Role of regular and leukocyte-free blood transfusions in the generation of broad sensitization.

The factors associated with the development of humoral sensitization were studied prospectively in 30 previously transplanted patients immediately after graft rejection. Lymphocyte antibodies were measured both by conventional cytotoxicity in 30 panel cells and by flow cytometry in up to 10 target cells. Although lymphocyte antibodies induced by graft rejection alone were detected in 12 of 26 patients (46%), lymphocytotoxic antibodies were present in only 2 of 27 patients. Of the 25 patients without lymphocytotoxic antibodies, 13 developed them later. In all cases panel antibody reactivity developed after the patients received blood transfusions. No other factor was associated with the development of lymphocytotoxic antibodies, including transplant nephrectomy. There were 12 patients who remained negative for lymphocytotoxic antibodies even though 5 of them were transfused. The powerful role of blood transfusions in the generation of broad sensitization was further documented in 5 patients who received blood units completely depleted of leukocytes by cottonwool filtration and red cell washing. Four of these patients showed significant increases in the level of lymphocytotoxic antibodies, even when stored blood units were used. One additional patient became broadly sensitized by the transfusion of frozen blood. These results show (A) that broad sensitization may not develop if patients are not transfused after graft rejection; (B) that blood transfusions lead to broad sensitization in most (76%) pretransplanted patients; and (C) that transfusion of leukocyte-free blood may delay, but not avoid, the development of broad sensitization.

Planned random donor blood transfusion in preparation for transplantation. Sensitization and graft survival.

Random donor blood transfusions were used to prepare 183 prospective recipients for one-haplotype living-related donor (LRD) grafts or cadaver donor (CD) grafts. Five units of packed red blood cells were administered over a 7-10 day period, and weekly sera were monitored for six weeks. Sensitization was uncommon in men and nulliparous women (8/153), was of low reactivity, and was not a barrier to transplantation. Multiparous women had a 44% frequency of sensitization on presentation and 11/24 initially lacking cytotoxicity developed reactive serum following transfusion. Single-haplotype LRD recipients had 96% one-year graft survival. CD recipients had one-year graft survival of 72%. The rate of transplantation in surviving candidates exceeded 90%, and supports the hypothesis of a protective immune response.

Technetium-99m sulfur colloid accumulation as a predictor of acute renal transplant rejection.

Renal transplantation is the preferred treatment for end-stage renal disease in children. Most transplant failures are due to allograft rejection. To date, only histopathological findings on renal biopsy can establish this diagnosis. Prior to the availability of cyclosporine, technetium-99m sulfur colloid nuclear scans (TSC) were used in a limited number of institutions to detect rejection episodes. The purpose of this study was to determine whether TSC could predict acute rejection in the cyclosporine era. A prospective study involving 41 pediatric renal transplant patients (M = 25, F = 16) was conducted from 6/1/89 to 10/31/91. Patients who received a TSC and biopsy (41 patients, 62 studies) within one week of clinical and laboratory evidence of acute rejection were included in the study. A qualitative method of determining sulfur colloid uptake was used by comparing allograft uptake with that of the fifth lumbar vertebrae (L5) marrow uptake: 3(+)--allograft with greater than L5 marrow uptake, 2(+)--same as, 1(+)--less than, and 0--no allograft uptake. Transplant accumulation of > or = 2+ was considered consistent with acute rejection (P < 0.001). Acute rejection was noted in 53 of 62 renal biopsies. Of those with biopsy-proved acute rejection, SC was positive (> or = 2+) in 46 of 53. SC of > or = 2+ has proved to be a good predictor of acute rejection. This technique has a sensitivity of 98%, specificity of 53%, positive predictive value of 87%, and negative predictive value of 89%.

Late results of renal transplantation.

A total of 315 (64%) of 491 primary cadaver and living-related donor transplants performed from 1975 through 1984 were still functioning at 24 months. These selected patients were examined further to assess the impact of several risk factors on late graft and patient survival. Black recipients, patients with underlying diabetes mellitus or hypertension, patients with poor renal function at 24 months, and recipients of cadaver grafts had significantly poorer long-term graft survival. Age greater than or equal to 40, diabetes or hypertension, poor 24-month function, and cadaver donor transplantation were associated with poorer long-term patient survival. Considerable improvement in graft survival at 24 months was seen in 1980-1984 compared with the earlier period, coincident with our adoption of routine pretransplant random donor blood transfusion. In contrast, long-term graft survival in patients with functioning graft at two years did not improve significantly over the same period. Although living-related donor transplants showed greater graft and patient survival than cadaver donor grafts by univariate analysis, no such advantage was demonstrated by multivariate analysis.

