Younger Age and Antibody Induction Increase the Risk for Infection in Pediatric Renal Transplantation: A NAPRTCS Report

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.     

肝移植术后早期肺部细菌感染的危险因素分析

目的 分析原位肝移植术后早期肺部细菌感染的发生情况及其危险因素。方法 回顾性分析笔者所在医院2010年1月至2012年6月期间行下腔静脉逆灌注法原位肝移植术的96例终末期肝病患者的临床资料。采用多因素非条件logistic回归分析探索肝移植术后早期肺部细菌感染的危险因素。结果 96例患者中有29例于肝移植术后早期发生肺部细菌感染,感染率为30.21%,其中感染G-需氧菌19例（65.52%）,感染G＋需氧菌10例（34.48%）。患者的术前终末期肝病模型评分（OR=2.165,P=0.001）、术中输血量（OR=1.952,P=0.003）、术后3 d血肌酐平均值（OR=1.913,P=0.001）、术后3 d液体负平衡时间（OR=0.196,P=0.023）及术后住院时间（OR=1.923,P=0.003）均与术后早期肺部细菌感染有关。结论 原位肝移植术后早期易发生肺部细菌感染。术前改善患者基础状况、术中控制输血量、术后控制输液量和住院时间及术后改善肾功能均可减少术后早期肺部细菌感染的发生。     

Mycoplasma hominis Septic Arthritis in a Pediatric Renal Transplant Recipient: Case Report and Review of the Literature

Septic arthritis (SA) typically occurs in young children, often from Staphylococcus. With chronic immunosuppression, however, pathogens may be atypical. A 15-year-old African-American female developed Mycoplasma hominis SA in her right hip 2 months following cadaveric renal transplant (Tx). Her presentation was subtle and indolent, without fever or leukocytosis. Although reported in adult Tx recipients, M. hominis infections have not been described in pediatric recipients. Early immunosuppression (basiliximab, prednisone, tacrolimus, mycophenolate mofetil and Thymoglobulin) may have increased her susceptibility to M. hominis. Optimal therapy for M. hominis SA is not well established and relapses occur. This patient underwent joint incision and drainage, treatment for 8 weeks with doxycycline and levofloxacin guided by in vitro sensitivities, and a reduction in immunosuppression. She has been free of ongoing infection for 3 years with stable graft function (Cr 1.1 mg/dL) on moderate immunosuppression with prednisone, tacrolimus and MMF.     

Transplantation of Kidneys from Donors at Increased Risk for Blood-Borne Viral Infection: Recipient Outcomes and Patterns of Organ Use

Kidney transplantation from deceased donors classified as increased risk for viral infection by the Centers for Disease Control (CDC) is controversial. Analyses of Organ Procurement and Transplantation Network (OPTN) data from 7/1/2004 to 7/1/2006 were performed. The primary cohort included 48 054 adults added to the kidney transplant wait list. Compared to receiving a standard criteria donor (SCD) kidney or remaining wait-listed, CDC recipients (HR 0.80, p = 0.18) had no significant difference in mortality. In a secondary cohort of 19 872 kidney recipients at 180 centers, SCD (reference) and CDC (HR 0.91, p = 0.16) recipients had no difference in the combined endpoint of allograft failure or death. Among centers performing >10 kidney transplants during the study period, the median proportion of CDC transplants/total transplants was 7.2% (range 1.1–35.6%). Higher volume transplant centers were more likely to use CDC kidneys compared to low and intermediate volume centers (p < 0.01). An analysis of procured kidneys revealed that 6.8% of SCD versus 7.8% of CDC (p = 0.13) kidneys were discarded. In summary, center use of CDC kidneys varied widely, and recipients had good short-term outcomes. OPTN should collect detailed data about long-term outcomes and recipient viral testing so the potential risks of CDC kidneys can be fully evaluated.     

Adenovirus Disease after Kidney Transplantation: Course of Infection and Outcome in Relation to Blood Viral Load and Immune Recovery

Information on the clinical spectrum and management of adenovirus infection after kidney transplantation is limited. From April 2007 to April 2010, 17 kidney transplant recipients were diagnosed with adenovirus disease. The median time to infection was 5 (range, 2–300) weeks after transplantation. Of the 17 patients, 13 (76.5%) presented early, within 3 months posttransplant, and four (23.5%) presented late, more than 3 months after transplant. Besides urinary tract, involvement of other organs was common (63.6%) among patients with adenovirus viremia. Despite reduction of immunosuppression, six patients subsequently had a rise in the level of blood viral load, mostly within a week after diagnosis. However, only three (27.3%) patients with early infection developed disease progression. Compared to the late infection group, patients with early infection had significantly lower absolute lymphocyte counts at week 1 (p = 0.01) and 3 (p = 0.002) after diagnosis. Four patients received intravenous cidofovir. At 6‐month follow‐up, 10 (90.9%) patients had reversible graft dysfunction. Only one (5.7%) died from bacterial sepsis. Adenovirus disease is a significant complication following kidney transplantation. Early case recognition with reduction of immunosuppression is critical. Serial blood adenovirus viral loads and assessment of lymphocyte recovery are also useful in monitoring the course of infection.     

