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ABSTRACT: Scarce data exist regarding the incidence of donor-specific antibodies (DSAs) in kidney transplant patients receiving everolimus-based immunosuppression without calcineurin inhibitors (CNIs). The aim of this retrospective case-control study was to compare the incidence of de novo DSAs in patients converted to an everolimus-based regimen without CNIs with that seen in patients maintained on CNIs. Sixty-one DSA-free kidney transplant patients who had been converted to an everolimus-based regimen (everolimus group) were compared to 61 other patients maintained on CNIs-based regimen (control group). Patients were matched according to age, gender, induction therapy, date of transplantation, and being DSA-free at baseline. At last follow-up, the incidence of DSAs was 9.8% in the everolimus group and 5% in the control group (p = ns). In the everolimus group, the increased incidence of DSAs between baseline and last follow-up was statistically significant. Antibody-mediated rejection occurred in 6.5% in the everolimus group and 0% in the CNIs group. The incidence of DSAs is numerically increased in kidney transplant patients treated with an everolimus-based without CNIs. A study including a larger number of patients is required to determine whether a CNI-free everolimus-based immunosuppression significantly increases DSAs formation.
Clinical Transplantation 04/2013; · 1.67 Impact Factor
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ABSTRACT: OBJECTIVES: Scarce data exist regarding the effect of acute graft pyelonephritis on kidney histology after a kidney transplant. This study sought to assess the kidney histology at 1 month, and kidney function at 1 year, after acute graft pyelonephritis in kidney transplant patients. MATERIALS AND METHODS: All kidney transplant patients with acute graft pyelonephritis between October 2006, and December 2008, underwent a kidney biopsy 1 month later (n=28). Histologic findings were compared with those observed in a control group (n=28) who underwent a protocol kidney biopsy at 1 year posttransplant and did not present with acute graft pyelonephritis. Patients were matched according to age, sex, and immunosuppressive regimen. RESULTS: Kidney function was impaired by the acute graft pyelonephritis episodes at the time of biopsy. In 40% of patients, the estimated glomerular filtration rate did not return to baseline by 1 month after acute graft pyelonephritis and remained impaired thereafter. Three patients had features of acute rejection. Tubulitis was seen more frequently in the acute graft pyelonephritis group, especially in patients in whom estimated glomerular filtration rate did not completely recover by 1 month after acute graft pyelonephritis. Patients with acute graft pyelonephritis who had inflammatory infiltrate of > 20% 1 month after acute graft pyelonephritis had worse kidney function 1 year later. CONCLUSIONS: After transplant, when kidney function remains impaired 1 month after acute graft pyelonephritis, kidney biopsies allowed graft rejection diagnosis and predicted kidney function recovery.
Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation. 03/2013;
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Joelle Guitard,
Sophie Edouard,
Hubert Lepidi,
Christine Segonds,
Marion Grare,
Marie-Laure Ranty-Quintyn,
Isabelle Rouquette,
Olivier Cointault,
Lionel Rostaing,
Nassim Kamar,
Florence Fenollar
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ABSTRACT: TO THE EDITOR: A man, 56 years of age, was admitted to the hospital for epigastric pain, fever, and fatigue 8 years after a cardiac transplant. His immunosuppressive regimen consisted of cyclosporine A, mycophenolate mofetil, and steroids. Clinical examination revealed a 4-kg weight loss within 3 months without peripheral lymph node enlargement.
