Publications by authors named "Bruno Hurault de Ligny"

59 Publications

Paternity in male kidney transplant recipients: a French national survey, the PATeRNAL study.

BMC Nephrol 2020 11 16;21(1):483. Epub 2020 Nov 16.

Centre Universitaire des Maladies Rénales, CHU de Caen, Avenue de la côte de Nacre, 14033, Caen, Cedex 9, France.

Background: There is concern about the impact of immunosuppressive agents taken by male kidney transplant (KT) recipients on the risk of foetal malformations. The aim of our survey was to estimate the paternity rate and the outcomes of pregnancies fathered by kidney transplanted males.

Methods: This survey analysed 1332 male KT recipients older than 18 years, followed in 13 centres in France. A self-reported questionnaire was used to collect data on the patients, treatments at the time of conception and the pregnancy outcomes.

Results: The study included data on 349 children from 404 pregnancies fathered by 232 male KT recipients. The paternity rate was 17% (95% CI [15-20]). There were 37 (9%, 95% CI [7-12]) spontaneous abortions, 12 (3%, 95% CI [2-5]) therapeutic abortions, 2 (0.5%, 95% CI [0.1-1]) still births, and 13 (4%, 95% CI [2-6]) malformations reported. Compared to the general population, there was no difference in the proportion of congenital malformations nor unwanted outcomes whether the father was exposed or not to immunosuppressive agents.

Conclusions: This survey does not provide any warning signal that pregnancies fathered by male patients exposed to immunosuppressive agents, notably the debated MMF/MPA, have more complications than pregnancies in the general population.
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http://dx.doi.org/10.1186/s12882-020-02115-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667842PMC
November 2020

[Nephropathy associated with hypocomplementemic urticarial vasculitis: A case report and literature review].

Nephrol Ther 2020 Mar 9;16(2):124-135. Epub 2020 Jan 9.

Centre universitaire des maladies rénales, CHU de Caen, avenue de la côte de Nacre, 14033 Caen cedex 9, France; Unicaen, UFR de médecine, Normandie Université, 2, rue des Rochambelles, 14032 Caen cedex, France. Electronic address:

Hypocomplementemic urticarial vasculitis is a rare systemic vasculitis, affecting small vessels, characterised by chronicle urticaria, hypocomplementemia, and systemic manifestations. Renal involvement, whose prevalence varies between 9% and 60%, is mainly glomerular. We here report the case of a 59 years old woman presenting kidney failure, associated with chronicle urticaria and arthralgias. Laboratory investigation showed haematuria, proteinuria, hypocomplementemia and anti-SSa antibody positivity. A percutaneous kidney biopsy revealed focal and segmental glomerulonephritis associated with an acute interstitial nephritis. Hypocomplementemic urticarial vasculitis diagnosis was established after identifying anti-C1q antibodies. The lack of a dry syndrome, the negativity of a Schirmer test and the lack of sialadenitis on a salivary gland biopsy excluded an associated Gougerot-Sjögren Syndrome. The patient was treated with hydroxychloroquine and low-dose steroids, enabling a clinical and biological recovery. Of the 82 cases in the literature describing hypocomplementemic urticarial vasculitis associated nephropathies, 72 (88%) were a glomerular impairment, most frequently secondary to membranoproliferative glomerulonephritis. Only 6 (7%) tubulo-interstitial nephritis have been reported, 4 of them being associated with a glomerulonephritis. Patients were more likely to be women, aged in their third decade. The most frequent renal manifestations were haematuria (60%), and proteinuria (52%). Kidney failure was rarely observed (22%), with a fairly good renal prognosis. Hypocomplementemic urticarial vasculitis was associated with a systemic disease in 11 (13%) patients. In the absence of recommendations, the treatment strategy remains to be defined.
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http://dx.doi.org/10.1016/j.nephro.2019.09.004DOI Listing
March 2020

Risk Factors for Early Graft Failure and Death After Kidney Transplantation in Recipients Older Than 70 Years.

Kidney Int Rep 2019 May 28;4(5):656-666. Epub 2019 Jan 28.

Department of Nephrology, Centre Hospitalo-Universitaire de Rouen, Rouen, France.

Introduction: Although kidney transplantation carries a survival benefit compared with dialysis, mortality, especially the first year after transplantation, is high in recipients older than 70. The aim of this study was to evaluate early death and graft failure, and to determine the risk factors associated with these events in this specific population.

Methods: All patients older than 70 years who received a kidney transplant between January 2000 and December 2014 in the North-West of France were included ( = 171). Baseline characteristics and outcomes after transplantation were studied. Kaplan-Meier analysis was performed to assess patient and graft survival, and Cox regression analysis to evaluate risk factors for graft failure and patient death.

Results: The mean recipient age was 73.3 ± 2.5 years. Death-censored graft survival at 1, 3, and 5 years were 82.6%, 78.7%, and 75.4%, respectively. Patient survival at 1, 3, and 5 years was 90.1%, 82.5%, and 68.1%, respectively. One year after transplantation, 17 patients (9.9%) were dead, mainly from infectious (58.5%) or cardiovascular disease (29.4%). According to the Cox multivariate analysis, the independent risk factors for death or graft failure during the first year were arrhythmia (odds ratio [OR] 2.26; 95% confidence interval [CI] 1.08-4.8), left-ventricular ejection fraction (LVEF) under 56% (OR 2.38; 95% CI 1.18-4.83), human leucocyte antigen (HLA) antibodies (OR 2.1; 95% CI 1.04-4.2), deceased donor from cardiovascular cause (OR 5.18; 95% CI 1.22-6.3), and acute rejection (OR 2.77; 95% CI 1.2-6.3).

Conclusion: In kidney transplant recipients older than 70 years, cardiac evaluation and immunosuppression optimization seem to be crucial to improve short-term patient and graft survival.
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http://dx.doi.org/10.1016/j.ekir.2019.01.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6506713PMC
May 2019

Epitope load identifies kidney transplant recipients at risk of allosensitization following minimization of immunosuppression.

Kidney Int 2019 06 5;95(6):1471-1485. Epub 2019 Mar 5.

Laboratoire d'Immunologie et Histocompatibilité Hôpital Saint-Louis, Paris, France; INSERM UMRs 1160, Institut Universitaire d'Hématologie, Université Paris Diderot, Paris, France.

