ABSTRACT
While guidelines support metformin as a therapeutic option for diabetic patients with mild-to-moderate renal insufficiency, the frequency and outcomes of metformin use in kidney transplant recipients are not well described. We integrated national U.S. transplant registry data with records from a large pharmaceutical claims clearinghouse (2008-2015). Associations (adjusted hazard ratio, 95% LCL aHR95% UCL ) of diabetes regimens (with and excluding metformin) in the first year post-transplant with patient and graft survival over the subsequent year were quantified by multivariate Cox regression, adjusted for recipient, donor, and transplant factors and propensity for metformin use. Among 14 144 recipients with pretransplant type 2 diabetes mellitus, 4.7% filled metformin in the first year post-transplant; most also received diabetes comedications. Compared to those who received insulin-based regimens without metformin, patients who received metformin were more likely to be female, have higher estimated glomerular filtration rates, and have undergone transplant more recently. Metformin-based regimens were associated with significantly lower adjusted all-cause (aHR 0.18 0.410.91 ), malignancy-related (aHR 0.45 0.450.99 ), and infection-related (aHR 0.12 0.320.85 ) mortality, and nonsignificant trends toward lower cardiovascular mortality, graft failure, and acute rejection. No evidence of increased adverse graft or patient outcomes was noted. Use of metformin-based diabetes treatment regimens may be safe in carefully selected kidney transplant recipients.
Subject(s)
Diabetes Mellitus, Type 2/physiopathology , Graft Rejection/mortality , Insurance, Pharmaceutical Services/statistics & numerical data , Kidney Failure, Chronic/mortality , Kidney Transplantation/mortality , Metformin/therapeutic use , Postoperative Complications , Adolescent , Adult , Child , Diabetes Mellitus, Type 2/drug therapy , Female , Follow-Up Studies , Glomerular Filtration Rate , Graft Rejection/drug therapy , Graft Rejection/epidemiology , Graft Survival , Humans , Hypoglycemic Agents/therapeutic use , Kidney Failure, Chronic/drug therapy , Kidney Failure, Chronic/surgery , Kidney Function Tests , Male , Middle Aged , Prognosis , Registries/statistics & numerical data , Retrospective Studies , Risk Factors , Survival Rate , Transplant Recipients , United States , Young AdultABSTRACT
Direct-acting antiviral medications (DAAs) have revolutionized care for hepatitis C positive (HCV+) liver (LT) and kidney (KT) transplant recipients. Scientific Registry of Transplant Recipients registry data were integrated with national pharmaceutical claims (2007-2016) to identify HCV treatments before January 2014 (pre-DAA) and after (post-DAA), stratified by donor (D) and recipient (R) serostatus and payer. Pre-DAA, 18% of HCV+ LT recipients were treated within 3 years and without differences by donor serostatus or payer. Post-DAA, only 6% of D-/R+ recipients, 19.8% of D+/R+ recipients with public insurance, and 11.3% with private insurance were treated within 3 years (P < .0001). LT recipients treated for HCV pre-DAA experienced higher rates of graft loss (adjusted hazard ratio [aHR] 1.34 1.852.10 , P < .0001) and death (aHR 1.47 1.681.91 , P < .0001). Post-DAA, HCV treatment was not associated with death (aHR 0.34 0.671.32 , P = .25) or graft failure (aHR 0.32 0.641.26 , P = .20) in D+R+ LT recipients. Treatment increased in D+R+ KT recipients (5.5% pre-DAA vs 12.9% post-DAA), but did not differ by payer status. DAAs reduced the risk of death after D+/R+ KT by 57% (0.19 0.430.95 , P = .04) and graft loss by 46% (0.27 0.541.07 , P = .08). HCV treatment with DAAs appears to improve HCV+ LT and KT outcomes; however, access to these medications appears limited in both LT and KT recipients.
