Assessing associations between medication adherence and potentially modifiable psychosocial variables in pediatric kidney transplant recipients and their families.

Post-transplant immunosuppressant (IS) medication adherence is essential for long-term graft survival and relatively little is known about psychosocial barriers that interfere with optimum medication adherence in pediatric kidney transplant patients. The objective of this prospective observational cohort study was to assess the impact of modifiable psychosocial variables on medication adherence. Our hypothesis was that parental stress, dysfunctional parent-child interactions and child behavior problems would be associated with poorer medication adherence. Thirteen pediatric kidney transplant patients and their caregivers were enrolled. Transplant recipients who were able to read and caregivers of all the transplant recipients completed behavioral and attitudinal surveys. A subgroup of seven families dispensed their primary IS medication from an electronic monitoring vial (MEMS Smart Cap). For these patients, medication adherence was calculated by computing a ratio of the medication taken divided by the prescribed dose. In addition, for the entire group, serial IS levels were reviewed by two board certified pediatric nephrologists who categorized all 13 transplant recipient families as either 'probably adherent (PA)' or 'possibly non-adherent (PNA)'. Pearson correlation coefficients and independent samples Student t-tests were used to assess the association between medication adherence and psychosocial variables measured by standardized questionnaires. In this study, elevated parental stress, dysfunctional parent-child interactions, and child behavior problems were associated with poorer medication adherence. In addition, we found evidence to support the relationship between subjective dissatisfaction with appearance and poorer medication adherence. These findings suggest that pre-transplant recipient evaluations of risk factors for poor adherence are warranted.

The impact of dialysis and transplantation on children.

Effective methods to treat end stage renal disease (ESRD) in children have become available in the United States during the last 3 decades. Since the United States Congress created the Medicare ESRD Program in 1972, most children with ESRD have the option of Medicare insurance. Medicare expenditures for children with ESRD range from $14,000 for transplant recipients to $43,000 for dialysis patients per year. The tremendous expense of ESRD treatment has led to research to determine which treatment options are associated with the best health outcomes and the best value (quality/cost) for the money spent treating ESRD. The National Kidney Foundation's Dialysis Outcomes Quality Initiative recommends the use of quality of life and health status measures to gauge the impact of renal replacement therapy on quality of life in the ESRD population. In adult patients with renal failure, several generic and disease-specific quality of life measures have been validated and tested for reliability. In contrast, little research using validated and reliable health status measures has been performed in pediatric patients to measure the impact of ESRD. This article summarizes existing literature on how we currently measure the impact of dialysis and transplantation on children, discusses existing health status measures for children and adolescents, and describes how these measures might be used to improve our care of patients and long-term outcomes for children with kidney failure.

Does growth retardation indicate suboptimal clinical care in children with chronic renal disease and those undergoing dialysis?

Growth failure is an important problem for children with end-stage renal disease (ESRD). Patients receiving replacement therapy for longstanding renal failure since childhood are likely to report dissatisfaction with certain aspects of their lives, especially with final adult height. Additionally, recent data suggest that growth failure in children with ESRD is associated with adverse clinical outcomes, including more frequent hospitalizations, and increased mortality. Although poor growth is unlikely to be the cause of this increased morbidity, growth failure may be a marker for a group of patients at high risk of adverse events. In this review, the authors describe the prevalence of growth retardation in children in the US with chronic renal disease, and present recent data on morbidity associated with growth failure. After reviewing published reports documenting available strategies to optimize growth, the authors conclude that despite vigilance and aggressive clinical management, a subset of children with long-term renal insufficiency and ESRD may still have poor linear growth. A discussion of "optimal care" leads one to consider evidence of current variability in the management of growth retardation in ESRD, and the strengths and limitations of developing practice guidelines to optimize growth in this population.

Relation between pediatric experience and treatment recommendations for children and adolescents with kidney failure.

CONTEXT: Children and adolescent patients with renal failure are frequently cared for by adult subspecialists. While peritoneal dialysis is used in less than 17% of adults with kidney failure, it is the preferred dialysis treatment for children. National data show that 45% of children receiving dialysis are treated with peritoneal dialysis and pediatric nephrologists report its use in 65% of patients receiving dialysis. Whether differences in peritoneal dialysis use among children are due to the pediatric experience of the clinician has not been examined. OBJECTIVE: To assess whether the pediatric experience of nephrologists directly affects treatment recommendations for children with kidney failure. DESIGN: Cross-sectional survey using 10 case vignettes per survey based on random combinations of 8 patient characteristics (age, sex, race, distance from facility, cause of renal failure, family structure, education, and compliance). SETTING AND PARTICIPANTS: National random sample of office-, hospital-, and academic medical center-based adult and pediatric nephrologists, stratified by geographic region and conducted June to November 1999. Of 519 eligible physicians, 316 (61%) responded, including 191 adult and 125 pediatric nephrologists. MAIN OUTCOME MEASURE: Treatment recommendations for peritoneal dialysis vs hemodialysis, compared based on nephrologists' pediatric experience. RESULTS: After controlling for patient characteristics, pediatric nephrologists were 60% more likely than adult nephrologists to recommend peritoneal dialysis for identical patients (odds ratio, 1.61; 95% confidence interval, 1.35-1.92). This was true regardless of dialysis training, years in practice, practice setting, geography, or patient characteristics. CONCLUSIONS: Our data indicate that pediatric specialization of clinicians influences treatment recommendations for children and adolescents with end-stage renal disease. Referring children to adult subspecialists may lead to differences in treatment choices and processes of care.