Increased antibody responsiveness to blood transfusions in pediatric patients.

Heightened immune responsiveness has been proposed as one of the reasons underlying suboptimal renal transplant results in very young children or African American recipients. Because multiple factors influence graft outcome, it has been difficult to provide experimental evidence to confirm or refute this suggestion. In the present study we measured IgG antibodies with confirmed HLA specificity produced in response to blood transfusions. The patients evaluated were renal transplant candidates who had not had previous pregnancies or transplants. The overall incidence of HLA sensitization was 12%. Age was the most influential factor in sensitization: patients < 20 years old were 4-5 times as likely to produce anti-HLA antibodies than patients > 20 (P = 0.0018). Female patients were also high responders. However, this was explained by the higher proportion of children among nulliparous female patients rather than by differences in gender. In contrast, the antibody response of black and white recipients was similar. The antibody levels in most patients were low and decreased significantly with time. We conclude that the immunoregulatory influences in patients < 20 years old favor the production of anti-HLA antibodies in response to blood transfusions, a fact that may explain some clinical observations in pediatric transplant recipients.

Effects of kidney transplantation on cognitive performance in a pediatric population.

The cognitive functioning of 20 children and adolescents with end-stage renal disease was assessed 1 to 3 weeks prior to the onset of hemodialysis, and at 1 month and 1 year after successful kidney transplantation, and results were compared with those of a matched control group. A battery of intelligence, achievement, problem solving, learning, memory, and attention tasks were administered. Both groups had significantly improved scores over time on most measures. The group with renal disease exhibited significantly greater improvement than the control group from initial testing to 1 month after transplantation on the performance IQ and full-scale IQ as well as in mathematics achievement. This significant difference was not maintained, however, at 1 year after transplantation. Cognitive performance was less impaired the later the onset of renal failure or the fewer the years in end-stage renal disease. BUN nitrogen, serum creatinine levels, and BP did not consistently correlate with any of the cognitive or academic achievement measures.

Liver dysfunction in children and adolescents during hemodialysis and after renal transplantation.

Liver dysfunction is common in patients on hemodialysis or during the posttransplant period. Twelve children in the End-Stage Renal Disease Program at the University of Florida ranging in age from 4 to 18 years, developed persistent, elevated liver enzymes (SGOT or SGPT greater than 100 IU/liter) during hemodialysis in preparation for renal transplantation. Eleven of 12 developed enzyme elevations within six weeks of the initiation of hemodialysis. The other child exhibited enzyme elevations after one year on dialysis while awaiting a second transplant. Most of the children were anicteric and asymptomatic. Potential hepatotoxic drugs were discontinued when serum transaminase elevations were noted. Hepatitis B surface antigenemia was associated with enzyme elevations in one patient; cytomegalovirus seroconversion had occurred in eight patients, but only three had associated enzyme elevations. Liver biopsies were performed in all the patients before or at the time of renal transplantation. The histology was variable and ranged from normal in six patients, mildly abnormal with changes compatible with acute hepatitis in four patients, and granulomatous hepatitis in one patient, to severely abnormal with chronic hepatitis inthe remaining patient. Seven of the 12 children underwent successful transplantation with return of enzyme levels to normal in five and persistent elevations in the others. These findings suggest that evaluation of liver histology provides the only accurate means of assessment of persistent liver dysfunction in children and adolescents on hemodialysis and after renal transplantation.

Clinical significance of the presence of cryoglobulins in patients with glomerulopathies not associated with systemic disease.

Serial serum samples from 102 children with glomerulopathies not associated with systemic diseases and from 23 normal controls were examined for the presence of cryoglobulins. Sera from controls, from patients with glomerulopathies thought to be mediated by immune complexes, and from those with non-immunologically mediated glomerulopathies demonstrated similar incidence of cryoglobulins. There was no correlation between cryoglobulin concentration or composition and the glomerular immunohistologic findings. Furthermore, persistence of cryoglobulinemia could not be correlated with progression of renal disease. Although cryoglobulins may contain immune complexes, determination of serum cryoglobulin concentration appears to be of little value in the diagnosis of immune complex mediated renal disease, nor in the assessment of disease activity or monitoring therapy in patients with glomerulopathies unassociated with systemic disease.

Total parathyroidectomy and autotransplantation for tertiary hyperparathyroidism in children with chronic renal failure.