Subject(s)
Antiviral Agents/therapeutic use , Graft Survival , Hepacivirus/drug effects , Hepatitis C/drug therapy , Kidney Transplantation/economics , Liver Transplantation/economics , Waiting Lists/mortality , Adolescent , Adult , Aged , Female , Follow-Up Studies , Hepatitis C/virology , Humans , Kidney Transplantation/mortality , Liver Transplantation/mortality , Male , Middle Aged , Prognosis , Registries , Retrospective Studies , Risk Factors , Survival Rate , Tissue Donors/supply & distribution , Transplant Recipients , Young AdultABSTRACT
Evolving literature suggests that the epidemic of prescription opioid use affects the transplant population. We examined a novel database wherein national U.S. transplant registry records were linked to a large pharmaceutical claims warehouse (2007-2015) to characterize prescription opioid use before and after kidney transplant, and associations (adjusted hazard ratio, 95%LCL aHR95%UCL ) with death and graft loss. Among 75 430 eligible patients, 43.1% filled opioids in the year before transplant. Use was more common among recipients who were women, white, unemployed, publicly insured, and with longer pretransplant dialysis. Of those with the highest level of pretransplant opioid use, 60% continued high-level use posttransplant. Pretransplant opioid use had graded associations with one-year posttransplant outcomes; the highest-level use predicted 46% increased risk of death (aHR 1.28 1.461.66 ) and 28% increased risk of all-cause graft failure (aHR 1.17 1.281.41 ). Effects of high-level opioid use in the first year after transplant were stronger, predicting twice the risk of death (aHR 1.93 2.242.60 ) and 68% higher all-cause graft failure risk (aHR 1.50 1.681.89 ) over the subsequent year; increased risk persisted over five years. While associations may, in part, reflect underlying conditions or behaviors, opioid use history is relevant in assessing and providing care to transplant candidates and recipients.
Subject(s)
Analgesics, Opioid/adverse effects , Graft Rejection/mortality , Graft Survival , Kidney Failure, Chronic/mortality , Kidney Transplantation/mortality , Opioid-Related Disorders/drug therapy , Postoperative Complications/mortality , Adolescent , Adult , Delayed Graft Function , Female , Follow-Up Studies , Graft Rejection/etiology , Humans , Kidney Failure, Chronic/surgery , Kidney Transplantation/adverse effects , Male , Middle Aged , Postoperative Complications/etiology , Prognosis , Registries , Retrospective Studies , Risk Factors , United States , Young AdultABSTRACT
BACKGROUND: There is no standardized approach to the management of JDM-associated calcinosis and its phenotypes. Current knowledge of treatment outcomes is confined to small series and case reports. We describe physician perspectives toward diagnostic approach, classification and treatment directly targeting calcinosis, independent of overall JDM therapy. METHODS: An electronic survey of 22 questions was organized into sections regarding individual practices of assessment, classification and treatment of calcinosis, including perceived successes of therapies. Invitations to complete the survey voluntarily and anonymously were sent to CARRA physician members and the Pediatric Rheumatology Bulletin Board, an electronic list-serv. Results were analyzed by descriptive statistics and chi-square analyses. RESULTS: Of 139 survey responses, 118 were included in analysis. Of these, 70% were based in the USA and 88 (75%) were CARRA members. Only 17% of responders have seen more than 20 cases of calcinosis, and only 28% perform screening imaging studies on new JDM diagnoses. Increasing systemic immunosuppression is first-line therapy for 67% of respondents. Targeted therapy against calcinosis is most often instituted for symptomatic patients. IVIG and bisphosphonates are most frequently used and considered most successful, but many other agents are used. Experienced physicians are more likely to use bisphosphonates, calcium channel blockers and topical sodium thiosulfate (p< 0.002 or lower). CONCLUSIONS: Coexisting JDM disease activity influences whether calcinosis is considered active disease or targeted directly. Experience treating JDM-related calcinosis is low, as are rates of formal screening for calcinosis. Experienced physicians are more likely to use non-immunosuppressive treatments.
Subject(s)
Calcinosis/diagnosis , Dermatomyositis/complications , Practice Patterns, Physicians'/statistics & numerical data , Rheumatologists/statistics & numerical data , Calcinosis/etiology , Calcinosis/therapy , Child , Humans , Rheumatology , Surveys and QuestionnairesABSTRACT
Several viruses, such as Epstein-Barr virus, are now known to be associated with several human cancers, but not all patients with these viral infections develop cancer. In transplantation, such viruses often have a prolonged time gap from infection to cancer development, and many are preceded by a period of circulating and detectable nucleic acids in the peripheral blood compartment. The interpretation of a viral load as a measure of posttransplant risk of developing cancer depends on the virus, the cancer and associated pathogenic factors. This review describes the current state of knowledge regarding the utility and limitations of peripheral blood nucleic acid testing for Epstein-Barr virus in surveillance and risk prediction for posttransplant lymphoproliferative disorders.
