Gerald S. Arbus

The Association Between Idiopathic Hemolytic Uremic Syndrome and Infection by Verotoxin-Producing Escherichia coli

Forty pediatric patients with idiopathic hemolytic uremic syndrome (HUS) were investigated for evidence of infection by Verotoxin-producing Escherichia coli (VTEC). Fecal VTEC (belonging to at least six different O serogroups including O26, O111, O113, O121, O145, and O157) or specifically neutralizable free-fecal Verotoxin (VT) or both were detected in 24 (60%) patients but were not detected in 40 matched controls. Ten of 15 of the former developed fourfold or greater rises in VT-neutralizing antibody titers, as did six other patients who were negative for both fecal VTEC and VT. A total of 30 (75%) patients had evidence of VTEC infection by one or more criteria. We concluded that a significant association exists between idiopathic HUS and infection by VTEC. The detection of free-fecal VT was the most important procedure for the early diagnosis of this infection because, in our study, VTEC were never isolated in the absence of fecal VT, whereas fecal VT was often present even when VTEC were undetectable.

The 1989 report of the North American Pediatric Renal Transplant Cooperative Study - This report is prepared under the auspices of the scientific advisory committee of the North American Pediatric Renal Transplant Cooperative Study

This report of the North American Pediatric Transplant Cooperative Study summarizes data contributed by 57 participating centers on 754 children with 761 transplants from 1 January 1989 to 16 February 1989. Data collection was initiated in October 1987 and follow-up of all patients is ongoing. Transplant frequency increased with age; 24% of the patients were less than 5 years, with 7% being under 2 years. Common frequent diagnoses were: aplastic/dysplastic kidneys (18%), obstructive uropathy (16%), and focal segmental glomerulosclerosis (12%). Preemptive transplant, i.e., transplantation without prior maintenance dialysis, was performed in 21% of the patients. Dialytic modalities pretransplant were peritoneal dialysis in 42% and hemodialysis in 25%. Bilateral nephrectomy was reported in 29%. Live-donor sources accounted for 42% of the transplants. Among cadaveric donors, 41% of the donors were under 11 years old. During the first post-transplant month, maintenance therapy was used similarly for live-donor and cadaver source transplants, with prednisone, cyclosporine, and azathioprine used in 93%, 83%, and 81%, respectively. Triple therapy with prednisone, cyclosporine, and azathioprine was used in 78%, 75%, and 75% of functioning cadaver source transplants at 6 months, 12 months, and 18 months as opposed to 60%, 63%, and 54% for live-donor procedures, with single-drug therapy being uncommon. Rehospitalization during months 1–5 occurred in 62% of the patients, with treatment of rejection and infection being the main causes. Additionally, 9% were hospitalized for hypertension. During months 6–12 and 12–17, 30% and 28% of the patients with functioning grafts were rehospitalized. Times to first rejection differed significantly for cadaver and live-donor transplants. The median time to the first rejection was 36 days for cadaver transplants and 156 days for live-donor transplants. Overall, 57% of treated rejections were completely reversible although the complete reversal rate decreased to 37% for four or more rejections. One hundred and fifty-two graft failures had occurred at the time of writing, with a 1-year graft survival estimate of 0.88 for live-donor and 0.71 for cadaver source transplants. In addition to donor source, recipient age is a significant prognostic factor for graft survival. Among cadaver donors, decreasing donor age is associated with a decreasing probability of graft survival. Thirty-five deaths have occurred; 16 attributed to infection and 19 to other causes. The current 1-year survival estimate is 0.94. There have been 9 malignancies.

Characterization and clinical application of the "significance band" for acute respiratory alkalosis.

Abstract The acid-base composition of plasma during hypocapneic anesthesia in man has been used to construct a 95 per cent significance band defining the acute steady-state response to reduced carb...

Acquired Renal Scars in Children

To determine the important factors involved in the etiology of renal scarring we studied 37 children with renal scars seen at our hospital since 1965. This is the second largest series reported to date. Children who had neurogenic bladders or any structural abnormalities of the urinary tract other than vesicoureteral reflex were excluded. The study group included 36 girls and 1 boy. The average age at first detection of renal scars was 5.7 years. Acute pyelonephritic episodes, which were treated early and aggressively, infrequently led to renal scarring. However, the initial prolonged or poorly treated episode of acute pyelonephritis was followed invariably by the development of renal scarring. The severity of renal scarring was related to the grade of vesicoureteral reflux (p less than 0.05), although some scars did develop in the absence of reflux. Neither the shape and position of the ureteral orifice nor the ureteral tunnel length correlated with the severity of renal scarring. Treatment with prophylactic antibiotics may have lessened the severity of renal scarring (0.1 less than p less than 0.2) but treatment with reimplantation surgery did not appear to alter the course of renal scarring. This study suggests that the key to the prevention of renal scarring is the early and aggressive treatment of acute pyelonephritis.

Compliance with cyclosporine in adolescent renal transplant recipients.

