UGT1A9, UGT2B7, and MRP2 genotypes can predict mycophenolic acid pharmacokinetic variability in pediatric kidney transplant recipients.

BACKGROUND: Mycophenolic acid (MPA) exposure in pediatric patients with kidney transplant receiving body surface area (BSA)-based dosing exhibits large variability. Several genetic variants in glucuronosyltransferases (UGTs) and of multidrug resistance-associated protein 2 (MRP2) have independently been suggested to predict MPA exposure in adult patients with varying results. Here, the combined contribution of these genetic variants to MPA pharmacokinetic variability was investigated in pediatric renal transplant recipients who were on mycophenolic mofetil maintenance therapy. METHODS: MPA and MPA-glucuronide concentrations from 32 patients were quantified by high-performance liquid chromatography. MPA exposure (AUC) was estimated using a 4-point abbreviated sampling strategy (predose/trough and 20 minutes, 1 hour, and 3 hours after dose) using a validated pediatric Bayesian estimator. Genotyping was performed for all of the following single nucleotide polymorphisms (SNPs): UGT1A8 830G>A(*3), UGT1A9 98T>C(*3), UGT1A9-440C>T, UGT1A9-2152C>T, UGT1A9-275T>A, UGT2B7-900A>G, and MRP2-24T>C. RESULTS: Recipients heterozygous for MRP2-24T>C who also had UGT1A9-440C>T or UGT2B7-900A>G (n = 4), and MRP2-24T>C-negative recipients having both UGT1A9-440C>T and UGT2B7-900A>G (n = 5) showed a 2.2 and 1.7 times higher dose-dependent and BSA-normalized MPA-AUC compared with carriers of no or only 1 UGT-SNP (P < 0.001 and P = 0.01, respectively) (n = 7). Dose-dependent and BSA-normalized predose MPA concentrations were 3.0 and 2.4 times higher, respectively (P < 0.001). Interindividual variability in peak concentrations could be explained by the presence of the UGT1A9-440C>T genotype (P < 0.05). CONCLUSION: Our preliminary study demonstrates that combined UGT1A9-440C>T, UGT2B7-900A>G, and MRP2-24T>C polymorphisms can be important predictors of interindividual variability in MPA exposure in the pediatric population.

Effectiveness of home visits to pediatric peritoneal dialysis patients.

Home visits by trained personnel to patients undergoing home dialysis are required, but little is reported about the effectiveness of such home visits. We retrospectively reviewed home visits to 22 pediatric patients undergoing continuous cycling peritoneal dialysis (PD) at home. A trained dialysis nurse completed each home visit. An average of 1.5 pertinent dialysis findings and 1 pertinent medication finding was noted for each home visit to these patients. The interdisciplinary dialysis team reviewed the home visit findings and made specific recommendations after each home visit. In addition, the training process has been enhanced to incorporate visit findings for future home PD patients. Although not statistically significant in this small number of patients, peritonitis rates declined in the 6 months after initiation of the home visit program. The average cost for a dialysis nurse to complete a home visit is less than the cost of antibiotics for 1 episode of peritonitis. Home visits are valuable for improving clinical care in pediatric patients on home PD.

Factors related to long-term renal transplant function in children.

Short-term renal allograft survival in children has improved. It is therefore important to determine the factors leading to long-term graft function. To this end, we evaluated patients in the NAPTRCS registry who were <12 years old when they received their renal transplant between 1987 and 1993. Children with 10 years of post-transplant follow-up were compared to those in whom the transplant failed within 10 years. Children with a failed transplant within 10 years of the surgery tended to be older, female, and non-Caucasian; they also manifested obstructive uropathy less often and had focal segmental glomerulosclerosis more often, and they received more deceased donor kidneys. Children with a failed renal transplant had fewer HLA donor and recipient matches, received pre-transplant dialysis compared to a preemptive transplant, required dialysis in the first week post-transplant, and required more antihypertensives the first month post-transplant. Allograft function was examined at 10 years. Patients with continued allograft function and a serum creatinine

Hajdu-Cheney syndrome: report of a case.