Subject(s)
Biomarkers/blood , DNA, Viral/genetics , Epstein-Barr Virus Infections/complications , Herpesvirus 4, Human/genetics , Neoplasms/diagnosis , Postoperative Complications , DNA, Viral/blood , Epstein-Barr Virus Infections/genetics , Epstein-Barr Virus Infections/virology , Humans , Neoplasms/blood , Neoplasms/genetics , Neoplasms/virology , Risk FactorsABSTRACT
Kidney transplantation has become more resource intensive as recipient complexity has increased and average donor quality has diminished over time. A national retrospective cohort study was performed to assess the impact of kidney donor and recipient characteristics on transplant center cost (exclusive of organ acquisition) and Medicare reimbursement. Data from the national transplant registry, University HealthSystem Consortium hospital costs, and Medicare payments for deceased donor (N = 53 862) and living donor (N = 36 715) transplants from 2002 to 2013 were linked and analyzed using multivariate linear regression modeling. Deceased donor kidney transplant costs were correlated with recipient (Expected Post Transplant Survival Score, degree of allosensitization, obesity, cause of renal failure), donor (age, cause of death, donation after cardiac death, terminal creatinine), and transplant (histocompatibility matching) characteristics. Living donor costs rose sharply with higher degrees of allosensitization, and were also associated with obesity, cause of renal failure, recipient work status, and 0-ABDR mismatching. Analysis of Medicare payments for a subsample of 24 809 transplants demonstrated minimal correlation with patient and donor characteristics. In conclusion, the complexity in the landscape of kidney transplantation increases center costs, posing financial disincentives that may reduce organ utilization and limit access for higher-risk populations.
Subject(s)
Kidney Failure, Chronic/economics , Kidney Transplantation/economics , Living Donors/supply & distribution , Practice Patterns, Physicians'/economics , Tissue and Organ Procurement/economics , Adult , Age Factors , Female , Graft Survival , Histocompatibility , Humans , Kidney Failure, Chronic/surgery , Male , Patient Selection , Registries , Retrospective StudiesABSTRACT
BACKGROUND: Modern immunosuppression therapies (ISx) have many side effects, and transplant recipients must take an array of "comedications" to help mitigate complications. Comedication use patterns are not well described in large, representative samples because of lack of data. METHODS: We integrated national U.S. transplant registry data with pharmacy records (2005-2010) from a large pharmaceutical claims clearinghouse to examine treatments for anemia, metabolic disorders, and infections in relation to ISx regimens in months 6-12 post-transplantation (N = 22,453). Associations of ISx with comedication use (adjusted odds ratio [aOR]) were quantified with multivariate logistic regression including adjustment for recipient, donor, and transplant factors. RESULTS: Compared to a reference regimen of tacrolimus, mycophenolic acid, and prednisone, sirolimus-based ISx was associated with significantly more common use of erythropoiesis-stimulating agents (aOR 2.52, 95% confidence interval [CI] 2.06-3.09), iron (aOR 2.26, 95% CI 1.92-2.65), statins (aOR 1.47, 95% CI 1.33-1.63), fibrates (aOR 2.35, 95% CI 1.90-2.90), and phosphorous binders (aOR 2.85, 95% CI 1.80-4.50). Patterns were similar after adjustment for first-year estimated glomerular filtration rate, except the association with phosphorous binders was no longer significant. Cyclosporine-based ISx was associated with more common erythropoiesis-stimulating agent use, including after estimated glomerular filtration rate adjustment (aOR 1.61, 95% CI 1.24-2.10). Compared to those who were being administered triple ISx, recipients receiving tacrolimus-based dual and monotherapies had lower use of statins, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEi/ARBs), and antibacterial agents. Recipients of steroid-free ISx were less commonly treated for post-transplantation diabetes. CONCLUSIONS: Alternate ISx regimens are associated with varying treatment requirements for hematologic, metabolic. and infectious complications. Comedication use should be considered in the cost-effectiveness and individualization of ISx regimens.