Emerging Infectious Diseases 08/2012; 18(8):1386-8. · 6.79 Impact Factor
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Nassim Kamar,
Chakib Maaroufi,
Céline Guilbeau-Frugier,
Aude Servais,
Vannary Meas-Yedid,
Ivan Tack,
Eric Thervet,
Olivier Cointault,
Laure Esposito, Joelle Guitard,
Laurence Lavayssière,
Clarisse Panterne,
Fabrice Muscari,
Christophe Bureau,
Lionel Rostaing
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ABSTRACT: Histological renal lesions observed after liver transplantation are complex, multifactorial, and interrelated. The aims of this study were to determine whether kidney lesions observed at five yr after liver transplantation can predict long-term kidney function. Ninety-nine liver transplant patients receiving calcineurin inhibitor (CNI)-based immunosuppression, who had undergone a kidney biopsy at 60 ± 48 months post-transplant, were included in this follow-up study. Kidney biopsies were scored according to the Banff classification. Estimated glomerular filtration rate (eGFR) was assessed at last follow-up, that is, 109 ± 48 months after liver transplantation. eGFR decreased from 92 ± 33 mL/min at transplantation to 63 ± 19 mL/min after six months, to 57 ± 17 mL/min at the kidney biopsy, to 54 ± 24 mL/min at last follow-up (p < 0.0001). At last follow-up, only three patients required renal replacement therapy. After the kidney biopsy, 13 patients were converted from CNIs to mammalian target of rapamycin inhibitors, but no significant improvement in eGFR was observed after conversion. Elevated eGFR at six months post-transplant and a lower fibrous intimal thickening score (cv) observed at five yr post-transplant were the two independent predictive factors for eGFR ≥60 mL/min at nine yr post-transplant. Long-term kidney function seems to be predicted by the kidney vascular lesions.
Clinical Transplantation 07/2012; · 1.67 Impact Factor
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Arnaud Del Bello,
Nicolas Congy-Jolivet,
Federico Sallusto,
Celine Guilbeau-Frugier,
Isabelle Cardeau-Desangles,
Marylise Fort,
Laure Esposito, Joelle Guitard,
Olivier Cointault,
Laurence Lavayssière,
Marie Béatrice Nogier,
Antoine Blancher,
Lionel Rostaing,
Nassim Kamar
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ABSTRACT: Within the last few years, anti-human leukocyte antigen detection assays have significantly improved. This study asked, using the Luminex single-antigen assay, whether an allograft nephrectomy allowed donor-specific alloantibodies to appear that were not previously detected in the serum when the failed kidney was still in place.
After losing the kidney allograft and stopping immunosuppressive therapy, the proportions of donor-specific alloantibodies and nondonor-specific alloantibodies were compared in patients who had (n=48; group I) and had not (n=21; group II) undergone an allograft nephrectomy. Allograft nephrectomies were performed at 150 days after kidney allograft loss, and the time between allograft nephrectomy and last follow-up was 538 ± 347 days.
At kidney allograft loss, donor-specific alloantibodies were detected in three group II patients (14.2%) and six group I patients (12.5%). At last follow-up, donor-specific alloantibodies were detected in 11 patients (52.4%) without and 39 patients (81%) with an allograft nephrectomy (P=0.02). Anti-human leukocyte antigen class I donor-specific alloantibodies were positive in 23.8% of group II and 77% of group I patients (P<0.001); anti-human leukocyte antigen class II donor-specific alloantibodies were positive in 42.8% of group II and 62.5% of group I patients. Independent predictive factors for developing donor-specific alloantibodies after losing kidney allograft and stopping immunosuppressants were number of anti-human leukocyte antigen A/B mismatches at transplantation (zero versus one or more) and allograft nephrectomy.
The development of donor-specific alloantibodies was significantly greater in patients with a failed kidney who had undergone an allograft nephrectomy compared with those patients who had not undergone allograft nephrectomy.
Clinical Journal of the American Society of Nephrology 05/2012; 7(8):1310-9. · 5.23 Impact Factor
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Arnaud Del Bello,
Nicolas Congy,
Federico Sallusto,
Isabelle Cardeau-Desangles,
Marylise Fort,
Laure Esposito, Joelle Guitard,
Olivier Cointault,
Laurence Lavayssière,
Marie Béatrice Nogier,
Xavier Game,
Antoine Blancher,
Lionel Rostaing,
Nassim Kamar
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ABSTRACT: The occurrence of de novo anti-human leukocyte antigen (HLA) antibodies and donor-specific antibodies (DSAs) after early graft loss is not well known. The aims of this single-center study were to evaluate the incidence of de novo DSAs and non-DSA anti-HLA antibodies after allograft nephrectomy for early graft loss and to seek the predictive factors for the development of DSAs.
