Glenn H. Bock

Accelerated growth rates in children treated with growth hormone after renal transplantation.

To determine the usefulness of growth hormone treatment among children with renal allografts, we treated nine children with functioning renal transplants who were less than 16 years of age and had poor growth. The nine children, who were aged 12.6 +/- 4.0 years, had (1) heights greater than 2.5 SD less than the mean for age, (2) growth rates less than or equal to 5 cm/yr, and (3) additional growth potential, as assessed by bone age (8.9 +/- 2.8 year). Insulin-like growth factor I, thyrotropin, and thyroid hormone levels were normal for age in all children. Growth hormone treatment increased growth rates from 1.9 +/- 1.1 cm/yr to 7.2 +/- 1.8 cm/yr without accelerating skeletal maturation and without advancing pubertal status. During growth hormone treatment, serum creatinine concentration rose from 140 +/- 50 to 190 +/- 80 mumol/L (1.6 +/- 0.6 to 2.1 +/- 0.9 mg/dl) (p less than 0.05), and creatinine clearances decreased from 0.79 +/- 0.37 to 0.58 +/- 0.30 ml/sec per 1.73 m2 (47 +/- 22 to 35 +/- 18 ml/min per 1.73 m2) (p less than 0.05) but then remained stable. Growth rates of two patients returned to pretreatment rates when growth hormone treatment was discontinued after 5 and 7 months because of increased serum creatinine values. Growth hormone treatment may be useful as adjunctive therapy for increasing growth rates in selected children with renal allografts who have poor growth; however, serum creatinine concentrations should be closely monitored during such treatment.

Cytomegalovirus infections following renal transplantation – effects of antiviral prophylaxis: a report of the North American Pediatric Renal Transplant Cooperative Study

Post-transplant cytomegalovirus (CMV) infections are a source of significant morbidity. However, the extent of the problem and the benefits of various antiviral prophylactic therapies remain incompletely understood. The North American Pediatric Renal Transplant Cooperative Study registry was screened to identify patients hospitalized for CMV infections during the 1st post-renal transplant year between 1987 and 1993. Using a control group of transplant recipients, we performed a retrospective analysis of risk factors for CMV disease among these hospitalized patients and studied the effects of various viral prophylactic strategies on CMV risk, clinical manifestations, and outcome. We identified 142 patients hospitalized with CMV infections, the majority of which included major organ involvement. A CMV-positive kidney donor was the most significant risk factor for hospitalization [odds ratio (OR) = 5.2, P<0.0001] irrespective of recipient age or CMV immune status. As opposed to antiviral agents (acyclovir, ganciclovir) or pooled IgG, prophylaxis with enriched anti-CMV IgG significantly reduced the risk of CMV hospitalization (OR = 0.31, P = 0.03). The prophylactic use of antiviral agents was associated with a decreased risk of major organ involvement during the CMV infection (OR = 0.34, P<0.005). Among the patients with CMV, the 3-year graft survival was significantly better for those who received any form of prophylaxis compared with those who received none (88% vs. 52%, P<0.001). Our findings suggest a role for combined CMV-enriched IgG and antiviral agent prophylaxis for post-transplant CMV disease. Such an approach could diminish the incidence and severity of CMV infection and appears to have an independent favorable effect on graft outcome.

Feeding disorders and gastroesophageal reflux in infants with chronic renal failure

Twenty-two infants (mean age 7.5 months) with chronic renal failure (CRF) were studied for their nutrition, growth, and upper gastrointestinal function. Most infants had a history of poor caloric intake and 7 had received supplemental feeding (SF) prior to the investigation. All infants were undergrown, underweight, and malnourished. The infants were characterized as having only a fair interest in food, refusing feedings, and vomiting excessively. Sixteen of 22 infants (73%) had significant gastroesophageal (GE) reflux demonstrated by 24-h esophageal pH monitoring. Gastroesophageal scintiscans were less sensitive and specific in detecting the reflux. Infants with GE reflux were significantly younger and more often required SF than those without GE reflux. There were no significant differences in the degree of renal failure, growth failure, caloric intake, protein intake, or nutritional status between the infants with and without GE reflux. From these studies we conclude that GE reflux should be considered as one of the factors contributing to the feeding problems of infants with CRF.

