scholarly journals Torque teno viral load reflects immunosuppression in paediatric kidney-transplanted patients—a pilot study

2020 ◽  
Vol 36 (1) ◽  
pp. 153-162 ◽  
Author(s):  
Phoebe Uhl ◽  
Andreas Heilos ◽  
Gregor Bond ◽  
Elias Meyer ◽  
Michael Böhm ◽  
...  
Keyword(s):  
Viral Load ◽  
Graft Function ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Kidney Graft ◽  
Post Transplant ◽  
The Individual ◽  
Almost All ◽  
Plasma Load

Abstract Background Chronic deterioration of kidney graft function is related to inadequate immunosuppression (IS). A novel tool to assess the individual net state of IS in transplanted patients might be the monitoring of Torque teno virus (TTV) viral load. TTV is a non-pathogen virus detectable in almost all individuals. TTV level in the peripheral blood has been linked to the immune-competence of its host and should thus reflect IS after solid organ transplantation. Methods TTV plasma load was quantified monthly by RT-PCR for a period of 1 year in 45 kidney-transplanted children. Post-transplant time was at least 3 months. The relation of the virus DNA levels to IS and transplant-specific clinical and laboratory parameters was analysed longitudinally. Results TTV DNA was detectable in 94.5% of the plasma samples. There was a significant association with the post-transplant follow-up time as well as with the type of IS regimen, with lower virus loads in patients after longer post-transplant time and mTOR inhibitor–based IS. Furthermore, a significant positive correlation with the dose of prednisolone and mycophenolate mofetil was found. Conclusions TTV levels show an association/correlation with the strength of IS. Further studies are needed in order to evaluate TTV measurement as a tool for IS monitoring for hard clinical outcomes such as presence of donor-specific antibodies, rejections or infections—common consequences of insufficient or too intense IS.

scholarly journals Conversion from calcineurin inhibitors to sirolimus of recipients with chronic kidney graft disease grade iii for a period 2003-2011

2013 ◽  
Vol 70 (9) ◽  
pp. 848-853 ◽  
Author(s):  
Ljiljana Ignjatovic ◽  
Rajko Hrvacevic ◽  
Dragan Jovanovic ◽  
Zoran Kovacevic ◽  
Neven Vavic ◽  
...  
Keyword(s):  
Serum Creatinine ◽  
Immunosuppressive Therapy ◽  
Graft Function ◽  
Solid Organ Transplantation ◽  
Calcineurin Inhibitors ◽  
Solid Organ ◽  
Kidney Graft ◽  
Group I ◽  
Grade Iii

