Elevated Urinary CCL2: Cr at 6 Months Is Associated With Renal Allograft Interstitial Fibrosis and Inflammation at 24 Months

Transplantation - Most Popular Articles Elevated Urinary CCL2: Cr at 6 Months Is Associated With Renal Allograft Interstitial Fibrosis and Inflammation at 24 Months

BackgroundWe have demonstrated that 6-month urinary CCL2: Cr is a predictor of interstitial fibrosis and tubular atrophy (IFTA) on 24-month biopsy and death-censored graft loss. However, IFTA is no longer considered prognostically significant, whereas patients with graft loss frequently have interstitial fibrosis and inflammation (IF+i=ci>0+i>0). As early CCL2: Cr predicts late graft loss, the goal of this study was to determine if 6-month urinary CCL2: Cr was a predictor of IF+i at 24 months. MethodsUrinary CCL2 at 6 months was measured with ELISA and correlated with IF+i on 24-month surveillance biopsies from a prospective, multicenter adult renal transplant cohort (n=111). ResultsSix-month urinary CCL2: Cr was significantly higher in IF+i and transplant glomerulopathy patients compared with normal histology at 24 months. By multivariate analysis, 6-month urinary CCL2: Cr was independently correlated with IF+i at 24 months (OR 2.78, 95% CI 1.38–6.12, AUC 0.695, P=0.003). Six-month urinary CCL2: Cr was also an independent correlate of 6-month IF+i (OR 1.99, 95% CI 1.03–4.18, AUC 0.63, P=0.04). Six-month urinary CCL2: Cr distinguished noninflamed renal tissue (normal, fibrosis) from IF+i with a sensitivity/specificity of 0.71/0.62 at a cutoff of 15 ng CCL2/mmol Cr (AUC 0.695, P=0.003, n=91). ConclusionsUrinary CCL2: Cr may be useful for the noninvasive identification of patients with or at risk for IF+i. These patients may benefit from avoidance of drug minimization/withdrawal protocols and more intensive post-transplant surveillance. Furthermore, urinary CCL2: Cr may also identify individuals who may benefit from novel interventional trials targeting IF+i.


http://journals.lww.com/transplantjournal/Fulltext/2014/07150/Elevated_Urinary_CCL2__Cr_at_6_Months_Is.7.aspx

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Evolution of donor specific antibodies and incidence of de novo donor specific antibodies in solid organ transplant recipients after switch to everolimus alone or associated with low dose of calcineurin inhibitors

Clinical Transplantation Evolution of donor specific antibodies and incidence of de novo donor specific antibodies in solid organ transplant recipients after switch to everolimus alone or associated with low dose of calcineurin inhibitors

Abstract

Background

Everolimus (EVR) is used in organ transplantation to minimize calcineurin-inhibitors (CNI). Some studies pointed out an increase in rejection and de novo donor specific antibodies (DSA) incidence in kidney transplant patients after switch to EVR and CNI withdrawal. The aims of our study were to determine the evolution of anti-HLA antibodies and the incidence of de novo DSA in transplant recipients after conversion to EVR.

Methods

Heart, lung, kidney and liver transplant recipients were included in a retrospective, monocentric case-control study. Anti-HLA antibodies were identified at transplantation, pre-switch, and at 3, 6 and 12 months post-switch.

Results

Conversion to EVR was performed about 6 years after the transplant and low dose CNI was maintained in 60% of patients. We found no statistical difference for rejection, evolution of preformed anti-HLA antibodies or de novo DSA, after conversion to EVR or not. Incidence of anti-class II DSA tended to increase at month 12 whatever the immunosuppressive regimen.

Conclusions

Late conversion to EVR appears to be safe and to not modify the natural evolution of anti-HLA antibodies in organ transplantation. As 60% of patients received EVR and low doses of CNI, it seems that such combinations could be used with a good outcome.

This article is protected by copyright. All rights reserved.

http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Fctr.12418

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More Potent Lipid-Lowering Effect by Rosuvastatin Compared With Fluvastatin in Everolimus-Treated Renal Transplant Recipients

Transplantation - Most Popular Articles More Potent Lipid-Lowering Effect by Rosuvastatin Compared With Fluvastatin in Everolimus-Treated Renal Transplant Recipients

BackgroundDyslipidemia is a risk factor for premature cardiovascular morbidity and mortality in renal transplant recipients (RTRs). Pharmacotherapy with mTOR inhibitors aggravates dyslipidemia, thus necessitating lipid-lowering therapy with fluvastatin, pravastatin, or atorvastatin. These agents may not sufficiently lower lipid levels, and therefore, a more potent agent like rosuvastatin maybe needed. MethodsWe have aimed to assess the lipid-lowering effect of rosuvastatin as compared with fluvastatin in RTR receiving everolimus. Safety was assessed as the pharmacokinetic (PK) interaction potential of a rosuvastatin/everolimus combination in RTR. A 12-hour everolimus PK investigation was performed in 12 stable RTR receiving everolimus and fluvastatin (80 mg/d). Patients were then switched to rosuvastatin (20 mg/d), and a follow-up 12/24-hour PK investigation of everolimus/rosuvastatin was performed after 1 month. All other drugs were kept unchanged. ResultsIn RTR already receiving fluvastatin, switching to rosuvastatin further decreased LDL cholesterol and total cholesterol by 30.2±12.2% (P<0.01) and 18.2±9.6% (P<0.01), respectively. Everolimus AUC0–12 was not affected by concomitant rosuvastatin treatment, 80.3±21.3 μg*h/L before and 78.5±21.9 μg*h/L after, respectively (P=0.61). Mean rosuvastatin AUC0-24 was 157±61.7 ng*h/mL, approximately threefold higher than reported in the literature for nontransplants. There were no adverse events, and none of the patients had or developed proteinuria. ConclusionRosuvastatin showed a superior lipid-lowering effect compared to fluvastatin in stable RTR receiving everolimus. The combination of everolimus/rosuvastatin seems to be as safe as the everolimus/fluvastatin combination.