肾移植术后深部真菌感染10例报告

１９９１年１月－１９９３年１２月我所３３１例肾移植患者中发生深部真菌感染１０例，其中９例为念珠菌感染，１例为曲霉菌感染。经咪康唑或大扶康的正规治疗后，除１例发展为真菌性败血症死亡外，余９例感染治愈，但有３例移植肾因此丧失功能。我们认为肾移植术后应重视深部真菌感染问题，抗真菌药物以大扶康的首选。     

Monitoring of Immunoglobulin Levels Identifies Kidney Transplant Recipients at High Risk of Infection

We aimed to analyze the incidence, risk factors and impact of hypogammaglobulinemia (HGG) in 226 kidney transplant (KT) recipients in which serum immunoglobulin (Ig) levels were prospectively assessed at baseline, month 1 (T₁), and month 6 (T₆). The prevalence of IgG HGG increased from 6.6% (baseline) to 52.0% (T₁) and subsequently decreased to 31.4% (T₆) (p < 0.001). The presence of IgG HGG at baseline (odds ratio [OR] 26.9; p = 0.012) and a positive anti‐HCV status (OR 0.17; p = 0.023) emerged as risk factors for the occurrence of posttransplant IgG HGG. Patients with HGG of any class at T₁ had higher incidences of overall (p = 0.018) and bacterial infection (p = 0.004), bacteremia (p = 0.054) and acute pyelonephritis (p = 0.003) in the intermediate period (months 1–6). Patients with HGG at T₆ had higher incidences of overall (p = 0.004) and bacterial infection (p < 0.001) in the late period (>6 month). A complementary log–log model identified posttransplant HGG as an independent risk factor for overall (hazard ratio [HR] 2.03; p < 0.001) and bacterial infection (HR 2.68; p < 0.0001). Monitoring of humoral immunity identifies KT recipients at high risk of infection, offering the opportunity for preemptive immunoglobulin replacement therapy.     

Incidence, Clinical Characteristics and Risk Factors of Late Infection in Solid Organ Transplant Recipients: Data from the RESITRA Study Group

Information describing the incidence and clinical characteristics of late infection (LI) in solid organ transplantation (SOT) is scarce. The aim of this study was to define the incidence, clinical characteristics and risk factors for LI (>6 months) as compared with infection in the early period (<6 months) after SOT. By the online database of the Spanish Network of Infection in Transplantation (RESITRA) we prospectively analyzed 2702 SOT recipients from September 2003 to February 2005. Univariate and multivariate analysis using logistic regression were performed to calculate the risk factors associated with the development of LI. A total of 131 patients developed 176 LI episodes (8%). Global incidence of LI was 0.4 per 1000 transplant-days, ranging from 0.3/1000 in kidney transplants to 1.4 in lung transplants. Independent risk factors for LI in were: acute rejection in the early period (OR 1.5; CI 95%: 1.1-2.3), chronic graft malfunction (OR 2; CI 95%: 1.4-3), re-operation (OR 1.9; CI 95%: 1.3-2.8) relapsing viral infection apart from CMV (OR 1.9; CI 95%: 1.1-3.5), previous bacterial infection (OR 1.8; CI 95%: 1.2-2.6) and lung transplantation (OR 4.5; CI 95%: 2.6-7.8). Severe LI occurs in a subgroup of high-risk SOT recipients who deserve a more careful follow-up and could benefit from prolonged prophylactic measures similar to that performed in the early period after transplantation.     

A Prospective Randomized Trial of Steroid-Free Maintenance Regimens in Kidney Transplant Recipients—An Interim Analysis

We compared three maintenance immunosuppressive regimens in a rapid discontinuation of prednisone protocol. From March 1, 2001, through December 31, 2003, 239 first and second kidney transplant recipients (166 LD; 73 DD) were randomized. All recipients were treated with Thymoglobulin; all received steroids intraoperatively and for 5 days postoperatively. Randomization was to cyclosporine-mycophenolate mofetil (n = 85); high-level tacrolimus (TAC) (8-12 ng/mL)-low-level sirolimus (SRL) (3-7 ng/mL) (n = 72); or low-level TAC (3-7 ng/mL)-high-level SRL (8-12 ng/mL) (n = 82). We found no difference at 24 months between groups in patient, graft, death-censored graft, or acute rejection-free graft survival, or in kidney function. Wound complications were more common in SRL-treated recipients (p = 0.02); we found no other differences between groups in complication rates. Our data suggest that excellent patient and graft survival and low rejection rates can be obtained using a variety of maintenance protocols without prednisone.     

