Bone Disease after KidneyTransplantation Antoine Bouquegneau,* Syrazah Salam, † Pierre Delanaye,* Richard Eastell, ‡ and Arif Khwaja †
Bone and mineral disorders occur frequently in kidney transplant recipients and are associated with a high risk of fracture, morbidity, and mortality. There is a broad spectrum of often overlapping bone diseases seen after transplantation, including osteoporosis as well as persisting high– or low–turnover bone disease. The patho- physiology underlying bone disorders after transplantation results from a complex interplay of factors, including preexisting renal osteodystrophy and bone loss related to a variety of causes, such as immunosuppression and alterations in the parathyroid hormone-vitamin D-fibroblast growth factor 23 axis as well as changes in mineral metabolism. Management is complex, because noninvasive tools, such as imaging and bone biomarkers, do not have sufficient sensitivity and specificity to detect these abnormalities in bone structure and function, whereas bone biopsy is not a widely available diagnostic tool. In this review, we focus on recent data that highlight improvements in our understanding of the prevalence, pathophysiology, and diagnostic and therapeutic strategies of mineral and bone disorders in kidney transplant recipients.
for incident kidney transplant recipients from 2020, with also anti HLA specificity and MFI.
EKiTE is a novel, large European multinational cohort with a large amount of baseline data from the recent era of kidneytransplantation that is updated annually and has a low level of missing data. It will allow epide- miologic studies to be performed to better assess the western European transplantation patient profile and allow benchmarking to improve clinical practices. Other European centers are invited to join the EKiTE network. For details on the process of inclusion of a new center you can take note of the “Consortium Agreement for the EKiTE network” (provided in Additional file 1 ) or make contact with a network member at the following address www.labcom-risca. com/ekite-en . External investigators of the EKiTE net- work, are also welcome to ask for access to this open database for scientific works.
After his brother, who had given bone marrow to him 14 years earlier, was found to be an acceptable donor, kidneytransplantation was performed in April 2000, without any immunosuppressive therapy. The transplanted kidney func- tioned immediately, and a kidney biopsy performed 6 months after the transplant did not show any sign of graft rejection (Fig. 1). Now, more than 2 years after kidney transplanta- tion, the patient is well with normal renal function and without any sign of GVHD or CML.
Potentially relevant studies were identified with a struc- tured computerised search of the English literature of Ovid Medline, Embase and Cochrane databases. Keywords included ‘donation after cardiac death’, ‘donation after circulatory death’, ‘nonheart beating donor’, ‘kidneytransplantation’ ‘viability’, ‘extracorporeal membrane oxy- genation’, ‘cold storage’, ‘hypothermic machine perfusion (HMP)’, ‘hypertension’, ‘diabetes’, ‘obesity’, ‘organ preser- vation’, ‘tissue and organ procurement’ ‘transplantation’, ‘warm ischemia time’ and ‘outcome’ combined with free text searching. The level of scientific evidence of the rele- vant studies was assessed, and accordingly, recommenda- tions were made and graded by an expert panel. These recommendations were presented at 6th International Con- ference on Organ Donation after Circulatory Death in Paris of the European Society of Organ Transplantation, where the concept recommendations were presented, discussed with the various expert panels and congress participants.
CONCLUSIONS: In conclusion, with current steroid minimization immunosuppres- sive protocols, BMD changes after renal transplantation are limited and related to bone remodeling activity rather than corticosteroid exposure.
FP716 NFKB1 PROMOTER POLYMORPHISM: A NEW PREDICTIVE MARKER OF CMV INFECTION AND RENAL INJURY AFTER KIDNEYTRANSPLANTATION
4. Sarak B, Wald R, Goldstein MB, Deva DP, Leipsic J, Kiaii M, Leung G, Barfett JJ, Perl J, Yuen DA, Connelly KA and Yan AT. Relationship between changes in blood pressure and left ventricular mass over 1 year in end-stage renal disease. J Hypertens. 2017;35:1709-1716. 5. Hawwa N, Shrestha K, Hammadah M, Yeo PSD, Fatica R and Tang WHW. Reverse Remodeling and Prognosis Following KidneyTransplantation in Contemporary Patients With Cardiac Dysfunction. J Am Coll Cardiol. 2015;66:1779-1787.