Risk factors for urolithiasis in children on the ketogenic diet.

Kidney stones have been associated with use of the ketogenic diet in children with refractory seizure disorders. We performed a case-control study examining risk factors for the development of stones on the ketogenic diet, and prospectively followed children initiating the ketogenic diet to evaluate the incidence of urolithiasis. Clinical characteristics of 18 children presenting with stones (8 uric acid stones, 6 mixed calcium/uric acid stones, 1 calcium oxalate/phosphate stone, 3 stones not evaluated) were compared with characteristics of non-stone-forming children initiating the ketogenic diet at Johns Hopkins since July 1996. Since July 1996, 112 children initiating the ketogenic diet have been followed for development of stones. Follow-up times on the diet range from 2 months to 2.5 years. Of 112 children, 6 have developed stones (3 uric acid, 3 mixed calcium/uric acid stones) (0.8 children developing stones/ 100 patient-months at risk). Comparisons of children presenting with stones on the ketogenic diet with characteristics of the entire cohort initiating the ketogenic diet suggest younger age at diet initiation and hypercalciuria are risk factors for the development of stones. Prospective evaluation of children initiating the ketogenic diet revealed that almost 40% of patients had elevated fasting urine calcium: creatinine ratios at baseline; this increased to 75% after 6 months on the diet. Median urine pH was 5.5 at diet initiation, and remained at 6.0 thereafter. In a subset of patients tested, urinary citrate excretion fell from a mean of 252 mg/24 h pre diet initiation to 52 mg/24 h while on the diet. Uric acid excretion remained normal. Patients maintained on the ketogenic diet often have evidence of hypercalciuria, acid urine, and low urinary citrate excretion. In conjunction with low fluid intake, these patients are at high risk for both uric acid and calcium stone formation.

Racial differences in access to the kidney transplant waiting list for children and adolescents with end-stage renal disease.

CONTEXT: Renal transplantation is the treatment of choice for pediatric patients with end-stage renal disease (ESRD). Black patients wait longer for kidney transplants than do white patients. OBJECTIVE: To determine whether the increased time to transplantation for black pediatric patients is attributable not only to a shortage of suitable donor organs, but also to racial differences in the time from a child's first treatment for ESRD until activation on the cadaveric kidney transplant waitlist. DESIGN: National longitudinal cohort study. SETTING: US Medicare-eligible, pediatric ESRD population. PATIENTS: Children and adolescents

Immunizations for pediatric dialysis patients.

Children maintained on chronic dialysis are at high risk for infection, and although the burden of vaccine-preventable disease in this population has not been fully documented, primary care of these patients should include careful compliance with the routine childhood immunization schedule. There have been considerable changes in this schedule in recent years, and an update is provided. In addition the supplemental vaccines for pneumococcal and influenza vaccines are discussed. Where available, data regarding vaccine response in children on dialysis are presented.

[Hormone replacement therapy after endometrial or ovarian cancer]. / Traitement hormonal substitutif après cancer de l'endomètre ou de l'ovaire.

Use of hormonal replacement therapy after treatment of ovarian or endometrial cancer remains a matter of debate. Novel adjuvant therapies tend to increase the survival of these patients, who are exposed to risk factors of hormonal deficiency subsequent to primary therapy. Therefore, the aims of the present review of literature was to analyse epidemiologic and clinical parameters on behalf on hormonal replacement therapy in this population.

For-profit versus not-for-profit dialysis care for children with end stage renal disease.

OBJECTIVE: Over the last 2 decades, for-profit dialysis units have become the most common providers of renal replacement therapy for adults with end stage renal disease (ESRD) and have had an increasing role in the dialysis of children. We undertook a study to determine whether dialysis facility profit status influences the choice of dialysis therapy in the pediatric population. DESIGN: Cross-sectional study of national data from the Health Care Financing Administration. SETTING: Free-standing and hospital-based outpatient dialysis facilities in the United States. PATIENTS: A total of 1568 children and adolescents (

Plasmapheresis, intravenous cytomegalovirus-specific immunoglobulin and reversal of antibody-mediated rejection in a pediatric renal transplant recipient: a case report.