Human leukocyte antigen (HLA) mismatching and minimization of immunosuppression are two major risk factors for the development of de novo donor-specific antibodies, which are associated with reduced kidney graft survival. Antibodies do not recognize whole HLA antigens but rather individual epitopes, which are short sequences of amino acids in accessible positions. However, compatibility is still assessed by the simple count of mismatched HLA antigens. We hypothesized that the number of mismatched epitopes, or ("epitope load") would identify patients at the highest risk of developing donor specific antibodies following minimization of immunosuppression. We determined epitope load in 89 clinical trial participants who converted from cyclosporine to everolimus 3 months after kidney transplantation. Twenty-nine participants (32.6%) developed de novo donor specific antibodies. Compared to the number of HLA mismatches, epitope load was more strongly associated with the development of donor specific antibodies. Participants with an epitope load greater than 27 had a 12-fold relative risk of developing donor-specific antibodies compared to those with an epitope load below that threshold. Using that threshold, epitope load would have missed only one participant who subsequently developed donor specific antibodies, compared to 8 missed cases based on a 6-antigen mismatch. DQ7 was the most frequent antigenic target of donor specific antibodies in our population, and some DQ7 epitopes appeared to be more frequently involved than others. Assessing epitope load before minimizing immunosuppression may be a more efficient tool to identify patients at the highest risk of allosensitization.
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http://dx.doi.org/10.1016/j.kint.2018.12.029DOI Listing
June 2019

Clinical utility of leflunomide for BK polyomavirus associated nephropathy in kidney transplant recipients: A multicenter retrospective study.

Transpl Infect Dis 2019 Apr 1;21(2):e13058. Epub 2019 Mar 1.

Nephrology and Transplantation Department, Universitary Hospital, Strasbourg, France.

Background: BK polyomavirus associated nephropathy (BKPyVAN) is a significant clinical issue in kidney transplant (KT) recipients. No specific therapy is currently available, although treatment with leflunomide may be part of the therapeutic strategy. Here, we sought to examine the impact of leflunomide on the evolution of BKPyVAN.

Methods: This was an observational retrospective study conducted in 3 French transplant centers. KT recipients who developed BKPyVAN and received leflunomide after failure of other treatment approaches were deemed eligible. Graft function, viral clearance, patient survival, rejection rates, treatment tolerability, and immunosuppression levels served as the main outcome measures.

Results: A total of 55 patients were included. Treatment with leflunomide was started after a mean of 1.4 ± 4.1months  after BKPyVAN diagnosis. Between the introduction of leflunomide and the end of follow-up, creatinine levels increased by 31 ± 118% (P = 0.04), whereas viremia decreased by 79 ± 37% (P < 0.001). Blood viral clearance was observed in 76% of the study patients. Rejection episodes occurred in 33% of the participants. Eleven patients lost their graft (9 of which because of BKPyVAN). Ten patients developed adverse effects and 3 discontinued leflunomide.

Conclusion: We cannot conclude about the exact place of leflunomide in the therapeutic strategy of BKPyVAN. It may be a part of the therapy to promote BK polyomavirus clearance in cases of BKPyVAN who fail to improve after immunosuppression lowering alone. Unfortunately, a significant decline in renal function and high rejection rates remain major clinical challenges.
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http://dx.doi.org/10.1111/tid.13058DOI Listing
April 2019

Recurrence of Renal Cell Cancer After Renal Transplantation in a Multicenter French Cohort.

Transplantation 2018 05;102(5):860-867

Nephrology-Transplantation Department, University Hospital, Strasbourg, France.

Background: Renal cancer accounts for 3% of adult malignancies; renal cell carcinoma (RCC) represents 80% of all renal cancers, and is characterized by late recurrences. Recurrences after kidney transplantation are associated with a high mortality rate. We aimed to determine if recurrences are linked to tumor characteristics and to delays between diagnosis and transplantation.

Methods: We retrospectively analyzed data from French kidney-transplanted patients with medical histories of pretransplant renal cancer, focusing on the most common histological subtypes: clear cell and papillary cancers. Characteristics of the tumors, patients, and kidney transplantations were documented, and posttransplant patient survival was analyzed.

Results: Of 143 patients, 13 experienced cancer recurrence after kidney transplantation. The mean delay in recurrence was 3 ± 2.3 years posttransplantation, and the cumulative incidences of recurrence were 7.7% at 5 years and 14.9% at 10 years. The risk of recurrence was higher in patients with clear cell RCC (13% vs 0%, P = 0.015). There was no correlation between posttransplant recurrence and the interval before transplantation. Factors associated with a higher risk of cancer recurrence were histological clear cell RCC (P = 0.025), tumor stage pT2 (P = 0.002), and Fuhrman grade IV (P < 0.001). Recurrences were associated with a high mortality rate; 76.9% of patients with recurrences had died by the end of the follow-up period.

Conclusions: Recurrences of clear cell RCC are not uncommon after kidney transplantation and are associated with very poor prognoses. These results should be considered before listing patients with a history of renal cancer for transplantation.
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http://dx.doi.org/10.1097/TP.0000000000002009DOI Listing
May 2018

[Outcome of living kidney donors for transplantation].

Nephrol Ther 2017 Nov 12;13(6):448-459. Epub 2017 Oct 12.

Service de néphrologie, dialyse et transplantation, CUMR, CHU de Caen, avenue de la Côte-de-Nacre, 14033 Caen cedex 9, France; Normandie université, Unicaen, UFR de médecine, 2 rue des rochambelles, 14032 Caen cedex, France.

Nowadays, several treatments exist to treat terminal chronic renal failure. Best results for the recipients are obtained with kidney transplantation concerning mortality and quality of life. Transplantation is also the cheaper option for society. Living kidney donation raises the issue of the becoming of the donor, an absolutely healthy subject who gets to a surgical procedure. The becoming of living kidney donors has been compared with the one of controls subjects in several studies. The evaluations focused on the complications of nephrectomy in the short and long-term: kidney failure, hypertension, proteinuria, possibility of pregnancy, quality of life, and mortality. The first results did not show any risk linked to kidney donation, compared to general population. However, since 2013, kidney donors were found at higher risk for kidney failure and even for mortality, compared with controls selected like donor candidates. The risk of kidney donation is nevertheless acceptable and minimal, on the condition of rigorous selection of candidates and regular follow-up.
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http://dx.doi.org/10.1016/j.nephro.2017.02.011DOI Listing
November 2017

[Encapsulating peritoneal sclerosis].