Background/Aim. Tremendous breakthrough in solid organ transplantation was made with the introduction of calcineurin inhibitors (CNI). At the same time, they are potentially nephrotoxic drugs with influence on onset and progression of renal graft failure. The aim of this study was to evaluate the outcome of a conversion from CNIbased immunosuppressive protocol to sirolimus (SRL) in recipients with graft in chronic kidney disease (CKD) grade III and proteinuria below 500 mg/day. Methods. In the period 2003-2011 24 patients (6 famale and 18 male), mean age 41 ? 12.2 years, on triple immunosuppressive therapy: steroids, antiproliferative drug [mycophenolate mofetil (MMF) or azathiopirine (AZA)] and CNI were switched from CNI to SRL and followe-up for 76 ? 13 months. Nine patients (the group I) had early postransplant conversion after 4 ? 3 months and 15 patients (the group II) late conversion after 46 ? 29 months. During the regular outpatient controls we followed graft function through the serum creatinine and glomerular filtration rate (GFR), proteinuria, lipidemia and side effects. Results. Thirty days after conversion, in all the patients GFR, proteinuria and lipidemia were insignificantly increased. In the first two post-conversion months all the patients had at least one urinary or respiratory infection, and 10 patients reactivated cytomegalovirus (CMV) infection or disease, and they were successfully treated with standard therapy. After 21 ? 11 months 15 patients from both groups discontinued SRL therapy due to reconversion to CNI (10 patients) and double immunosuppressive therapy (3 patients), return to hemodialysis (1 patient) and death (1 patient). Nine patients were still on SRL therapy. By the end of the follow-up they significantly improved GFR (from 53.2 ? 12.7 to 69 ? 15 mL/min), while the increase in proteinuria (from 265 ? 239 to 530.6 ? 416.7 mg/day) and lipidemia (cholesterol from 4.71 ? 0.98 to 5.61 ? 1.6 mmol/L and triglycerides from 2.04 ? 1.18 to 2.1 ? 0.72 mmol/L) were not significant. They were stable during the whole follow-up period. Ten patients were reconverted from SRL to CNI due to the abrupt increase of proteinuria (from 298 ? 232 to 1639 ? 1641/mg day in 7 patients), rapid growth of multiple ovarian cysts (2 patients) and operative treatment of persisted hematoma (1 patient). Thirty days after reconversion they were stable with an insignificant decrease in GFR (from 56.10 ? 28.09 to 47 ? 21 mL/min) and significantly improved proteinuria (from 1639 ? 1641 to 529 ? 688 mg/day). By the end of the follow-up these patients showed nonsignificant increase in the serum creatinine (from 172 ? 88 to 202 ? 91 mmol/L), decrease in GFR (from 56.10 ? 28.09 to 47 ? 21 mL/day) and increased proteinuria (from 528.9 ? 688 to 850 ? 1083 mg/min). Conclusion. In this small descriptive study, conversion from CNI to SRL was followed by an increased incidence of infections and consecutive 25-50% dose reduction in the second antiproliferative agent (AZA, MMF), with a possible influence on the development of glomerulopathy in some patients, which was the major reason for discontinuation of SRL therapy in the 7 (29%) patients. Nine (37.5%) of the patients experienced the greatest benefit of CIN to SRL conversion without serious post-conversion complications.

Adapted Management of EBV Reactivation After Solid Organ Transplantation: An Effective Prevention of Post Transplantation Lymphoproliferative Disorders (PTLD). Results of the Largest Prospective Study on 251 Patients

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 592-592
Author(s):  
Sylvain Choquet ◽  
Shaida Varnous ◽  
Claire Deback ◽  
Alain Pavie ◽  
Véronique Leblond
Keyword(s):  
Viral Load ◽  
Board Of Directors ◽  
Organ Transplantation ◽  
Solid Organ Transplantation ◽  
First Year ◽  
Solid Organ ◽  
Post Transplantation ◽  
Advisory Committees ◽  
Ebv Reactivation

Abstract Abstract 592 Background: PTLD represent a rare but aggressive graft complication. Patients who have received a solid organ transplantation have a 20 to 120 fold higher incidence of non-Hodgkin's lymphoma. EBV reactivation represents a major predictive factor for PTLD, especially during the first year after transplantation, but there is no consensual attitude in this situation Aim: We conducted a monocentric prospective study in the Hospital of Pitie Salpêtriere, Paris, France, on all new heart transplanted patients. EBV viral load (EVL) on whole blood samples was systematically followed and confirmed reactivations were treated depending on viral load. Methods: All heart transplanted patients who had at least one EVL between January 2004 and December 2008 were included. Immunosuppression consisted on anti-lymphocyte sera, ciclosporin, mycophenolate-mofetyl (MM) and prednisone. Twelve to 15 blood samples per year were analysed. If the EVL was more than 105 copies/ml, a CT scan or a PET-san was performed in order to detect any PTLD and patients were treated by diminution of the immunosupression (DIS), mainly by MM arrest. One injection of Rituximab (R) (375 mg/m2) was used in case of failure and/or if EVL was over 106 copies/ml. Results: A total of 251 patients were included, 59 femals/192 men, of a median age of 50 years [16-72]. All but 6 were EBV positive before the graft. Reactivations were detected in 29 cases (11,55%) and treated by DIS only in 20 cases, DIS followed by R in 5 and directly by DIS and R in 4. All EBV negative patients developed a primoinfection in the first year, 2 with an EVL over 105, one presented non documented hepatic lesions which disappeared after DIS. All EBV reactivations were controlled, with a relapse in only one case (reactivations treated the first time by DIS, 10 months later by DIS and R and 6 months later by DIS). With a median follow-up of 1118 days [53-2100] only one PTLD has been diagnosed (in a patient lost to follow up and taken in charge in an other unit) and 24 patients died (9,5%). Analyse of DIS +/− R on graft rejection and potential link between CMV reactivation and EBV reactivation will be presented at the ASH. From 1987 to December 2003, 24 (1,8/year) PTLD have been treated in the same unit (18 EBV positive, 5 negative, 1 unknown), of which 13 were early PTLD (all EBV positive) diagnosed within one year post transplantation. Conclusions: EBV reactivation after organ transplantation can be managed by diminution of immunosupression and/or rituximab, depending on viral load, without serious complication. This adapted management seems to decrease dramatically the incidence of EBV positive PTLD. Disclosures: Choquet: ROCHE: Consultancy. Leblond:ROCHE: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MUNDIPHARMA: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CELGENE: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Thyroid cancer and renal transplantation: a meta-analysis