Thirty-two patients, who experienced an early graft loss (<3 months after transplantation) and required an allograft nephrectomy, and who were considered for retransplantation, were included in the study. Anti-HLA antibodies were assessed, using the Luminex assay, before transplantation, on day 15 and at months 1, 3, 6, and 9 after the nephrectomy, and then every 3 to 6 months until the last follow-up.
The median time between transplantation and allograft nephrectomy was 2.5 (0-81) days. The median follow-up was 335 (30-1441) days. At month 9, postallograft nephrectomy, the incidence of DSAs was 56.6% (17/30). Anti-HLA class I and class II DSAs were detected, respectively, in 33.3% (10/30) and 30% (9/30) of patients. The incidence of de novo non-DSA anti-HLA antibodies was 64% (19/30): of these, 83.3% reacted to the donors' epitopes. Induction therapy (type and dose) and the time between transplantation and allograft nephrectomy did not influence the incidence of DSAs. No independent predictive factor for the development of DSAs was identified.
Even after a short transplantation period, DSAs and non-DSA anti-HLA antibodies may develop in more than 50% of patients whose immunosuppression has been stopped after an allograft nephrectomy.
Transplantation 03/2012; 93(9):936-41. · 4.00 Impact Factor
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Nassim Kamar,
Hugo Weclawiak,
Céline Guilbeau-Frugier,
Florence Legrand-Abravanel,
Olivier Cointault,
David Ribes,
Laure Esposito,
Isabelle Cardeau-Desangles, Joelle Guitard,
Federico Sallusto,
Fabrice Muscari,
Jean Marie Peron,
Laurent Alric,
Jacques Izopet,
Lionel Rostaing
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ABSTRACT: Hepatitis E virus (HEV) infection is an emerging disease in industrialized countries. Few data regarding genotype 3 HEV extrahepatic manifestations exist.
We assessed kidney function and histology in solid-organ transplant patients during HEV infection. In all, 51 cases of genotype 3 HEV infections were diagnosed (34 kidney, 14 liver, and 3 kidney-pancreas transplant patients). Of these, 43.2% were cleared of the virus spontaneously within 6 months of infection, whereas 56.8% evolved to chronic hepatitis. Twelve of these patients completed a 3-month antiviral therapy and were followed up for 6 months posttreatment. Kidney function (estimated glomerular filtration rate [eGFR] obtained by the Modification of Diet in Renal Disease equation) and proteinuria were assessed before infection, during HEV infection and during follow-up. Kidney biopsies were obtained from patients with high proteinuria and decreased eGFR levels.
During HEV infection, there was a significant decrease in eGFR in both kidney- and liver-transplant patients. Glomerular diseases were observed in kidney biopsies obtained during the acute and chronic phases. This included membranoproliferative glomerulonephritis and relapses in IgA nephropathy. The majority of patients had cryoglobulinemia that became negative after HEV clearance. Kidney function improved and proteinuria decreased after HEV clearance.
HEV-associated glomerulonephritis seems to be an HEV-related extrahepatic manifestation. Further studies are required to confirm these observations.
Transplantation 01/2012; 93(6):617-23. · 4.00 Impact Factor
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ABSTRACT: Tenofovir therapy has been found to be efficient in treating hepatitis B virus (HBV) in nontransplant patients. However, in the setting of solid-organ transplantation, the efficacy of tenofovir has not been tested. The aim of this pilot study was to assess the clinical and biologic response and tolerance to tenofovir therapy in HBV-positive organ transplant recipients.
Seven patients, three kidney, three liver, and one cardiac transplant recipients, with chronic HBV infection were partial responders to adefovir (n=7), lamivudine (n=7), or entecavir (n=5) therapy. Consequently, they were placed on tenofovir therapy (245 mg daily, which was adapted to renal function) alone (n=4) or in combination with lamivudine (n=3). Tenofovir therapy was assessed at 1, 3, 6, and 12 months postinitiation or at the last follow-up.
HBV DNA viral load (4.16 [2.03-5.56] log10 copies/mL at baseline) became significantly decreased to 3.15 (1.08-5.17), 2.88 (1.3-4.3), 3.53 (1.3-5.75), 3.33 (1.3-7.57), and 2.31 (1.3-4.81) log copies/mL at 1, 3, 6, and 12 months posttenofovir initiation and at last follow-up, respectively (P=0.02). Three patients were HBV DNA negative at the last follow-up. Liver enzyme levels did not change significantly throughout the follow-up period. Clinical and biologic tolerance was excellent.
