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1.
J Fish Biol ; 83(1): 28-38, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23808690

ABSTRACT

As part of the SERPENT Project, five observations of apparently healthy oarfish Regalecus glesne by remotely operated vehicles are reported from the northern Gulf of Mexico. Regalecus glesne were observed between 2008 and 2011 at depths from within the epipelagic and mesopelagic zones. These observations include the deepest verified record of R. glesne (463-492 m) and the first record of an arthropod ectoparasite (isopod).


Subject(s)
Fishes , Animals , Gulf of Mexico , Robotics
2.
Am J Transplant ; 12(10): 2710-8, 2012 Oct.
Article in English | MEDLINE | ID: mdl-23009139

ABSTRACT

Monitoring of renal graft status through peripheral blood (PB) rather than invasive biopsy is important as it will lessen the risk of infection and other stresses, while reducing the costs of rejection diagnosis. Blood gene biomarker panels were discovered by microarrays at a single center and subsequently validated and cross-validated by QPCR in the NIH SNSO1 randomized study from 12 US pediatric transplant programs. A total of 367 unique human PB samples, each paired with a graft biopsy for centralized, blinded phenotype classification, were analyzed (115 acute rejection (AR), 180 stable and 72 other causes of graft injury). Of the differentially expressed genes by microarray, Q-PCR analysis of a five gene-set (DUSP1, PBEF1, PSEN1, MAPK9 and NKTR) classified AR with high accuracy. A logistic regression model was built on independent training-set (n = 47) and validated on independent test-set (n = 198)samples, discriminating AR from STA with 91% sensitivity and 94% specificity and AR from all other non-AR phenotypes with 91% sensitivity and 90% specificity. The 5-gene set can diagnose AR potentially avoiding the need for invasive renal biopsy. These data support the conduct of a prospective study to validate the clinical predictive utility of this diagnostic tool.


Subject(s)
Graft Rejection/diagnosis , Kidney Transplantation , Acute Disease , Graft Rejection/blood , Humans , Polymerase Chain Reaction , Sensitivity and Specificity
3.
Am J Transplant ; 12(10): 2730-43, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22694733

ABSTRACT

Steroid avoidance is safe and effective in children receiving kidney transplants in terms of graft function and survival, but the effects on allograft histology are unknown. In this multicenter trial, 130 pediatric renal transplant recipients were randomized to steroid-free (SF; n = 60) or steroid-based (SB; n = 70) immunosuppression, and underwent renal allograft biopsies at the time of graft dysfunction and per protocol at implantation and 6, 12 and 24 months after transplantation. Clinical follow-up was 3 years posttransplant. Subclinical acute rejection was present in 10.6% SF versus 11.3% SB biopsies at 6 months (p = 0.91), 0% SF versus 4.3% SB biopsies at 1 year (p = 0.21) and 0% versus 4.8% at 2 years (p = 0.20). Clinical acute rejection was present in 13.3% SF and 11.4% SB patients by 1 year (p = 0.74) and in 16.7% SF and 17.1% SB patients by 3 years (p = 0.94) after transplantation. The cumulative incidence of antibody-mediated rejection was 6.7% in SF and 2.9% in SB by 3 years after transplantation (p = 0.30). There was a significant increase in chronic histological damage over time (p < 0.001), without difference between SF and SB patients. Smaller recipient size and higher donor age were the main risk factors for chronic histological injury in posttransplant biopsies.


Subject(s)
Kidney Transplantation/adverse effects , Steroids/administration & dosage , Adolescent , Child , Female , Graft Rejection , Humans , Immunosuppressive Agents/administration & dosage , Male
4.
Am J Transplant ; 12(10): 2719-29, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22694755