2010 ◽  
Vol 17 (1) ◽  
pp. 159-167 ◽  
Author(s):  
Dheeraj Karamchandani ◽  
Ramiro Arias-Amaya ◽  
Nora Donaldson ◽  
Jackie Gilbert ◽  
Klaus-Martin Schulte
Keyword(s):  
Thyroid Cancer ◽  
Renal Transplantation ◽  
Meta Analysis ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Post Transplantation ◽  
Post Transplant ◽  
Increased Risk

Kidney transplantation and the associated immune suppression are associated with a significantly increased risk of developing cancer during long-term follow-up. Thyroid cancer has been recognised as a potential post-transplant risk but has not yet been subject of a focused review. We therefore performed a meta-analysis on data of 50 861 patients with a total follow-up of 198 595 patient-years and identified a 6.9-fold higher standardised incidence ratio (95% confidence interval 5.6–8.7, P<0.001) of thyroid cancer post renal transplantation as compared with a non-transplant group. All such cancers were of papillary type as far as histopathology was known. The mean time to discovery was 6.0 years post transplantation. This puts thyroid cancer into the group of high cancer risk following solid organ transplantation which already includes cervical cancer, non-melanoma skin cancer, oral and lip cancer and haematological malignancies. It is unclear what causes the increased cancer incidence. Inclusion of thyroid ultrasound in long-term post-transplant evaluation may help to ensure timely recognition of this condition.

scholarly journals Impacts of High Intra- and Inter-Individual Variability in Tacrolimus Pharmacokinetics and Fast Tacrolimus Metabolism on Outcomes of Solid Organ Transplant Recipients

2020 ◽  
Vol 9 (7) ◽  
pp. 2193 ◽  
Author(s):  
Charat Thongprayoon ◽  
Panupong Hansrivijit ◽  
Karthik Kovvuru ◽  
Swetha R. Kanduri ◽  
Tarun Bathini ◽  
...  
Keyword(s):  
Solid Organ Transplantation ◽  
Organ Transplant ◽  
Therapeutic Index ◽  
Individual Variability ◽  
Solid Organ ◽  
Dose Ratio ◽  
Post Transplant ◽  
Patients At Risk ◽  
Poor Outcomes ◽  
The Individual

Tacrolimus is a first-line calcineurin inhibitor (CNI) and an integral part of the immunosuppressive strategy in solid organ transplantation. Being a dose-critical drug, tacrolimus has a narrow therapeutic index that necessitates periodic monitoring to maintain the drug’s efficacy and reduce the consequences of overexposure. Tacrolimus is characterized by substantial intra- and inter-individual pharmacokinetic variability. At steady state, the tacrolimus blood concentration to daily dose ratio (C/D ratio) has been described as a surrogate for the estimation of the individual metabolism rate, where a low C/D ratio reflects a higher rate of metabolism. Fast tacrolimus metabolism (low C/D ratio) is associated with the risk of poor outcomes after transplantation, including reduced allograft function and survival, higher allograft rejection, CNI nephrotoxicity, a faster decline in kidney function, reduced death-censored graft survival (DCGS), post-transplant lymphoproliferative disorders, dyslipidemia, hypertension, and cardiovascular events. In this article, we discuss the potential role of the C/D ratio in a noninvasive monitoring strategy for identifying patients at risk for potential adverse events post-transplant.