A Retrospective Analysis of Ezetimibe Treatment in Renal Transplant Recipients

A retrospective review was conducted to determine the safety and efficacy of ezetimibe as a treatment option for renal transplant recipients. We evaluated the medical records of 34 adult renal transplant recipients receiving ezetimibe as monotherapy or combination therapy. Fasting lipid profiles were obtained at baseline and at 1-6 months post-ezetimibe initiation. Twenty patients received cyclosporine, 12 patients received tacrolimus, 1 patient received either sirolimus or no calcineurin therapy at the time of ezetimibe initiation. Monotherapy was started in 8 patients, who had all previously failed statins, and combination therapy was utilized in 26 patients. Monotherapy or combination therapy resulted in a mean reduction in total cholesterol of 23.3%, triglycerides 40.2%, low-density lipoproteins 16.8% and high-density lipoproteins 4.8% after 3.1 months of therapy. Ezetimibe as combination or monotherapy is a safe and effective treatment option for dyslipidemia in renal transplant recipients without changes in calcineurin inhibitor levels or renal function.     

HLA Mismatching Increases the Risk of BK Virus Nephropathy in Renal Transplant Recipients

BK virus (BKV) nephropathy is a serious complication in kidney transplant recipients that may lead to irreversible graft failure. We have analyzed the degree of donor/recipient HLA compatibility and HLA antigen association in 40 kidney transplant patients with BKV nephropathy in comparison with a control group of 404 unaffected transplant recipients who were on tacrolimus-based immunosuppression with no induction. HLA compatibility was assessed by determining the number of HLA-A, -B, -DR-mismatched antigens. BK virus nephropathy was diagnosed histologically and confirmed by immunochemistry. Univariate and multiple logistic regression statistical analyses have shown a significant association between BKV nephropathy and HLA mismatching. This analysis showed also that BKV nephritis is associated with a greater number of rejection episodes and a higher incidence of steroid-resistant rejection requiring antilymphocyte treatment. There was no association between BKV nephropathy and any specific HLA allele. We propose that HLA mismatching promotes the development of BKV nephropathy through rejection-related inflammatory processes and heavy immunosuppression which cause virus reactivation and injury of the tubular epithelium.     

Risk of End‐Stage Renal Disease Among Liver Transplant Recipients With Pretransplant Renal Dysfunction

Guidelines recommend restricting simultaneous liver–kidney (SLK) transplant to candidates with prolonged dialysis or estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m² for 90 days. However, few studies exist to support the latter recommendation. Using Scientific Registry of Transplant Recipients and Medicare dialysis data, we assembled a cohort of 4997 liver transplant recipients from February 27, 2002–January 1, 2008. Serial eGFRs were calculated from serum creatinines submitted with MELD reports. We categorized recipients by eGFR patterns in the 90 days pretransplant: Group 1 (eGFR always >30), Group 2 (eGFR fluctuated), Group 3 (eGFR always <30) and Group 4 (short‐term dialysis). For Group 2, we characterized fluctuations in renal function using time‐weighted mean eGFR. Among liver‐alone recipients in Group 3, the rate of end‐stage renal disease (ESRD) by 3 years was 31%, versus <10% for other groups (p < 0.001). In multivariable Cox regression, eGFR Group, diabetes (HR 2.65, p < 0.001) and black race (HR 1.83, p = 0.02) were associated with ESRD. Among liver‐alone recipients in Group 2, only diabetics with time‐weighted mean eGFR <30 had a substantial ESRD risk (25.6%). In summary, among liver transplant candidates not on prolonged dialysis, SLK should be considered for those whose eGFR is always <30 and diabetic candidates whose weighted mean eGFR is <30 for 90 days.     

Relationship Among Viremia/Viral Infection,Alloimmunity, and Nutritional Parameters in the First Year After Pediatric Kidney Transplantation

The Immune Development in Pediatric Transplantation (IMPACT) study was conducted to evaluate relationships among alloimmunity, protective immunity, immune development, physical parameters, and clinical outcome in children undergoing kidney transplantation. We prospectively evaluated biopsy‐proven acute rejection (BPAR), de novo donor‐specific antibody (dnDSA) formation, viremia, viral infection, T cell immunophenotyping, and body mass index (BMI)/weight Z scores in the first year posttransplantation in 106 pediatric kidney transplant recipients. Outcomes were excellent with no deaths and 98% graft survival. Rejection and dnDSAs occurred in 24% and 22%, respectively. Pretransplant cytomegalovirus (CMV) and Epstein–Barr virus (EBV) serologies and subsequent viremia were unrelated to BPAR or dnDSA. Viremia occurred in 73% of children (EBV, 34%; CMV, 23%; BMK viremia, 23%; and JC virus, 21%). Memory lymphocyte phenotype at baseline was not predictive of alloimmune complications. Patients who developed viral infection had lower weight (?2.1) (p = 0.028) and BMI (?1.2) (p = 0.048) Z scores at transplantation. The weight difference persisted to 12 months compared with patients without infection (p = 0.038). These data indicate that there is a high prevalence of viral disease after pediatric kidney transplantation, and underweight status at transplantation appears to be a risk factor for subsequent viral infection. The occurrence of viremia/viral infection is not associated with alloimmune events.