Nephrol Ther 2017 Jun 30;13(4):211-219. Epub 2017 May 30.

Service de néphrologie, dialyse et transplantation, CUMR, CHU de Caen, 14033 Caen cedex, France.

Encapsulating peritoneal sclerosis is a rare but devastating complication of long-term peritoneal dialysis with a high mortality rate. The incidence is between 0.5 and 2.5%, decreasing with time. PSE is defined as a clinical syndrome with signs of gastrointestinal obstruction, inflammation parameters, radiological and macroscopic changes. The duration of treatment and the cessation of peritoneal dialysis are the main risks. About 75% occured in patients on hemodialysis or after kidney transplantation. Morphological alterations are disappearance of mesothelial layer, submesothelial fibrosis, interstitial sclerosis and vasculopathy. Ultrafiltration failure, fast transport status of the peritoneal membrane and loss of sodium sieving, the most powerful predictor, are the functional abnormalities. Biomarkers in peritoneal effluent include cancer antigen 125, interleukin-6. The pathophysiology is probably a consequence of a multiple-hit process in which expression of growth factors and cytokines play a central role. Medical strategies (corticosteroids, tamoxifen) in association with parenteral nutrition and/or surgery (enterolysis) are discussed. Prevention is the use of physiological peritoneal dialysis solutions, icodextrine instead of high glucose concentration solutions and peritoneal lavage after peritoneal dialysis stopping.
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http://dx.doi.org/10.1016/j.nephro.2017.01.020DOI Listing
June 2017

Successful renal retransplantation after graft loss from BK polyomavirus infection in a human immunodeficiency virus-positive patient.

Transpl Infect Dis 2016 Dec 10;18(6):946-949. Epub 2016 Nov 10.

Department of Nephrology, CHU de Caen, Caen, France.

We report the case of a human immunodeficiency virus-seropositive patient whose initial kidney transplant failed because of BK polyomavirus-induced nephropathy, and who underwent a second transplantation 3 years later. BK viruria was detected 1 day after transplantation. After 1 month, BK viremia developed along with a donor-specific antibody. After decreasing tacrolimus and mycophenolic acid and 2 courses of intravenous immunoglobulins, BK viremia and donor-specific antibody permanently disappeared, with stable renal function.
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http://dx.doi.org/10.1111/tid.12615DOI Listing
December 2016

A Lack of Significant Effect of POR*28 Allelic Variant on Tacrolimus Exposure in Kidney Transplant Recipients.

Ther Drug Monit 2016 Apr;38(2):223-9

*Department of Medical Informatics and Public Health, Hôpital Européen Georges Pompidou, Assistance Publique Hôpitaux de Paris; †Paris Descartes University; Sorbonne Paris Cité, INSERM UMRS 1147; ‡Clinical Chemistry, Hôpital Européen Georges Pompidou Assistance Publique Hôpitaux de Paris; §Department of Nephrology, CHU Rouen; ¶Department of Nephrology, CHU Tours; ‖Department of Nephrology, CHU Caen; **Department of Nephrology, CHU Amiens; ††Department of Nephrology, CHU Reims; ‡‡Department of Nephrology, CHU Poitiers; §§Department of Nephrology, CHU Rennes; ¶¶Department of Nephrology, CHU Strasbourg; ‖‖Department of Nephrology, CHU Limoges; ***Department of Nephrology, CHU Clermont-Ferrand; †††Department of Nephrology, CHU Angers; ‡‡‡Department of Nephrology, Necker Hospital, Assistance Publique Hôpitaux de Paris; and §§§Department of Nephrology, Hôpital Européen Georges Pompidou, Assistance Publique Hôpitaux de Paris, France.

Background: POR*28 is a recently newly described allelic variant of the cytochrome P450 oxidoreductase (POR), which might be associated with an increased metabolic activity of P450 cytochromes (CYP) 3A5 and 3A4. Consequently, carriers of at least 1 allele of this polymorphism could require increased calcineurin inhibitors doses to reach the target residual concentrations (C0). The objective of this study was to test whether the allelic variant of POR, which is associated with an increased metabolic activity of CYP3A, impacts tacrolimus (Tac) pharmacokinetics.

Methods: We tested this hypothesis in a population of 229 kidney transplant recipients (KTR) from a large, multicenter, prospective and randomized study. We have analyzed the association between POR*28 genotype and the proportion of individuals reaching the target Tac residual concentration (Tac C0) 10 days after transplantation. We have also measured the association between POR*28 and the Tac C0, and adjusted Tac C0 (Tac C0/Tac dose) over time using generalized mixed linear models.

Results: Ten days after transplantation, there was no difference of frequencies of KTR within the target range of Tac C0 (C0 10-15 ng/mL) according to the POR*28 genotype (P = 0.8). The mean Tac C0 at day 10 in the POR*1/*1 group was 15.3 ± 9.7 ng/mL compared with 15.7 ± 7.8 ng/mL in the POR*1/*28 group and 14.2 ± 6.8 ng/mL, in the POR*28/*28 group, P = 0.8. The adjusted Tac C0 was not associated with POR*28 genotype over time (random effects model, P = 0.9). When restricted to KTR expressing CYP3A5, POR*28 genotype did not impact the proportion of individuals within the Tac C0 target range neither the adjusted Tac C0 (random effects model, P = 0.1).

Conclusions: POR*28 does not significantly influence Tac pharmacokinetic parameters in a large cohort of KTR. This study does not confirm recent findings indicating that POR*28 carriers require more Tac to reach target C0.
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http://dx.doi.org/10.1097/FTD.0000000000000267DOI Listing
April 2016

[BK virus infections in kidney transplantation].

Nephrol Ther 2016 Apr 28;12(2):76-85. Epub 2016 Jan 28.

