Proteinuria and focal segmental glomerulosclerosis in severely obese adolescents.

OBJECTIVE: To describe the clinical and laboratory features of obesity associated proteinuria and focal segmental glomerulosclerosis. STUDY DESIGN: The patients were seen over a 12-year period at two large children's hospitals. Renal biopsies, performed for the diagnosis of unexplained heavy proteinuria and prepared for light, immunofluorescent, and electron microscopy, were read independently by two pediatric pathologists. Blood pressure, body mass index, serum levels of creatinine, albumin, and cholesterol, and 24-hour urinary protein were measured. RESULTS: Seven African American adolescents were identified with obesity-associated proteinuria, which was characterized by severe obesity (120 +/- 30 kg), markedly elevated body mass index (46 +/- 11), mild hypertension (134/74 +/- 10/18 mm Hg), slightly low to normal serum albumin levels (3.6 +/- 0.2 g/dL), moderately elevated serum cholesterol levels (196 +/- 60 mg/dL), and elevated 24-hour protein excretion (3.1 +/- 1.3 g/dL). Calculated creatinine clearance was normal in 6 patients and decreased in one. Typical renal histologic features included glomerular hypertrophy, focal segmental glomerulosclerosis, increased mesangial matrix and cellularity, relative preservation of foot process morphology, and absence of evidence of inflammatory or immune-mediated pathogenesis. One patient showed a dramatic reduction in proteinuria in response to weight reduction. Three patients who were given angiotensin-converting enzyme inhibitors had reduced urinary protein losses from 2.9 g to 0.7 g per day. One patient developed end-stage renal disease. CONCLUSION: Obese adolescents should be monitored for proteinuria, which has distinct clinical and pathologic features and may be associated with significant renal sequelae. Such proteinuria may respond to weight reduction and/or treatment with angiotensin-converting enzyme inhibitors.

Is growth a valid outcome measure of dialysis clearance in children undergoing peritoneal dialysis?

OBJECTIVE: Our study evaluated growth as a clinical outcome measure of peritoneal dialysis (PD) adequacy in children with end-stage renal disease (ESRD). DESIGN: This retrospective single-center study was carried out in our tertiary-care medical center. PATIENTS: The study enrolled 24 patients who initiated dialysis after January 1, 1995, and who had been on dialysis for a minimum of 1 year. RESULTS: The weekly mean total [PD + residual renal function (RRF)] creatinine clearance (C(Cr)) and Kt/V(urea) were 70.3 +/- 18 L per 1.73 m2 and 3.45 +/- 0.73, respectively. Of the 24 patients, 12 (50%) were anuric. The mean height standard deviation score (SDS) changed to -1.78 at the end of 1 year from -1.58 at baseline. Catch-up growth (positive delta height SDS) was observed in 9 patients (37%), 7 of whom (78%) had residual renal function (RRF). In contrast, only 5 of 15 patients (33%) with a negative deltaSDS for height had RRF (p < 0.025). The mean height SDS in patients with RRF improved to -1.64 from -1.78; in patients without RRF, it worsened to -1.90 from -1.37 (p = 0.01). While the weekly total Kt/V(urea) in patients with RRF (3.53) was similar to that in patients without RRF (3.37, p = 0.6), only the native Kt/V(urea) had a significant (but weak) positive correlation with delta height SDS (r2 = 0.17, p = 0.04). In contrast, the total weekly C(Cr) was significantly higher (p = 0.001) in patients with RRF (81.1 L/1.73 m2) as compared with those without RRF (59.5 L/1.73 m2). However, only the native C(Cr)--and not the dialysis C(Cr)--had a significant (but weak) positive correlation with delta height SDS (r2 = 0.17, p = 0.04). CONCLUSIONS: These preliminary data provide evidence for a correlation between solute clearance and growth, with RRF exerting a significant influence on that outcome. The Kt/V(urea) data also appear to contradict the presumed equivalence of PD and native clearance in children with ESRD.

Success and safety of same-day kidney biopsy in children and adolescents.

