunoassays. MethodsSerial HLA antibody data were merged with transfusion data from the US Renal Data System for 1324 patients on the kidney transplant waitlist (2004–2010). Two study groups were identified: a matched cohort consisting of 89 patients who received transfusion and 251 patients who did not receive transfusion and a crossover cohort consisting of 69 patients. Changes in antibody levels and calculated panel-reactive antibody (CPRA) were compared using χ2 and Sign tests, respectively. Logistic regression was used to estimate the relative risk of antibody responses. ResultsAmong the matched cohort, 20% of those who received transfusion compared to 3% of those who did not receive transfusion exhibited an antibody response (P=0.001), whereas in the crossover cohort, 19% exhibited a response in those who received transfusion compared to 1% of those who did not receive transfusion (P=0.0001). Moreover, 26.3% of those who received transfusion had increased CPRA compared to 5.8% of those who did not receive transfusion . These effects were greater in women and blacks compared to men and whites, respectively. Importantly, patients who received transfusion were at an increased risk of a potentially crossmatch positive response (odds ratio=9.6, 95% confidence interval=3.0–30.7). ConclusionsSensitization from transfusion can occur in up to 20% of transplant candidates, resulting in higher antibody levels and CPRA values that adversely impact access to transplantation. These results support transfusion avoidance whenever possible.


http://journals.lww.com/transplantjournal/Fulltext/2014/03150/Red_Blood_Cell_Transfusions_and_the_Risk_of.9.aspx

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Concomitant Proton Pump Inhibitors With Mycophenolate Mofetil and the Risk of Rejection in Kidney Transplant Recipients

Transplantation - Most Popular Articles Concomitant Proton Pump Inhibitors With Mycophenolate Mofetil and the Risk of Rejection in Kidney Transplant Recipients

BackgroundRecent pharmacokinetic studies have demonstrated that proton pump inhibitors (PPI) reduce exposure of mycophenolic acid. However, the clinical significance of this drug–drug interaction on transplantation outcomes has not been determined. MethodsThis was a retrospective cohort study in kidney transplant recipients who were prescribed rabbit antithymocyte globulin, calcineurin inhibitor, mycophenolate mofetil, and steroids. We evaluated the impact of PPI use on the 1-year rates of biopsy-proven acute rejection (BPAR). ResultsTwo hundred thirteen patients who were prescribed PPI were compared with 384 patients who were on standard acid-suppressive therapy with ranitidine. BPAR occurred in similar rates in both groups (15% vs. 12%; P=0.31). In a multivariable analysis, black race was associated with a higher risk of rejection (risk ratio [RR], 2.38; 95% confidence interval [CI], 1.41–4.03). While controlling for rejection risk factors, PPI exposure was associated with an increased risk of rejection in black patients (RR, 1.93; 95% CI, 1.18–3.16) but not in non-black patients (RR, 0.54; 95% CI, 0.19–1.49). At 1 year, BPAR type, BPAR grade, patient and graft survival, graft function, and time to BPAR were not associated with PPI exposure. ConclusionIn this retrospective study, PPI use in the first transplant year was associated with an increased risk for BPAR in black patients but not in non-black patients. It is possible that a reduction in mycophenolic acid exposure contributed to the increased risk.


http://journals.lww.com/transplantjournal/Fulltext/2014/03150/Concomitant_Proton_Pump_Inhibitors_With.8.aspx

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Management of Intraocular Hypertension During Hemodialysis by Intravenous Glucose Administration

American Journal of Kidney Diseases Management of Intraocular Hypertension During Hemodialysis by Intravenous Glucose Administration

A 64-year-old woman with end-stage renal disease and retinopathy secondary to type 2 diabetes mellitus presented with recurrent episodes of left ocular pain and acute loss of visual acuity during hemodialysis. During these episodes, markedly elevated intraocular pressures were measured. Several local and systemic antiglaucoma drugs were administered without improvement of intraocular pressure, resulting in the necessity of a glaucoma drainage device (Ahmed valve). Due to a local infection, it had to be removed, after which intraocular pressure elevations recurred during hemodialysis. Assuming that intraocular changes in osmolality during hemodialysis caused the intraocular pressure increases, intradialytic administration of a 20% glucose solution (100mL/h) was initiated. This completely abrogated the development of both intraocular pain and increases in intraocular pressure.


http://www.ajkd.org/article/S0272-6386(13)01286-9/abstract?rss=yes

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