An association between chronic renal failure and skeletal deformities in the adolescent patient was first documented by Lucas in 1883. Since then it has been established that the kidneys play a major role in the regulation of calcium, phosphate, and parathyroid hormone, and that chronic renal failure is characterized by profound alterations in the normal metabolic homeostasis of the human body. With the hyperphosphatemia of uremia, compensatory hyperparathyroidism is also a well known complication. Due to these factors, loss of normal renal function ultimately leads to derangement in mineral and bone metabolism resulting in severe skeletal deformities. Reports in the English literature suggest that the changes of renal osteodystrophy are much more pronounced in the pediatric patient, as compared to those in the adult. In the last two decades, renal transplantation has come to be recognized as a satisfactory modality for controlling renal failure and its complications. This procedure is often not available as an option, however, in small patients, especially those under three years of age. The pediatric nephrologist is often forced to manage these patients for long periods with conservative therapy, in an attempt to control the ravages of renal osteodystrophy. The problem becomes unmanageable when the compensatory hyperparathyroidism proceeds to autonomy. When this occurs, despite maintenance of normal serum calcium levels, the renal osteodystrophy progresses rapidly, producing pain, deformities and growth retardation. At this point, the condition is often refractory to medical management and resection of parathyroid tissue remains the only satisfactory modality for control.(ABSTRACT TRUNCATED AT 250 WORDS)

Urinary tract infections in children: effect of short course antibiotic therapy on recurrence rate in children with previous infections.

Eighty-five girls, ages 3-16, with a past history of recurrent urinary tract infections were treated for 10 days with either trimethoprim/sulfamethoxazole, ampicillin or cephalexin. Patients with normal roentgenograms as well as those with reflux and cortical scarring were included. In the 12 weeks following completion of treatment, a significantly lower recurrence rate was noted in children who received trimethoprim/sulfamethoxazole. There was no difference in the recurrence rate whether or not radiographic abnormalities were present. No serious side effects were noted with any drug regimen.

Cephalexin in the management of bacteriuria.

This report evaluates the effectiveness of cephalexin in the treatment of bacteriuria in 93 children. Cephalexin therapy eradicated sensitive organisms in 97 per cent of the cases regardless of recurrence, structural abnormality, or status of renal function. Nevertheless, recurrences with a new, resistant organism occurred significantly in certain patients, expecially those with major anatomic abnormalities, during a six-week follow-up period. The incidence of drug reactions was low.

A pathophysiologic basis for the diagnosis and treatment of the renal hypertensions.

Hypertension is a major medical problem with significant short- and long-term sequelae. Previous investigators have reported childhood hypertension to be secondary and when sexondary, renal. However, recent studies have shown primary (essential) hypertension to be more prevalent than secondary. Children with blood pressures at the 95th percentile for age deserve comprehensive evaluation and follow-up. Those with systemic evidence of side-effects will require therapy. Modern therapy should be based on pathophysiologic principles which include an understanding of volume-dependent and renin-dependent hypertension. The stepwise approach to therapy will produce the maximal therapeutic benefit.

Factors affecting cyclosporine-induced gingival overgrowth in pediatric renal transplant recipients.

The purpose of this research was to study the occurrence of gingival overgrowth (GO) in children after kidney transplantation and to investigate the relationship of GO to medical and dental parameters. Forty-nine kidney transplant patients taking the immunosuppressive drug cyclosporine A (CsA) were evaluated for plaque (PI), calculus (CI), gingival inflammation (GI), probing depth (PD), width of keratinized gingiva (GW), and gingival overgrowth (GO). Blood trough levels and oral dosages of CsA were obtained from medical charts on the day of examination. Most (77.5%) subjects exhibited GO, suggesting that GO is a frequent problem in children and adolescents ingesting CsA. GI, PD, and GW were found to be statistically significantly greater in subjects with GO than in those without GO. CsA dose/day was not significantly different between subjects with GO and those without GO. CsA dose/kg body weight and blood trough levels of CsA were significantly higher in subjects without GO, but the average length of time subjects without GO had been ingesting CsA was only 1.3 months, compared with an average 3.5 years for subjects with GO. The results indicate that in young subjects, duration of CsA ingestion may be the most critical factor related to eventual GO development.

Perceptions of parenting stress and family relations by fathers of children evaluated for organ transplantation.

18 fathers of children evaluated for solid organ or bone marrow transplantation completed measures of parenting stress and family functioning. Comparisons with normative data indicated that these fathers reported less parenting stress, less family conflict, more concern about family finances, and more limitations in family activities. These data highlight the need for family-based assessments in pediatric transplantation.