Renal biopsy is crucial for the diagnosis, management, and monitoring of many kidney diseases. Although percutaneous renal biopsy is considered a routine safe procedure in children, the optimal length of in-hospital observation following the procedure is not yet known. We prospectively studied two comparable groups of children to compare the success and safety of performing native renal biopsy as an outpatient procedure versus keeping the children hospitalized post biopsy. Doppler ultrasonography of the biopsied kidney was performed approximately 2 weeks after the procedure. For 40 children the biopsy was performed on a same-day basis (study group) and another 15 children were kept for overnight observation (control group). All biopsies yielded adequate tissue for histopathological diagnosis. There was no difference between the two groups in the amount of reported pain and analgesics used after the procedure. Only 1 child in the study group was readmitted 5 days after the biopsy for 48 h, but no major complications were detected. The incidence of post-biopsy intra- or perirenal hematoma detection by sonography was not statistically different between the two groups (39% study group, 43% control group). Follow-up imaging studies were performed on 10 of the 20 children who had an early post-biopsy hematoma and all were completely normal. Patients and their families appreciated being discharged home the same day. In addition, total charges for hospitalization were significantly less for the study group than the control group. We conclude that in selected patients, same-day discharge after renal biopsy may be performed safely without an increased risk of complications.

Tenckhoff catheters prove superior to cook catheters in pediatric acute peritoneal dialysis.

Peritoneal dialysis (PD) is the most common form of renal replacement therapy in infants and young children with acute renal failure (ARF). The two most commonly used catheters for performing acute PD are the Cook catheter (CC), placed at the bedside, and the surgically placed Tenckhoff catheter (TC). In the present study, we compared the complications and survival rates of the two catheters. The records of 59 children (age, 1 day to 16.7 years) who underwent PD for ARF from March 1989 through June 1999 in our hospital were reviewed. The initial (primary) catheter was a TC in 22 patients and a CC in 37 patients. The age of the patients who received a primary TC (2.8 +/- 4.5 years) was no different than the age of those with a primary CC (1.4 +/- 2.0 years; P = not significant). The duration of use (mean +/- SD) of TCs (16.5 +/- 14.2 days) was significantly greater than the duration of CC use (4.9 +/- 4.2 days; P < 0.001). Only two patients with a TC (9%) developed complications, whereas 18 patients with a CC (49%) developed complications, 13 of whom required catheter replacement (P < 0.01). Thirty-five patients (59%) recovered renal function after undergoing dialysis for 11.5 +/- 8.0 days. Twenty-three of those patients (66%) required dialysis for more than 5 days. Only 4 patients with a primary CC had successful completion of dialysis without catheter-associated complications compared with 15 patients with a primary TC. Kaplan-Meier survival analysis showed that by day 6 of dialysis, only 46% of primary CCs were functioning without complications compared with 90% of TCs that were free of complications. We conclude that the use of a CC is associated with significantly more complications than a TC, and nearly one half of the CCs are likely to be nonfunctional beyond 5 days of dialysis, at a time when two thirds of the patients are still expected to be undergoing dialysis. Therefore, when possible, a TC should be the catheter of choice when initiating acute PD in children. In those patients for whom a CC is chosen as the initial catheter, an elective change to a TC should be considered once dialysis is expected to extend beyond 5 days.

Single-dose pharmacokinetics of a pleconaril (VP63843) oral solution in children and adolescents. Pediatric Pharmacology Research Unit Network.

Pleconaril is an orally active, broad-spectrum antipicornaviral agent which demonstrates excellent penetration into the central nervous system, liver, and nasal epithelium. In view of the potential pediatric use of pleconaril, we conducted a single-dose, open-label study to characterize the pharmacokinetics of this antiviral agent in pediatric patients. Following an 8- to 10-h period of fasting, 18 children ranging in age from 2 to 12 years (7.5 +/- 3.1 years) received a single 5-mg/kg of body weight oral dose of pleconaril solution administered with a breakfast of age-appropriate composition. Repeated blood samples (n = 10) were obtained over 24 h postdose, and pleconaril was quantified from plasma by gas chromatography. Plasma drug concentration-time data for each subject were fitted to the curve by using a nonlinear, weighted (weight = 1/Ycalc) least-squares algorithm, and model-dependent pharmacokinetic parameters were determined from the polyexponential parameter estimates. Pleconaril was well tolerated by all subjects. A one-compartment open-model with first-order absorption best described the plasma pleconaril concentration-time profile in 13 of the subjects over a 24-h postdose period. Pleconaril pharmacokinetic parameters (means +/- standard deviations) for these 13 patients were as follows. The maximum concentration of the drug in serum (Cmax) was 1,272.5 +/- 622.1 ng/ml. The time to Cmax was 4.1 +/- 1.5 h, and the lag time was 0.75 +/- 0.56 h. The apparent absorption rate constant was 0.75 +/- 0.48 1/h, and the elimination rate constant was 0.16 +/- 0.07 1/h. The area under the concentration-time curve from 0 to 24 h was 8,131.15 +/- 3,411.82 ng.h/ml. The apparent total plasma clearance was 0.81 +/- 0.86 liters/h/kg, and the apparent steady-state volume of distribution was 4.68 +/- 2.02 liters/kg. The mean elimination half-life of pleconaril was 5.7 h. The mean plasma pleconaril concentrations at both 12 h (250.4 +/- 148.2 ng/ml) and 24 h (137.9 +/- 92.2 ng/ml) after the single 5-mg/kg oral dose in children were higher than that from in vitro studies reported to inhibit > 90% of nonpolio enterovirus serotypes (i.e., 70 ng/ml). Thus, our data support the evaluation of a 5-mg/kg twice-daily oral dose of pleconaril for therapeutic trials in pediatric patients with enteroviral infections.

