Papers by Lionel Rostaing
Nephrology Dialysis Transplantation, 2007
Revue d Épidémiologie et de Santé Publique
Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation, 2015
We implemented a desensitization program at our center to enable transplant in kidney-transplant ... more We implemented a desensitization program at our center to enable transplant in kidney-transplant candidates who have a living human-leukocyte antigen-incompatible (HLAi) donor. We report on the efficacy of semispecific immunoadsorption to allow HLAi kidney transplant in 6 highly sensitized patients. We chose immunoadsorption as the apheresis technique coupled to hemodialysis as a means to decrease donor-specific alloantibodies in kidney transplant candidates submitted to a pretransplant desensitization program to remove detrimental antibodies. Six highly sensitized kidney-transplant patients (5 females), awaiting their first (n = 1) or second (n = 5) kidney transplant from a living donor, were enrolled in this desensitization program. They had 1 (n = 2), 2 (n = 1), 3 (n = 2), or 4 (n = 1) donor-specific alloantibodies; their mean fluorescent intensities at predesensitization ranged from 1200 to 19 000. Each patient underwent between 10 and 16 immunoadsorption sessions. At the time o...
Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation, 2015
We conducted a desensitization program in our center in patients undergoing kidney transplant for... more We conducted a desensitization program in our center in patients undergoing kidney transplant for end-stage renal disease. These patients had a living-donor either ABO incompatible and/or human-leukocyte antigen-incompatible. The safety and efficacy of this program were evaluated. A pretransplant desensitization program relies on immunosuppressants and apheresis to remove detrimental antibodies. We chose immunoadsorption as the apheresis technique, and coupled this with hemodialysis in a tandem procedure. We report on the efficacy of this new method in 120 procedures performed in 20 patients (14 ABO incompatible, 6 ABO incompatible/human leukocyte antigen-incompatible). The tandem procedure was well tolerated, and saved time compared with conducting sequential immunoadsorption and hemodialysis (6 h vs 10 h). The tandem procedure was associated with significantly decreased isoagglutinin titers and donor-specific alloantibodies (assessed by mean fluorescence intensity). Dialysance was...
Annals of transplantation : quarterly of the Polish Transplantation Society, 2014
Pharmacokinetic data regarding a drug-drug interaction between everolimus and tacrolimus are spar... more Pharmacokinetic data regarding a drug-drug interaction between everolimus and tacrolimus are sparse. In a pharmacokinetic substudy of the randomized ASSET trial, 46 de novo kidney transplant patients receiving very low (1.5-3 ng/mL) or low (4-7 ng/mL) tacrolimus exposure after month 3, both with everolimus and steroids, provided area under the curve (AUC) concentration profiles at day 5 and months 1, 3, and 12. At month 12, mean values for tacrolimus trough concentration (C0), peak concentration (Cmax), and AUC0-12 in the very low tacrolimus group were approximately half that in the low tacrolimus group, but everolimus dose, C0, Cmax, and AUC0-12 were virtually identical in both groups. In a cross-study comparison with data at months 1 and 3 from the pharmacokinetic substudy of the A2307 trial, in which patients received cyclosporine, mean values for everolimus C0, Cmax and AUC0-12 were similar to those in the ASSET trial but the everolimus dose needed to achieve similar exposure wa...
Case reports in transplantation, 2014
Belatacept has been found to be efficient at preserving good kidney function in maintenance kidne... more Belatacept has been found to be efficient at preserving good kidney function in maintenance kidney-transplant patients. Herein, we report on the use of belatacept as a rescue therapy for two kidney-transplant patients presenting with severe adverse events after treatment with calcineurin inhibitors (CNIs) and mammalian target-of-rapamycin (mTOR) inhibitors. Two kidney-transplant patients developed severely impaired kidney function after receiving CNIs. The use of everolimus was associated with severe angioedema. Belatacept was then successfully used to improve kidney function in both cases, even though estimated glomerular-filtration rate before conversion was <20 mL/min. These case reports show that belatacept can be used as a rescue therapy, even if kidney function is very low in kidney-transplant patients who cannot tolerate CNIs and/or mTOR inhibitors.