Even though HBV DNA clearance was not achieved in all patients, the results of this pilot study are encouraging and demonstrate that tenofovir therapy is safe and efficacious in treating HBV-positive organ transplant patients. However, a larger trial is needed to confirm these preliminary results.
Transplantation 02/2011; 91(8):916-20. · 4.00 Impact Factor
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ABSTRACT: New-onset diabetes mellitus after transplantation (NODAT) is an important complication after kidney transplantation, responsible for increased mortality mainly related to cardiovascular events and infections. It has been also identified as an independent risk factor associated with graft loss. The varying definitions of diabetes used in the literature, and the prevalence and incidence of NODAT, are difficult to establish: it varies from 2 to 50% in the kidney transplant population. However, using the World Health Organization and the American Diabetes Association criteria, it occurs in ~15% of transplant recipients at 1 year in the USA, and ~5-10% in Europe. The main recipient-related risk factors include old age, high body weight and high body mass index (BMI) before transplantation, Afro-American or Hispanic ethnicity, hepatitis C virus (HCV) infection, and impaired fasting glucose level before transplantation. The other significant risk factors include male donor, acute rejection episodes, cytomegalovirus (CMV) infection and the immunosuppressive regimen, especially the use of tacrolimus (FK506), steroids, or mammalian target for rapamycin inhibitors. While some risk factors cannot be modified, others, such as recipient body weight, BMI, HCV or CMV infection, and immunosuppressive regimen can be controlled with an appropriate diet or treatment. Screening for impaired fasting glucose should be done before transplantation in dialysis or end-stage renal disease patients to identify patients at risk for NODAT. In patients with increased BMI, weight loss before transplantation reduces the risk of NODAT. HCV infection should be treated before transplantation. Prolonged anti-CMV prophylaxis may be used. Cyclosporine A is preferred to tacrolimus in patients at high risk of NODAT. A steroid-free regimen or early steroid withdrawal is encouraged to reduce the risk of NODAT.
Contributions to nephrology 01/2011; 170:247-55. · 1.49 Impact Factor
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Nassim Kamar,
Céline Guilbeau-Frugier,
Aude Servais,
Ivan Tack,
Eric Thervet,
Olivier Cointault,
Laure Esposito, Joelle Guitard,
Laurence Lavayssière,
Fabrice Muscari,
Christophe Bureau,
Lionel Rostaing
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ABSTRACT: Chronic kidney disease is a common complication after liver transplantation. However, few reports regarding kidney histology exist for this setting.
Inulin clearance was measured and a kidney biopsy was performed in 99 patients at 60 ± 48 months after liver transplantation. Kidney biopsies were scored according to the Banff classification, and interstitial fibrosis was measured by a computerized quantitative method.
There was a steep decrease in kidney function within the first 6 months following transplantation, but this lessened thereafter. At kidney biopsy, inulin clearance and estimated glomerular filtration rate (eGFR) (using the abbreviated Modification of Diet in Renal Disease equation) were highly correlated (r(2) = 0.47, P < 0.0001). A decrease in eGFR at 6 months post-transplant was the sole predictive factor for inulin clearance of < 60 mL/min/1.73 m(2) at 5 years post-transplant. Few patients had a specific pattern of kidney histopathology and all patients had complex primary lesions. Lowered eGFR at 6 months post-transplant was a predictive factor for > 50% sclerotic glomeruli on the kidney biopsy. The duration of tacrolimus therapy, as compared to cyclosporine A, was a protective factor for < 20% interstitial fibrosis on the kidney biopsy.
In the setting of liver transplantation, this is the largest kidney-histology study to confirm that histological kidney lesions are complex, multiple and interrelated. Kidney function at 6 months post-transplant can predict long-term kidney function and histology.