Neonatal outcome in pregnancies associated with renal replacement therapy.

Pregnancy in women receiving renal replacement therapy is not without risk to the mother and fetus. This article reviews the information on fetal outcome in pregnancies associated with renal transplantation and dialysis. The incidence of neonatal mortality, prematurity, and small-for-gestational-age infants is increased in pregnancies associated with maternal renal replacement therapy. Conversely, there does not appear to be a significant increase in the rate of congenital malformations. Whereas the fetal risk for inheritable renal disease is clearly defined in most cases, the risk associated with a host of new immunosuppressive medications is poorly understood. In addition, the newborn may be at risk for abnormalities in water homeostasis caused by the large solute load transferred from the mother receiving dialysis and requires close observation. Continued accumulation of clinical data will permit women receiving dialysis or with a kidney transplant to make informed decisions about current or future pregnancies.

Peritoneal penetration of amphotericin B lipid complex and fluconazole in a pediatric patient with fungal peritonitis.

Fungal peritonitis is a rare event in patients receiving peritoneal dialysis. This case report describes the blood and dialysate concentrations of fluconazole and amphotericin B following intravenous administration in a 5-month-old infant with Candida albicans peritonitis receiving continuous cyclic peritoneal dialysis. Fluconazole rapidly and efficiently penetrated the peritoneal fluid achieving concentrations that exceed the minimal inhibitory concentration (MIC) for most Candida species. In contrast, the amount of amphotericin B in the dialysate was below the limit of quantification despite measurable blood concentrations. This suggests that fluconazole represents a better choice for antifungal therapy because of its excellent peritoneal penetration.

Compliance with cyclosporine in adolescent renal transplant recipients.

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 > or = 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 noncompliance 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.

Nephrotic syndrome associated with an Epstein-Barr virus infection.

A 19-month-old child developed the nephrotic syndrome coincident with an Epstein-Barr virus (EBV) infection. This rare association was confirmed by EBV titers. There was a spontaneous resolution of the nephrotic syndrome temporally related to the abatement of the EBV infection.

Midodrine efficacy and pharmacokinetics in a patient with recurrent intradialytic hypotension.

Recurrent intradialytic hypotension, a complication of hemodialysis, is a consequence of an inadequate compensatory response or a paradoxic response to ultrafiltration-induced volume reduction. We report the use of midodrine, an alpha agonist, in an 18-year-old man with Bardet-Biedl syndrome and recurrent intradialytic hypotension. The clinical features of the intradialytic hypotensive spells are consistent with a paradoxic withdrawal of sympathetic activity, although an underlying abnormality in autonomic dysfunction cannot be excluded. Midodrine significantly increased the intradialytic blood pressure and decreased the intradialytic hypotensive episodes requiring intervention. The pharmacokinetic characteristics of the prodrug midodrine and the active metabolite de-glymidodrine in this patient with end-stage renal disease approximate those reported for patients with normal renal function. However, the prolonged terminal half-life for the active metabolite, de-glymidodrine, warrants careful administration in patients with renal failure.

Ultrasound findings in juvenile nephronophthisis.