scholarly journals Malignant Post-Transplant Lymphoproliferative Disorder of Nasopharynx in Myelodysplastic Disorder

Healthcare ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 217
Author(s):  
Chih-Wei Luan ◽  
Chih-Cheng Chen ◽  
Kam-Fai Lee ◽  
Ming-Shao Tsai ◽  
Yao-Te Tsai ◽  
...  
Keyword(s):  
Organ Transplantation ◽  
Lymphoproliferative Disorder ◽  
Histopathological Examination ◽  
Solid Organ Transplantation ◽  
Low Grade ◽  
Solid Organ ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Low Dose Radiotherapy

(1) Background: Post-transplant lymphoproliferative disorder (PTLD) is a hematological disease and occurs because of immunosuppression after organ transplantation. Only a few studies have reported PTLD in the nasopharynx. In most cases, PTLD developed after solid organ transplantation, and cases of PTLD after bone marrow transplantation, are uncommon. (2) Case presentation: We report the case of a 40-year-old woman with myelodysplastic disorder who underwent hematopoietic stem cell transplantation (HSCT). After 3 months, she developed low-grade fever, progressive nasal obstruction, and bloody rhinorrhea. Endoscopy revealed a mass completely occupying the nasopharynx. A polymorphic PTLD was diagnosed on the basis of histopathological examination results. Reduction in immunosuppression and low-dose radiotherapy were prescribed for treatment. After a 3-year follow-up, no recurrence of PTLD or myelodysplastic disorder was detected. (3) Conclusions: While nasopharyngeal PTLD is rare, a routine examination of the nasopharynx should be considered in the post-transplant follow-up of patients for early detection and treatment of PTLD.

scholarly journals Donor-derived TB after kidney transplantation: a case report

2021 ◽  
Author(s):  
Luiz Roberto de Sousa Ulisses ◽  
Helen Souto Siqueira Cardoso ◽  
Inara Creão Costa Alves ◽  
Isabela Novais Medeiros ◽  
Camilla Garcia de Oliveira ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Case Report ◽  
Organ Transplantation ◽  
Fluid Collection ◽  
Graft Function ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Mortality And Morbidity ◽  
Contralateral Kidney ◽  
Post Transplant

Abstract Introduction: Tuberculosis (TB) is a possible serious complication of solid organ transplantation, associated with high mortality and morbidity. Post-transplant TB has varied pathogenesis with many approaches to its prevention, which is the most important way to reduce its incidence. Treatment of TB in organ recipients is challenging because of drug toxicity and interaction with immunosuppressants. Case report: an 18-year-old woman that underwent kidney transplantation from a deceased donor and was discharged with fair renal function was readmitted at 37th postoperative day with fever. CT showed signs of miliary TB and fluid collection besides graft fistulization through the skin. The patient presented positive BAAR in the drained fluid and Koch's bacillus in the urine. She was treated with a four-drug regimen (rifampicin, isoniazid, pyrazinamide, and etambutol), with great response and preserved graft function. We were informed that the recipient of the contralateral kidney also presented post-transplant TB, implying in a donor-derived origin. Conclusion: TB is an important differential diagnosis for infectious complications in patients after solid-organ transplantation, especially in endemic regions. Its initial clinical presentation can be unspecific and it should be suspected in the presence of fever or formation of fluid collections. The suspicion of TB is the key to early diagnosis and satisfactory outcomes in post-transplant TB.

scholarly journals 1396. Live Virus Vaccination Following Pediatric Liver Transplantation: Results from Two Academic Children’s Hospitals

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S707-S708
Author(s):  
Alexander M Newman ◽  
Leila C Posch ◽  
Lauren Gianchetti ◽  
Elizabeth B Rand ◽  
Saeed Mohammad ◽  
...  
Keyword(s):  
Injection Site Reaction ◽  
Solid Organ Transplantation ◽  
Clinical Findings ◽  
Solid Organ ◽  
Dose Frequency ◽  
Live Virus ◽  
Varicella Zoster ◽  
Virus Vaccination ◽  
Post Transplant