ABSTRACT

To determine whether steroid avoidance in pediatric kidney transplantation is safe and efficacious, a randomized, multicenter trial was performed in 12 pediatric kidney transplant centers. One hundred thirty children receiving primary kidney transplants were randomized to steroid-free (SF) or steroid-based (SB) immunosuppression, with concomitant tacrolimus, mycophenolate and standard dose daclizumab (SB group) or extended dose daclizumab (SF group). Follow-up was 3 years posttransplant. Standardized height Z-score change after 3 years follow-up was -0.99 ± 2.20 in SF versus -0.93 ± 1.11 in SB; p = 0.825. In subgroup analysis, recipients under 5 years of age showed improved linear growth with SF compared to SB treatment (change in standardized height Z-score at 3 years -0.43 ± 1.15 vs. -1.07 ± 1.14; p = 0.019). There were no differences in the rates of biopsy-proven acute rejection at 3 years after transplantation (16.7% in SF vs. 17.1% in SB; p = 0.94). Patient survival was 100% in both arms; graft survival was 95% in the SF and 90% in the SB arms (p = 0.30) at 3 years follow-up. Over the 3 year follow-up period, the SF group showed lower systolic BP (p = 0.017) and lower cholesterol levels (p = 0.034). In conclusion, complete steroid avoidance is safe and effective in unsensitized children receiving primary kidney transplants.


Subject(s)
Immunosuppressive Agents/administration & dosage , Kidney Transplantation , Steroids/administration & dosage , Adolescent , Adult , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Male , Young Adult
5.
Am J Transplant ; 11(4): 751-8, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21446977

ABSTRACT

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 Outcome
6.
Am J Transplant ; 10(1): 81-8, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19663893

ABSTRACT

In an effort to reduce rejection, extend allograft survival and minimize complications, we hypothesized that robust immunosuppression during the first 6 months after transplantation would allow for the safe withdrawal of steroids. A total of 274 pediatric subjects were enrolled and received an anti-CD25 antibody, sirolimus, calcineurin inhibitor and steroids. At 6 months after transplantation, subjects were randomized to steroid withdrawal (n=73) versus continued low-dose steroids (n=59). This study was stopped prior to target enrollment because of the incidence of post-transplant lymphoproliferative disorder. At the time of study termination, 132 subjects had been randomized and were available for analysis. At 18 months after transplantation, there was no difference in the standardized height z score; however, the standardized height velocity was greater in the steroid withdrawal group compared to the control group (p=0.033). There were no differences in acute rejection episodes between treatment groups. The 3-year allograft survival rate was 84.5% in the control group and 98.6% in the steroid withdrawal group (p=0.002). The immunosuppressive protocol utilized in this study allowed for the withdrawal of steroids without an increased risk of rejection or allograft loss. However, the complications associated with the use of this immunosuppressive protocol were too high to recommend its routine use in pediatric patients.


Subject(s)
Adrenal Cortex Hormones/administration & dosage , Immunosuppressive Agents/administration & dosage , Kidney Transplantation/methods , Acute Disease , Adolescent , Adrenal Cortex Hormones/adverse effects , Adrenal Cortex Hormones/therapeutic use , Body Height/drug effects , Child , Child, Preschool , Double-Blind Method , Female , Graft Rejection/prevention & control , Graft Survival/drug effects , Humans , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Infant , Kidney Transplantation/adverse effects , Kidney Transplantation/physiology , Lymphoproliferative Disorders/etiology , Male , Risk Assessment , Time Factors , Young Adult
7.
Am J Transplant ; 8(4 Pt 2): 935-45, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18336697

ABSTRACT

This article represents the sixth annual review of the current state of pediatric transplantation in the United States from the Scientific Registry of Transplant Recipients (SRTR). It presents updated trends, discussion of analyses presented during the year by the SRTR to the committees of the Organ Procurement and Transplantation Network (OPTN) and discussion of important issues currently facing pediatric organ transplantation. Unless otherwise stated, the statistics in this article are drawn from the reference tables of the 2007 OPTN/SRTR Annual Report. In this article, pediatric patients are defined as candidates, recipients or donors aged 17 years or less. Data for both graft and patient survival are reported as unadjusted survival, unless otherwise stated (adjusted patient and graft survival are available in the reference tables). Short-term survival (3 month and 1 year) reflects outcomes for transplants performed in 2004 and 2005; 3-year survival reflects transplants from 2002 to 2005; and 5-year survival reports on transplants performed from 2000 to 2005. Details on the methods of analysis employed may be found in the reference tables themselves or in the technical notes of the 2007 OTPN/SRTR Annual Report, both available online at http://www.ustransplant.org.