Nephrology Dialysis Transplantation 11/2010; 26(7):2355-61. · 3.40 Impact Factor
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Nassim Kamar,
Pierre Marquet,
Peggy Gandia,
Fabrice Muscari,
Laurence Lavayssière,
Laure Esposito, Joelle Guitard,
Cindy Canivet,
Jean Marie Peron,
Laurent Alric,
Bertrand Suc,
Franck Saint-Marcoux,
Lionel Rostaing
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ABSTRACT: Therapeutic drug monitoring of mycophenolate mofetil (MMF) was found to be beneficial in preventing acute rejection after kidney transplantation. The aim of this pilot prospective study was to evaluate the efficacy of MMF dose adjustment in de novo liver transplant patients receiving MMF at fixed versus concentration-controlled doses [ie, adapted to mycophenolic acid (MPA) AUC0-12h] and tacrolimus during the first 12 months posttransplant. Twenty-nine patients received steroids only up to day 10, induction therapy by lymphoglobulins followed by tacrolimus and MMF. In all patients, MPA AUC0-12h were measured on posttransplant days 7 and 14 and at months 1, 2, 3, 6, and 12. From March 2006 to March 2007, 15 patients received MMF at a fixed dose of 1 g twice a day for 12 months. From April 2007 to December 2007, MMF was given to 14 patients at a dose of 1 g twice a day until day 7 and was then adapted to reach an MPA AUC0-12h target of 30-60 mg x h/L. The proportion of MPA AUC0-12h values within the target range was similar in both groups. The proportion of patients with MPA AUC0-12h below 30 mg x h/L tended to be higher in the fixed dose group within the first month posttransplant. However, MMF dose did not differ significantly between the 2 groups at any period except month 1. MPA AUC0-12h tended to be higher in the concentration-controlled group at day 14 and month 2 and was significantly so at month 1. Tacrolimus trough concentrations tended to be lower in the concentration-controlled group at all study periods and was significantly so at month 3. At 12 months posttransplant, patient and graft survivals, acute rejection rate, and adverse events were similar in both groups. We concluded that adapting the dose of MMF resulted in a significant increase in MPA AUC0-12h at month 1. There was a trend toward a lower proportion of patients with MPA AUC0-12h below 30 mg x h/L in the concentration-controlled group. No difference in outcome was found between both groups.
Therapeutic drug monitoring 07/2009; 31(4):451-6. · 2.43 Impact Factor
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ABSTRACT: Darbepoetin alfa is used to treat renal anemia; however, little information is available concerning its use during the posttransplant period, especially in HCV-positive patients treated with ribavirin for active hepatitis C.
This study investigated the efficacy and safety of using darbepoetin alfa in this population during a 6-month treatment period. All anemic patients were HCV/RNA-positive, treated with ribavirin, and had impaired renal function. Patients (n=7) who had not been treated previously with recombinant human erythropoietin (rHuEPO) were placed in "group no rHuEPO." Patients previously with recombinant human erythropoietin (n=16; "group rHuEPO") were switched to darbepoetin alfa according to the European summary of product characteristics.
Seventy-three percent of the patients were men. The mean creatinine clearance at baseline was 58.7 -/+ 21.5 mL/min. All patients received an immunosuppressive treatment. Although mean hemoglobin levels remained stable in group no rHuEPO and increased in group rHuEPO, the difference was not statistically significant. Also, the median darbepoetin-alfa-weighted dose in group no rHuEPO increased while it remained stable in group rHuEPO, as did the median daily dosage of ribavirin; however, these differences were not statistically significant. Creatinine levels and creatinine clearance levels remained stable throughout the study. No significant medical events related to the treatment were reported during the study.
Darbepoetin alfa was found to be efficient and well tolerated in correcting renal anemia in transplant recipients treated with ribavirin for active hepatitis C.
Experimental and clinical transplantation: official journal of the Middle East Society for Organ Transplantation 01/2009; 6(4):271-5. · 0.81 Impact Factor
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ABSTRACT: In the setting of kidney transplantation, cinacalcet has been given, mainly, once daily, but also twice daily. The aims of this prospective study were to assess the acute pharmacodynamic effect of cinacalcet administrated once or twice daily to kidney transplant patients with normal renal function and persisting hypercalcaemia due to hyperparathyroidism and to evaluate 1-year efficacy and tolerance of cinacalcet given at a dose of 30 mg b.i.d.