Transplantation of the adult kidney into the very small child: Long-term outcome

Adult kidneys were transplanted into 12 children weighing between 5,400 and 8,800 gm. Ten received parental and two received cadaver grafts. Ten of the 12 children are alive 18 months to 9 years post transplant; eight have their original grafts and two required retransplantation-their original grafts were lost at 4 and 9 years because of chronic rejection. All but these two surviving children had normal or accelerated growth rates despite growth retardation prior to transplant. All children evidenced moderate to severe delay in psychomotor development prior to transplant. Seven of the ten survivors now have normal psychomotor function. Two are behind in school, and one with a degenerative central nervous system disease prior to transplant remains profoundly retarded. We conclude that because of donor availability, capacity for good donor-recipient matching, and minimization of time on dialysis, transplantation of adult kidneys into pediatric patients is preferable to awaiting the relatively uncommon pediatric cadaver donor. We further conclude that the procedure is warranted.

Transplantation of the adult kidney into the very small child: Technical considerations

Transplantation of adult kidneys into very small children is not performed in most centers because of concerns regarding the technical difficulty of the procedure. Advantages of the procedure include the possibility of living related donor transplantation and the increased availability of adult donor kidneys as compared with pediatric cadaver donor kidneys. We have transplanted adult kidneys into 12 children aged 11 months to 3.5 years who weighed 5,400 to 8,800 g. Ten children received living related donor and two cadaver donor grafts. Herein we describe in detail the pretransplant management, surgical strategies, intraoperative management, surgical techniques, and postoperative management which we use for transplantation of adult kidneys into very small children. Intraoperative and postoperative complications have been described to illustrate the evolving clinical principles in this area. Since 10 of the children are presently alive, 8 with their original grafts, 16 months to 9 years after transplantation, we advocate this approach for suitable small children with terminal renal failure.

Renovascular hypertension in children: Current concepts in Evaluation and treatment

Since 1981, we have evaluated and treated 22 children with renovascular hypertension (RVH). Seventeen patients had stenosis of their native renal arteries, and five had stenosis of the artery in a transplanted kidney. RVH was caused by fibromuscular dysplasia in 13 patients, by trauma in 2 patients, and by arteritis in 2 patients. Among the patients who had transplanted kidneys, three had technical causes for stenosis and two had stenosis due to rejection. The disease was unilateral in 10 patients, bilateral in 5, and present in a solitary kidney in 7, including the five renal transplants. Diagnostic studies that strongly suggested the presence of renovascular disease were an initial diastolic blood pressure greater than 100 mm Hg, an elevated peripheral vein renin activity level, and an abnormal renal scan if the patients hypertension was being controlled with an angiotensin-converting enzyme inhibitor (ACEI). Only the renal arteriogram was 100% accurate in confirming the presence of RVH. Percutaneous angiographic correction was attempted in 13 patients and resulted in lasting improvement of the hypertension in five (38%). Surgical revascularization was attempted in 17 children, including the 8 with failed angioplasty, with improvement or cure of the hypertension in 15 patients (88%). Combining percutaneous transluminal angioplasty (PTA) and surgical results gave 20 of 22 patients (91%) with cure or improvement of their hypertension. Four of 27 affected kidneys (15%) could not be revascularized and were removed. We conclude from this series of patients that despite improvements in noninvasive studies, renal arteriogram remains the only study that is 100% accurate in evaluating children for RVH.(ABSTRACT TRUNCATED AT 250 WORDS)

Disturbances of brain maturation and neurodevelopment during chronic renal failure in infancy

Fifteen infants with moderate to severe congenital renal disease were prospectively studied by serial renal, neurodevelopmental, neurophysiologic, and anthropometric assessments. The observation period ranged from 3 to 25 months (mean = 10.9). Eight patients maintained a Mental Development Index (MDI) above the 16th percentile (greater than -1 SD) and comprised group 1. Of the remaining seven patients (group 2), three had an MDI less than 16th percentile when first studied and four had serial decreases of the MDI to less than 16th percentile. Although motor development was more delayed in group 2 at study entry, there were no significant changes of motor performance levels for either group during the study period. Group 2 patients had smaller length (p less than 0.05) and head circumference (p less than 0.05) standard deviation scores in comparison with group 1, and they had higher serum creatinine values (mean = 3.8 vs 1.3 mg/dl, respectively; p less than 0.01). By spectral electroencephalography, the expected progressive increase of the frequency of cerebral cortical background activity with age was demonstrated in group 1 but was not seen in group 2 (multivariate analysis of variance p less than 0.03). This increase of faster-frequency activity was primarily manifested in the left cerebral hemisphere of group 1 patients (p less than 0.01), a finding that was also absent in group 2. The frequent occurrence of neurodevelopmental abnormalities in infants with renal failure is possibly a consequence of impaired dominant hemispheric maturation in the first several years of life, which is clinically manifested as deterioration of cognitive function.