Subject(s)
Transplantation/statistics & numerical data , Adolescent , Adult , Child , Child, Preschool , Follow-Up Studies , Heart Transplantation/statistics & numerical data , Humans , Intestines/transplantation , Kidney Transplantation/statistics & numerical data , Liver Transplantation/statistics & numerical data , Middle Aged , Patient Selection , Registries , Survival Analysis , Time Factors , Tissue Donors/statistics & numerical data , Transplantation/trends , United States , Waiting Lists
9.
Int J Artif Organs ; 30(12): 1116-21, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18203074

ABSTRACT

PURPOSE: Well-functioning vascular access is essential for the provision of adequate CRRT. However, few data exist to describe the effect of catheter size or location on CRRT performance in the pediatric population. METHODS: Data for vascular access site, size, and location, as well as type of anticoagulant used and patient demographic data were gathered from the ppCRRT registry. Kaplan-Meier curves were generated and then analyzed by log-rank test or Cox Proportional Hazards model. RESULTS: Access diameter was found to significantly affect circuit survival. None of the 5 French catheters lasted longer than 20 hours. Seven and 9 French, but not 8 French, catheters fared worse than larger diameter catheters (p=0.002). Circuits associated with internal jugular access survived longer than subclavian or femoral access associated circuits (p<0.05). Circuit survival was also found to be favorably associated with the CVVHD modality (p<0.001). CONCLUSIONS: Functional CRRT circuit survival in children is favored by larger catheter diameter, internal jugular vein insertion site and CVVHD. For patients requiring catheter diameters less than 10 French, CRRT circuit survival might be optimized if internal jugular vein insertion is feasible. Conversely, when a vascular access site other than the internal jugular vein is most prudent, consideration should be given to using the largest diameter catheter appropriate for the size of the child. The CVVHD modality was associated with longer circuit survival, but the mechanism by which this occurs is unclear.


Subject(s)
Catheterization, Central Venous , Catheterization, Peripheral , Hemofiltration , Kidney Failure, Chronic/therapy , Registries , Renal Dialysis , Adolescent , Adult , Catheters, Indwelling , Child , Child, Preschool , Cohort Studies , Humans , Infant , Infant, Newborn , Proportional Hazards Models , United States
10.
Pediatr Transplant ; 6(1): 69-77, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11906646

ABSTRACT

African-American race is associated with an increased risk of allograft loss, suggesting that African-American patients may form an immunologically higher risk group. Previously, we demonstrated that immune cell costimulatory molecule expression is significantly higher in African-Americans than in Caucasians. Polymorphic variations in the genes for cytokines have been associated with a number of immunological conditions, and with transplant rejection. This study was performed to determine the distribution, in African-American and Caucasian renal transplant recipients, of single nucleotide polymorphisms (SNPs) in the following cytokine genes: tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin (IL)-6, IL-10, and transforming growth factor-beta (TGF-beta). Cytokine production from blood cells was determined, and cell-surface B7 (CD80, CD86) expression was measured. There was a significant link between IL-10 genotype and acute rejection episodes, but only in African-American patients (p < 0.01). Also, African-American patients had a significantly higher probability of having the IL-6 G-allele (p < 0.0001), which is associated with a high production of IL-6 protein. Incubation of blood cells with IL-6 resulted in increased expression of surface CD80 and CD86, while IL-10 decreased CD80 expression. This study demonstrated a clear correlation of the IL-6 G-allele with increased cellular CD80 expression and the IL-10 G-allele with decreased CD80 expression. These data raise the possibility that specific genotypes are associated with local cytokine regulation of cell-surface costimulatory molecule expression. African-American patients may have a genetically determined, quantitatively different immune response than Caucasian patients, contributing to adverse transplant outcomes.