Annals of transplantation : quarterly of the Polish Transplantation Society, 2014
Patients with a simultaneous pancreas-kidney transplant (SPKT), especially those with gastropares... more Patients with a simultaneous pancreas-kidney transplant (SPKT), especially those with gastroparesis, often have gastro-intestinal (GI) disorders that can modify immunosuppressant pharmacokinetics. We compared the MPA 12-hours area under the curve (AUC(0-12)) in SKPT patients with severe gastroparesis receiving mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS). Fifteen SKPT patients having a severe gastroparesis were switched, at 182 (69-1523) days post-transplantation, from MMF to EC-MPS because of GI disorders. MPA AUC(0-12) values were obtained before and after the switch, ie, under MMF (500 mg b.i.d.) at 169 (51-1522) days post-transplantation and EC-MPS (360 mg b.i.d.) at 102 (26-355) days after the switch. Mean MPA AUC(0-12) h did not differ significantly under MMF and EC-MPS, ie, 40.13±14 and 38.24±15.5 mg*h/L, respectively. Trough and maximal MPA concentrations were similar with both MPA formulations. Although all patients had GI disorders under MMF ...
Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation, 2012
This retrospective single-center study evaluated long-term renal function after conversion from c... more This retrospective single-center study evaluated long-term renal function after conversion from calcineurin inhibitors to sirolimus-based immunosuppression in kidney transplant recipients. From 2001 to 2009, one hundred fifty kidney transplant recipients were converted from calcineurin inhibitors to sirolimus at least 3 months after transplant. After a mean follow-up of 171 weeks, 56.7% of converted patients remained on sirolimus. The 5-year survival rate of the patients (including intent-to-treat) and grafts was 85.5% and 83.6%. Patients on sirolimus showed significant improvement in renal function with a creatinine clearance of 50.9 ± 20.7 and 52.9 ± 20.8 mL/minute at month 0 and month 24. Independent predictive factors associated with a stable estimated glomerular filtration rate at the last follow-up of sirolimus patients were (1) having a living donor, (2) absence of anti-HLA alloantibodies at month 0, and (3) cyclosporine versus tacrolimus used before conversion. Adverse effec...
Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation, 2009
Cytomegalovirus (CMV) infection has an enormous impact in solid-organ transplant patients. In imm... more Cytomegalovirus (CMV) infection has an enormous impact in solid-organ transplant patients. In immunocompromised patients, CMV is associated with well-known direct effects. We herein describe 3 unusual patterns occurring in the setting of tissue-invasive CMV associated with high viral load. Of our 3 cases, the first patient after kidney transplant presented with cholestasis related to radiological cholangitis; the second patient after heart transplant presented with erythema nodosum with CMV infection as the sole cause; and the third patient after kidney transplant presented with acute renal failure related to mild interstitial nephritis with acute tubular necrosis and tubulitis. The first patient's cholestasis resolved with antiviral therapy, as did the erythema nodosum and CMV infection of the heart transplant patient. The third patient's acute renal failure resolved by increased steroid dosage, plasma exchanges, and ganciclovir therapy. These 3 unusual presentations of tis...
Nephrology Dialysis Transplantation, 2014
Kidney transplantation increases the chances for pregnancy and live birth for women with end-stag... more Kidney transplantation increases the chances for pregnancy and live birth for women with end-stage kidney disease. The aims of this study were to describe the outcomes of pregnancies in women with a kidney transplant and to evaluate the impact on anti-human leucocyte antigen (HLA) alloimmunization. We analysed 61 pregnancies that occurred in 46 patients after having excluded 10 miscarriages during the first trimester and 10 other pregnancies from which important data were missing. Anti-HLA antibodies were screened using the Luminex assay. Overall, the live birth rate was 83% (94% after exclusion of miscarriages during the first trimester). Pre-eclampsia and gestational diabetes occurred in 26 and 21% of cases, respectively. The use of tacrolimus was an independent predictive factor for gestational diabetes. Twenty-four newborns (42%) were premature (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;37 weeks). The median birth weight was 2720 (1040-3730) g. Nine newborns (15%) had low birth weights (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;2.5 kg). At least one severe complication occurred in 56% of pregnancies. A high glomerular-filtration rate (GFR) before pregnancy was the sole independent protective factor that avoided a severe complication. Death-censored kidney-allograft survival was 80.4% at 6 years. De novo donor-specific anti-HLA antibodies were detected after only 5.9% of pregnancies: for two women, the father had the same HLA antigens as those from the deceased organ donor. The determination of the HLA of the father before pregnancy can better inform the woman about the possible impact of pregnancy on her kidney-allograft function. Despite many complications, the outcomes for pregnancy and kidney allografts are good. The risk of anti-HLA alloimmunization was low.