Service de néphrologie, dialyse et transplantation, CUMR, CHU de Caen, avenue de la Côte-de-Nâcre, 14033 Caen cedex, France. Electronic address:

BK virus is near ubiquitous, with a seroprevalence of around 80% in the general population. Subsequent to an asymptomatic primary infection, BK virus then remains dormant in healthy subjects. Reactivation occurs in immunocompromised people. BKv is pathogenic mainly among patients who have received a kidney transplant, in whom the virus can cause specific tubulo-interstitial nephritis and even result in graft failure among approximately 20 to 30% of nephritic cases. Since the mid 90 s, incidence has increased with the use of new powerful immunosuppressor treatments. The cornerstone of BK virus infection or BK virus-associated nephropathy treatment is a decrease of the immunosuppressive regimen, which must then be offset with the risk of rejection. The use of several adjuvant therapies has been submitted (fluoroquinolones, leflunomide, intravenous immunoglobulins, cidofovir), with no sufficient proof enabling the recommendation of first-line prescription. The high frequency of this infection and its potential harmfulness argue for the use of prevention strategies, at least among patients presenting risk factors. Retransplantation is safe after a first kidney allograft loss caused by BK-virus nephropathy, on condition that a screening for viremia is frequently conducted.
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http://dx.doi.org/10.1016/j.nephro.2015.11.003DOI Listing
April 2016

The DESCARTES-Nantes survey of kidney transplant recipients displaying clinical operational tolerance identifies 35 new tolerant patients and 34 almost tolerant patients.

Nephrol Dial Transplant 2016 06 12;31(6):1002-13. Epub 2016 Jan 12.

Nephrology-Renal Transplantation Department, Universitair Ziekenhuis Antwerp, Antwerp, Belgium Université Libre de Bruxelles (ULB), Brussels, Belgium.

Background: Kidney recipients maintaining a prolonged allograft survival in the absence of immunosuppressive drugs and without evidence of rejection are supposed to be exceptional. The ERA-EDTA-DESCARTES working group together with Nantes University launched a European-wide survey to identify new patients, describe them and estimate their frequency for the first time.

Methods: Seventeen coordinators distributed a questionnaire in 256 transplant centres and 28 countries in order to report as many 'operationally tolerant' patients (TOL; defined as having a serum creatinine <1.7 mg/dL and proteinuria <1 g/day or g/g creatinine despite at least 1 year without any immunosuppressive drug) and 'almost tolerant' patients (minimally immunosuppressed patients (MIS) receiving low-dose steroids) as possible. We reported their number and the total number of kidney transplants performed at each centre to calculate their frequency.

Results: One hundred and forty-seven questionnaires were returned and we identified 66 TOL (61 with complete data) and 34 MIS patients. Of the 61 TOL patients, 26 were previously described by the Nantes group and 35 new patients are presented here. Most of them were noncompliant patients. At data collection, 31/35 patients were alive and 22/31 still operationally tolerant. For the remaining 9/31, 2 were restarted on immunosuppressive drugs and 7 had rising creatinine of whom 3 resumed dialysis. Considering all patients, 10-year death-censored graft survival post-immunosuppression weaning reached 85% in TOL patients and 100% in MIS patients. With 218 913 kidney recipients surveyed, cumulative incidences of operational tolerance and almost tolerance were estimated at 3 and 1.5 per 10 000 kidney recipients, respectively.

Conclusions: In kidney transplantation, operational tolerance and almost tolerance are infrequent findings associated with excellent long-term death-censored graft survival.
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http://dx.doi.org/10.1093/ndt/gfv437DOI Listing
June 2016

Minimization of maintenance immunosuppressive therapy after renal transplantation comparing cyclosporine A/azathioprine or cyclosporine A/mycophenolate mofetil bitherapy to cyclosporine A monotherapy: a 10-year postrandomization follow-up study.

Transpl Int 2016 Jan;29(1):23-33

Service de Néphrologie-Hémodialyse-Transplantation rénale, CHU de Poitiers, Poitiers, France.

Long-term outcomes in renal transplant recipients withdrawn from steroid and submitted to further minimization of immunosuppressive regimen after 1 year are lacking. In this multicenter study, 204 low immunological risk kidney transplant recipients were randomized 14.2 ± 3.7 months post-transplantation to receive either cyclosporine A (CsA) + azathioprine (AZA; n = 53), CsA + mycophenolate mofetil (MMF; n = 53), or CsA monotherapy (n = 98). At 3 years postrandomization, the occurrence of biopsy for graft dysfunction was similar in bitherapy and monotherapy groups (21/106 vs. 26/98; P = 0.25). At 10 years postrandomization, patients' survival was 100%, 94.2%, and 95.8% (P = 0.25), and death-censored graft survival was 94.9%, 94.7%, and 95.2% (P = 0.34) in AZA, MMF, and CsA groups, respectively. Mean estimated glomerular filtration rate was 70.4 ± 31.1, 60.1 ± 22.2, and 60.1 ± 19.0 ml/min/1.73 m(2), respectively (P = 0.16). The incidence of biopsy-proven acute rejection was 1.4%/year in the whole cohort. None of the patients developed polyomavirus-associated nephropathy. The main cause of graft loss (n = 12) was chronic antibody-mediated rejection (n = 6). De novo donor-specific antibodies were detected in 13% of AZA-, 21% of MMF-, and 14% of CsA-treated patients (P = 0.29). CsA monotherapy after 1 year is safe and associated with prolonged graft survival in well-selected renal transplant recipient (ClinicalTrials.gov number: 980654).
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http://dx.doi.org/10.1111/tri.12627DOI Listing
January 2016

[PRETAGREF study: Prevalence of tobacco use and factors associated with smoking cessation in kidney transplant recipients].

Nephrol Ther 2016 Feb 23;12(1):48-55. Epub 2015 Nov 23.

Service de néphrologie, CHU Clémenceau, avenue de la Côte-de-Nacre, 14033 Caen cedex, France.

Introduction: Tobacco use increases the risk of mortality, cancers and cardiovascular diseases in transplanted patients. Transplanted patients are encouraged to quit tobacco use before and after renal transplantation. This study was carried out to evaluate the prevalence of tobacco consumption in transplanted patients in one French region. This survey was also conducted to identify factors associated with failure in smoking cessation.

Materials And Method: A questionnaire was sent by mail to transplanted patients followed in our center between the 1/01/95 and the 31/12/10. A second mail was sent to increase the response rate.

Results: During the study period, 544 questionnaires were sent to kidney transplant recipients. Among these 544 patients, there were 362 responders. Of these 362 patients, 121 patients (33.4%) were past smokers, and 21 (5.8%) were active smokers. Among the smokers, 20% were exposed to second-hand smoke, 48% had criteria for tobacco moderate to high dependency, and 13.4% were addicted to alcohol. In the multivariate analysis, exposure to second-hand smoke and living alone at home were associated with failure in smoking cessation.

