Superior outcomes in pediatric renal transplantation

BACKGROUND: Nationally, results of renal transplantation in children, particularly in small children, are inferior to those obtained in adults. OBJECTIVE: To determine factors important for success in renal transplantation in children. DESIGN: Results of 108 consecutive renal transplantations performed in patients aged 7 months to 18 years were reviewed and compared with those reported by the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS), the national registry. RESULTS: One-, 2-, and 3-year graft survival rates (+/-SE) were 99% +/- 1%, 95% +/- 3%, and 93% +/- 4%, respectively, for living donor grafts and 97% +/- 3%, 92% +/- 6%, and 92% +/- 6%, respectively, for cadaver grafts. Incidence of acute rejection was half that reported by NAPRTCS. There were no graft losses for technical reasons (19% in NAPRTCS). Twelve percent of patients were younger than 2 years (6% in NAPRTCS); 17% were 2 to 5 years old (16% in NAPRTCS). Most small children received an adult-sized kidney. Ninety-three percent of recipients weighing 15 kg or less received postoperative mechanical ventilation assistance to optimize fluid resuscitation and perfusion of adult-sized kidneys. Structural abnormalities of the urinary tract were present in 53.7% of the patients (48.5% in NAPRTCS; adults, 5.3%). Nephroureterectomy was required in 38 children; in 27 (71%) of them, it was performed at the time of transplant surgery. CONCLUSIONS: Excellent results can be obtained in pediatric renal transplantation by strict adherence to surgical detail, tight immunosuppressive management, aggressive fluid management in the small child, and careful integration of urologic and transplant surgery.     

Long-term results of pediatric liver transplantation: an analysis of 569 transplants

The present study has investigated the therapeutic potential of a type 4 phosphodiesterase (PDE) inhibitor, rolipram, in experimental lung injury. Acute lung injury was induced in the mouse by combined treatment with lipopolysaccharide (LPS; 10 mg/kg, i.v.) and zymosan (3 mg/kg, i.v.), and assessed using extravascular albumin accumulation; neutrophil sequestration in pulmonary capillaries was also measured. The results show that pretreatment with rolipram (5 mg/kg, i.p.) was protective against the induction of lung injury by combined LPS and zymosan; extravascular albumin accumulation was reduced by 89% and neutrophil sequestration in lung tissue, as assessed by lung myeloperoxidase (MPO) activity was reduced by 75%. Pretreatment with rolipram also attenuated increases in serum tumor necrosis factor alpha (TNFalpha) levels induced by LPS and zymosan treatment, measured after 2.5 h. The role of endogenous TNFalpha in the induction of lung injury was therefore assessed. Blockade of endogenous TNFalpha by treatment with the soluble receptor p55-IgG fusion protein or an anti-murine TNFalpha monoclonal antibody, TN3. 19.12, had no protective effect against LPS and zymosan-induced lung injury. This suggests that there is a disassociation between TNFalpha production and the induction of injury in this model. Administration of rolipram after LPS and before zymosan treatment obliterated the increase in pulmonary vascular permeability, but its effect on sequestration of neutrophils in pulmonary microvessels, as measured by MPO, was less marked. The results of the present study suggest that use of agents such as rolipram that inhibit PDE4 may have a therapeutic role in treatment of acute lung injury, since we have shown that it is effective in attenuation of neutrophil activation even after sequestration. However, its effect appears to be independent of TNFalpha inhibition.     

Early risk factors in pediatric renal transplantation at a single center

BACKGROUND/PURPOSE: Renal transplantation is the preferred treatment for renal failure in childhood, but the incidence of graft failure is generally higher than that in adult recipients. A single center was studied to determine if there were any correctable factors that could contribute to graft failure. METHODS: Recipient, donor, and perioperative factors were analyzed using standard statistical tests in 59 pediatric renal transplants performed between 1992 and 1995 using standard cyclosporin-based immunosuppression. RESULTS: Three factors were found to be significantly different between those recipients with good graft function and those who either died or were returned to dialysis. Any history of donor hypotension was a detrimental factor (P < .05, chi(2) test). In addition, those with failed grafts were more likely to have received their grafts from younger donors (P = .025, Mann Whitney U test). A third risk factor was a low postoperative central venous pressure in those whose graft ultimately failed (P = .0012, Mann Whitney U test). CONCLUSIONS: With a pediatric recipient who is stable and has a low priority for a renal graft, small donors, particularly those who have experienced hypotension, should be considered not suitable for transplantation. The chances of a successful graft can be improved by good communication between surgeon, pediatrician, and anesthetist. The importance of maintaining a positive central venous pressure is emphasised.     

Treatment of end-stage renal disease by transplantation: clinical results with 111 cases

The efficacy of renal transplantation for patients with end-stage renal disease was reviewed in 108 patients receiving 111 transplants followed for an average of two and one-half years after transplantation. Overall patient survival decreased 10 per cent per year from 90 per cent after the first year to 70 per cent at three years. Kidney survival was slightly less, with a similar pattern. Patients with better tissue matches and living related donor allografts had fewer and less severe rejections and better ultimate function than did patients with poor tissue matches and cadaver allografts. However, a significant number of patients with poor tissue matches and cadaver allografts had excellent results. Eighty-six per cent of all survivors with functioning kidneys had serum creatinines of 2.0 mg./100 ml. or below. Mortality was associated primarily with sepsis from a variety of bacterial, fungal, viral and protozoan organisms often associated with other complications such as rejection or gastrointestinal bleeding. Recipients over the age of 40 were in a higher risk group. Rejection per se, however, played a minor role. Urological and skeletal complications were a major source of morbidity but were not associated with mortality.     