The ultrasound finding of renal medullary cysts associated with increased echogenicity has been suggested to be diagnostic of juvenile nephronophthisis. The lack of cysts in several of our patients with juvenile nephronophthisis lead us to review the ultrasound findings at presentation in our patient population. Of 11 children with the diagnosis of juvenile nephronophthisis, 10 demonstrated increased echogenicity with loss of corticomedullary differentiation on initial ultrasound. Only 2 children had a single cyst each. On follow-up ultrasound, 2, 4.5, and 7 years later, 3 patients developed visible renal cysts. We conclude that at presentation the ultrasound finding consistent with the diagnosis of juvenile nephronophthisis is most often that of hyperechogenic kidneys without cysts; namely the lack of cysts does not rule out the diagnosis of juvenile nephronophthisis.

Interactions of drugs with the developing kidney.

Interactions between drugs and the kidney are necessary for renal drug elimination, metabolism, and occasionally for therapeutic effect. These interactions may result also in renal toxicity. Understanding the kidney's role in drug-handling helps the clinician to be aware of potential drug interactions and toxicity. Drug disposition, elimination, and toxicity may differ with development and are to be considered when prescribing drugs for children. Nephrotoxicity associated with drugs, although common, is usually reversible with discontinuation of the drug; however, when drug therapy with a well-known nephrotoxic drug (e.g., cisplatin) is necessary, pharmacologic modulators may play a role in limiting the associated nephrotoxicity.

Isoniazid-associated rhabdomyolysis.

We report the occurrence of rhabdomyolysis and hepatitis in a 17-year-old girl after the ingestion of up to 10.8 g of isoniazid. The initial isoniazid concentration in the blood was 1,230 mmol/L. There were no findings indicating the ingestion of other substances known to be associated with rhabdomyolysis. In addition to rhabdomyolysis (peak creatine phosphokinase 88,000 U/L), the patient had a significant elevation of her liver enzymes (peak aspartate aminotransferase 1,980 U/L). She recovered completely without evidence of liver or renal damage. Rhabdomyolysis and isoniazid-induced hepatitis are complications that should be considered when caring for patients with acute isoniazid ingestion.

Renal-pancreatic-hepatic dysplasia in siblings.

Fewer than 20 children with complete renal-pancreatic-hepatic dysplasia have been reported since first described in 1959. We report two brothers with renal-pancreatic-hepatic dysplasia, one of whom had hypertrophic cardiomyopathy and pancreatic exocrine insufficiency, previously unreported associated findings.

The treatment of Staphylococcus aureus nasal carriage in pediatric peritoneal dialysis patients.

This study evaluates the dialysis-related infection rate in children receiving peritoneal dialysis with Staphylococcus aureus nasal carriage. Children with S. aureus nasal carriage were randomized to treatment with rifampin and bacitracin or no treatment. The children were observed for one month after randomization for evidence of a S. aureus dialysis-related infection. Individuals with nasal carriage had a higher incidence of S. aureus dialysis-related infection than those patients without carriage (p < 0.05). Those children treated for nasal carriage had a lower dialysis-related infection rate than those who were untreated (p < 0.05). We conclude that children receiving peritoneal dialysis with nasal carriage of S. aureus are at a greater risk of developing a S. aureus dialysis-related infection. The treatment of nasal carriage in this population decreased the risk of a S. aureus dialysis-related infection.

Peritoneal dialysis in the neonatal period: outcome data.

Scant information exists on the prognosis of infants with renal failure who receive peritoneal dialysis in the first month of life. We reviewed the outcome of 23 such patients 1 year after the onset of renal failure. Diagnoses included acute tubular necrosis (11 infants), renal dysplasia (5), obstructive uropathy (4), polycystic kidney disease (1), renal vein thrombosis (1), and renal artery thrombosis (1). Seven of the eleven patients with acute tubular necrosis had had cardiac surgery. At 1 year, eight (35%) of the patients had died, six (26%) had a full recovery, seven (30%) were receiving long-term dialysis awaiting a transplant, and two (9%) had chronic renal failure. Effective dialysis, characterized by the reversal of metabolic disturbances or attainment of fluid balance, was accomplished in all patients. The mean duration of dialysis was 4.5 months (range, 0.1 to 12 months). The most common complications of dialysis were peritonitis and catheter exit site infection. Despite the provision of supplemental calories via nasogastric tube, the majority of patients receiving long-term dialysis showed impaired growth and mild developmental abnormalities. Peritoneal dialysis is an effective means of renal replacement therapy in the neonatal period; however, the morbidity and mortality rate for this population remains high.