Lorraine A. Hamiwka

Recurrence of Membranoproliferative Glomerulonephritis Type II in Renal Allografts: The North American Pediatric Renal Transplant Cooperative Study Experience

Membranoproliferative glomerulonephritis type II (MPGN II) is an uncommon form of complement-dependent acquired renal disease. Although it has been recognized since the 1970s that MPGN II recurs almost universally in renal transplants, data regarding the long-term consequences of disease recurrence are limited. Therefore, a retrospective comparative analysis of 75 patients with MPGN II contained in the North American Pediatric Renal Transplant Cooperative Study transplantation database was performed. Five-year graft survival for patients with MPGN II was significantly worse (50.0 +/- 7.5%) compared with the database as a whole (74.3 +/- 0.6%; P < 0.001). Living related donor organs had a significantly better 5-yr survival (65.9 +/- 10.7%) compared with cadaveric donor organs (34.1 +/- 9.8%; P = 0.004). The primary cause of graft failure in 11 (14.7%) patients was recurrent disease. Supplemental surveys were obtained on 29 (38%) of 75 patients. Analysis of these data indicated that recurrent disease occurred in 12 (67%) of the 18 patients with posttransplantation biopsies. Although there was no correlation between pretransplantation presentation, pre- or posttransplantation C3 levels, and either disease recurrence or graft failure, there was a strong association between heavy proteinuria and disease recurrence. The presence of glomerular crescents in allograft biopsies had a significant negative correlation with graft survival. At last follow-up, patients with recurrent disease had significantly higher serum creatinine and qualitatively more proteinuria than patients without biopsy-proven disease. These data indicate that recurrent MPGN II has a significant negative impact on renal allograft function and survival.

Incidence of Wegener's granulomatosis in children.

Objective. To determine the incidence and longitudinal trends of Wegener’s granulomatosis (WG) in the pediatric population of Southern Alberta over the last 15 years. Results. Fifteen cases of childhood WG were confirmed. The average annual incidence was 2.75 cases/million/year, with a steep increase over the last 5 years to 6.39 cases/million/year. Conclusion. In Southern Alberta the incidence of childhood WG during the past 15 years was comparable to the incidence reported in adults and it seems to be increasing. Further studies are required to determine if this is a regional or global phenomenon.

Are children with epilepsy at greater risk for bullying than their peers

The primary goal of this study was to determine the prevalence of bullying in children with epilepsy compared with their healthy peers and peers with chronic disease. Children with epilepsy were compared with healthy children and a cohort of children with chronic kidney disease (CKD). The following self-report questionnaires were completed: Revised Olweus Bully/Victim, Piers-Harris Self-Concept Scale, Revised Child Manifest Anxiety Scale, Child Depression Index, and Social Skills Rating System. Children with epilepsy were more frequently victims of bullying (42%) than were healthy controls (21%) or children with CKD (18%) (P = 0.01). Epilepsy factors such as early age at seizure onset, seizure type, and refractory epilepsy were not found to be predictors of victim status. Surprisingly, poor social skills, increased problem behaviors, poor self-concept, depression, and anxiety did not correlate with bully victim status. The relatively high prevalence of bullying behaviors in these children is concerning and, from a clinical standpoint, requires greater research specifically addressing peer relationships and consideration of the implementation of anti-bullying measures and coping strategies for children with epilepsy.

Physical activity and health related quality of life in children following kidney transplantation

Abstract:  Participation in PA is often diminished in children with CKD. Limited research exists on exercise tolerance/capacity but no studies to date have investigated lifestyle PA and its determinants in these children. The aim of this study was to investigate level of PA and potential physiological and psychological associations in a group of pediatric KTx recipients compared with CS. Twenty KTx and 33 CS participated. PA was measured by PAQ. HRQOL (PedsQL 4.0) and CY‐PSPP were also measured. BMI and WC was recorded in all subjects; GFR, BP and immunosuppressants in KTx. Body measurements indicated the two groups were similar: 25% KTx and 24% CS had BMI >85th percentile. KTx were less physically active than CS in total exercise minutes (p = 0.005). CS reported higher HRQOL than KTx (p = 0.001). Higher perceptions of HRQOL were significantly correlated with higher number of steps/day in both groups (p = 0.034). KTx showed significantly lower perceptions of sports competence (p = 0.007) and physical conditioning (p = 0.001) than CS. Higher PAQ activity scores were significantly correlated with higher perceptions of body attractiveness (p = 0.019), Sport (p = 0.003) and Conditioning (p = 0.001). These results suggest that PA may play a role in overall well‐being and HRQOL in KTx.