PATIENTS, MATERIALS AND METHODS
Patients: 71 patients suffering from biopsy proven corticosteroid resistant INS and who had
undergone a kidneytransplantation from September 1983 to April 2007 were included in this study. Patients who presented an immediate proteinuria after transplantation, persisting above 3g/d at one month, with a kidney graft biopsy showing minimal change glomerulonephritis or isolated FSGS lesions without other transplant specific lesion, were defined as recurrent patients (R, n=31). All patients were treated with an immunosuppressive regimen including calcineurin inhibitors (CNI) and antimetabolic drugs (Mycophenolate Mofetil or Azathioprin) and/or by plasmapheresis or immunoadsorption. Pre transplant sera were collected within the 12 hours before surgery, and kept frozen at -20°C. At post transplantation serum harvesting, recurrent patients presented a persistent proteinuria above 2g/d. On the contrary, non-recurrent INS patients (NR, n=40) displayed less than 1g/d of proteinuria one week after transplantation, and remained below 0.5g/d at any times thereafter. The control group consisted of 34 proteinuric transplanted patients with non-INS related end stage renal failure (diabetes, uropathy, IgA glomerulonephritis, nephroangiosclerosis, chronic interstitial nephropathy, renal polykystosis) (Table 1). In this group, the proteinuria was related to different kidney graft lesions: allograft glomerulonephritis, recurrence of IgA nephritis or diabetes.
MD PhD 1 , Olivier Detry MD PhD 1 ; 1 CHU Liège, Liège,
Wallonia, Belgium; 2 CHU Liège, Liège, Wallonia,
Introduction: Delayed graft function (DGF) occurs more frequently after kidneytransplantation (KT) from donation after cardiovascular death (DCD) than from donation after brain death (DBD). In DBD-KT, DGF reduces graft survival. We investigated the effect of DGF on post-transplant outcomes in controlled DCD-KT. Patients and Methods: This single-center retrospective study recruited 80 controlled DCD-KT performed from January 2005 to December 2011. Mean follow-up was 28.5 months. Results: There was no primary non-function. DGF rate was 35.5%. Overall graft survivals in groups with and without DGF were 92.4% and 95.2% at 1 year, 92.4% and 87.1% at 3 years, and 84.7% and 87.1% at 5 years, respectively (p= NS). Patients with and without DGF had the same survival rates at corresponding time points (92.4% and 97.2%, 92.4% and 93.9%, and 84.7% and 93.9%, p=ns). Estimated glomerular filtration rate was significantly lower in DGF group at hospital discharge (29 vs 42 ml/min, p<0.01) and up to 6 months post-transplant (46 vs 52, p<0.05), but the difference disappeared afterward (47 vs 52 at 1 year, 50 vs 48 at 3 years, and 54 vs 53 at 5 years, p=ns). DGF did not increase the risk of acute rejection (29.6% vs 30.6%, p=ns) or surgical complications (33.3% vs 26.5%, p=ns). DGF significantly prolonged hospitalization length in DGF compared to non-DGF patients (18.9 vs 13 days, p<0.01). Donor BMI*30, recipient BMI*30 and pre-transplant dialysis duration increased DGF risk in multivariate logistic regression analysis. Conclusions: DGF had no deleterious impact on
Michel Tauc 1* , Nicolas Melis 1* , Miled Bourourou 2 , Sébastien Giraud 3 , Thierry Hauet 3 ,
and Nicolas Blondeau 2
One of the biggest challenges in medicine is to dampen the pathophysiological stress induced by an episode of ischemia. Such stress, due to various pathological or clinical situations, follows a restriction in blood and oxygen supply to tissue, causing a shortage of oxygen and nutrients that are required for cellular metabolism. Ischemia can cause irreversible damage to target tissue leading to a poor physiological recovery outcome for the patient. Contrariwise, preconditioning by brief periods of ischemia has been shown in multiple organs to confer tolerance against subsequent normally lethal ischemia. By definition, preconditioning of organs must be applied preemptively. This limits the applicability of preconditioning in clinical situations, which arise unpredictably, such as myocardial infarction and stroke. There are, however, clinical situations that arise as a result of ischemia-reperfusion injury, which can be anticipated, and are therefore adequate candidates for preconditioning. Organ and more particularly kidneytransplantation, the optimal treatment for suitable patients with end stage renal disease (ESRD), is a predictable surgery that permits the use of preconditioning protocols to prepare the organ for subsequent ischemic/reperfusion stress. It therefore seems crucial to develop appropriate preconditioning protocols against ischemia that will occur under transplantation conditions, which up to now mainly referred to mechanical ischemic preconditioning that triggers innate responses. It is not known if preconditioning has to be applied to the donor, the recipient, or both. No drug/target pair has been envisioned and validated in the clinic. Options for identifying new target/drug pairs involve the use of model animals, such as drosophila, in which some physiological pathways, such as the management of oxygen, are highly conserved across evolution. Oxygen is the universal element of life existence on earth. In this review we focus on a very specific pathway of pharmacological preconditioning identified in drosophila that was successfully transferred to mammalian models that has potential application in human health. Very few mechanisms identified in these model animals have been translated to an upper evolutionary level. This review highlights the commonality between oxygen regulation between diverse animals.