CHARACTERIZATION OF A NEW IL-6- DEPENDENT HUMAN B-LYMPHOMA CELL LINE IN LONG TERM CULTURE

We have established a cell line (DS-1) of B-cell lineage in long-term culture. It was derived from an immunodeficient patient with intestinal lymphangiectasia and lymphoma by culturing malignant pleural effusion cells with IL-6 in vitro. The cell surface phenotype was; PCA-1, HLA Class II(+); CD25, CD19, CD20, CD30, CD38(-). Cell proliferation was poor in medium and exhibited an eight-fold, dose-dependent increase of proliferation in response to rIL-6 of human but not murine origin. The secretion of IgG into culture supernatants by DS-1 was not enhanced by rIL-6. While constitutive production of IL-6 was not detected by bioassay using murine B9 hybridoma cells or by ELISA, the presence of IL-6 message was detected in polyA+ selected mRNA by Northern analysis. Spontaneous proliferation of DS-1 cells was inhibited by neutralizing polyclonal antibodies to IL-6 (37%) and mAb to IL-6 (54%) and IL-6R (53%). DS-1 expressed both high and low affinity IL-6 receptors (Kd 1.2 x 10(-11) and 6.7 x 10(-10), respectively) by radiolabelled binding and Scatchard analysis. Thus, DS-1 represents an autocrine IL-6-producing cell line of B-cell lineage which resembles lymphoid malignancies arising in patients with AIDS and other immunodeficiency diseases. Despite constitutive IL-6 production, the in vitro growth of DS-1 is dependent upon exogenous IL-6. DS-1 may thus be useful as a model of IL-6 dependency. This cell line may also facilitate development of strategies for diagnosis and treatment of B-cell lymphomas in immunocompromised patients.

An Assessment of Serum and Urine Soluble Interleukin-2 Receptor Concentrations During Renal Transplant Rejection

During rejection, renal transplant recipients have increased concentrations of soluble interleukin-2 receptors (sIL-2R) in their serum and urine. However, the clinical application of this measurement in the diagnosis of rejection or the assessment of treatment efficacy is limited by the variance of the measurement in sample populations. We examined the serum and urine sIL-2R concentrations in 20 renal transplant recipients, 12 of whom experienced 13 episodes of allograft rejection. There was no statistical difference in the mean serum sIL-2R concentration at the time of rejection compared with the baseline value (2,817 +/- 801 v 1,943 +/- 255 U/mL). By contrast, the urinary excretion rate, expressed as units of sIL-2R per milligram creatinine, was 26.2 +/- 6.4 compared with 14.2 +/- 2.5 (P < 0.05). Furthermore, when urinary sIL-2R was expressed as a fractional excretion (FE), both the absolute measurement (4.4% +/- 1.7%) and the percent increase (+245%) at the time of rejection provided the greatest degree of discrimination of rejection from those values during allograft stability (1.2% +/- .2% and +2.5%, respectively; P < 0.005). We conclude that (1) serum and urine sIL-2R concentrations are affected by a number of factors during rejection; (2) FE calculations of sIL-2R improve discrimination of rejection from graft stability; and (3) serial measurement of sIL-2R excretion may be a useful adjunct to the diagnosis of rejection and, possibly, the subsequent assessment of response to immunotherapy.

Vancomycin Prevents Polytetrafluoroethylene Graft Infections in Pediatric Patients Receiving Chronic Hemodialysis

Polytetrafluoroethylene (PTFE) grafts have been a useful addition to the pediatric hemodialysis vascular access armamentarium. In this study, 17 pediatric patients underwent 331 total months of hemodialysis via PTFE grafts. There was a statistically significant (P less than .025) decrease in the incidence of graft infections in 12 patients (235 patient-months) while receiving prophylactic parenteral vancomycin compared with 9 patients (96 patient-months) while receiving no vancomycin (0% v 44%). Vancomycin side effects were uncommon and mild. Vancomycin is a safe and effective agent for the prevention of PTFE graft infections in pediatric patients receiving chronic hemodialysis.