Adolescent Transition to Adult Care in Solid Organ Transplantation: a consensus conference report.

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.

Outcome after transplantation of young patients with systemic lupus erythematosus: a report of the North American pediatric renal transplant cooperative study.

BACKGROUND: The risk of progressing to end-stage renal disease in children with lupus glomerulonephritis is 18% to 50%. Published reports of transplantation secondary to end-stage renal failure in adult patients with systemic lupus erythematosus (SLE) demonstrate equivalent patient and graft survival. The purpose of this analysis is to compare patient and graft outcomes of pediatric SLE renal transplant recipients with an age-, race-, and gender-matched control group. METHODS: A retrospective analysis of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) database identified 100 renal transplants performed in 94 young SLE patients. A control group of 470 children having received 501 renal transplants was identified. RESULTS: The SLE cohort was primarily female (82%), non-Caucasian (61%), adolescents and differed from the control group in being less likely to be preemptively transplanted, in receiving longer pretransplant dialysis, and in being likely to have received more than five pretransplant transfusions. After transplantation, there were no differences seen in patient survival at 3 years (89% vs. 95%, SLE vs. control) or in overall graft failure rates (31% vs. 29%, SLE vs. control). There was a trend toward poorer graft survival in non-white SLE patients receiving living donor grafts compared with white SLE patients. An increased graft failure rate was seen among those SLE cadaveric transplant recipients receiving peritoneal dialysis before transplant compared with controls and compared with SLE patients receiving hemodialysis. No differences were seen in rates of acute tubular necrosis or overall acute rejection incidence, although there was a significant increase in the percentage of living donor SLE patients who experienced greater than four rejection episodes. There were nonsignificant trends toward increased graft loss due to patient death with a functioning graft as well as increased mortality secondary to infection in the SLE patients. CONCLUSIONS: The results of renal transplantation in young SLE patients are comparable to those seen in an age-, race- and gender-matched control group. The similar patient and graft survival is seen despite the SLE patients having an underlying disease with multiorgan involvement and despite receiving immunosuppression for potentially prolonged periods before transplantation. No outcome differences were seen except for an unexplained increase in the incidence of recurrent rejections (> or =4) in the living donor SLE patients as well as increased graft failure rate in those patients receiving cadaveric renal transplants after a period of peritoneal dialysis. The nonsignificant trends toward increased graft failures in non-white SLE patients receiving living donor grafts, increased graft loss secondary to death with a functioning graft, as well as the increased mortality due to infection deserve recognition and further study.

ANCA-associated crescentic glomerulonephritis with mesangial IgA deposits.

Antineutrophil cytoplasmic autoantibodies (ANCA) are commonly associated with a necrotizing and crescentic glomerulonephritis (GN) that is pauci-immune, with few or no glomerular immune complex deposits detectable by immunofluorescence (IF) or electron microscopy (EM). Immunoglobulin A (IgA) nephropathy may also be manifest as a crescentic GN, but it is characterized by mesangial immune complex deposits containing IgA and is rarely associated with myeloperoxidase (MPO)- or proteinase 3 (PR3)-specific ANCA when an enzyme immunoassay is used to detect these antibodies. This report describes six patients with severe crescentic GN with mesangial IgA deposits by IF and mesangial electron-dense deposits by EM in patients with positive ANCA serological test results (four patients, anti-PR3; one patient, anti-MPO; one patient, anti-PR3 and anti-MPO). Patients presented with acute or progressive renal insufficiency, hematuria, proteinuria (nephrotic range in two patients), and hypertension. Three patients had evidence of systemic vasculitis: two patients at initial presentation and one patient later in the clinical course. Renal biopsy specimens showed crescents in greater than 50% of glomeruli in all cases, but only mild, focal and segmental mesangial and endocapillary hypercellularity, more typical of ANCA-associated crescentic GN than of crescentic IgA nephropathy without associated ANCA. Semiquantitative analysis of mesangial and endocapillary cellularity performed on renal biopsy slides from these six patients and from eight ANCA-negative patients with IgA nephropathy and crescents in greater than 50% of glomeruli showed significantly greater hypercellularity in the ANCA-negative cases. Three of five ANCA-positive patients for whom follow-up clinical data were available showed improved renal function after treatment with cyclophosphamide and corticosteroids and have not developed end-stage renal disease 17, 20, and 25 months postbiopsy. The remaining two patients were dialysis dependent at the time of biopsy and have remained so despite treatment with cyclophosphamide and corticosteroids. The findings suggest an overlap syndrome of ANCA-associated crescentic GN and IgA nephropathy that resembles the former both histologically and in its potential to respond to aggressive therapy if detected relatively early in its course.