Subject(s)
Drug Prescriptions/statistics & numerical data , Immunosuppressive Agents/administration & dosage , Kidney Transplantation/adverse effects , Pharmacies/statistics & numerical data , Postoperative Complications/drug therapy , Registries/statistics & numerical data , Adult , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Cross-Sectional Studies , Cyclosporine/administration & dosage , Drug Therapy, Combination , Glomerular Filtration Rate , Humans , Information Storage and Retrieval , Mycophenolic Acid/administration & dosage , Odds Ratio , Postoperative Period , Prednisone/administration & dosage , Retrospective Studies , Sirolimus/administration & dosage , Tacrolimus/administration & dosage , United StatesABSTRACT
Immunosuppression management in kidney transplantation has evolved to include an increasingly diverse choice of medications. Although informed by patient and donor characteristics, choice of immunosuppression regimen varies widely across transplant programs. Using a novel database integrating national transplant registry and pharmacy fill records, immunosuppression use at 6-12 and 12-24 mo after transplant was evaluated for 22 453 patients transplanted in 249 U.S. programs in 2005-2010. Use of triple immunosuppression comprising tacrolimus, mycophenolic acid or azathioprine, and steroids varied widely (0-100% of patients per program), as did use of steroid-sparing regimens (0-77%), sirolimus-based regimens (0-100%) and cyclosporine-based regimens (0-78%). Use of triple therapy was more common in highly sensitized patients, women and recipients with dialysis duration >5 years. Sirolimus use appeared to diminish over the study period. Patient and donor characteristics explained only a limited amount of the observed variation in regimen use, whereas center choice explained 30-46% of the use of non-triple-therapy immunosuppression. The majority of patients who received triple-therapy (79%), cyclosporine-based (87.6%) and sirolimus-based (84.3%) regimens continued them in the second year after transplant. This population-based study of immunosuppression practice demonstrates substantial variation in center practice beyond that explained by differences in patient and donor characteristics.
Subject(s)
Evidence-Based Medicine , Graft Rejection/drug therapy , Immunosuppression Therapy/methods , Immunosuppressive Agents/therapeutic use , Kidney Failure, Chronic/surgery , Kidney Transplantation , Transplantation Immunology/drug effects , Adult , Drug Therapy, Combination , Female , Glomerular Filtration Rate , Graft Rejection/epidemiology , Graft Survival/drug effects , Graft Survival/immunology , Humans , Kidney Function Tests , Male , Middle Aged , Postoperative Complications , Prevalence , Prognosis , Risk FactorsABSTRACT
The infrequent use of ABO-incompatible (ABOi) kidney transplantation in the United States may reflect concern about the costs of necessary preconditioning and posttransplant care. Medicare data for 26 500 live donor kidney transplant recipients (2000 to March 2011), including 271 ABOi and 62 A2-incompatible (A2i) recipients, were analyzed to assess the impact of pretransplant, transplant episode and 3-year posttransplant costs. The marginal costs of ABOi and A2i versus ABO-compatible (ABOc) transplants were quantified by multivariate linear regression including adjustment for recipient, donor and transplant factors. Compared with ABOc transplantation, patient survival (93.2% vs. 88.15%, p = 0.0009) and death-censored graft survival (85.4% vs. 76.1%, p < 0.05) at 3 years were lower after ABOi transplant. The average overall cost of the transplant episode was significantly higher for ABOi ($65 080) compared with A2i ($36 752) and ABOc ($32 039) transplantation (p < 0.001), excluding organ acquisition. ABOi transplant was associated with high adjusted posttransplant spending (marginal costs compared to ABOc - year 1: $25 044; year 2: $10 496; year 3: $7307; p < 0.01). ABOi transplantation provides a clinically effective method to expand access to transplantation. Although more expensive, the modest increases in total spending are easily justified by avoiding long-term dialysis and its associated morbidity and cost.