Conclusion: This study shows that the prevalence of tobacco use is not high in transplanted patients. Only 6% of our patients report tobacco use at the study time. Environmental factors are associated with failure in tobacco cessation. Living alone and exposure to second-hand smoke are associated with smoking. Therefore, in transplantation centers, programs devoted to tobacco cessation should be implemented and should take care of patients' lifestyle.
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http://dx.doi.org/10.1016/j.nephro.2015.08.001DOI Listing
February 2016

Eight-year results of the Spiesser study, a randomized trial comparing de novo sirolimus and cyclosporine in renal transplantation.

Transpl Int 2016 Jan;29(1):41-50

Service de Néphrologie et Immunologie clinique, CHRU de Tours, Tours, France.

We present the results at 8 years of the Spiesser study, a randomized trial comparing de novo sirolimus and cyclosporine in kidney transplant recipients at low immunologic risk. We assessed estimated glomerular filtration (eGFR), graft, patient, and death-censored graft survival (log-rank compared), de novo DSA appearance, risk of malignancy, post-transplant diabetes mellitus (PTDM), and anemia. Intent-to-treat and on-treatment analyses were performed. Graft survival was similar in both groups (sirolimus: 73.3%, cyclosporine: 77.7, P = 0.574). No difference was observed between treatment groups concerning patient survival (P = 0.508) and death-censored graft survival (P = 0.858). In conditional intent-to-treat analysis, mean eGFR was greater in sirolimus than in cyclosporine group (62.5 ± 27.3 ml/min vs. 47.8 ± 17.1 ml/min, P = 0.004), in particular because graft function was excellent in patients maintained under sirolimus (eGFR = 74.0 ml/min). Importantly, no detrimental impact was observed in patients in whom sirolimus has been withdrawn (eGFR = 49.5 ml/min). Overall, 17 patients showed de novo DSAs, with no difference between the two groups (P = 0.520). Malignancy did not differ by treatment. An initial maintenance regimen based on sirolimus provides a long-term improvement in renal function for kidney transplant patients, especially for those maintained on sirolimus.
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http://dx.doi.org/10.1111/tri.12656DOI Listing
January 2016

Access to preemptive registration on the waiting list for renal transplantation: a hierarchical modeling approach.

Transpl Int 2015 Sep 28;28(9):1066-73. Epub 2015 Apr 28.

Service de Néphrologie, CHU Clémenceau, Caen, France.

Preemptive kidney transplantation is associated with both longer patient and graft survival. This study was carried out to estimate the association between the renal units and preemptive registration on the waiting list for first deceased donor renal transplantation in a French network of care. From 2008 to 2012, 1529 adult patients followed in 48 units of the French North-West network and registered on the waiting list for a first deceased donor renal allograft were included. We used a mixed logistic regression with renal units as random-effects term for statistical analysis. Of the 1529 patients included, 407 were placed on the waiting list preemptively. There was a significant variability across renal units (variance 0.452). In multivariate analysis, factors independently associated with preemptive registration were cardiovascular disease (odds ratio (OR) 0.57, [95% CI: 0.42-0.79]), social deprivation (OR 0.73, [95% CI 0.57-0.94]), and renal units' characteristics (ownership of the facility: academic hospital, reference-community hospital, OR 0.44, [95% CI 0.24-0.80]-private hospital, OR 0.35, [95% CI 0.18-0.69] and transplant center; P < 0.10]. Variability between renal units was reduced after taking into account their characteristics but was not influenced by patient characteristics. Preemptive registration is associated with renal units, transplant centers, and social deprivation and can be partly explained by disparities in practices.
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http://dx.doi.org/10.1111/tri.12592DOI Listing
September 2015

Mutations of CEP83 cause infantile nephronophthisis and intellectual disability.

Am J Hum Genet 2014 Jun 29;94(6):905-14. Epub 2014 May 29.

INSERM, UMR 1163, Laboratory of Inherited Kidney Diseases, 75015 Paris, France; Paris Descartes - Sorbonne Paris Cité University, Imagine Institute, 75015 Paris, France. Electronic address:

Ciliopathies are a group of hereditary disorders associated with defects in cilia structure and function. The distal appendages (DAPs) of centrioles are involved in the docking and anchoring of the mother centriole to the cellular membrane during ciliogenesis. The molecular composition of DAPs was recently elucidated and mutations in two genes encoding DAPs components (CEP164/NPHP15, SCLT1) have been associated with human ciliopathies, namely nephronophthisis and orofaciodigital syndrome. To identify additional DAP components defective in ciliopathies, we independently performed targeted exon sequencing of 1,221 genes associated with cilia and 5 known DAP protein-encoding genes in 1,255 individuals with a nephronophthisis-related ciliopathy. We thereby detected biallelic mutations in a key component of DAP-encoding gene, CEP83, in seven families. All affected individuals had early-onset nephronophthisis and four out of eight displayed learning disability and/or hydrocephalus. Fibroblasts and tubular renal cells from affected individuals showed an altered DAP composition and ciliary defects. In summary, we have identified mutations in CEP83, another DAP-component-encoding gene, as a cause of infantile nephronophthisis associated with central nervous system abnormalities in half of the individuals.
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http://dx.doi.org/10.1016/j.ajhg.2014.05.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4121475PMC
June 2014

[Who is the physician in charge with the primary care of the dialysis patients?].

Nephrol Ther 2014 Apr 30;10(2):106-11. Epub 2013 Dec 30.

Service de néphrologie, CHU Clémenceau, 14033 Caen cedex, France. Electronic address:

Introduction: The role played by nephrologists in hemodialysis patients' primary care is not well known. We hypothesized that primary care are provided by nephrologists and not by general practitioners for most of these patients. The aim of this study was to estimate the rate of hemodialysis patients having a nephrologist as primary care provider, and to determine which factors were associated with non-resort to a general practitioner for primary care.

Methods: Patients older than 18 years treated by hemodialysis for more than 3 months in the Calvados district were included and were interviewed with a standardized questionnaire. A log-binomial regression was used to study factors associated with non-resort to a general practitioner for primary care.

Results: Only 26% of patients had a general practitioner involved in the primary care; whereas 47% considered that nephrologists were the physician in charge of the primary care. Time spent in hemodialysis was associated with non-resort to a general practitioner, while patients living in nursing home were more likely to have regularly a regular follow up by a general practitioner. Dialysis center was a factor associated with the general practitioner as a primary care provider.

Conclusion: Primary care of the hemodialysis patient is provided by nephrologists.
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http://dx.doi.org/10.1016/j.nephro.2013.09.005DOI Listing
April 2014

Does daily urine output really matter in renal transplantation?