http://journals.lww.com/transplantjournal/Fulltext/2014/06270/More_Potent_Lipid_Lowering_Effect_by_Rosuvastatin.13.aspx

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15-Year Follow-up of a Multicenter, Randomized, Calcineurin Inhibitor Withdrawal Study in Kidney Transplantation

Transplantation - Most Popular Articles 15-Year Follow-up of a Multicenter, Randomized, Calcineurin Inhibitor Withdrawal Study in Kidney Transplantation

BackgroundCalcineurin inhibitors (CNIs) are essential immunosuppressive drugs after renal transplantation. Because of nephrotoxicity, withdrawal has been a challenge since their introduction. MethodsA randomized multicenter trial included 212 kidney patients transplanted between 1997 and 1999. All patients were initially treated with mycophenolate mofetil (MMF), cyclosporine A (CsA), and prednisone (pred). At 6 months after transplantation, 63 patients were randomized for MMF/pred, 76 for MMF/CsA, and 73 for MMF/CsA/pred. Within 18 months after randomization 23 patients experienced a rejection episode: MMF/pred (27.0%), MMF/CsA (6.8%) and MMF/CsA/pred (1.4%) (P<0.001). ResultsDuring 15 years of follow-up, 73 patients died with a functioning graft, and 43 patients lost their graft. Ninety-six were alive with a functioning graft. Intention-to-treat analysis did not show a significant difference in patient and graft survival. In multivariate analysis, death-censored graft survival was significantly associated with serum creatinine at 6 months after transplantation and maximum PRA but not with the randomization group. CNI withdrawal did not result in a reduced incidence of or death by malignancy or cardiovascular disease. Death-censored graft survival was significantly worse in those patients randomized for CNI withdrawal that had to be reverted to CNI. Independent of randomization group, compared with no rejection, death-censored graft survival was significantly worse in 23 patients with acute rejection after randomization. ConclusionFifteen years after conversion to a CNI free regimen, there was no benefit regarding graft and patient survival or regarding prevalence of or death by comorbidities. However, rejection shortly after CNI withdrawal was associated with decreased graft survival.


http://journals.lww.com/transplantjournal/Fulltext/2014/07150/15_Year_Follow_up_of_a_Multicenter,_Randomized,.8.aspx

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Cochrane Database of Systematic Reviews 2014 Jun 23; 6 : CD007469. Vitamin D supplementation for prevention of cancer in adults. Goran Bjelakovic, Lise Lotte Gluud, Dimitrinka Nikolova, Kate Whitfield, Goran Krstic, Jørn Wetterslev, Christian Gluud PMID: 24953955

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Effects of Obesity on Kidney Transplantation Outcomes: A Systematic Review and Meta-Analysis.

Transplantation - Published Ahead-of-Print Effects of Obesity on Kidney Transplantation Outcomes: A Systematic Review and Meta-Analysis.

Background: The effects of obesity on outcomes reported after kidney transplantation have been controversial. The purpose of this systematic review and meta-analysis was to elucidate this issue. Methods: MEDLINE, EMBASE, Cochrane Library, and gray literature were searched up to August 6, 2013. Studies that compared obese and nonobese patients who underwent kidney transplantation and evaluated one of these outcomes-delayed graft function (DGF), acute rejection, graft or patient survival at 1 or 5 years after transplantation, or death by cardiovascular disease (CVD)-were included. Two independent reviewers extracted the data and assessed the quality of the studies. Results: From 1,973 articles retrieved, 21 studies (9,296 patients) were included. Obesity was associated with DGF (relative risk, 1.41; 95% confidence interval, 1.26-1.57; I2=8%; Pheterogeneity=0.36), but not with acute rejection. Graft loss and death were associated with obesity only in the analysis of studies that evaluated patients who received a kidney graft before year 2000. No association of obesity with graft loss and death was found in the analysis of studies that evaluated patients who received a kidney graft after year 2000. Death by CVD was associated with obesity (relative risk, 2.07; 95% confidence interval, 1.17-3.64; I2=0%; Pheterogeneity=0.59); however, most studies included in this analysis evaluated patients who received a kidney graft after year 2000. Conclusion: In conclusion, obese patients have increased risk for DGF. In the past years, obesity was a risk factor for graft loss, death by CVD, and all-cause mortality. However, for the obese transplanted patient today, the graft and patient survival is the same as that of the nonobese patient. (C) 2014 by Lippincott Williams & Wilkins


http://pdfs.journals.lww.com/transplantjournal/9000/00000/Effects_of_Obesity_on_Kidney_Transplantation.98165.pdf

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