Subject(s)
Black People/genetics , Cytokines/genetics , Graft Rejection/genetics , Kidney Transplantation/methods , Nucleotides/genetics , Polymorphism, Genetic , Adult , Alleles , Case-Control Studies , Child , Child, Preschool , Female , Flow Cytometry , Genotype , Graft Survival , Humans , Male , Prognosis , Prospective Studies , Risk Assessment , Transplantation, Homologous
11.
Transplantation ; 71(5): 692-5, 2001 Mar 15.
Article in English | MEDLINE | ID: mdl-11292304

ABSTRACT

BACKGROUND: The issue of racial differences in immune responses has been seldom investigated, despite the increased incidence of transplant rejection and inferior allograft outcomes in African-Americans (AA). We previously reported significantly increased expression of costimulatory molecules on peripheral blood cells from healthy adult AA compared with Caucasian (CS) volunteers. This report extends the study to pediatric kidney allograft recipients. METHODS: Surface antigen expression by peripheral blood mononuclear cells (MNC) from AA and CS transplant patients was determined by flow cytometry, after staining with specific antibodies. In vitro proliferation, in a one-way mixed lymphocyte response (MLR), was measured after stimulation with allogeneic irradiated mononuclear cells. The concentration of cyclosporine (CsA) achieving 50% inhibition (IC50) of in vitro proliferative responses to PHA and OKT3 was calculated. RESULTS: MNC from AA patients were shown to have significantly higher expression of CD80 (CS 5.2% +/- 0.6, AA 9.6% +/- 1.2, P < 0.0001) than cells from CS patients. Additionally, the cells from AA transplant recipients proliferated significantly more in an MLR (stimulation index: CS 8 +/- S2, AA 25 +/- 8, P < 0.05), and the CsA IC50 values, during proliferation to PHA and OKT3, were significantly higher in AA compared to CS patients. CONCLUSIONS: Although socioeconomic factors and therapeutic compliance are undoubtedly important issues in long-term allograft survival, our data suggest that AA patients mount more vigorous immune responses to antigens. The increased requirement for immunosuppression may be linked to racial variations in costimulatory molecule expression on antigen-presenting cells.


Subject(s)
Antigens, CD/blood , Black People , HLA-DR Antigens/blood , Kidney Transplantation/immunology , Adolescent , Adult , Black or African American , Cell Division/drug effects , Cells, Cultured , Child , Child, Preschool , Cyclosporine/pharmacology , Female , Humans , Immunosuppressive Agents/pharmacology , Lymphocyte Culture Test, Mixed , Male , Monocytes/immunology , Transplantation, Homologous , White People
12.
Transplantation ; 70(7): 1107-10, 2000 Oct 15.
Article in English | MEDLINE | ID: mdl-11045652

ABSTRACT

In an attempt to identify potential markers of steroid-resistance in focal segmental glomerulosclerosis (FSGS) we evaluated intra-graft gene expression of IkappaBalpha, nuclear factor-kappaB (NF-kappaB), and angiotensinogen in 60 biopsies from 27 pediatric renal transplant recipients. Intra-graft NF-kappaB expression was significantly elevated in recurrent FSGS (R-FSGS) (218.3 + 55.6 ag/fg versus NON-FSGS 121.1 + 19.9, P=0.04) but not in acute rejection. NF-kappaB:IkappaBalpha ratios were higher in cadaveric donor versus living related donor recipients (15.7 + 2.8 vs. 8.8 + 1.3, respectively, P=0.015), and in African-American versus Caucasian recipients (15.6 + 2.9 vs. 9.1 + 1.3, respectively, P=0.03). Intra-graft angiotensinogen gene expression was significantly elevated in R-FSGS (30.5 + 8.8 ag/fg R-FSGS vs. 16.0 + 4.7 NON-FSGS, P=0.009). We conclude that increased NF-kappaB and angiotensinogen gene expression are associated with R-FSGS. Increased NF-kappaB:IkappaBalpha ratios are associated with cadaveric donor recipients and African-American race.


