Encephalopathy in infants and children with chronic renal disease.

The examination of five pediatric patients with encephalopathy secondary to chronic renal failure has indicated a stereotyped sequence of neurologic signs and symptoms including ataxia, loss of motor abilities, myoclonus, seizures, dementia, and bulbar dysfunction. Both the patients with CNS dysfunction and a control group selected for a similar degree of renal failure had increased levels of serum phosphate, alkaline phosphatase, and parathyroid hormone. Serial EEGs in the affected group revealed progressive slowing and an increase in paroxysmal features. No specific neuropathologic findings were noted in one patient.

Adverse effects of mycophenolate mofetil in pediatric renal transplant recipients with presumed chronic rejection.

BACKGROUND: Mycophenolate mofetil (MMF) has been shown to be superior to azathioprine in reducing the incidence of acute rejection in adult renal transplant recipients. Although MMF is also being widely used in pediatric transplant patients, data documenting its safety are limited. METHODS: A retrospective review of the transplant records at St. Christopher's Hospital for Children was conducted to identify patients who had received MMF. RESULTS: Twenty-four children were switched from azathioprine to MMF, 4.8+/-2.9 years after transplantation. After an additional 0.8+/-0.4 years, MMF had been discontinued in 13 patients (54%) because of adverse effects (AE). The only variable that predicted the development of AE was a lower calculated creatinine clearance at the time of initiation of MMF. CONCLUSIONS: In pediatric renal transplant recipients with impaired renal function, the use of MMF at the recommended dose is associated with an unacceptably high incidence of AE; in such patients, the MMF dose may require modification for the level of renal function.

Effect of recipient's race on pediatric renal allograft survival: a single-center study.

One hundred twenty-seven children (83 males, 44 females, 86 white, 41 nonwhite; mean age 12.1 years) who received 160 renal transplants between 1980 and 1989 were retrospectively studied. Variables such as age, sex, primary diagnosis, type, HLA-DR mismatching, and repeated transplants were compared between races and found not to be significant. However, HLA-A and -B cadaveric-graft mismatching, which was equivalent between whites and nonwhites prior to 1985 (pre-cyclosporine A era), has significantly favored whites (49% with 0 to 2 HLA-A and -B mismatch vs 16% in nonwhites) since 1985 (P less than .05), and a significantly higher proportion of nonwhite patients (59%) were receiving medical assistance (P less than .0001). Graft survival was evaluated with significantly poorer results in nonwhites as compared to whites (P less than .05). Although no difference was found between white and nonwhite cadaveric-graft survival before 1985, nonwhites had significantly worse graft survival since 1985 (72% vs 59% for 1 year and 61% vs 24% for 3 years in whites and nonwhites, respectively; P less than .05). Subpopulations such as nonwhite adolescents, nonwhite females, nonwhites with repeated transplants, and all low socioeconomic patients were identified as high-risk children with poor long-term survival. It is concluded that secondary to poorer matching since 1985 there has been decreased graft survival in nonwhites despite cyclosporine A. Attempts to improve matching and attention to high-risk groups are needed for equivalent survival.

Transperitoneal solute movement in children.

The transperitoneal movement of solute in children was examined by means of a theoretical consideration of the peritoneal clearance formula and by the performance of peritoneal solute diffusion curves and measurement of peritoneal clearances of multiple solutes. Theoretical considerations led to the conclusion that when dialysis mechanics are held constant, peritoneal clearances scaled for weight are similar in individuals of widely varying weight when the volume of infused dialysate is also scaled for weight if peritoneal permeability and surface area are constant. In one group of studies, solute diffusion curves and weight-scaled peritoneal clearances of urea, phosphate, creatinine, and urate were similar in 3 children ages 4 to 18 months compared to 4 children ages 2.5 to 18.5 years. In a second group of studies, weight-scaled peritoneal clearances of inulin but not urea were shown to be marginally lower in 4 children who had been dialyzed longer than 6 months compared with 4 children dialyzed less than 1 month. Hypertonic glucose dialysis in these children was shown to enhance urea clearance but not that of inulin. It is concluded that comparative studies of peritoneal clearances can characterize the transperitoneal movement of solute in children of widely varying body size. Such studies are of greatest value when systematically performed and similar ratios of dialysate volumes to body pools of solute are used.

Pharmacokinetics of cyclosporine after renal transplant in children.