26. Locke JE, Mehta S, Sawinski D, Gustafson S, Shelton BA, Reed RD et al. Access to KidneyTransplantation among HIV-Infected Waitlist Candidates. Clin J Am Soc Nephrol 2017;12(3):467-475.
27. Couchoud C, Stengel B, Landais P, Aldigier JC, de Cornelissen F, Dabot C et al. The renal epidemiology and information network (REIN): a new registry for end-stage renal disease in France. Nephrol Dial Transplant 2006;21(2):411-418.
A 49-year old male patient received a deceased donor renal allograft in our institution. He was born and raised in Haiti, immigrated in France 2 years before the kidneytransplantation, but maintained regular trips to Haiti. He had a history of long-standing hypertension. His chronic kidney disease was discovered in France, when it had already reached end stage. Kidneytransplantation induc- tion therapy consisted in rabbit anti-thymocyte globu- lines, and one steroid pulse of 1000 mg. Maintenance immunosuppression comprised tacrolimus, mycopheno- late mofetil and prednisone (20 mg daily for the first 3 months, progressively tapered to 5 mg per day at month 9 post-transplantation). The lowest serum cre- atinine was of 140 μmol/l. Five months after transplant- ation, the patient acquired diabetes mellitus which required insulin therapy.
Correspondence and offprint requests to: Franc¸ois Jouret; E-mail: firstname.lastname@example.org
Arteriovenous fistula (AVF) is regarded as the best vascular access for chronic haemodialysis (HD). Still, AVF inherently causes significant haemodynamic changes. Although the necessity for vascular access despite its putative cardiovascular complications favours AVF creation in patients under chronic HD, one may question whether sustaining a functional AVF after successful kidneytransplantation extends the haemodynamic threat. Small prospective series suggest that AVF ligation causes rapid and sustained reduction in left ventricular hypertrophy. Still, the benefits of such a cardiac
without the complication of immunogenic factors or re- cipient characteristic. In addition, porcine kidneys are of similar size and weight than adult human kidney and are one of the two biomedical animals (with large primates) presenting a multilobular and multipapillary kidney and an elaborate system of interlobular and segmental arter- ies to supply the numerous kidney lobes, it is therefore well adapted for the modeling of kidneytransplantation . The present study uses an isograft model, devoid of the influence of both brain death and immunosuppres- sants. This route was chosen because we felt that immu- nosuppressors, with their own set of deleterious side effects, would bias our results. Furthermore, machine perfusion has been developed to optimize graft preserva- tion, hence address ischemia reperfusion injury, leading us to run this first series of tests on a non-brain dead ani- mal. It is also important to note that our model is designed to follow the setting of classes I and II of the Maastricht criteria, but does not fit it exactly. Indeed, this criteria includes no more than 30 min arrest before start- ing the CPR procedure, which is then continued during the transport to the hospital (generally with a machine); then as failure to resuscitate is pronounced there is a 5 min no touch period. All these steps should not exceed 150 min before femoral vessels canulation. The donor is then either cold perfused or an extracorporeal circuit is put in place, giving enough time to secure consent from the family and collect the organs, which are then machine perfused. Our current model does not include all these steps, however we trust that 60 min WI repro- duces as closely as possible the conditions of DCD. Lastly, although our model does not include brain death and thus cannot be used to draw direct conclusions in regards to ECD organ transplantation, the high degree of injury encountered by the organ suggest that any intervention proven beneficial in this model is likely to improve ECD organ quality and thus would warrant a dedicated investigation with an appropriate model.