Eleven patients, who received a transplant 6 (6-59) months previously, were included in the study. A first kinetic was done after administration of 60 mg of cinacalcet at 8 a.m. After a washout period of 1 week, the second kinetic was performed with cinacalcet given at 30 mg b.i.d within a 12-h period.
During both kinetics, serum calcium (sCa), ionized calcium (sCa(2+)), albumin-corrected Ca and parathyroid hormone (PTH) levels decreased significantly. At 24 h after the second kinetic, sCa(2+) was significantly lower. After 1 year of cinacalcet treatment, given at the dose of 30 mg b.i.d., there was a significant decrease in sCa, sCa(2+), PTH levels and calcium x phosphorus (Ph) product. In contrast, Ph levels increased significantly. There was no significant change in renal function.
Once- or twice-daily acute administration of cinacalcet to kidney-transplant patients has similar efficacy. One-year administration of cinacalcet, given as two daily doses, is safe and efficient.
Nephrology Dialysis Transplantation 07/2008; 23(11):3720-6. · 3.40 Impact Factor
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ABSTRACT: Mycoplasma hominis has been incriminated in several genital and extragenital infections. Here, we report the first case of perihepatitis associated with a perinephric abscess in a woman who had received a kidney transplant. Four months after the transplant, the patient was admitted for perirenal allograft pain, fever, and elevated inflammatory parameters and liver enzyme levels. A renal ultrasonography found a collection of fluid. Results of blood and urine analyses were within normal limits. Fluid aspiration of the peritoneal cavity was performed, and the results of cultures for bacteria and fungi were negative. The patient was treated by surgical lavage of the peritoneal cavity. Her fever resolved 5 days later. Two months after surgical lavage of the peritoneal cavity, her liver enzyme levels returned to the normal range. Three months after surgical lavage, cultures of the perinephric fluid showed Mycoplasma hominis. We conclude that in patients who present with perinephric fluid suspected of being infected, bacteriologic analysis of the fluid (from surgical lavage of the peritoneal cavity) should be performed. Antibiotics active against intracellular bacteria should be administered.
Experimental and clinical transplantation: official journal of the Middle East Society for Organ Transplantation 01/2008; 5(2):708-9. · 0.81 Impact Factor
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Stanislas Faguer,
Nassim Kamar,
Céline Guilbeaud-Frugier,
Marylise Fort,
Anne Modesto,
Arnaud Mari,
David Ribes,
Olivier Cointault,
Laurence Lavayssière, Joelle Guitard,
Dominique Durand,
Lionel Rostaing
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ABSTRACT: A pilot study was performed on eight consecutive renal-transplant (RT) patients presenting with acute humoral rejection (AHR) to assess the efficacy of monoclonal anti-B cell antibodies, such as rituximab (375 mg/m weekly) for 3 to 5 consecutive weeks, in addition to plasma exchange (PE), steroids, mycophenolate mofetil, and tacrolimus. AHR was associated with increased serum creatinine, the appearance of donor-specific alloantibodies (DSA), and the presence of C4d in a transplant biopsy. After a follow-up of 10 months (range 7-23), patient and graft survivals were 100% and 75%, respectively. Renal function improved in six cases in which serum creatinine decreased from 297+/-140 to 156+/-53 micromol/L (P=0.015); graft loss occurred in two cases; and four patients had infectious complications. At last follow-up, DSA had disappeared or decreased in four cases. Rituximab therapy, in addition to PE, might be of benefit for RT patients presenting with AHR.
Transplantation 06/2007; 83(9):1277-80. · 4.00 Impact Factor
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ABSTRACT: Mycophenolic acid dose modifications after renal transplantation seem to adversely affect renal allograft outcome. The aim of this retrospective study was to examine the effect of mycophenolic acid dose modifications on renal function 1 year after transplantation and to determine the factors predictive of those dose modifications within the first year after renal transplantation.
All 130 patients at our institution who were treated de novo between January 2002 and April 2003 with either a mycophenolate mofetil-based or an enteric-coated mycophenolate sodium-based therapy and who had a functioning renal allograft 1 month after transplantation were included in this study.