Subject(s)
ABO Blood-Group System/immunology , Blood Group Incompatibility/economics , Graft Rejection/economics , Kidney Failure, Chronic/economics , Kidney Transplantation/economics , Living Donors , Adolescent , Adult , Databases, Factual , Female , Follow-Up Studies , Glomerular Filtration Rate , Graft Rejection/etiology , Humans , Kidney Failure, Chronic/surgery , Kidney Function Tests , Kidney Transplantation/adverse effects , Male , Medicare , Middle Aged , Prognosis , Retrospective Studies , Risk Factors , United States , Young AdultABSTRACT
In a prior multiorgan transplant database study, recipient Epstein-Barr virus (EBV) seronegativity was not associated with increased risk for posttransplant lymphoproliferative disorders (PTLD) in liver transplants (LTX), at variance with prior single center reports and with data from kidney and heart transplants (KTX and HTX). The Scientific Registry of Transplant Recipients (SRTR) in the United States is the only other registry with data on the required variables for comparison.Our study set comprised 112 756 KTX (580 PTLDs; 0.51%), 13 937 HTX (140 PTLDs; 1.0%) and 40 437 LTX (383 PTLDs; 0.95%) performed January 2003 onward. The unadjusted hazard ratio (HR) for PTLD if recipient EBV seronegative was 5.005 for KTX, 6.528 for HTX and 2.615 for LTX (p < 0.001 for all). In models adjusted for multiple covariates, the adjusted HR was 3.583 (p < 0.001) for KTX, 4.037 (p < 0.001) for HTX, 1.479 (p = 0.03) for LTX. Interaction models using EBV seropositive KTX as reference group showed significantly higher risk for all other EBV seronegative organ transplant groups and also for EBV seropositive LTX (AHR 2.053, p < 0.0001).Recipient EBV seronegativity is still significantly associated with risk for PTLD in LTX, though less so because of higher baseline risk in the EBV seropositive LTX group.
Subject(s)
Epstein-Barr Virus Infections/etiology , Herpesvirus 4, Human/pathogenicity , Lymphoma/complications , Lymphoproliferative Disorders/etiology , Transplants/adverse effects , Adolescent , Epstein-Barr Virus Infections/blood , Epstein-Barr Virus Infections/epidemiology , Female , Follow-Up Studies , Humans , Lymphoma/therapy , Lymphoma/virology , Lymphoproliferative Disorders/epidemiology , Lymphoproliferative Disorders/mortality , Male , Registries , Risk Factors , Seroepidemiologic Studies , Survival Rate , United States/epidemiologyABSTRACT
Posttransplantation lymphoproliferative disorder (PTLD) is an important complication of transplantation. Risk factors include increased overall immunosuppression exposure and inadequate antiviral prophylaxis; however, the effects of T-cell-depleting agents on PTLD are unclear. A systematic literature review was conducted to assess PTLD in clinical studies published 1999-2009 in transplant patients with ≥ 3 years follow-up who received Thymoglobulin for induction. Twenty studies were identified (12 kidney, 7 heart, and 1 liver), of which 3 were excluded for insufficient PTLD reporting. The final study group comprised 2,246 kidney and heart transplant recipients (liver study excluded) who received Thymoglobulin. At a median follow-up of 5 years, the incidence of PTLD was 0.98% (kidney, 0.93%; heart, 1.05%) among Thymoglobulin-treated patients. The cumulative Thymoglobulin dose reported in these studies was not associated with the development of PTLD (P = NS). However, incidence of PTLD was significantly lower with antiviral prophylaxis (0.63%) than without (1.87%; P = .013). Heart transplant recipients not receiving antiviral prophylaxis had the highest PTLD incidence, possibly attributable to a greater overall immunosuppressive burden. This analysis revealed that PTLD incidences in kidney and heart transplant recipients receiving Thymoglobulin were low overall and perhaps related more to concomitant anti-viral prophylaxis use.