Childhood hypertension. An update on etiology, diagnosis, and treatment.

In the general population, an estimated 70% or more of premature morbidity can be attributed to tobacco use, undertreatment of hypertension, and obesity. From a public health perspective, health-related behaviors that reduce the risk for cardiovascular disease should be encouraged for all children and their families. Pediatricians are obligated to accurately and frequently monitor patients' blood pressures. When discovered, elevated blood pressure should be appropriately investigated, with the evaluation being tailored to the age of the child and to the severity of the blood pressure elevation. Investigation should focus on not only a search for a cause but also target organ effects. Timely recognition of abnormal blood pressure and appropriate interventions are necessary to affect the future development of cardiovascular and renal morbidity and mortality.

Renal outcomes in pediatric liver transplantation.

The outcomes of 294 orthotopic liver transplants performed in 221 children at The University of Chicago Children's Hospital between October 1984 and October 1992 have been retrospectively reviewed. Medical information for 281 transplant in 210 children was sufficient for inclusion in this analysis. The mean age at transplant was 4.1 +/- 5.0 yr. Forty-four percent of the children were male, and 16% of the transplants were living-related. Four children received combined liver-kidney transplants. Seventy-six percent of the children are currently alive. The incidence of acute renal failure occurring following transplantation and requiring dialysis was 6.2% with a mortality rate of 85%. Early postoperative hypertension was seen in 65% of the children and persistent hypertension of greater than 12 months duration was seen in 28%. Sixteen percent of children developed metabolic acidosis requiring sustained sodium bicarbonate supplementation. Aggregate and longitudinal analysis of serial calculated glomerular filtration rates revealed abnormal renal function in approximately one third of children at any given time period following transplantation. The renal dysfunction was unrelated to age at transplant, type of transplant, gender, previous transplants, rejection episodes, courses of nephrotoxic drugs, presence of hypertension, or cyclosporin dose. This review supports prior studies which document abnormal renal function following orthotopic liver transplantation in a significant proportion of children.

OKT3 induction in pediatric renal transplantation.

Twenty cadaveric renal transplant patients (mean age 12.5 +/- 4.8 years) received 14 days (mean 13.0 +/- 2.8 days) of OKT3 (mean dose 0.16 +/- 0.09 mg/kg) along with prednisone 0.5 mg/kg per day, azathioprine 2 mg/kg per day and cyclosporine 5 mg/kg per day which was increased to obtain therapeutic levels before the discontinuation of OKT3. Actuarial patient and graft survival were 100% and 50%, respectively, at both 1 and 5 years. Four children lost their grafts within the first 48 h. One loss was technical in origin, the remaining 3 had pathological evidence of vascular thrombosis. Of the remaining 16 children, 12 (75%) experienced rejection episodes within the first 2 months post transplant (mean 27 +/- 15 days). Successful reversal of early rejection episodes was achieved in 11 of 12 patients. Clinically significant cytomegalovirus infection occurred in 4 patients and resulted in graft loss in 2 patients. Circulating OKT3 levels ranging from 1,000 to 32,000 ng/ml were seen in all patients within the first 48 h. There was a rapid and total depletion of circulating CD3-positive lymphocytes in all patients. Anti-isotypic and anti-idiotypic OKT3 antibodies were assessed by enzyme-linked immunosorbent assay (ELISA), and blocking anti-idiotypic antibodies were detected by immunofluorescence inhibition assay. Positive OKT3 antibody titers were detected in 11 children by ELISA and 10 children by immunofluorescence inhibition assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Severe hypercalcemia following neonatal liver transplantation.

A 3-week-old infant with liver failure underwent an orthotopic liver transplant. Following a prolonged second surgical procedure in which he received massive amounts of blood products, his serum calcium was 31.3. mg/dl (7.8 mmol/l). This patient represents a case of severe hypercalcemia secondary to intraoperative calcium infusions given in an effort to overcome infusion-related citrate toxicity in a neonate with hepatic dysfunction.

Linear growth after pediatric liver transplantation.