. Decker E, Coimbra C, Weekers L, Detry O, Honoré P, Squifflet JP, Meurisse M, De Roover A. A retrospective monocentric review of simultaneous pancreas kidneytransplantation. . de Jonge H, Naesens M, Vanrenterghem Y, Kuypers DR. The pregnane X receptor
(NR112) C-25385T single nucleotide polymorphism does not affect tacrolimus pharma- cokinetics in a large cohort of renal transplant recipients.
Keywords: creatinine, delayed graft function, graft survival, ischaemia reperfusion injury, kidneytransplantation, proteinuria
Kidneytransplantation (KT) is the treatment of choice for end- stage chronic kidney disease (CKD) due to the better survival of patients treated with KT when compared with dialysis [ 1 ], as well as its cost-effectiveness [ 2 , 3 ]. Short-term graft survival rates have improved markedly in recent decades, whereas long- term graft survival rates have improved only marginally. This difference is likely largely due to humoral chronic rejection, but also the greater use of grafts from expanded-criteria donors (ECDs) [ 4 ], who possibly are more prone to early graft injuries, especially ischaemia-reperfusion injury (IRI) lesions and acute calcineurin inhibitor (CNI) nephrotoxicity.
Kidney transplant recipients (KTR) are at increased risk of infections. Infections are the second cause of mortality after KT, and are reported to be associated with graft dysfunction and loss. Opportunistic infections (OI) also represent an important burden after kidneytransplantation, despite prophylaxis and prevention programs. Specific risk factors have been identified per pathogen, but few data exist regarding global OI risk factors. Also, there is no data on risk factors for multiple OI in KTR. Thus, the aim of our study was to describe opportunistic infections, especially multiple OI, and to determinate the factors associated with multiple OI in KTR.
HCV infection is associated with reduced patient survival following combined liver-kidneytransplantation (LKT). The aim of this study was to assess the efficacy and safety of second generation direct active antiviral (DAAs) in this difficult-to-treat population. The ANRS CO23 CUPILT study is a prospective cohort including transplant recipients with recurrent HCV treated with DAAs. The present work focused on recipients with recurrent HCV following LKT .
Vascular and Transplantation, Department of Surgery, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
Background: Duration of retaining ureteric stent after kidneytransplantation was still controversy. Short duration of ureteric stent may reduce urinary tract infection (UTI) after kidneytransplantation. This study aims to determine ben- efits and risks of early versus routine stent removal in kidneytransplantation. Methods: Single-center parallel randomized controlled, open label, trial. Ran- domization was computer-generated block of 4, allocation concealment by sealed opaque envelops. 80 patients who underwent kidneytransplantation at a University-based hospital in Thailand from April2010- January2011 were enrolled. Patients were randomized to early ureteric stent removal (8 days) or routine ureteric stent removal (15 days) after kidneytransplantation. The pri- mary outcome was rate of UTI during postoperative to 1 week after discharge. Chi-square or Fisher’s exact was used to compare the proportion of UTI be- tween groups.
Autres publications hors thèse
* Zuber J, Frimat M, Caillard S, Kamar N, Gatault P, Petitprez F, Couzi L, Jourde-Chiche N, Chatelet V Gaisne R, Bertrand D, Bamoulid J, Louis M, Sberro Soussan R, Navarro D, Westeel PF, Frimat L, Colosio C, Thierry A, Rivalan J, Albano L, Arzouk N, Cornec-Le Gall E, Claisse G, Elias M, El Karoui K, Chauvet S, Coindre JP, Rerolle JP, Tricot L, Sayegh J, Garrouste C, Charasse C, Delmas Y, Massy Z, Hourmant M, Servais A, Loirat C, Fakhouri F, Pouteil-Noble C, Peraldi MN, Legendre C, Rondeau E, Le Quintrec M, Frémeaux-Bacchi VUse of Highly Individualized Complement Blockade Has Revolutionized Clinical Outcomes after KidneyTransplantation and Renal Epidemiology of Atypical Hemolytic Uremic Syndrome. J Am Soc Nephrol. 1 oct 2019 (in press).