Ann Transplant 2013 Dec 27;18:716-20. Epub 2013 Dec 27.

Department of Urology and Transplantation, CHU Cote de Nacre, Caen, France.

Background: Our objective was to clarify the clinical outcome of renal transplantation based on residual daily urine output (RDUO).

Material And Methods: We retrospectively analyzed a prospective database of 276 patients who underwent renal transplantation (Tx) between January 2008 and December 2012. Patients had pre-transplantation daily urine output measurement of 24-h proteinuria and were clinically re-evaluated the day before transplantation. We included patients with no daily urine output and those with residual daily urine output. Real bladder capacity was not measured. We excluded patients with a history of lower urinary tract malformation, those treated by trans-ileal conduit or enterocystoplasty, and those with early graft thrombosis or graft primary non-function.

Results: Sex ratio, age at Tx, pre-Tx MHC antibodies levels, donor age, and cold ischemia duration were not significantly different between the 2 groups. Dialysis duration was longer in group I (p<0.001). The dialysis duration was correlated with the volume of residual urine output (r=0.12, p<0.0001). We found 14 (19.4%) urological complications in Group I (11 urinary leaks and 3 urethral stenosis) and 13 (6.4%) in Group II (5 urinary leaks and 8 stenosis). This difference was significant (p=0.0013 and relative risk [RR]=2.2). Absence of residual daily urine output was a risk factor of post-transplantation urinary leak (p<0.0001: RR=2.95). At 3 years, graft survival was 74.7% and 94.6%, respectively, in Group I and II (p=0.003).

Conclusions: The absence of residual daily urine output seems to be a major risk factor for urological complications. Taking into account recipient residual daily urine output should modify surgical strategy during renal transplantation.
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http://dx.doi.org/10.12659/AOT.889629DOI Listing
December 2013

Progression of pulse pressure in kidney recipients durably exposed to CsA is a risk factor for epithelial phenotypic changes: an ancillary study of the CONCEPT trial.

Transpl Int 2014 Apr 28;27(4):344-52. Epub 2014 Jan 28.

Département de Santé Publique, APHP, Hôpital Tenon, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S1155, Paris, France.

In this ancillary study of the CONCEPT trial, we studied the role of CsA withdrawal at 3 months (3M) post-transplant on the intensity of epithelial phenotypic changes (EPC, an early marker for kidney fibrogenesis) on the 12 M surveillance biopsy. Although conversion from CsA to sirolimus (SRL) at 3M was reported to have improved mean graft function at 12 M, it did not reduce the score of EPC (1.73 ± 1.15 in the SRL group vs. 1.87 ± 1 in the CsA group, P = 0.61). Acute rejection, which had occurred twice more frequently in SRL-converted patients included here, was associated with 12 M EPC. Interestingly, we observed that the patients durably exposed to CsA and who developed 12 M EPC had a significant progression of blood pulse pressure (pp) from 1 to 6M post-transplantation (Δpp = +12.3 mmHg, P = 0.0035). Pulse pressure at 4, 6, and 9 M and pp progression from 1 to 6M were significantly associated with the development of EPC at 12 M in renal grafts. Logistic regression analysis revealed that a high 6M pp (≥ 60 mmHg) was an independent risk factor for 12 M EPC with an odds ratio of 2.25 per additional 10 mmHg pp (95%CI: 1.14-4.4, P = 0.02) after adjustment with recipient's and donor's age, acute rejection incidence and immunosuppressive regimen. A post hoc analysis of the data collected in the whole population CONCEPT study revealed that pp was significantly higher at 6 months in patients maintained on CsA and that at this time point pp correlated negatively with GFR at 1 year.
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http://dx.doi.org/10.1111/tri.12253DOI Listing
April 2014

Post-transplantation lymphoproliferative disorder after kidney transplantation: report of a nationwide French registry and the development of a new prognostic score.

J Clin Oncol 2013 Apr 19;31(10):1302-9. Epub 2013 Feb 19.

Nephrology-Transplantation Department, Strasbourg University Hospital, Strasbourg, France.

Purpose: Post-transplantation lymphoproliferative disorder (PTLD) is associated with significant mortality in kidney transplant recipients. We conducted a prospective survey of the occurrence of PTLD in a French nationwide population of adult kidney recipients over 10 years.

Patients And Methods: A French registry was established to cover a nationwide population of transplant recipients and prospectively enroll all adult kidney recipients who developed PTLD between January 1, 1998, and December 31, 2007. Five hundred patient cases of PTLD were referred to the French registry. The prognostic factors for PTLD were investigated using Kaplan-Meier and Cox analyses.

Results: Patients with PTLD had a 5-year survival rate of 53% and 10-year survival rate of 45%. Multivariable analyses revealed that age > 55 years, serum creatinine level > 133 μmol/L, elevated lactate dehydrogenase levels, disseminated lymphoma, brain localization, invasion of serous membranes, monomorphic PTLD, and T-cell PTLD were independent prognostic indicators of poor survival. Considering five variables at diagnosis (age, serum creatinine, lactate dehydrogenase, PTLD localization, and histology), we constructed a prognostic score that classified patients with PTLD as being at low, moderate, high, or very high risk for death. The 10-year survival rate was 85% for low-, 80% for moderate-, 56% for high-, and 0% for very high-risk recipients.

Conclusion: This nationwide study highlights the prognostic factors for PTLD and enables the development of a new prognostic score. After validation in an independent cohort, the use of this score should allow treatment strategies to be better tailored to individual patients in the future.
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http://dx.doi.org/10.1200/JCO.2012.43.2344DOI Listing
April 2013

Kidney graft dysfunction in simultaneous pancreas-kidney recipients after pancreas failure: analysis of early and late protocol biopsies.

Clin Transplant 2013 May-Jun;27(3):E249-55. Epub 2013 Feb 13.

Service de Néphrologie et Transplantation, Hôpital Saint-Louis, Paris, France.

Background: Kidney graft survival in simultaneous pancreas-kidney (SPK) recipients is known to decrease after pancreas graft failure.

Methods: Sixty-three consecutive SPK recipients were retrospectively reviewed. Kidney graft function and proteinuria were evaluated at three months after the transplantation and at last follow-up. Histopathologic findings of protocol biopsies performed three months and one yr after transplantation were analyzed.