Transplantation, Jan 15, 2005
Corticosteroid-free maintenance immunosuppression after organ transplantation eliminates the well... more Corticosteroid-free maintenance immunosuppression after organ transplantation eliminates the well-known corticosteroid-related side effects and may help to improve long-term outcome. We investigated whether a corticosteroid-free tacrolimus (Tac)/mycophenolate mofetil (MMF) regimen, in combination with daclizumab (Dac) induction therapy, provides adequate immunosuppression after renal transplantation. This 6-month, open-label, multicenter, parallel-group study involved 538 renal patients randomized (1:1) to a Dac/Tac/MMF regimen (n = 260) or a Tac/MMF/corticosteroids regimen (n = 278) as a control group. Of the patients who completed the study, 88.8% in the Dac/Tac/MMF group were free from corticosteroid therapy at month 6. The incidence of biopsy-proven acute rejection was 16.5% in both treatment groups; the incidence of biopsy-proven corticosteroid-resistant acute rejection was 4.3% and 5.0% with Tac/MMF/corticosteroids and Dac/Tac/MMF, respectively (P = NS for both comparisons). R...
Background : Following renal transplantation (RT), chronic immunosuppression is associated in hep... more Background : Following renal transplantation (RT), chronic immunosuppression is associated in hepatitis B virus (HBV) (+) patients with a flare-up of the disease, which might be harmful in the long term. Objectives : We report on the effect of long-term lamivudine therapy given at an initial daily dose of 100 mg in 18 HBV (+) RT patients. Results : When lamivudine therapy was commenced, 14 patients (77%) had an increase in their aspartate (AST) and alanine (ALT) aminotransferase levels. During a mean follow-up, under treatment, of 36.5 ± 3.5 months (up to 66 months), 10 patients (55%) had a sustained partial (HBV DNA < 4 × 10 5 copies/ml) (n = 4) or complete (HBV DNA < 400 copies/ml) (n = 6) virological response. Overall, 12 virological breakthroughs were observed. Of those who were HBe Ag(+) prior to lamivudine therapy (n = 4), one seroconverted to HBe Ab during therapy. At the last follow-up, AST and ALT levels were normal in 13 patients. When liver biopsy was repeated during treatment (n = 15), the virological responders showed a significant decrease in total Knodell score from 10 ± 0.6 to 7 ± 1 (P = 0.04), but no significant change in the stage of fibrosis. Conversely, in those patients with high HBV DNA titers, there were no significant changes in the total Knodell score or in the grade of fibrosis. Conclusion : In conclusion, lamivudine therapy is safe in HBV(+)ve renal-transplant patients. However, even if the full and partial virological response rates are still high (55%) in the long term, relapse or primary non-responses occur. The implementation of alternative efficient strategies is warranted.
Journal of nephropathology, 2013
Hepatitis C virus (HCV) infection leads to chronic liver disease, but also to extra-hepatic manif... more Hepatitis C virus (HCV) infection leads to chronic liver disease, but also to extra-hepatic manifestations. Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO) and Web of Science have been searched. Herein, we provide an overview of renal diseases related to HCV and their therapies, as well as the treatment options available for HCV (+)/RNA (+) dialysis patients. We will not mention, however, HCV infection-related complications in the post-kidney transplantation setting. Extra-hepatic manifestations of HCV infection include mixed cryoglobulinemia, lymphoproliferative disorders, and renal disease. HCV infection has been reported in association with distinct histological patterns of glomerulonephritis in native kidneys.
Journal of transplantation, 2014
The human polyomavirus BK (BKV) is associated with severe complications, such as ureteric stenosi... more The human polyomavirus BK (BKV) is associated with severe complications, such as ureteric stenosis and polyomavirus-associated nephropathy (PVAN), which often occur in kidney-transplant patients. However, it is unknown if BKV can replicate within bone marrow. The aim of this study was to search for BKV replication within the bone marrow of kidney-transplant patients presenting with a hematological disorder. Seventy-two kidney-transplant patients underwent bone-marrow aspiration for cytopenia. At least one virus was detected in the bone marrow of 25/72 patients (35%), that is, parvovirus B19 alone (n = 8), parvovirus plus Epstein-Barr virus (EBV) (n = 3), cytomegalovirus (n = 4), EBV (n = 2), BKV alone (n = 7), and BKV plus EBV (n = 1). Three of the eight patients who had BKV replication within the bone marrow had no detectable BKV replication in the blood. Neutropenia was observed in all patients with BKV replication in the bone marrow, and blockade of granulocyte maturation was obs...
Journal of virology, 2014
Little is known about virus adaptation in immunocompromised patients with chronic genotype 3 hepa... more Little is known about virus adaptation in immunocompromised patients with chronic genotype 3 hepatitis E virus (HEV3) infections. Virus-host recombinant strains have been isolated recently from chronically infected patients. The nature and incidence of such recombinant events occurring during infections of solid-organ transplant (SOT) recipients are essentially unknown. The polyproline region (PPR) of strains isolated from SOT patients was sequenced during the acute-infection phase (n = 59) and during follow-up of patients whose infections became chronic (n = 27). These 27 HEV strains included 3 (11%) that showed recombinant events 12, 34, 48, or 88 months after infection. In one strain, parts of the PPR and the RNA-dependent RNA polymerase were concomitantly inserted. In the second, a fragment of a human tyrosine aminotransferase (TAT) gene was inserted first, followed by a fragment of PPR. A fragment of the human inter-α-trypsin inhibitor (ITI) gene was inserted in the third. All ...