The pharmacokinetics of cyclosporine and the relationship between blood levels and average drug concentration were prospectively evaluated in 18 children 1 month after renal transplantation. All children had normal renal function and no hepatic or gastrointestinal dysfunction. Cyclosporine was administered after an overnight fast, and serial blood samples were drawn over a 24-hour period. Analysis of cyclosporine levels was performed by means of monoclonal radio immunoassay on whole blood. Children were divided into three age groups for comparison: 2-5 years, 5-10 years, and > 10 years. There were no differences between age groups in serum protein, serum lipids, or hemoglobin levels, or in the pharmacokinetic parameters of cyclosporine except as follows: significant differences were noted in cyclosporine dose based on body weight, apparent steady-state volume of distribution, and apparent blood clearance, with the youngest children (2-5) requiring higher doses, a relative greater distribution, and exhibiting more rapid drug clearance than those > 10 years of age. In addition, we observed diurnal variation in trough levels, with morning levels (0 hr) significantly higher than those obtained in the evening (12 hours after administration of cyclosporine). Trough levels demonstrated a fair correlation with area under the concentration-time curve (AUC) and average concentration (Cav), but an abbreviated kinetic profile using cyclosporine levels 1 and 3.5 hours after administration accurately predicted AUC.

Urolithiasis in childhood.

Urolithiasis occurs less frequently in children than it does in adults living in contemporary industrialized nations. However, renal calculi continue to be identified with greater frequency in certain children: those who live in some areas of North America (e.g., the Southeastern United States), in those with relatively common metabolic disorders such as idiopathic hypercalciuria or with congenital urinary tract malformations, and in patients who have remained immobilized for long periods. Evaluation of children with suspected urolithiasis should include a careful history and physical examination to identify associated symptoms and signs and factors known to predispose to calculus formation, appropriate radiographic and blood studies, and timed urine collections. Appropriate management varies with etiology but should include maintaining adequate fluid intake, and long-term monitoring of the activity of the stone disease.

Fusarium peritonitis in a child on peritoneal dialysis: case report and review of the literature.

OBJECTIVE: To review various aspects of the management of peritonitis due to Fusarium, a soil mold which infrequently causes infections in humans. DATA SOURCES: A case of Fusarium peritonitis in a child on chronic peritoneal dialysis (PD) is presented. The child developed Fusarium peritonitis 2 weeks after an episode of bacterial peritonitis. His Tenckhoff catheter was removed, and he was maintained on hemodialysis while receiving intravenous amphotericin. Following 2 weeks of treatment with amphotericin, he was successfully returned to PD. A literature review of all previously reported cases of Fusarium peritonitis was then conducted to determine features common to infections caused by Fusarium. Emphasis was also placed on unique characteristics of the organism that may affect patient management, as well as patient characteristics that may increase the risk for infection by Fusarium. RESULTS: Fusarium may cause infection in immunosuppressed individuals, such as cancer patients or patients on chronic PD. The organism has a propensity to attach to foreign bodies such as intravascular and intraperitoneal catheters. Therefore, successful treatment of infections caused by Fusarium may require catheter removal in addition to systemic antifungal therapy. CONCLUSIONS: This report presents the first known case of Fusarium peritonitis in a child. In view of the difficulties posed by this unusual organism, optimal therapy of Fusarium peritonitis should consist of immediate catheter removal and treatment with systemic antifungal drugs.

Growth of children following the initiation of dialysis: a comparison of three dialysis modalities.

Maintenance dialysis usually serves as an interim treatment for children with end-stage renal disease (ESRD) until transplantation can take place. Some children, however, may require dialytic support for an extended period of time. Although dialysis improves some of the problems associated with growth failure in ESRD (acidosis, uremia, calcium, and phosphorus imbalance), many children continue to grow poorly. Therefore, three different dialysis modalities, continuous ambulatory peritoneal dialysis (CAPD), cycler/intermittent peritoneal dialysis (CPD), and hemodialysis (HD), were evaluated with regard to their effects on the growth of children initiating dialysis and remaining on that modality for 6-12 months. Growth was best for children undergoing CAPD when compared with the other two modalities with regard to the following growth parameters: incremental height standard deviation score for chronological age [-0.55 +/- 2.06 vs. -1.69 +/- 1.22 for CPD (P < 0.05) and -1.80 +/- 1.13 for HD (P < 0.05)]; incremental height standard deviation score for bone age [-1.68 +/- 1.71 vs. -2.45 +/- 1.43 for CPD (P = NS) and -2.03 +/- 1.28 for HD (P = NS)]; change in height standard deviation score during the dialysis period [0.00 +/- 0.67 vs. -0.15 +/- .29 for CPD (P = NS) and -0.23 +/- .23 for HD (P = NS)]. The reasons why growth appears to be best in children receiving CAPD may be related to its metabolic benefits: lower levels of uremia, as reflected by the blood urea nitrogen [50 +/- 12 vs. 69 +/- 16 mg/dl for CPD (P < 0.5) and 89 +/- 17 for HD (P < 0.05)], improved metabolic acidosis, as indicated by a higher serum bicarbonate concentration [24 +/- 2 mEq/l vs. 22 +/- 2 for CPD (P < 0.05) and 21 +/- 2 for HD (P < 0.05)]. In addition, children undergoing CAPD receive significant supplemental calories from the glucose absorbed during dialysis. CAPD, and possibly, other types of prolonged-dwell daily peritoneal dialysis appear to be most beneficial for growth, which may be of particular importance for the smaller child undergoing dialysis while awaiting transplantation.