Fifty-seven patients (43.8%) underwent a dose modification during the first year after transplantation. One, 3, 6, and 12 months after transplantation, renal function was significantly improved in the patients who did not receive a dose modification. A mycophenolic acid dose that 1 year after transplantation was less than the initial dose received just after transplantation was an independent factor associated with deteriorating renal function. Sirolimus immunosuppression, Cytomegalovirus infection, and pretransplant lymphocyte counts were independent factors associated with mycophenolic acid dose modifications within the first year after kidney transplantation.
Modification of the mycophenolic acid dose may adversely affect renal function 1 year after transplantation.
Experimental and clinical transplantation: official journal of the Middle East Society for Organ Transplantation 01/2007; 4(2):510-7. · 0.81 Impact Factor
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ABSTRACT: The aim of our study was to determine the prevalence and predictive factors for post-transplant anemia (PTA) at 6 (M6) and 12 (M12) months after orthotopic liver-transplant (OLT) in a cohort of 97 consecutive patients.
Anemia was defined at M6 and M12 according to the World Health Organization criteria, i.e., a hemoglobin level of <12 g/dL for women and <13 g/dL for men. Immunosuppression relied on tacrolimus and steroids with or without mycophenolate mofetil.
Anemia was present in 64.5%, 50%, and 52.8% of patients before OLT and at M6 and M12, respectively. Of the anemic patients, 33% (M6) and 30.3% (M12) received recombinant erythropoietin therapy. In multivariate analysis, the independent predictive factors for anemia at M6 were mean corpuscular volume (<85 fl) at day 7, daily steroid dosage (<0.3 mg/kg), serum creatinine (>130 micromol/L), and hemoglobin level (<11 g/dL) 1 month after OLT (M1). Independent predictive factors for anemia at M12 were daily steroid dosage at M1 (<0.3 mg/kg), hematocrit at M1 (<33%), red blood cell count at M6 (<3.75 T/L), daily dosage at M1 of cyclosporine and tacrolimus, and OLT for causes other than alcohol abuse.
Anemia is highly prevalent within the first year post-OLT. This deserves further investigation and appropriate treatment.
Transplantation 07/2006; 81(11):1525-31. · 4.00 Impact Factor
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ABSTRACT: Chronic renal failure (CRF) is increasingly prevalent in solid-organ-transplant patients. This is in part related to the long-term use of calcineurin inhibitor (CNI) agents. However, in orthotopic liver-transplant (OLT) patients, the effects of superimposed hepatitis C virus (HCV)-related renal lesions could also be a factor. The aim of this cohort study (February 2000 to September, 2003) was to identify the predictive factors at one year post-transplantation for CRF in OLT patients associated with induction therapies. CRF was defined as having a creatinine clearance (CC) lower than 60 mL/min. Of the 97 transplants performed during that period, 72 were still functioning after one year. Of these, 33 patients (45.8%) had CRF. In univariate analysis, the predicting factors for CRF were recipient sex (female), initial liver disease (HCV-related cirrhosis), pre-transplant CC (<80 mL/mn), and post-transplant serum creatinine >130 micromol/L at day 3 and months (M) 1, 3, and 6. In multivariate analysis, the independent predictive factors for CRF included female sex [OR: 11.5 (2.3-58.3); p = 0.003], HCV infection [OR: 5.01 (1.1-22.7); p = 0.03], pre-OLT CC <80 mL/mn [OR: 5.4 (1.2-23.7); p = 0.025], and serum creatinine at M6 greater than 130 micromol/L [OR: 19.6 (3.7-102.5); p = 0.0004]. Among all of the predictive factors for post-OLT CRF, only one is modifiable: post-transplant serum creatinine, which could be, to some extent, related to the long-term use of CNIs.
Renal Failure 02/2006; 28(5):419-25. · 0.82 Impact Factor
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Grégoire Basse,
David Ribes,
Nassim Kamar,
Marion Mehrenberger,
Laure Esposito, Joelle Guitard,
Laurence Lavayssière,
Françoise Oksman,
Dominique Durand,
Dominique Dur,
Lionel Rostaing
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ABSTRACT: Type II or III cryoglobulins are fairly prevalent in renal-transplant (RT) patients, and are often related to chronic hepatitis C virus (HCV) infection. However, they rarely result in graft dysfunction. They are sustained by proliferation of oligoclonal B-cells. Systemic B-cell depletion and clinical remission of the systemic effects of cryoglobulins have been achieved in HCV-positive immunocompetent patients with a human/mouse chimeric monoclonal antibody that specifically reacts with the CD20 antigen (i.e., rituximab). Thus, this provides the rationale to use rituximab for cryoglobulin-related graft dysfunction in RT patients.