Results: Twelve patients lost the pancreas graft. Donors' characteristics were similar in patients with or without pancreas failure. After a median follow-up of 36 months, mean eGFR with a functional pancreas was 69.5 mL/min/1.73 m² vs. 56.3 mL/min/1.73 m² (p = 0.01) after pancreas loss. Patients who lost pancreas had a median proteinuria of 0.28 g vs. 0.13 g per 24 h (p = 0.02). Analysis of three-month protocol biopsies revealed more frequent isolated glomerulitis after pancreas failure (p = 0.0001), without peritubular capillaritis or C4d deposition. No donor-specific anti-HLA antibodies were detectable in these patients. Chronic tubulointerstitial changes were more frequent in patients with pancreas loss. There was no evidence of diabetic nephropathy recurrence.

Conclusion: SPK recipients develop an early kidney graft dysfunction after pancreas failure. Histopathologic findings revealed frequent glomerulitis without antibody-mediated rejection and early chronic changes.
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http://dx.doi.org/10.1111/ctr.12095DOI Listing
January 2014

Hydration status of patients with end-stage renal disease after kidney transplantation.

Clin Transplant 2011 Nov-Dec;25(6):E656-63. Epub 2011 Aug 24.

Nephrology Department, CHU Clemenceau, Caen, France.

Background: This study was carried out to estimate the modification of hydration status within the first three months of renal transplantation.

Subjects And Methods: Fifty patients who underwent a first kidney allograft were prospectively followed for three months after renal transplantation to assess hydration status by bioimpedance spectroscopy.

Results: Two hours before the transplant procedure, 10/42 (23.8%) patients were overhydrated. Two days after surgery, 32/40 (80.0%) patients were overhydrated and at three months, 14/27 (51.9%) patients remained fluid-overloaded. Peritoneal dialysis (PD) patients had a lower hydration status (-0.60 L) than hemodialysis (HD) patients (0.70 L; p < 0.05) and better residual diuresis (41.7 vs. 8.3 mL/h for HD patients, p < 0.01). Compared with patients who had a delayed graft function (DGF) or a slow graft function (SGF), the immediate graft function (IGF) group had a better hydration status before transplantation (p = 0.031). At three months, 12/14 of the overhydrated patients had a creatinine clearance between 30 and 60 mL/min/1.73 m(2) .

Conclusion: Patients receiving a first kidney transplant frequently have a hydration disorder. Transplantation is associated with increased hydration status, which seems to persist if DGF or SGF occurs.
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http://dx.doi.org/10.1111/j.1399-0012.2011.01496.xDOI Listing
May 2012

[Treatment of iron deficiency by a bolus intravenous iron dextran in peritoneal dialysis].

Nephrol Ther 2011 Dec 28;7(7):558-61. Epub 2011 Jun 28.

Service de néphrologie, CHU Clémenceau, avenue G.-Clémenceau, 14033 Caen cedex, France.

Introduction: The main objective of this study is to determine whether a single dose of iron dextran can correct iron deficiency during a period of four months in peritoneal dialysis patients.

Method: This was a prospective observational study in peritoneal dialysis patients who had anemia (hemoglobin<11g/dL) and iron deficiency (ferritin<100μg/L and/or transferrin saturation<20%). Patients who were resistant to oral iron or who could not tolerate oral iron were included in the study. At baseline, based on the iron deficiency estimation, a single dose of iron dextran was infused over four hours.

Results: Of 17 patients included, 12 completed the study. The mean iron dose infused was 742±150mg. No clinically significant adverse event was reported during the infusion. Four months after the iron dextran infusion there was a significant increase of the mean hemoglobin level (10.1±0.7g/dl vs 11.4±1.2g/dL, P<0.05), the mean blood ferritin level (66±46mg/L vs 212±121mg/L, P<0.05) and the mean transferrin saturation (14±5% vs 23±8, P<0.05). Four months after the iron infusion 10 patients had a blood ferritin level higher than 100μg/L and a transferrin saturation higher than 20%. There was no significant modification of the erythropoietin dose during the four months period.

Conclusion: In patients treated by peritoneal dialysis, the anemia due to iron deficiency can be treated by a single infusion of iron dextran for a period of four months.
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http://dx.doi.org/10.1016/j.nephro.2011.03.010DOI Listing
December 2011

Lymphomatoid granulomatosis treated successfully with rituximab in a renal transplant patient.

J Transplant 2011 19;2011:865957. Epub 2011 Apr 19.

Department of Nephrology and Renal Transplantation, Caen University Hospital, 14033 Caen, France.

Lymphomatoid granulomatosis (LYG) in renal transplant recipients is rare multisystemic angiocentric lymphoproliferative disorder with significant malignant potential. Here, we describe LYG in a 70-year-old renal allograft recipient who, 4 years after transplantation, on tacrolimus and mycophenolate mofetil and prednisone maintenance immunosuppression, complained of low-grade fever, persistent headache and gait disturbance. The MRI of the brain revealed diffuse periventricular cerebral and cerebellar contrast-enhanced lesions. The CT scan of the thorax showed multiple pulmonary nodular opacities in both lung fields. The patient was diagnosed LYG based on the cerebral biopsy showing perivascular infiltration of CD20-positive B-lymphocytes with granulomatous lesions and immunofluorescence staining with anti-EBV antibodies. With careful reduction of the immunossuppression combined with the use of rituximab, our patient showed a complete disappearance of LYG, and she is clinically well more than 4 years after the diagnosis, with good kidney function. No recurrence has been observed by radiological imaging until now. This is the first report of a durable (>4 years) complete remission of LYG after treatment with rituximab in renal transplantation.
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http://dx.doi.org/10.1155/2011/865957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3087939PMC
July 2011

Impact of pre-transplant dialysis modality on post-transplant diabetes mellitus after kidney transplantation.

Clin Transplant 2011 Sep-Oct;25(5):794-9. Epub 2010 Dec 16.

Department of Nephrology, Dialysis, and Renal Transplantation, Saint Jacques University Hospital, Besançon, France.