Subject(s)
Antilymphocyte Serum/administration & dosage , Heart Transplantation/adverse effects , Kidney Transplantation/adverse effects , Lymphoproliferative Disorders/etiology , HumansABSTRACT
Post-transplant lymphoproliferative disorder (PTLD) has been associated with high mortality, but recent anecdotal survival appeared better. From 1988 to 2010, the NAPRTCS registry had 235 registered PTLD cases. We sent a special 25-point questionnaire study to the NAPRTCS centers with the most recent 150 cases to obtain additional follow-up data not collected in the master registry, our objective being to determine the recent outcomes after PTLD and determine prognostic factors. We received 92 completed responses, in which only 12 (13%) deaths were reported, 2 from nonmedical causes, 10 with a functioning graft. Kaplan-Meier-calculated patient survival was 90.6% at 1 year and 87.4% at 3, 4 and 5 years post-PTLD. Graft survival post-PTLD was 81.8% at 1 year, 68.0% at 3 years and 65.0% at 5 years. Seven patients received a retransplant after PTLD, with no PTLD recurrence reported. Using all 235 PTLD cases, the covariates associated with better patient survival were more recent year of PTLD diagnosis (adjusted hazard ratio AHR 0.86, p < 0.001), and with worse survival were late PTLD (AHR 1.98, p = 0.0176) and patient age above 13 at PTLD (AHR 3.43, p value 0.022). In children with kidney transplants, patient survival has improved with more recent PTLDs.
Subject(s)
Graft Survival , Kidney Transplantation/adverse effects , Lymphoproliferative Disorders/etiology , Lymphoproliferative Disorders/mortality , Postoperative Complications , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Retrospective Studies , Risk Factors , Surveys and Questionnaires , Survival Rate , Treatment OutcomeABSTRACT
BK virus (BKV) has emerged as a major complication of kidney transplantation. Since June 30, 2004, the OPTN in the USA collects BKV as a primary or secondary cause of graft loss and also if treatment for BK virus (TBKV) is administered. In this study, we determined characteristics of those recipients of repeat kidney transplants from the OPTN database, where either (a) a graft loss occurred between June 30, 2004 and December 31, 2008 and database recorded prior TBKV in that allograft or (b) a graft loss between June 30, 2004 and December 31, 2008 was attributed primarily or secondarily due to BKV. In the study time period, 823 graft losses have occurred where TBKV or graft failure attributable to BKV was reported in prior transplant; of these, 126 have received a retransplant as of June 5, 2009. Induction and maintenance immunosuppression usage mirrored current trends. As of June 5, 2009, 118/126 grafts are still functioning, one graft failure attributed to BKV. TBKV was reported in 17.5% of the retransplants. In the retransplants performed through December 31, 2007, 1-year acute rejection rate was 7%, 1-year and 3-year Kaplan-Meier graft survival rates and median GFR were 98.5%, 93.6%, 65.5 and 68.4 mL/min, respectively. Retransplantation after BKV appears to be associated with good results.
Subject(s)
BK Virus , Kidney Diseases/virology , Kidney Transplantation , Clinical Laboratory Techniques , Databases, Factual , Glomerular Filtration Rate , Graft Rejection/virology , Humans , Immunosuppression Therapy , Kidney/virology , Research , Survival Rate , United StatesABSTRACT
Transition of care from pediatric to adult-oriented health care providers is difficult for children with special health care needs. Children who have received solid organ transplants and their providers experience the same difficulties and frustrations as children with other major illnesses. A consensus conference was organized by several transplant organizations to identify major issues in this area and recommend possible approaches to easing the process of transition for solid organ transplant recipients. This report summarizes the discussions and recommendations.
Subject(s)
Adolescent Medicine/organization & administration , Delivery of Health Care/methods , Organ Transplantation/methods , Adolescent , Adult , Child , Continuity of Patient Care , Humans , Patient Compliance , Pediatrics/methodsABSTRACT
Post-transplant lymphoproliferative disease (PTLD) can occur in different sites, such as lymph nodes, allograft, and central nervous system. We report a 6-year-old girl with end-stage renal disease secondary to hypoplastic-dysplastic kidneys, who received a kidney transplant. Thirty months post transplant, she developed PTLD in the tongue, an area of muscular tissue only. At that time her peripheral blood Epstein-Barr viral (EBV) load was only 40 copies/10(5) lymphocytes, though the tumor was EB early RNA (EBER) positive. Immunosuppression was reduced with initial improvement in her symptoms. One month later, she returned with abdominal complaints and a contained cecal abscess. The excised cecal tissue revealed CD20 and EBER-positive lymphoid cells. At the same time, her peripheral blood EBV copy number rose to 400 copies/10(5) lymphocytes. She was successfully treated for the progressive PTLD by complete cessation of immunosuppression and a modified reduced-dose chemotherapy protocol plus rituximab. Partial immunosuppression was eventually re-introduced with sirolimus and prednisone. She remains in remission 60 months post transplant, and 30 months post PTLD, with serum creatinine value maintained at 1.3 mg/dL. Unusual localization of PTLD to areas in non-lymphoid tissue without regional lymphoid involvement may result in misleading low peripheral blood EBV viral loads.