Subject(s)
Angiotensinogen/genetics , Glomerulosclerosis, Focal Segmental/genetics , NF-kappa B/genetics , Adolescent , Child , Child, Preschool , Gene Expression , Humans , Kidney Transplantation/adverse effects , Postoperative Complications/etiology , Postoperative Complications/metabolism , Recurrence
13.
Clin Exp Immunol ; 118(2): 247-52, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10540186

ABSTRACT

Despite the increased incidence and severity of many autoimmune diseases and transplant rejection in African-Americans (AA) compared with Caucasians (CS), very few studies have addressed issues of racial variation during antigen presentation. This investigation was performed as a preliminary exploration of differences in peripheral blood cell costimulatory functions between healthy AA (n = 20) and CS (n = 20) subjects. The expression of surface costimulatory molecules on peripheral blood cells, mononuclear cells enriched by Ficoll density centrifugation, and plastic adherent antigen-presenting cells (APC) was determined by flow cytometry using fluorescent-labelled MoAbs. The expression of both B7 costimulatory molecules was significantly higher on the cells from AA subjects compared with cells from CS subjects (CD80, P < 0.05; CD86, P < 0.05). Also, following 18 h of culture with rhIL-1beta, there was a significant increase in the percentage of APC from AA expressing high levels of the costimulatory molecule CD80 (P < 0.05). Costimulatory function during mitogen and antigen presentation was determined by 3H-thymidine incorporation during T cell proliferation. Purified T cells from AA subjects demonstrated significantly increased proliferation to phytohaemagglutinin (PHA). The differences reported here suggest that racial variations in peripheral blood APC characteristics may exist. Given the importance of costimulation in maintaining long-term immune responses, these data suggest a further direction for the investigation of racial disparity in autoimmune disease pathology and transplant rejection rates.


Subject(s)
Antigen-Presenting Cells/metabolism , Antigens, CD/biosynthesis , Antigens, CD/blood , B7-1 Antigen/biosynthesis , B7-1 Antigen/blood , Black People , Membrane Glycoproteins/biosynthesis , Membrane Glycoproteins/blood , Adult , B7-2 Antigen , Female , Health Status , Humans , Immunologic Memory/immunology , Leukocytes, Mononuclear/metabolism , Lymphocyte Activation/immunology , Male , Mitogens/immunology , T-Lymphocytes/immunology , United States , Up-Regulation/immunology
14.
Pediatr Transplant ; 3(2): 152-67, 1999 May.
Article in English | MEDLINE | ID: mdl-10389139

ABSTRACT

This report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS), covering the years 1987-96 (January 15, 1997), analyzed data on 4898 patients who received 5362 transplants. Over the 10 yr of the study, 21.3% of the patients were under the age of 6 yr. Of the disorders that lead to end-stage renal disease (ESRD), structural and developmental anomalies of aplasia, dysplasia, and obstructive uropathy accounted for over 1500 patients. Despite the potential therapies for focal segmental glomerulosclerosis (FSGS), there has been little change in its incidence and this lesion continues to be the most common cause of renal failure and transplantation among acquired diseases. Eighty-nine per cent of patients with a functioning graft continue to receive cyclosporin A (CsA) 5 yr post-transplantation, and 84% of patients continue to receive azathioprine (AZA), whereas 26% of patients receive alternate-day steroid therapy at 4 yr post-transplant. Thirty-seven per cent of the living donor (LD) recipients and 47% of cadaver donor (CD) recipients were treated with the polyclonal T-cell antibody ATG/ALG for induction, and the monoclonal T-cell antibody, OKT3, was utilized for induction in 12% of LD patients and in 19% of CD patients. Twenty-five per cent of the 5362 transplants (1333) have failed over the 10-yr period. Graft survival is 90% at 1 yr and 74% at 6 yr for LD kidneys, and is 80% at 1 yr and 58% at 6 yr for CD patients. The most common cause for graft failure (30%) is chronic rejection. For recipients of LD grafts, relative risk (RR) factors for graft survival are African-American race (RR = 2.1, p < 0.001) and greater than five prior transfusions (RR = 1.6, p < 0.001). Prophylactic anti-T-cell antibody reduces the risk of graft failure (RR = 0.76, p = 0.009). For recipients of cadaver kidneys, risk factors are: recipient age < 2 yr (RR = 2, p < 0.001), donor age < 6 yr (RR = 1.3, p = 0.005), and absence of induction T-cell antibody (RR = 1.31, p < 0.001).