Clinics and research in hepatology and gastroenterology, 2015
Hepatitis E virus (HEV) infection is a worldwide disease. An improved understanding of the natura... more Hepatitis E virus (HEV) infection is a worldwide disease. An improved understanding of the natural history of HEV infection has been achieved within the last decade. Several reservoirs and transmission modes have been identified. It is an underdiagnosed disease because of the use of low-sensitivity serological assays; however, diagnostics tools, including nucleic-acid tests, have improved. HEV infection is usually an acute self-limiting disease, but causes chronic infection with rapidly progressive cirrhosis in adult and pediatric organ-transplant-patients. HEV infection evolves to chronic hepatitis in nearly 60% of HEV-infection solid-organ-transplant patients. HEV can also cause extra-hepatic manifestations, such as neurological symptoms and kidney injury. Reducing immunosuppression in transplant patients can lead to HEV clearance in one-third of patients with chronic hepatitis. The use of anti-viral therapies, such as pegylated-interferon and ribavirin, has been found to efficaci...
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2015
Twenty-four solid-organ-transplant recipients with chronic hepatitis E virus (HEV) infections wer... more Twenty-four solid-organ-transplant recipients with chronic hepatitis E virus (HEV) infections were given ribavirin therapy for 3 months. All the patients with protracted fecal HEV shedding during treatment suffered a relapse. Monitoring HEV fecal excretion could be used to determine the optimal duration of ribavirin therapy.
Contributions to Nephrology, 2012
The prevalence of chronic hepatitis C virus (HCV) infection after kidney transplantation (KT) var... more The prevalence of chronic hepatitis C virus (HCV) infection after kidney transplantation (KT) varies a lot from one country to another. In the setting of (powerful) immunosuppression, HCV replication can sharply increase, thereby leading to potential severe HCV-related liver damage such cirrhosis or fibrosing cholestatic hepatitis. In the setting of KT, α-interferon (α-IFN) therapy alone has been associated with a very low sustained virological response (SVR), and a poor tolerance, particularly with regard to the kidney allograft, i.e. it induces acute rejection. The combined use of α-IFN plus ribavirin leads to a greater rate of SVR, but randomized clinical trials are missing in order to evaluate its safety with respect to the allograft function. Ribavirin monotherapy, or ribavirin plus amantadine therapy are not able to induce SVR; ribavirin may have an effect upon HCV-related proteinuria. Finally, it seems advisable to try and eradicate HCV infection prior to KT, i.e. while the patient is on dialysis therapy. After KT, α-IFN plus ribavirin therapy could be attempted only in those patients developing rapid cirrhosis or in those developing fibrosing cholestatic hepatitis or in those having de novo cryoglobulinemic glomerulonephritis within the allograft.
Transplantation, 2005
The aim of our study was to identify the independent factors that might predict anemia at 6 (M6) ... more The aim of our study was to identify the independent factors that might predict anemia at 6 (M6) and 12 (M12) months posttransplantation. Postrenal transplant anemia (PTA) was defined as having a hemoglobin (Hb) level below 13 g/dl for men and below 12 g/dL for women. In this study, we included all the recipients who received a renal transplant in 2001 at our department, and for whom the graft was still functioning 1 year later (n=92). Anemia was observed in 78%, 35.5% and 25% of patients at day (D)0 and at M6 and M12, respectively. Iron deficiency was found in 14% of patients at D0 and in 13% of patients at M12. A total of 59.8% of patients had received at least one blood transfusion in the postoperative period, whereas 41.3% of patients had received recombinant erythropoietin (rEpo) therapy within the first months posttransplantation. In multivariate analysis, the independent predictive factors of anemia at M6 were Epo level at D0, initial nephropathy (polycystic kidney disease vs. others), posttransplantation rEpo therapy, hematocrit at M3, platelets at D7, and sirolimus therapy. The independent predictive factors of anemia at M12 were Epo level at D0, platelets at D7, delayed graft function (DGF), creatinine clearance at M12, serum creatinine at M12, and Hb level at M6. The prevalence of PTA was 25% at M12. DGF, renal function at M12, and anemia at M6 were independent risk factors for still having anemia at M12.
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Papers by Lionel Rostaing