Abstract.  Inadequate compliance with prescribed medication regimens in children is complex and poorly understood. We measured the extent and pattern of noncompliance with cyclosporine in our adolescent renal transplant population and attempted to determine factors associated with poor compliance. After informed consent, each patient was provided cyclosporine capsules in a medication bottle equipped with an electronic monitoring device (MEMS-4) in the lid. Of the 24 patients eligible, 19 patients (8 female, 11 male) completed the study. Four (21%) patients took less than 80% of the prescribed cyclosporine doses. Five (26%) patients took drug holidays involving ≥3 consecutive doses. There was a trend towards improved compliance with the evening dose (88.5% vs. 93.4%, P = 0.09) and a downward trend in compliance over the course of the study (P = 0.17). None of the variables tested were found to be associated with noncompliance. Experienced physicians and nurses were able to identify 2 of the 4 individuals who were identified by MEMS as noncompliant. Additionally, 2 of the 4 noncompliant patients demonstrated low cyclosporine trough levels (<50 ng/ml). Noncompliance with cyclosporine regimens occurs commonly in adolescent renal transplant recipients. Unexpectedly low cyclosporine levels are strongly suggestive of noncompliance, whereas other variables, including prediction by physicians and nurses intimately involved in the care, were not reflective of noncompliance.

Factors Influencing Patient and Graft Survival in 300 Cadaveric Pediatric Renal Transplants

We reviewed the results of 300 cadaveric pediatric renal transplantations performed at our institution. The procedures provided significant survival and improvement of the quality of life in the majority of children. Recipient and graft survival was better in patients more than 5 years old than in younger children. Early nontechnical thrombosis was a major specific problem in young recipients. The original disease did affect graft survival. Uncorrected congenital bladder storage and micturition inefficiency adversely affected graft survival.

Focal segmental glomerulosclerosis with idiopathic nephrotic syndrome: Three types of clinical response

In a retrospective analysis, 51 patients with focal segmental glomerulosclerosis and idiopathic nephrotic syndrome, who were treated with steroid or cyclophosphamide therapy, were divided into three clinical groups according to the remission profile of their nephrotic syndrome. Group 1 patients (19.37%) consistently responded to medication; none has progressive renal failure (mean follow-up 10.6 years). Group 2 patients (25, 40%) failed to respond to medication; terminal renal failure has occurred in 12 of them. Group 3 patients (7, 14%) initially appeared to be responsive to medication and continued to respond for up to 18 months, but subsequently became unresponsive to any therapy; five of them have required dialysis or transplantation. This third group of patients could not be separated clinically or pathologically from group 1 patients, all of whom have an excellent prognosis. One should, therefore, be cautious about predicting the outcome of steroid-responsive nephrotic patients, especially those with FSGS, until at least 18 months after the onset of illness.

Survival of cadaveric renal transplant grafts from young donors and in young recipients

Evidence from multicenter registries has suggested that cadaveric renal graft survival is poorer when either the recipient or the donor is very young. We therefore analyzed our results from a single pediatric center. There was a significant correlation between greater recipient age and improved cadaveric graft (P=0.002) and patient (P=0.0009) survival. The age of the donor also appeared important, particularly in very young children, but became less so as donor age rose. Forty-four percent of recipients under 3 years old who received cadaveric kidneys from donors less than 4 years old lost their grafts as a result of renal thrombosis, ischemia, or technical problems, compared with only 3% of recipients over 9 years of age, whose grafts came from donors who were also over 9 years. The 1-year first cadaveric graft survival rates for these two age groups were 33% and 82% respectively. Our experience confirms the poor findings reported in very young recipients and with very young donors.

A randomized prospective crossover trial of amlodipine in pediatric hypertension

Abstract Amlodipine has potential advantages in children since it can be dissolved into a liquid preparation and has a long elimination half-life, allowing for once-daily administration. The objective of this study was to compare the efficacy and compliance of amlodipine with that of standard long-acting calcium channel blockers (felodipine or nifedipine) in hypertensive children. A randomized, prospective, crossover study of 11 hypertensive children (9–17 years of age, 10 renal transplant patients) was performed with electronic monitoring of compliance. Each treatment arm was 30 days. No significant differences were observed in mean systolic (SBP) and diastolic blood pressures (DBP) between amlodipine and the other calcium channel blockers. Using 24-h blood pressure monitoring there were no significant differences over each drug treatment period in both mean day-time and night-time SBP and DBP. Patient compliance was similar in both the amlodipine and the nifedipine/felodipine treatment periods. These data suggest that amlodipine is as effective in pediatric nephrology patients as nifedipine and felodipine. Amlodipine may be optimally suited for treatment of young children because at present it is the only calcium channel blocker which can be administered once daily as a liquid preparation.

Effective removal of methotrexate by high-flux hemodialysis

Abstract. The purpose of the present study was to examine the clearance of methotrexate (MTX) by high-flux hemodialysis (HD) in pediatric oncology patients. We present three patients who experienced nephrotoxicity and prolonged exposure to toxic MTX concentrations following high-dose infusions during treatment for osteogenic sarcomas. Each patient was successfully treated with high-flux HD, followed by carboxypeptidase G2 (CPDG2) in two cases. Minimal systemic toxicity occurred. We review the literature and discuss guidelines for early and aggressive treatment for this complication of high-dose MTX therapy. Clinically important removal of MTX depends upon prompt initiation of HD after detection of nephrotoxicity and delayed clearance of MTX. Therapy is indicated in cases where compassionate use of CPDG2 may not be available, or while awaiting its delivery.