Subject(s)
Kidney Diseases/surgery , Kidney Transplantation/statistics & numerical data , Adolescent , Adult , Annual Reports as Topic , Child , Child, Preschool , Female , Graft Rejection , Graft Survival , Humans , Immunosuppression Therapy , Infant , Kidney Diseases/immunology , Kidney Transplantation/immunology , Living Donors , Male , North America , Time Factors
15.
Pediatr Transplant ; 3(1): 27-32, 1999 Feb.
Article in English | MEDLINE | ID: mdl-10359028

ABSTRACT

The North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) data registry has now compiled data for 11 years, and includes data on 6038 renal transplants in 5516 patients. With the availability of new data and immunosuppressive medications, trends in their usage continue to change. NAPRTCS data have previously demonstrated that increased doses of cyclosporin A (CsA) are associated with improved allograft outcomes, and there has been a steady increase in the dose of CsA given post-transplantation. Transplants that occurred in 1987, 1989, 1991, and 1993 received a mean one-year post-transplant dose of 6.5, 7.0, 7.7, and 8.2 mg/kg/d, respectively. In the 1995 cohort, the dose decreased to 7.4 mg/kg/d. Since the introduction of Neoral, its use has steadily increased. Of the 1997 cohort, 81% report Neoral as the formulation of CsA used. The dose of CsA given, however, has not changed. At day 30 post-transplant, the dose was 7.0 mg/kg/d for Sandimmune and 7.4 mg/kg/d for Neoral. Finally, the outcome in black transplant patients is inferior to that of nonblack. Evaluation of CsA blood levels revealed that at 1 year post-transplant, black patients consistently have CsA levels higher than nonblacks, and a lower percentage of black patients have a CsA level < 100 ng/mL. The percentage of patients using triple therapy (prednisone, azathioprine, and CsA) remained stable from 1987 to 1993 at 80-85%. However, in 1996 only 30% of patients were receiving triple therapy. This is probably due to the introduction of mycophenolate mofetil (MMF). Comparing the 1996-97 cohorts, there has been no significant change in the percentage of patients receiving prednisone (96.2% vs. 95.4%) or CsA (83.1% vs. 79.6%). However, during this time, the use of azathioprine has decreased from 50.0% to 35.8%, the use of tacrolimus has increased from 2.5% to 10.8%, and the use of MMF has increased from 6.5% to 35.8%.


Subject(s)
Immunosuppression Therapy/trends , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/immunology , Practice Patterns, Physicians'/trends , Adolescent , Azathioprine/therapeutic use , Child , Child, Preschool , Cyclosporine/therapeutic use , Drug Utilization , Female , Humans , Immunosuppression Therapy/methods , Infant , Infant, Newborn , Male , Mycophenolic Acid/analogs & derivatives , Mycophenolic Acid/therapeutic use , North America , Practice Patterns, Physicians'/statistics & numerical data , Prednisone/therapeutic use , Racial Groups , Registries , Treatment Outcome
16.
Pediatr Transplant ; 3(1): 33-7, 1999 Feb.
Article in English | MEDLINE | ID: mdl-10359029

ABSTRACT

The use of mycophenolate mofetil (MMF) in adult renal transplantation has been associated with significantly decreased incidence of acute rejection. However, limited data are available for children after renal transplantation. A total of 67 patients undergoing renal transplantation at the University of Alabama at Birmingham, AL, USA and Children's Hospital of Boston, MA, USA were enrolled into the Cooperative Clinical Trials in Pediatric Transplantation randomized controlled trial of induction with OKT3 vs. i.v. cyclosporin A (CsA) at the time of transplantation. The first 31 patients entered were begun on azathioprine (AZA), 2 mg/kg on the first post-operative day. The subsequent 36 patients were begun on MMF, 1000 mg/m2/d. Other maintenance immunosuppression included oral CsA and Prednisone. Biopsy confirmation was obtained for all suspected rejection episodes. Glomerular filtration rate (GFR) was calculated using the Schwartz formula. Data were analyzed using Kaplan Meier survival curves and compared using log-rank tests. At the time of analysis, 52 patients (mean age 10.1 +/- 5 yr) had completed at least 12 months and 15 others had completed at least 6 months of follow-up post-transplantation. Of these, there were 39 male/28 female; 48 white/15 black/4 other; 49 living donor/18 cadaver donor. There were no significant differences in the incidence of rejection episodes, number of rejection episodes, the GFR at 6 and 12 months, allograft, or patient survival between patients receiving MMF vs. AZA. We could demonstrate no significant differences in these outcomes based on sex, race or induction therapy, leading to the conclusion that pediatric patients treated under a consistent protocol in two institutions have no improvement in short-term allograft outcome with the addition of MMF therapy.