Hajdu-Cheney syndrome is a rare disorder characterized by short stature, joint hypermobility, distinctive craniofacial and skull abnormalities, dental anomalies, and acroosteolysis of the distal phalanges. Cystic kidneys have been associated with some cases. We report a case of a 12-year-old girl with renal failure who underwent bilateral nephrectomies. Histopathological examination revealed polycystic kidneys with numerous nodules located throughout the kidney composed of basaloid epithelial cells.

Management of childhood hypertension: a guide for primary care physicians.

Prevalence of pediatric hypertension has increased with the onset of obesity epidemic. Early detection and treatment of childhood hypertension is important due to its link with atherosclerosis in adult life. Accurate measurement of blood pressure is the key for the management and physicians should make effort to rule out the possibility of anxiety associated and white coat hypertension before the final diagnosis of hypertension. Secondary hypertension is more common in children as compared to adults but essential hypertension is also common in older children and adolescents. The younger children with severe hypertension are more likely to have secondary hypertension. Non-pharmacologic treatment should be tried before instituting the pharmacologic treatment, unless patient is symptomatic and has severe hypertension.

Nontuberculous mycobacterial exit-site infection and abscess in a peritoneal dialysis patient. A case report and review of the literature.

Nontuberculous mycobacterial infections of peritoneal dialysis catheter exit sites have rarely been reported in patients on peritoneal dialysis. We report here a case of Mycobacterium abscessus exit site infection with abdominal wall abscess formation in an adolescent on peritoneal dialysis, which required long-term antibiotic therapy, peritoneal dialysis catheter removal, and surgical debridement of the abscess. Nontuberculous mycobacteria should be considered as a possible causative organism for an exit site infection that fails to respond to usual antibiotic therapy. Nontuberculous mycobacterial exit site infections may require peritoneal dialysis catheter removal and surgical debridement.

Diabetes mellitus and the kidney in adolescents.

Diabetic nephropathy continues to be a major complication of both types I and II diabetes; renal disease in the two types of diabetes exhibits no major differences with regard to initiation, progression, or treatment. The increasing prevalence of type II diabetes among adolescents means that understanding diabetic nephropathy and its prevention and treatment strategies is increasingly important for physicians caring for this population. The most important prevention and treatment modalities for diabetic nephropathy are improved glycemic control and aggressive blood pressure control, beginning as soon as possible after the diagnosis of diabetes.

Polyoma nephropathy and progressive multifocal leukoencephalopathy in a renal transplant recipient.

Progressive multifocal leukoencephalopathy is a progressive and ultimately fatal white-matter disease of the brain that is associated with polyomavirus infection. It is uncommon in the general population, and even in the immunosuppressed patient, who is inherently at greatest risk for active infection with the virus, it is rare. The causative agent in progressive multifocal leukoencephalopathy, JC virus, has become increasingly important in recent years as its role in nephropathy in the renal transplant recipient has become better understood. We present a young renal transplant patient who developed nephropathy with renal biopsy changes consistent with polyomavirus lesions and then developed mental status changes and was diagnosed with progressive multifocal leukoencephalopathy.

"Flush before fill" in children receiving automated peritoneal dialysis.

OBJECTIVE: To evaluate the impact of the "flush before fill" technique on the frequency of peritonitis in children receiving automated peritoneal dialysis (APD). DESIGN: Randomized prospective multicenter study. SETTING: Participating pediatric dialysis programs of the Pediatric Peritoneal Dialysis Study Consortium. PATIENTS: 121 pediatric (< 21 years of age) patients that had received peritoneal dialysis for > or = 2 months and that were currently receiving APD were randomized to use (flush group) or non-use (no flush group) of the "flush before fill" option. 66 patients were followed for > or = 12 months. MAIN OUTCOME MEASURE: Peritonitis rates. RESULTS: Overall, patients enrolled in the flush group experienced a peritonitis rate of 1 infection every 16.8 patient months; patients in the no flush group experienced a rate of 1 infection every 12.6 patient months (p = 0.193). However, analysis by gender revealed the peritonitis rate of females in the flush group (1 infection every 44.7 patient months) to be significantly better than females in the no flush group (1 infection every 12.4 patient months) (p < or = 0.01). There was no difference noted in the male patients. CONCLUSION: The use of the "flush before fill" option in pediatric patients receiving APD is associated with a marked improvement in the peritonitis rate of female but not male patients. Further study is indicated to explain the gender differences.