This is a pediatric case report illustrating the development of antibody (Ab)-mediated rejection in a patient with low levels of pretransplant anti-human leucocyte antigen (HLA) panel reactive antibodies (PRA). The clinical course of this patient suggests that aggressive use of a combination of plasmapheresis, monoclonal anti-T-lymphocyte antibody therapy, and intravenous immunoglobulin (IVIG) therapy can reverse Ab-mediated rejection in previously allosensitized pediatric transplant recipients.

What is the role for mycophenolate mofetil in pediatric renal transplantation?

Mycophenolate mofetil (MMF) has gained considerable popularity in pediatric renal transplantation. This popularity is largely a result of data from three large trials of MMF in adult cadaveric transplant patients who demonstrated a decreased rate of acute rejection episodes when treated with cyclosporin A (CsA), prednisone, and MMF compared with those receiving CsA, prednisone, and azathioprine (AZA) or placebo. However, the ability of MMF to reduce acute rejection appears to be limited to the first month post-transplant, and its effectiveness with microemulsion CsA or tacrolimus-based regimens has not been proven. In addition, there are currently no data that convincingly demonstrate that this agent improves graft survival, patient survival, graft function or protects against chronic rejection. Finally, there may be an increased risk for severe cytomegalovirus (CMV) disease and lymphoproliferative disorder with central nervous system involvement in patients treated with MMF. These data call into question the role of MMF in current immunosuppressive regimens.

When noncongophilic glomerular fibrils do not represent fibrillary glomerulonephritis: nonspecific mesangial fibrils in sclerosing glomeruli.

In addition to fibrillary glomerulonephritis (FGN), Congo red negative mesangial fibrils may commonly be seen in sclerosing glomerular diseases. Rarely, these nonspecific mesangial fibrils (NMF) may mimic fibrils in FGN and cause a differential diagnostic pitfall. Following an interesting case of sclerosing crescentic glomerulonephritis with abundant NMF (which is presented in some detail) we have reviewed our renal biopsy files for a period of two and a half years and found additional 16 cases where the presence of NMF warranted studies to exclude FGN and other diseases with fibrillary deposits. The immunofluorescence pattern characteristically seen in FGN was not present in any of these cases. Our data confirm that mesangial fibrillary material seen ultrastructurally in sclerosing glomeruli with negative or nonspecific immunofluorescence (IF) represents a nonspecific reaction of the mesangial matrix to chronic glomerular injury. The presence of NMF should not lead to the erroneous diagnosis of FGN. Negative or nonspecific immunofluoresence, localization to the mesangium in a usually segmental fashion, and the more bundle-like than random arrangement of fibrils are helpful diagnostic hints in differentiating NMF from fibrils in FGN.

CLCN5 chloride-channel mutations in six new North American families with X-linked nephrolithiasis.

BACKGROUND: X-linked nephrolithiasis, or Dent's disease, encompasses several clinical syndromes of low molecular weight (LMW) proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, and renal failure, and is associated with mutations in the CLCN5 gene encoding a kidney-specific voltage-gated chloride channel. Some patients from Europe have rickets, and all symptomatic patients confirmed by mutation analysis have been male. METHODS: We analyzed the CLCN5 DNA sequence in six new families with this disease. RESULTS: In three probands, a single-base substitution yielded a nonsense triplet at codons 28, 34, and 343, respectively, and in two families, one of which was Hispanic, we found single-base deletions at codons 40 and 44, leading to premature termination of translation. In the sixth family, a single-base change from C to T predicted substitution of leucine for serine at codon 244, previously reported in two European families with prominent rickets, though this patient of Ashkenazi origin did not have rickets. Each of these mutations was confirmed by restriction endonuclease analysis, or repeat sequencing and CFLP. The R34X mutation occurred in a Canadian infant with severe rickets. The family with the R28X nonsense mutation included one woman with recurrent kidney stones and another woman with glomerular sclerosis. In another family, a woman heterozygous for the W343X mutation also had nephrolithiasis. CONCLUSIONS: These studies expand the range of mutations identified in this disease, and broaden the phenotypic range to include clinically affected women and the first North American case with severe rickets.

Chronic renal insufficiency in children and adolescents: the 1996 annual report of NAPRTCS. North American Pediatric Renal Transplant Cooperative Study.