Subject(s)
Azathioprine/therapeutic use , Cyclosporine/therapeutic use , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/immunology , Muromonab-CD3/therapeutic use , Mycophenolic Acid/analogs & derivatives , Prednisone/therapeutic use , Adolescent , Adult , Child , Drug Therapy, Combination , Female , Follow-Up Studies , Graft Rejection/etiology , Graft Rejection/pathology , Graft Rejection/prevention & control , Graft Survival/drug effects , Humans , Kidney Transplantation/adverse effects , Kidney Transplantation/mortality , Male , Mycophenolic Acid/therapeutic use , Survival Analysis , Treatment Outcome
17.
Pediatr Transplant ; 3(1): 83-7, 1999 Feb.
Article in English | MEDLINE | ID: mdl-10359037

ABSTRACT

Mycophenolate mofetil (MMF) has gained considerable popularity in pediatric renal transplantation. This popularity is largely a result of data from three large trials of MMF in adult cadaveric transplant patients who demonstrated a decreased rate of acute rejection episodes when treated with cyclosporin A (CsA), prednisone, and MMF compared with those receiving CsA, prednisone, and azathioprine (AZA) or placebo. However, the ability of MMF to reduce acute rejection appears to be limited to the first month post-transplant, and its effectiveness with microemulsion CsA or tacrolimus-based regimens has not been proven. In addition, there are currently no data that convincingly demonstrate that this agent improves graft survival, patient survival, graft function or protects against chronic rejection. Finally, there may be an increased risk for severe cytomegalovirus (CMV) disease and lymphoproliferative disorder with central nervous system involvement in patients treated with MMF. These data call into question the role of MMF in current immunosuppressive regimens.


Subject(s)
Graft Rejection/prevention & control , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/immunology , Mycophenolic Acid/analogs & derivatives , Adult , Azathioprine/therapeutic use , Cyclosporine/therapeutic use , Double-Blind Method , Graft Rejection/etiology , Humans , Immunosuppressive Agents/adverse effects , Kidney Transplantation/adverse effects , Mycophenolic Acid/adverse effects , Mycophenolic Acid/therapeutic use , Prednisone/therapeutic use , Randomized Controlled Trials as Topic , Research Design , Risk Factors , Treatment Outcome
18.
Transplantation ; 67(4): 544-7, 1999 Feb 27.
Article in English | MEDLINE | ID: mdl-10071025

ABSTRACT

BACKGROUND: Historically, young children undergoing renal transplantation have lower allograft survival than adults, and potential causes of this are being addressed by the North American Pediatric Renal Transplant Cooperative Study through the National Institutes of Health-sponsored study Cooperative Clinical Trials in Pediatric Transplantation. Included in this study is evaluation of surveillance renal biopsies (SB) and clinically indicated biopsies (CB). Few data exist in children to identify the risk involved with renal transplant biopsies. METHODS: Questionnaires were mailed to 21 participating centers asking for descriptions of adverse events associated with kidney biopsies, with choices limited to none, gross hematuria, perinephric hematoma, and other. Further clinical details were obtained from review of medical records of all patients with reported adverse events. Data were collected from 19 centers on 126 patients. RESULTS: Eighty-six patients had undergone 212 biopsies (75 SB and 137 CB). Nine biopsy-related adverse events were reported (4.2%): three SB (4.0%) and six CB (4.4%). Gross hematuria was reported in six patients (2.8%): two SB (2.7%) and four CB (2.9%). A perinephric hematoma was reported in one patient. Two patients with intraperitoneal kidneys developed significant bleeding after biopsy and required transfusions and surgical exploration. No patient lost kidney function or required nephrectomy after biopsy. No difference was noted in adverse events between SB at day 5 or 12 versus CB. CONCLUSION: Evaluation of transplanted kidney tissue may provide important information for the care of the transplantation patient. This analysis suggests that transplanted kidney biopsies can be performed with minimal risks in pediatric patients.