Predicting the response to cytotoxic therapy for childhood nephrotic syndrome: superiority of response to corticosteroid therapy over histopathologic patterns.

To determine the utility of steroid response in classifying childhood nephrotic syndrome, we reviewed 119 biopsies in 92 children aged 1 to 16 years who had been followed for a mean of 7.2 years. Steroid responses were classified as steroid resistant, steroid dependent, and frequent relapser as defined by the International Study of Kidney Disease in Children. Biopsy specimens were classified as showing focal glomerulosclerosis (FSGS) in 39 children, as showing lipoid nephrosis in 28, and as questionable in another 25 with either focal global sclerosis, IgM nephropathy, or mesangial prominence and tubular changes. A strong agreement (p less than 0.01) was found between children whose FSGS was steroid resistant and children whose lipoid nephrosis resulted in frequent relapses. The length of the remission after therapy with chlorambucil or cyclophosphamide was determined in 84 children. A significantly shorter length of remission after cytotoxic drug therapy (p less than 0.05) was identified for patients with FSGS versus those with lipoid nephrosis; this difference became more significant for steroid-resistant patients in comparison with those who were steroid dependent or were frequent relapsers (p less than 0.005). Among all steroid-resistant patients, those with FSGS had shorter remissions than patients with other histologic changes (p less than 0.001). The data suggest that patterns of response to corticosteroid therapy correlate with the histologic abnormality. Thus steroid-sensitive patients need not undergo renal biopsy before receiving cytotoxic drugs. Steroid-resistant patients would benefit from a biopsy, because the findings tend to predict the outcome.

Cerebral infarct with recurrence of hemolytic-uremic syndrome in a child following renal transplantation.

A white girl with a history of atypical hemolytic-uremic syndrome (HUS) and persistent microangiopathic anemia, and thrombocytopenia for 2 months after the initial presentation at age 7 months, received her first cadaveric renal transplant at age 3 years. During the first 2.5 days post transplant, she developed progressive thrombocytopenia and anemia followed by tonic-clonic seizures and loss of consciousness, secondary to a diffuse cerebral infarction of the left hemisphere. Renal histology showed evidence of glomerular microthrombi and microangiopathy. A large cerebral infarct, previously described in patients during their initial presentation with HUS, presented in our patient as part of the recurrence of the disease post renal transplantation.

Response to measles-mumps-rubella vaccine in children on dialysis.

Ten children receiving maintenance dialysis were immunized with the standard dose of measles-mumps-rubella vaccine between 15 and 33 months of age. Immune responses to vaccination were determined using commercially available enzyme-linked immunosorbent assays for measles, mumps, and rubella viruses. Eight children responded to measles vaccine, 5 to mumps vaccine, 8 to rubella vaccine, and only 3 children to all three vaccines, compared with a seroconversion rate of over 90% to all three vaccines in healthy children (P less than 0.0001). We contend that the relatively poor immunocompetence of our dialysis patients explains their less than optimal vaccine response and suggest that children vaccinated while undergoing dialysis be tested to confirm serological evidence of immunity.

Uric acid in childhood essential hypertension.

Serum uric acid concentrations and the fractional excretion of uric acid were determined in 31 children from 3 1/2 to 18 years of age with essential hypertension. While on an unrestricted sodium intake, elevated serum values of uric acid were found in 13 of 31 (42%) of the children. After ingesting a low-sodium diet (200 mg/day) for three days, mean serum uric acid values increased by 0.7 mg/dl (P less than 0.001). There was a significant inverse correlation between the serum uric acid concentrations and fractional excretion of uric acid during the normal and low-sodium diet. This study indicates that the major factor leading to hyperuricemia in our hypertensive patients was a decrease in urate clearance. Insofar as hyperuricemia may represent a cardiovascular risk factor, this abnormality already exists in a significant fraction of hypertensive children and adolescents.