The 1996 annual report of the Chronic Renal Insufficiency Arm of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) summarizes descriptive data and highlights important features on 1,725 patients from 130 centers. This database contains information on patients with an estimated glomerular filtration rate (GFR) < or = 75 ml/min per 1.73 m2 as calculated by the Schwartz formula, who were treated on or after 1 January 1994. Thus this report reflects 2 years of data entry. Analysis of the data revealed that nearly two-thirds of patients registered had a structural anomaly. On average, patients were 1.5 standard deviations below age- and sex-specific norms for height, and 0.6 standard deviations below weight norms. Mean serum creatinine for the entire group was 2.4 mg/dl and 68% of patients had a baseline GFR of at least 25 ml/min per 1.73 m2. The mean hematocrit for all children at registration was 33.3 +/- 6.3%, and did not vary among age groups. Overall, 30.9% of patients had a hematocrit < 30%. Only 12.8% of patients were receiving Epoetin therapy. Although still in infancy, the Chronic Renal Insufficiency Arm of the NAPRTCS database in providing important insights into this disorder.

Immunization guidelines for pediatric renal disease.

It is imperative that pediatric nephrologists monitor the immunization status of pediatric chronic renal insufficiency, dialysis and transplantation patients closely to reduce the risk of vaccine-preventable disease. Pediatric patients with chronic renal insufficiency and those on dialysis should receive all the standard immunizations according to the schedule as deliniated by the Red Book. In addition to these standard vaccines, these patients will also benefit from influenza and pneumococcal vaccine. Pediatric renal transplant recipients should also be immunized with standard and special vaccines; however, all live viral vaccines should be avoided in this population. Because patients with renal disease may not respond optimally to all immunizations, it is important to study antibody response to MMR and varicella in patients before transplantation. If these patients are unprotected, they should be immunized before transplantation. It seems that pediatric dialysis and transplantation patients may not respond optimally to hepatitis B vaccine. Therefore, if at all possible, this vaccine should be administered before these therapies. Doubling the recommended dose of hepatitis B vaccine may improve response. Antibody levels to hepatitis B should be monitored every other year, and this vaccine should be readministered when the antibody level decreases to less than 10 mIU/mL. Hopefully the morbidity and mortality associated with vaccine-preventable disease can be reduced in this population by ensuring that pediatric patients with chronic renal disease are adequately immunized.

Renal disease in Down syndrome: autopsy study with emphasis on glomerular lesions.

A range of renal diseases have been previously described in patients with Down syndrome. With increased survival, it appears that a growing number of these patients present with chronic renal failure. Definition of underlying causes of renal failure could potentially lead to prevention of progressive renal dysfunction in this population. We report two index cases of teenaged Down patients who presented with proteinuria and focal segmental glomerulosclerosis with hyalinosis, not previously described in this population. In addition, autopsy files were reviewed at the Johns Hopkins Hospital to assess renal and especially glomerular pathology in Down patients. Additional cases, including acute glomerulonephritis with early crescents and vasculitis, minimal change disease, and membranous nephropathy, were identified; the latter two diseases had not been previously reported in patients with Down syndrome. Semiquantitative studies on glomerular changes in all cases examined through autopsy also were performed. The only pathological finding that was significantly more common in the Down syndrome group, compared with age-matched cases from the autopsy files, was cystic dilation of Bowman's space. Histological findings described as increased in the Down population in previously published autopsy studies were also present in the control population, highlighting the need to adequately control such studies. The cases of acquired glomerular disease reported here were seen largely after the first decade of life. Monitoring of Down patients for renal and especially glomerular disease should be done regularly as patients age into the second and third decades.

Recommended immunization practices for pediatric renal transplant recipients.

To reduce the risk of morbidity and mortality from vaccine preventable disease, it is imperative that physicians caring for pediatric renal transplant recipients monitor the immunization status of their patients and keep abreast of changes in the recommended immunization guidelines. An update of the standard immunization guidelines of the AAP, ACIP and AAFP is provided, as well as the necessary modifications for and additional vaccines recommended for immunocompromised individuals. Where available, data regarding the safety of and response to the various vaccines in pediatric transplant patients are provided.

Effect of parental donor sex on rejection in pediatric renal transplantation: a report of the North American Pediatric Renal Transplant Cooperative Study.

Using the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) database, we performed a retrospective cohort study of 1,552 pediatric renal transplant patients who had received a graft from a biological parent to determine if parental donor sex influences the development of rejection. There were 102/675 (15.1%) graft failures in paternal grafts compared to 144/877 (16.4%) graft failures in maternal grafts. Overall graft survival (p=0.48) and time to first rejection (p>0.9) were not different in patients receiving paternal versus maternal grafts. The overall frequency of graft loss to rejection was also not different. However, maternal donation was associated with a significantly longer time to first rejection in patients less than one year of age at the time of transplantation (p=0.01). Time to first rejection was not different between maternal and paternal grafts in older recipients. In summary, the present study did not demonstrate a difference in graft survival between maternal and paternal donations, but the youngest patients may experience a longer time to first rejection with maternal donation. The number of young patients is small, however, and further data are necessary to confirm this observation.