Subject(s)
Biopsy/adverse effects , Kidney Transplantation , Kidney/pathology , Adolescent , Child , Child, Preschool , Humans , Infant
19.
Pediatr Nephrol ; 12(5): 397-400, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9686959

ABSTRACT

Patients with steroid-resistant focal and segmental glomerulosclerosis (FSGS) have a poor prognosis but may benefit from high-dose methylprednisolone or cyclosporine A therapy. Ten patients were treated with a protocol of methylprednisolone infusions for 8 weeks followed by a combination of cyclosporine A and alternate-day prednisone for maintenance of remission for 2 weeks. Eight of ten patients remitted the nephrotic syndrome within 8 weeks of beginning treatment. One patient remitted edema but remained proteinuric, and one did not respond. After observation for 12-24 months, seven patients maintained remission with normal glomerular filtration rate. One non-responder had renal insufficiency and one patient had secondary non-response and end-stage renal disease. No patients developed hypertension. One patient had the diagnosis of Hodgkin disease made after 10 months of therapy. Follow-up renal biopsy in four patients showed no evidence of progressive interstitial disease. There were no other major side effects. Steroid-resistant FSGS may be successfully treated with the described protocol. Additional studies will be needed to determine if this approach prevents progression of renal disease.


Subject(s)
Anti-Inflammatory Agents/administration & dosage , Cyclosporine/administration & dosage , Glomerulosclerosis, Focal Segmental/drug therapy , Immunosuppressive Agents/administration & dosage , Methylprednisolone/administration & dosage , Prednisone/administration & dosage , Adolescent , Child , Child, Preschool , Drug Therapy, Combination , Female , Humans , Infusions, Intravenous , Male , Treatment Outcome
20.
Pediatr Transplant ; 2(3): 216-23, 1998 Aug.
Article in English | MEDLINE | ID: mdl-10084746

ABSTRACT

Persistent hyperlipidemia and hypercholesterolemia post-transplantation are risk factors for accelerated atherosclerosis. To evaluate the natural history of lipid abnormalities in children post-transplantation, this study utilized a cohort of 29 patients who were all treated with the same three- drug maintenance immunosuppression (cyclosporine, azathioprine, and prednisone) and whose dosing regimen was rigidly controlled. Fasting blood samples were taken monthly to determine lipid profiles measuring total cholesterol (CHOL), triglycerides (TG), high-density lipoprotein cholesterol (HDL), very low density lipoprotein cholesterol (VLDL), and levels of lipoprotein (a) (LP(a)). A mean value was determined for each of five time periods: 0-3 months, 3-6 months, 6-9 months, 9-12 months and 12-15 months post-transplant. A single specimen of fasting lipid profile was drawn from 21 non-immunosuppressed children attending an ambulatory pediatric clinic and used as control. Despite significant reductions in the cyclosporine and prednisone doses post-transplantation, significant reduction in any of the lipid parameters was only noted after the first year. Reductions in the HDL fraction and in the TG level were noted during the 12-15 month period, however the values obtained in the patient population were significantly elevated for CHOL, TG, LDL and VLDL compared to controls. This study, using a fixed protocol, suggests that the lipid profile should be measured at one year post-transplant in all transplant patients, and if subsequent follow-up continues to exhibit abnormally elevated levels of CHOL and LDL, interventional therapy should be considered.


Subject(s)
Cholesterol/blood , Kidney Transplantation/physiology , Lipids/blood , Adolescent , Child , Child, Preschool , Female , Humans , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/immunology , Lipoprotein(a)/blood , Lipoproteins, LDL/blood , Male , Postoperative Period , Time Factors , Triglycerides/blood
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