Subject(s)
Epstein-Barr Virus Infections/diagnosis , Immunosuppression Therapy/adverse effects , Kidney Failure, Chronic/surgery , Kidney Transplantation/adverse effects , Lymphoproliferative Disorders/diagnosis , Postoperative Complications/diagnosis , Tongue Neoplasms/diagnosis , Abscess/etiology , Abscess/pathology , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Murine-Derived , Cecum/pathology , Child , Epstein-Barr Virus Infections/etiology , Epstein-Barr Virus Infections/virology , Female , Herpesvirus 4, Human/isolation & purification , Humans , Immunosuppressive Agents/administration & dosage , Lymphoproliferative Disorders/etiology , Lymphoproliferative Disorders/virology , Postoperative Complications/etiology , Postoperative Complications/virology , Prednisone/adverse effects , Prednisone/therapeutic use , Rituximab , Sirolimus/adverse effects , Sirolimus/therapeutic use , Tongue Neoplasms/etiology , Tongue Neoplasms/virology , Viral LoadABSTRACT
Transplant patients are at the risk for posttransplant lymphoproliferative disease (PTLD), a virally-driven malignancy. Induction with the depleting antibody preparations Thymoglobulin and OKT3 is associated with PTLD suggesting that the T-cell depletion increases PTLD risk. We therefore studied 59 560 kidney recipients from the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) database for a relationship between induction agent use and PTLD. Two agents with comparable T-cell depletional effects, alemtuzumab and Thymoglobulin, were compared to nondepletional induction agents or no induction. The overall incidence of PTLD was 0.46% and differed significantly by induction strategy (p < 0.01): without induction (0.43%), basiliximab (0.38%), daclizumab (0.33%), Thymoglobulin (0.67%) and alemtuzumab (0.37%). Thymoglobulin was associated with significantly increased PTLD risk (p = 0.0025), but alemtuzumab (p = 0.74), basiliximab (p = 0.33) and daclizumab, which trended toward a protective effect (p = 0.06), were not. Alemtuzumab and Thymoglobulin treated patients did not differ in any established parameter affecting PTLD risk although alemtuzumab is known to have a more pronounced B-cell depleting effect. Interestingly, maintenance therapy with an mTOR inhibitor was strongly associated with PTLD (0.71%, p < 0.0001). Thus, depletional induction is not an independent risk factor for PTLD. Rather, maintenance drug selection or perhaps the balance between B- and T-cell depletion may be more relevant determinants of PTLD risk.
Subject(s)
Antibodies, Monoclonal/adverse effects , Antibodies, Neoplasm/adverse effects , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/immunology , Lymphocyte Depletion/methods , Lymphoproliferative Disorders/immunology , Postoperative Complications/immunology , Adolescent , Adult , Alemtuzumab , Antibodies, Monoclonal, Humanized , Child , Drug Therapy, Combination , Follow-Up Studies , Humans , Lymphoproliferative Disorders/chemically induced , Lymphoproliferative Disorders/epidemiology , Postoperative Complications/chemically induced , Time FactorsABSTRACT
UNLABELLED: Infections now exceed rejection as a cause of hospitalization in the first 2 years post-renal transplantation. We analyzed data from the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) to determine risks for hospitalization for infection (HI), either bacterial (HBI) or viral (HVI). 3106 children transplanted between 1996 and 2002 with 2-year follow-up were analyzed. Univariate and multivariate logistic regression analyses identified factors for cause-specific hospitalization. RESULTS: 23.4% experienced HBI, 23.9% HVI; 8.9% were hospitalized for both. Children 0-1 years age at transplant had higher rates of HI (64.2%), HBI (40.3%) and HVI (43.3%) compared to >12 years (31%, 17.5% and 18.9%, p < 0.0001). In comparison to no induction, patients receiving monoclonal or polyclonal antibody were more likely to have HI (>42% vs. 34.0%), HBI (>24% vs. 21%) or HVI (>29% vs. 21%, all p < 0.003) but had equivalent graft survival (p = NS). Higher rates of HI, HBI and HVI were also seen with prophylactic antimicrobial use and with >5 transfusions pretransplant. Since antibody induction in recent era was not associated with better graft or patient survival but was associated with more HI and HVI, the need for routine antibody induction in children needs to be reassessed.