Encouraging results of split-liver transplantation

Two sisters affected with renal cell carcinoma (RCC) is an extremely rare finding, and may indicate a hereditary pattern or the presence of other predisposing factors. We describe here 2 sisters presenting with clear cell renal cell cancer. Examination for von Hippel-Lindau (VHL)-related features and tuberous sclerosis (M. Bourneville) was negative and both had a normal constitutional karyotype. Cytogenetic analysis of the tumor tissue of both patients showed a translocation involving chromosomes 3 and 5, resulting in loss of 3p sequences and gain of part of 5q. The 5q breakpoints were similar, but the breakpoints at 3p appeared to differ. Allelic imbalance analysis supported our observations. Microsatellite analysis revealed that both sisters inherited different chromosome 3 parental alleles. For chromosome 5, 3 different haplotypes could be deduced, but the chromosome 5 alleles overrepresented in the different tumor tissues were from different parental origin. The development of the 2 RCCs in these 2 sisters thus cannot be explained by the inheritance of a mutated VHL gene located at 3p25, nor by the inheritance of other gene defects at chromosomes 3p or 5q. Although the chance that 2 sisters develop sporadic RCC is very low, in the presented case it is probably coincidental or related to another genetic predisposition.     

Infection after pediatric heart transplantation: results of a multiinstitutional study. The Pediatric Heart Transplant Study Group

BACKGROUND: Detailed information regarding the spectrum and predictors of infection after heart transplantation in children is limited because of relatively small numbers of patients at any single institution. We therefore used combined data obtained from the Pediatric Heart Transplant Study Group to gain additional information regarding infectious complications in the pediatric population. METHODS: To determine the time-related risk of infection and death related to infection in a large pediatric patient population, we analyzed data related to 332 pediatric patients (undergoing heart transplantation between January 1, 1993, and December 31, 1994) from 22 institutions in the Pediatric Heart Transplant Study Group. RESULTS: Among the 332 total patients, 276 infections were identified in 136 patients. Of those patients with development of infection, a single infection episode was reported in 54% of patients, 21% had two infections, and 25% had three or more infections. Of the 276 infections, 164 (60%) were bacterial, 51 (18%) were due to cytomegalovirus, 35 (13%) were other viral (noncytomegalovirus) infections, 19 (7%) were fungal, and 7 (2%) were protozoal. Bacterial infections were more common in infants younger than 6 months of age at time of transplantation, comprising 73% of all infections as compared with 49% in patients older than 6 months of age. The incidence of bacterial infection peaked during the first month after transplantation, with the actuarial likelihood of a bacterial infection among all patients reaching 25% at 2 months. The most common sites of bacterial infection were blood and lung (74% of bacterial infections). Cytomegalovirus accounted for 59% of viral infections, with a peak hazard occurring at 2 months after transplantation. Among all infections, cytomegalovirus was less common in infants younger than 6 months of age (8% of all infections) than in older patients (25%). By multivariate analysis, risk factors for early infection included younger recipient age (p = 0.05), mechanical ventilation at time of transplantation (p = 0.0002), positive donor cytomegalovirus serologic study result with negative recipient result (p = 0.004), and longer donor ischemic time (p = 0.04). The overall mortality rate from infection was 5%, with an actuarial freedom from death related to infection of 92% at 1 year after transplantation. The mortality rate was high in patients with fungal infections (52%), yet was low for those with cytomegalovirus infection (6%). Infections accounted for 27% of the overall mortality rate in infants younger than 6 months of age, compared with 16% for older patients. CONCLUSIONS: Although most infections in pediatric heart transplant recipients are successfully treated, infection remains an important cause of posttransplantation morbidity and death, especially in infants. Bacterial infections predominate within the first month after transplantation, whereas the peak hazard for viral infections occurs approximately 2 months after transplantation. Cytomegalovirus infections are common in the pediatric transplant population, but death related to cytomegalovirus is low.     

Improving the results of coronary angioplasty

Coronary angioplasty has changed dramatically in the past three years with major reductions in suboptimal results and restenosis rates, and improvements in safety, efficacy and cost-effectiveness. Intracoronary stent implantation with optimisation of strut expansion and the abandonment of anticoagulants after deployment, have led to less entry-site complications, facilitated early hospital discharge, virtually abolished subacute stent thrombosis and resulted in a 50% reduction in target vessel revascularisation. Adjuvant medical treatment with anti-platelet agents, including glycoprotein IIb/IIIa receptor inhibitors, improves the safety of angioplasty and may further reduce the restenosis rate. Selective use of debulking devices has extended the indications for angioplasty. High resolution fluoroscopy, quantitative coronary angiography and intracoronary ultrasound leading to improved diagnosis, equipment selection and treatment have contributed to better outcomes. Further clinical trials will compare angioplasty and stent implantation with coronary bypass surgery in patients with multivessel coronary disease, and may extend the indications for percutaneous transluminal coronary angioplasty (PTCA) to selected patients with three vessel disease.     

Evaluation of the pediatric renal transplant recipient

Renal transplantation is the preferred therapy for children with end stage renal disease. A functioning renal allograft can dramatically improve a child's quality of life. Advances in immunosuppressive therapy and clinical practice approaches have significantly improved graft survival rates allowing children to attain near normal growth and development. Accurate assessment and appropriate nursing care enhances long-term survival of these young patients.