Post-transplant diabetes mellitus (PTDM) is a well-known complication in renal transplant recipients (RTRs). While a number of risk factors for PTDM have been identified, the potential impact of pre-transplant dialysis modality on subsequent development of PTDM has not yet been explored. We performed a multicenter retrospective study on 2010 consecutive RTRs who did not have a history of diabetes prior to renal transplantation. PTDM was defined as a need for anti-diabetic therapy in an RTR without a history of diabetes prior to transplantation. Analysis of the risk factors for development of PTDM was performed with respect to pre-transplant dialysis modality. A total of 137 (6.8%) patients developed PTDM; 7% in the hemodialysis group and 6.5% in the peritoneal dialysis (PD) group (p = 0.85). In the multivariate analysis, age (p < 0.001), body mass index (BMI) (p < 0.001), use of tacrolimus (p = 0.002), and rejection episodes (p < 0.001) were identified as independent risk factors for development of PTDM. Patients in the PD group were younger (p = 0.004), had lower BMI (p = 0.07), and were less likely to have a history of hepatitis C (p = 0.007) and autosomal dominant polycystic kidney disease (p = 0.07). Adjustment for these variables did not modify the results. The results of this study suggest that pre-transplant dialysis modality does not have an impact on the subsequent development of PTDM in RTRs.
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http://dx.doi.org/10.1111/j.1399-0012.2010.01367.xDOI Listing
February 2012

Comparative effects of sirolimus and cyclosporin on conduit arteries endothelial function in kidney recipients.

Transpl Int 2010 Nov;23(11):1135-43

Department of Pharmacology, Rouen University Hospital & INSERM U644, Institute for Biomedical Research, University of Rouen, Rouen, France.

This study attempted to establish whether a calcineurin inhibitor (CNI)-free immunosuppressant regimen based on sirolimus (SRL) is associated with a preservation of conduit arteries endothelial function in kidney recipients or not. Twenty-nine kidney recipients were randomized to receive since transplantation SRL (n=15) or cyclosporin A (CsA, n=14) associated with mycophenolate mofetil (MMF) and steroids (6months) in a parallel prospective study. Systolic, diastolic blood pressures, glomerular filtration rate (GFR) and radial artery flow-mediated dilatation (FMD) induced by postischaemic hyperaemia were assessed in a blind manner at one (M1) and 7months (M7) after transplantation. Endothelium-independent dilatation was assessed by glyceryl trinitrate spray. There was no difference between the groups for all vascular parameters at M1. At M7, systolic blood pressure was lower (SRL: 119±3 vs. CsA: 138±4mmHg, P<0.05) and FMD was higher in SRL compared with CsA (SRL: 13.1±0.9 vs. CsA: 9.9±0.9%, P<0.05) without any difference for hyperaemia, endothelium-independent dilatation and GFR (SRL: 66.7±1.05 vs. CsA: 67.5±1.22ml/min). Our results demonstrate that a CNI-free regimen based on SRL and MMF prevents conduit artery endothelial dysfunction compared with CsA and MMF in kidney recipients suggesting a beneficial arterial wall effect that may also contribute to the decrease in systolic blood pressure.
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http://dx.doi.org/10.1111/j.1432-2277.2010.01122.xDOI Listing
November 2010

Kidney and recipient weight incompatibility reduces long-term graft survival.

J Am Soc Nephrol 2010 Jun 20;21(6):1022-9. Epub 2010 May 20.

Institut de Transplantation et de Recherche en Transplantation, ITERT, CHU Nantes, Réseau Thématique de Recherche et de Soins Centaure, Nantes and INSERM U643 (Immunointervention dans les Allo et Xénotransplantation), Centre d'Investigation Clinique biothérapie, 30 bd Jean Monnet, 44093, Nantes, France.

Long-term function of kidney allografts depends on multiple variables, one of which may be the compatibility in size between the graft and the recipient. Here, we assessed the long-term consequences of the ratio of the weight of the kidney to the weight of the recipient (KwRw ratio) in a multicenter cohort of 1189 patients who received a transplant between 1995 and 2006. The graft filtration rate increased by a mean of 5.74 ml/min between the third and sixth posttransplantation months among patients with a low KwRw ratio (<2.3 g/kg; P<0.0001). In this low KwRw ratio group, the graft filtration rate remained stable between 6 months and 7 years but then decreased at a mean rate of 3.17 ml/min per yr (P<0.0001). In addition, low KwRw ratios conferred greater risk for proteinuria, more antihypertensive drugs, and segmental or global glomerulosclerosis. Moreover, a KwRw ratio<2.3 g/kg associated with a 55% increased risk for transplant failure by 2 years of follow-up. In conclusion, incompatibility between graft and recipient weight is an independent predictor of long-term graft survival, suggesting that avoiding kidney and recipient weight incompatibility may improve late clinical outcome after kidney transplantation.
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http://dx.doi.org/10.1681/ASN.2009121296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2900958PMC
June 2010

A 50% reduction in cyclosporine exposure in stable renal transplant recipients: renal function benefits.

Nephrol Dial Transplant 2010 Sep 17;25(9):3096-106. Epub 2010 Mar 17.

Department of Nephrology, Rouen University Hospital, and Inserm CIC 0204, Institute of Biomedical Research, University of Rouen, Rouen, France.

Background: Although cyclosporine maintenance therapy reduces the risk of acute rejection and increases short-term graft survival in renal transplant recipients, its associated nephrotoxicity increases the risk of chronic graft dysfunction. The dose that allows an optimal risk-to-benefit ratio has not been established.

Methods: This multicentre study enrolled stable renal allograft recipients receiving cyclosporine and mycophenolate mofetil without corticosteroids in their second year post-transplant. Patients were randomized to a cyclosporine dose targeted to a standard area under the concentration-time curve (AUC)(0-12 h) (usual exposure, n = 104) or 50% of the study standard AUC(0-12 h) (low exposure, n = 108) using a three-point pharmacokinetic sampling. The primary endpoint was the percentage of patients with treatment failure at 24 months (graft loss/acute rejection/nephrotoxicity/>15% serum creatinine level increase).

Results: Treatment failure was reported in 37 out of 101 (37%) patients in the usual-exposure and 19 out of 106 (18%) patients in the low-exposure groups (P = 0.003). Mean estimated glomerular filtration rate decreased from baseline to 2 years with usual exposure and increased with low exposure (P < 0.001). Mean systolic and diastolic blood pressures were lower with low exposure (P = 0.03 and P = 0.008, respectively).

Conclusion: In renal transplant recipients receiving maintenance therapy without corticosteroids, a minimization strategy using three-point pharmacokinetic sampling to reduce and maintain cyclosporine exposure to 50% of the usual levels is safe and reduces the risk of graft dysfunction.
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http://dx.doi.org/10.1093/ndt/gfq135DOI Listing
September 2010