Subject(s)
Antibodies/adverse effects , Bacterial Infections/epidemiology , Immunosuppression Therapy/adverse effects , Kidney Transplantation , Postoperative Complications/epidemiology , Virus Diseases/epidemiology , Antibodies/administration & dosage , Bacterial Infections/prevention & control , Child , Child, Preschool , Female , Hospitalization/statistics & numerical data , Humans , Infant , Infant, Newborn , Male , Postoperative Complications/prevention & control , Risk Factors , United States/epidemiology , Virus Diseases/prevention & controlABSTRACT
We previously showed that children are more likely to develop viral infections post-kidney transplant while adults are more likely to develop bacterial infections. In this study we determined the overall risk factors for hospitalization with either a bacterial (HBI) or a viral infection (HVI). We analyzed data from 28 924 United States Renal Data System (USRDS) Medicare primary renal transplant recipients from January 1996 to July 2000, for adjusted hazard ratio (AHR) for HBI or HVI in the first 3 years posttransplant. For HVI, significantly higher AHR was seen with (a) recipient age <18 years (AHR 1.57, 95% CI = 1.02, 2.42), (b) donor CMV positive (AHR 1.72, 95% CI = 1.34, 2.19). For HBI, significantly higher AHR was seen with (i) delayed graft function (AHR 1.28, 95% CI = 1.076, 1.518), (ii) primary renal diagnosis chronic pyelonephritis (AHR 1.71, 95% CI = 1.18, 2.49); (iii) associated pretransplant diabetes (AHR 1.80, 95% CI = 1.53, 2.12); (iv) female gender AHR 1.63, 95% CI = 1.41, 1.88). Lower AHR for HVI was seen in CMV-positive recipients and for HBI with more recent year of transplant. Other covariates did not impact significantly in either HVI or HBI.
Subject(s)
Bacterial Infections/epidemiology , Kidney Transplantation , Postoperative Complications/epidemiology , Virus Diseases/epidemiology , Adolescent , Adult , Bacterial Infections/prevention & control , Female , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Risk Factors , United States/epidemiology , Virus Diseases/prevention & controlSubject(s)
Escherichia coli Infections/diagnosis , Nephritis/diagnosis , Polycystic Kidney, Autosomal Dominant/diagnosis , Adolescent , Citrates , Escherichia coli Infections/complications , Escherichia coli Infections/diagnostic imaging , Female , Gallium , Humans , Magnetic Resonance Imaging , Nephritis/complications , Nephritis/diagnostic imaging , Polycystic Kidney, Autosomal Dominant/complications , Polycystic Kidney, Autosomal Dominant/diagnostic imaging , Radionuclide Imaging , RadiopharmaceuticalsABSTRACT
Epstein-Barr virus (EBV) infection can cause diverse renal manifestations ranging from microscopic hematuria to acute renal failure. Membranous nephropathy (MN) is an uncommon and usually secondary cause of nephrotic syndrome in children, and has been reported after chronic infections and antigenemia. We report two pediatric cases of secondary MN associated with acute and chronic systemic EBV infection. Patient 1 had a liver transplant for cirrhosis due to biliary atresia and developed chronic EB viremia. Membranous nephropathy occurred 3 years later and with aggressive therapy has partially subsided, in temporal association with a drop in blood EBV PCR levels. The other patient had a primary immunodeficiency and developed a lymphoproliferative disorder attributed to EBV. Nephrotic syndrome developed at initial presentation and was associated with MN on biopsy. The patient cleared the virus from blood, which was associated with eventual resolution of the MN. We postulate that EB viremia in patients lacking a fully competent immune system, but without a renal allograft, may create a susceptible environment for chronic systemic EB antigenemia that can then lead to immune-complex MN in the kidney. The association of EBV with renal histological changes consistent with MN has been suggested but not directly described before.