Three RT patients, of whom one was HCV-positive, developed renal-function impairment long after transplantation, as well as de novo nephrotic syndrome (n=2) and severe hypertension (n=2). This latter case was related to type III cryoglobulinemia and was associated with membranoproliferative glomerulonephritis. In addition to their baseline standard immunosuppression, the patients were given weekly rituximab infusions of 375 mg/m (two infusions in patient and four infusions for the other two cases).
This treatment resulted in a dramatic improvement in renal parameters, particularly in a sustained remittence of nephrotic syndrome, a sustained clearance of cryoglobulins in two cases, but also in severe infectious complications in two cases.
We conclude that rituximab therapy is highly effective in cryoglobulin-related renal dysfunction in RT patients; however, due to chronic immunosuppression, this is at the expense of infectious complications.
Transplantation 01/2006; 80(11):1560-4. · 4.00 Impact Factor
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ABSTRACT: Switching from calcineurin inhibitors (CNIs) to sirolimus might improve renal function in chronic renal transplant patients.
In a prospective study, we assessed long-term efficacy and safety parameters in 43 renal transplant recipients who were switched from a CNI (cyclosporin A, 65%; and tacrolimus, 35%) to sirolimus for either chronic allograft dysfunction (n = 38) or recurrent cutaneous cancers (n = 5). A kidney biopsy was done in 79% of patients prior to conversion, and showed either chronic allograft nephropathy (n = 26) or CNI nephrotoxicity (n = 7). Conversion was either abrupt or progressive, with CNI withdrawal over 3 weeks. All patients also received steroids with or without mycophenolate mofetil or azathioprin. Patient data were recorded at baseline (D0), at 1 (D30) and 6 months (D180), and at 1, 1.5 and 2 years post-conversion.
After a mean post-conversion follow-up of 27+/-1.5 months, 58% of the patients were still on sirolimus. The survival of intent to treat patients and grafts was 95.3 and 93%, respectively. Overall, there was significant improvement in renal function, creatinine clearance increasing from 49.4+/-14.9 to 53+/-16.3 ml/min at D30 (P = 0.01), and to 54.7+/-20 ml/min at D180 (P = 0.01). Thereafter, creatinine clearance was not different from baseline, i.e. 54.7+/-21.7, 52.8+/-20 and 51.7+/-20.3 ml/min at years 1, 1.5 and 2, respectively. We divided the patients into two groups: responders (n = 29), those with an increase in creatinine clearance at 6 months post-conversion compared with D0, and non-responders (n = 14), those with a decrease in creatinine clearance at 6 months post-conversion compared with D0. In univariate analysis, factors predictive of response included proteinuria at D0 and the magnitudes of the differences between D30 and D0 for serum creatinine and lactate dehydrogenase. The conversion was associated with (i) significant decreases in serum calcium, phosphorus and uric acid, and in haemoglobin levels; (ii) significant increases in serum alkaline phosphatase, total cholesterol, parathyroid hormone, and the number of patients on statin and recombinant erythropoietin therapies; and (iii) the appearance of de novo proteinuria of >1 g/day in 28% of patients (P < 0.0009), which was >2 g/day in 12% of the entire cohort. Kidney biopsies in 17 patients 2 years after conversion showed the same Banff scores as observed at baseline. We identified three independent predictive factors for a renal response to the switch: absence of proteinuria, presence of antihypertensive therapy at D0 and serum lactate dehydrogenase level at D30.
Conversion from CNIs to sirolimus in renal transplant patients with chronic allograft nephropathy was associated with improved renal function; however, 33% of the patients developed overt proteinuria.
Nephrology Dialysis Transplantation 12/2005; 20(11):2517-23. · 3.40 Impact Factor