Neurologic development of children with severe chronic renal failure from infancy.

A literature review was conducted to summarize current understanding of the effects of severe chronic renal failure (CRF), when present from infancy, on neurologic development. Data were obtained from the results of 95 examinations performed in 85 patients, most of whom had been studied after 12 months of age, or following initiation of maintenance dialysis or successful transplantation. CRF was diagnosed at birth or during the neonatal period in 71.7% of these patients; serum creatinine concentrations or calculated clearances were greater than or equal to 2.0 mg/dl (177 mumol/l) or less than 15 ml/min per 1.73 m2, respectively, in 75.8%. Head circumferences were greater than 2 standard deviations below the mean for age in 33 of 51 (64.7%) patients. Developmental delay was identified in 63.2% of all cases, and in 29 of 48 (60.4%), 16 of 19 (84.2%), and 4 of 13 (30.7%) patients studied while receiving conservative management or maintenance dialysis, or following successful transplantation, respectively. Moderate to severe delays were commoner for gross motor and language development. No significant relationships could be identified between age or severity of CRF at diagnosis and either the prevalence or severity of developmental delay. Other factors that may have contributed to observed developmental delays are also discussed, including aluminum loading, hyperparathyroidism, undernutrition, and psychosocial problems. New data are presented and discussed, and recommendations for future studies provided.

Vesicoureteral reflux and urinary tract infections in renal transplant recipients.

Fifty-six children who received kidney transplants were evaluated for postoperative vesicoureteral reflux and frequency of urinary tract infection. Two methods of ureteral implantation were compared: a nonantireflux extravesicular ureteroneocystostomy and an antireflux intravesicular ureteroneocystostomy. Reflux was found in 79% of children who had the nonantireflux procedure vs 19% of children who had the antireflux procedure. This disparity was present regardless of sex and age. Infections occurred at a rate of one per 11 patient-months after the nonantireflux procedure vs one per 40 patient-months after the antireflux procedure. Regardless of surgical technique, the incidence of infection was higher in children with reflux. The potentially harmful effect of infection with reflux warrants concern. Because of the need to maximize allograft function for a longer time period, an antireflux procedure is recommended in all pediatric kidney transplants.

CT demonstration of cerebral subcortical calcifications.

Neurological abnormalities are a major cause of the morbidity associated with renal failure. Substantial elevations in parathormone levels have been found to accompany significant increases in brain content of calcium. Two cases of cerebral subcortical calcifications are demonstrated by computed tomography in patients with severe chronic renal failure. To our knowledge this finding has not been described previously.

Cefazolin in children with renal insufficiency.

Cefazolin (7 mg/kg) were administered to 11 children with renal insufficiency and to ten children on hemodialysis. The serum half-life of the drug was progressively prolonged as glomerular filtration rate fell. The serum half-life of cefazolin was variably prolonged in those children on hemodialysis, but their serum levels of cefaxolin had dropped by 35 to 65% during dialysis. Most had no measurable level prior to the next dialysis. Dosage recommendations are made for both groups of patients.

Predictive value of race in post-transplantation recurrence of focal segmental glomerulosclerosis in children.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a leading cause of end-stage renal disease (ESRD) in children, and one of the most difficult to manage because of its high recurrence rate post-transplantation (Tx). Several predictive factors have been associated with disease recurrence (DR) although one in particular, the role of recipient race, has not been adequately evaluated. Herein we report our experience with DR in the post-Tx period in eight patients. METHODS: Records were reviewed for all renal transplants performed at St Christopher's Hospital for Children from 1971 to 1997. RESULTS: Twenty patients received 27 allografts for ESRD due to FSGS. Ten (37%) grafts went to African-American (AA) children, and 16 (59%) to those of Caucasian (C) origin. DR was observed in eight (30%) grafts after Tx. No differences were noted between the patients who developed DR and those who did not, with respect to age at diagnosis or time to ESRD. DR was observed in one (10%) of 10 grafts in AA, compared to seven (41%) of 17 grafts in the other (O) racial groups (P=0.19). At last follow-up, the only AA recipient with DR has maintained stable renal function, while three (43%) of seven in O have lost their grafts. CONCLUSION: In conclusion, in our population post-Tx recurrence of FSGS occurred more frequently and represented a greater threat to graft survival in O recipients than in those of AA descent. Recipient race should therefore be taken into consideration during pre-Tx counselling of families of children with FSGS.