Abstract Background Guidelines for immunization following solid organ transplantation discourage live virus vaccination (LVV) in most recipients. Single-center studies support LVV as safe and effective in orthotopic liver transplant (OLT) recipients on steroid-free immunosuppression (IS). We retrospectively evaluated LVV after OLT at 2 pediatric hospitals. Methods Records from OLT recipients between Jan 2007 and Dec 2017 at Lurie Children’s (Chicago) and Children’s Hospital of Philadelphia were reviewed. Patients who underwent OLT at either institution, had ≥ 2 years of follow up, and had documentation of vaccination prior to OLT were included. Adverse events (AEs) within two weeks of receipt of LVV were captured. Factors that might influence the selection of patients for LVV were reviewed, including choice, dose, frequency, and levels of IS medications. IS in non-vaccinated patients was compared to vaccinated patients at two year post-transplant follow-up in both groups using Chi-Square and T-test. Results Data from 249 patients met inclusion criteria. Varicella zoster (VZV) vaccine was given at least once to 92 patients post-transplant, and MMR to 91 (Table 1). Compared to patients who were re-vaccinated after transplant, those who received their first LVV after OLT were transplanted at a younger age (0.8 v 2.2 years) and received LVV sooner post-OLT (649 v 907 days). AEs were rare for either LVV: 2 experienced injection site reaction, 2 localized rash, and 1 had fever. One recipient experienced worsening rejection one month after MMR and received IV steroids and increased IS, but had no clinical findings concerning for viral infection from vaccination. Most LVV recipients were on a single IS agent both at time of LVV and 2 year post-OLT (Table 2), with tacrolimus the most frequent agent. Compared to those that did not received LVV post-OLT, those that did were on one IS agent more often. Tacrolimus levels were similar among patients receiving LVV post-OLT compared with those who did not. Table 1 Table 2 Conclusion In a series of pediatric OLT recipients, post-OLT LVV was generally safe and well tolerated. Patients who received LVV post-OLT were more often on one IS agent at 2 year follow up compared to those who did not. Our study supports prospective efforts to define guidelines for patients who may safely receive LVV after OLT. Disclosures Kevin J. Downes, MD, Merck, Inc. (Grant/Research Support)

MO941CLINICAL OUTCOMES IN KIDNEY RE-TRANSPLANTATION

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Clara Pardinhas ◽  
Rita Leal ◽  
Francisco Caramelo ◽  
Teofilo Yan ◽  
Carolina Figueiredo ◽  
...  
Keyword(s):  
Acute Rejection ◽  
Kidney Transplant ◽  
Graft Survival ◽  
Graft Failure ◽  
Graft Function ◽  
Delayed Graft Function ◽  
First Year ◽  
Kidney Transplant Recipients ◽  
Post Transplant