To determine growth patterns in a large cohort of unselected children undergoing liver transplantation, the outcomes of 294 orthotopic liver transplantations performed in 221 children at The University of Chicago between October 1984 and October 1992 were retrospectively reviewed; 66% were alive at the time of this analysis. The mean age at transplantation was 4.1 +/- 5.0 years; 44% of the children were male and 16% of the transplants were from living-related donors. The mean height z score at the time of transplantation was -1.6 +/- 1.8, and 39% of children had height z scores of < -2.0 at transplantation. When children with growth retardation at the time of transplantation (height z scores of < -2. 0) were compared with children with more normal growth, there were no significant differences in gender or re-transplantation rates, although children with growth retardation at transplantation were significantly younger than those with more appropriate growth (2.8 +/- 4.1 years vs 4.7 +/- 5.1 years, P <.05). The height z score of all children with biliary atresia at the time of transplantation was -1.9 +/- 1.7 compared with -1.2 +/- 2.0 in those children with underlying diseases other than biliary atresia. Catch-up growth was seen in 37% to 47% of children at any given time point after transplantation. Children with evidence of catch-up growth (growth velocity z score >0) 2 years after transplantation were more likely to be first-time transplant recipients, had more growth retardation at the time of transplantation, and were receiving lower doses of prednisone at 2 years after transplantation. Younger children were most likely to demonstrate catch-up growth after transplantation. In summary, a large proportion of children have growth retardation at the time of liver transplantation. This growth retardation is inversely correlated with age. Before transplantation, children with biliary atresia grow less well than children with other forms of liver disease. Up to one half of children demonstrate catch-up growth after liver transplantation. Growth after transplantation is proportional to the degree of growth retardation at transplantation and inversely correlated to age at transplantation. Children with poor growth after transplantation are more likely to be receiving higher doses of corticosteroid.

Antimouse antibody response after OKT3 administration for steroid resistant rejection.

OKT3 has become one of the more effective antirejection therapies for patients receiving kidney transplants. However, its usefulness is diminished or blocked by the development of antimouse/anti-OKT3 antibodies. We evaluated 17 children receiving OKT3 for steroid-resistant acute rejection for the development and persistence of antibodies after therapy. OKT3 was successful in reversing acute rejection in 14 of 17 patients. Eight children developed antimouse antibodies, 7 at a low titer (1:100). The retesting of all children 6 months later showed no detectable antibodies. Children develop anti-OKT3 antibodies at a rate similar to adults and with time lose detectable levels which may have significance if a subsequent course of OKT3 is needed.

The relationship of untreated borderline infiltrates by the Banff criteria to acute rejection in renal allograft biopsies.

The relationship of borderline infiltrates to acute rejection by Banff criteria in renal allografts of patients receiving only maintenance immunosuppression is not clear. Renal allograft biopsies with borderline lesions that were not treated with additional anti-rejection therapy were retrospectively studied. Sixty-five such biopsies were identified from 50 patients, and their outcome was determined by serum creatinine and/or histologic findings in subsequent biopsies, up to 40 d after the initial biopsy. In addition to the borderline infiltrates, there was evidence of acute cyclosporine or tacrolimus toxicity (58%), acute tubular necrosis (12%), and urinary obstruction (12%). Forty-day follow-up after 30 (46%) biopsies revealed serum creatinine < 110% of baseline, and repeat biopsies were not indicated. In 17 (26%), the serum creatinine initially decreased, then increased, and follow-up biopsies showed acute rejection in nine. In 18 (28%), the creatinine remained elevated and follow-up biopsies revealed acute rejection in nine. The untreated borderline infiltrates were thus nonprogressive after 47 biopsies (72%) and progressed to histologic acute rejection after 18 (28%). When there was increasing or persistently elevated creatinine after the initial biopsy, 51% of cases (18 of 35) progressed to acute rejection. Infiltrates that progressed to rejection had more frequent glomerulitis (7 of 18 versus 3 of 47, P = 0.003) and Banff acute score indices (i+t+v+g) >2 (16 of 18 versus 29 of 47, P = 0.03). A majority (72%) of borderline infiltrates not given additional anti-rejection therapy did not progress to acute rejection over 40 d of follow-up, suggesting that conservative management of these lesions, at least in the short term, may be more appropriate than routine treatment as acute rejection.