Abstract Background and Aims As kidney transplants are growing in absolute numbers, so are patients with failed allografts and thus potential candidates for re-transplantation. Re-transplantation is challenging due to immunological barriers, surgical difficulties and clinical complexities but it has been proven that successful second transplantation improves life expectancy over dialysis. It is important to evaluate re-transplantation outcomes since 20% of patients on the waiting list are waiting for a second graft. Our aim was to compare major clinical outcomes such as acute rejection, graft and patient survival, between patients receiving a first or a second kidney transplant. Method We performed a retrospective study, that included 1552 patients submitted to a first (N=1443, 93%) or a second kidney transplant (N=109, 7%), between January 2008 and December 2018. Patients with more than 2 grafts or multi-organ transplant were excluded. Demographic, clinical and histocompatibility characteristics of both groups were registered from our unit database and compared. Delayed graft function was defined has the need of dialysis in the first week post-transplant. All acute rejection episodes were biopsy proven, according to Banff 2017 criteria. Follow-up time was defined at 1st June 2020 for functioning grafts or at graft failure (including death with a functioning graft). Results Recipients of a second graft were significantly younger (43 ±12 vs 50 ± 13 years old, p&lt;0.001) and there were significantly fewer expanded-criteria donors in the second transplant group (31.5% vs 57.5%, p&lt;0.001). The waiting time for a second graft was longer (63±50 vs 48±29 months, p=0.011). HLA mismatch was similar for both groups but PRA was significantly higher for second KT patients (21.6±25% versus 3±9%; p&lt;0.001). All patients submitted to a second KT had thymoglobulin as induction therapy compared to 16% of the first KT group (p&lt;0.001). We found no difference in primary dysfunction or delayed graft function between groups. Acute rejection was significantly more frequent in second kidney transplant recipients (19% vs 5%, p&lt;0.001), being 10 acute cellular rejections, 7 were antibody mediated and 3 were borderline changes. For the majority of the patients (85%), acute rejection occurred in the first-year post-transplant. Death censored graft failure occurred in 236 (16.4%) patients with first kidney transplant and 25 (23%) patients with a second graft, p=0.08. Survival analysis showed similar graft survival for both groups (log-rank p=0.392). We found no difference in patients’ mortality at follow up for both groups. Conclusion Although second graft patients presented more episodes of biopsy proven acute rejection, especially at the first-year post-transplant, we found no differences in death censored graft survival or patients’ mortality for patients with a second kidney transplant. Second transplants should be offered to patients whenever feasible.

A systematic review of post-transplant lymphoproliferative disorder after lung transplant.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19046-e19046
Author(s):  
Mobeen Zaka Haider ◽  
Zarlakhta Zamani ◽  
Fnu Kiran ◽  
Hasan Mehmood Mirza ◽  
Muhammad Taqi ◽  
...  
Keyword(s):  
Lymphoproliferative Disorder ◽  
Lung Transplant ◽  
Late Onset ◽  
Adult Population ◽  
Solid Organ Transplantation ◽  
Chemotherapeutic Agents ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Post Transplant ◽  
Lung Transplant Recipients

e19046 Background: Post-transplant lymphoproliferative disorder (PTLD) is a serious complication after solid organ transplantation. This study aims to explore the association of PTLD diagnosed after lung transplant with infectious agents and immunosuppression regimen, explore types of PTLD, and their outcome. Methods: Following the PRISMA guideline, we searched the literature on PubMed, Cochrane, Embase, and clinicaltrials.gov. 1741 articles were screened and included five studies. Results: We analyzed data from five studies, n=13,643 transplant recipients with n=287 (2.10%) developed PTLD. Four studies showed that 32/63 (51%) PTLD patients were male and 31 (49%) were female. Three studies reported 53/55 (96.4%) patients were EBV positive at PTLD diagnosis. Courtwright. et al, reported that 217/224 (97%) PTLD was associated with either EBV positive donor or recipient. Four studies showed that the monomorphic B cell type 48/63 (76%) was the most common histological type of PTLD diagnosed with DLBCL the most common subtype 31/48 (64.6%). Data from 3 studies showed that the onset of PTLD following lung transplant varies with a median duration of 18.3 months (45 days to 20.2 years). Three studies showed that 26/55 (47.3%) patients had early-onset (≤ 1 yr of Tx) and 29/55 (52.7%) patients had late-onset PTLD (> 1 yr of Tx). Management of PTLD included a reduction in immunosuppression including corticosteroids, CNI, purine synthesis inhibitors, Rituximab, and chemotherapeutic agents. Three studies showed a mortality rate of 30/45 (66.7%) and 13/30 (43.3%) deaths were PTLD related. Conclusions: Our review concludes that PTLD is a serious complication, only 2% of lung transplant recipients developed PTLD. EBV seropositivity is the most factor associated with PTLD diagnosis. Monomorphic PTLD was reported as the most common type in the adult population and no association between gender and PTLD was found. The analysis shows that there is a slightly lower incidence of early (≤ 1 yr of Tx) than late-onset (> 1 yr of Tx) PTLD. Table 1 PTLD after a Lung transplant in adults - a review. [Table: see text]

Sign in / Sign up

Export Citation Format

Share Document