Outcomes of kidney transplantation in children with nephronophthisis: An analysis of the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) Registry

Abstract:  NPHP is an autosomal recessive chronic tubulointerstitial nephropathy that progresses to ESRD. In the 2006 NAPRTCS report, NPHP was the primary diagnosis in 2.8% of all renal transplant patients. At our pediatric center, that covers a population in which the NPHP1 gene is prevalent, 24% of transplant recipients had a primary diagnosis of NPHP. Since no previous literature reports have documented kidney transplant outcomes in patients with NPHP, a review of the 2006 NAPRTCS database was performed. The results of this review illustrate that patients with NPHP as their underlying kidney disease have a significantly better overall graft survival when compared with all other patients registered in the NAPRTCS database. Sub‐analysis demonstrated that this benefit is statistically significant only for LD kidney transplant recipients. CrCl was better in NPHP at all time points from transplant up to five‐yr follow‐up. Moreover, in NPHP LD transplant recipients the decline of CrCl over five yr was slower compared with non‐NPHP LD transplant recipients. Rates of thrombosis, acute, and chronic rejection as well as causes of graft failure were similar in NPHP patients and all other patients. This review demonstrates that NPHP transplant recipients have excellent outcomes that are shown to be better compared with the general pediatric transplant population.

Social skills in children with epilepsy: how do they compare to healthy and chronic disease controls?

Studies have shown poor long-term social outcomes in adults with childhood-onset epilepsy. Our goal was to compare social skills in children with epilepsy with those of healthy and chronic disease controls. Children (8-16 years) with epilepsy (n=59) were compared with age- and gender-matched children with chronic kidney disease (n=40) and healthy controls (n=41). Parents completed the Social Skills Rating System (SSRS) questionnaire. Children with epilepsy had significantly poorer SSRS total scores when compared with healthy controls (P=0.002); however, their scores did not differ from those of children with chronic kidney disease (P=0.52). Children with epilepsy were less cooperative (P=0.02), less assertive (P=0.004), and less responsible (P=0.05) and displayed poorer self-control (P=0.005) than healthy controls. Our results suggest that having a chronic disease plays a role in the social functioning of children with epilepsy. The impact of epilepsy itself on social functioning should be further elucidated through detailed prospective assessments over time.

Prednisone withdrawal in pediatric kidney transplant recipients on tacrolimus-based immunosuppression: Four-year data

Abstract: Corticosteroids have been used in renal transplant immunosuppression for over 40 yr. Despite their adverse effects, steroid therapy continues to be part of early as well as maintenance immunosuppression in most pediatric renal transplant centers. The association of steroids with growth retardation, weight gain, and acne may be particularly distressing during the critical years of adolescence and young adulthood, increasing the risk of medication non‐adherence. This study reviews the outcomes of pediatric renal transplant patients treated with low‐dose tacrolimus, mycophenolate mofetil, or azathioprine, and planned prednisone withdrawal. Thirty‐seven pediatric renal transplant recipients were withdrawn from steroids. The mean follow‐up after steroid withdrawal was 42±19 months. Graft and patient survival were 100%. The mean serum creatinine levels and calculated creatinine clearances remained stable throughout the period of observation. The mean creatinine clearance was 96±24 mL/min/1.73 m2 at steroid withdrawal and 93±20 mL/min/1.73 m2 at the latest follow‐up. Five patients restarted prednisone; in four (11%) it was for suspected or confirmed acute rejection. Improvements were observed in serum lipid profiles, blood pressure, and body mass index. Most patients experienced catchup or stable growth after prednisone withdrawal. Four patients developed viral infections; all were successfully treated. The potential benefits of steroid withdrawal in pediatric renal transplantation are supported by our results.

Acute Renal Replacement Therapy in Children with Diarrhea-Associated Hemolytic Uremic Syndrome: A Single Center 16 Years of Experience

Acute kidney injury (AKI) is becoming more prevalent among hospitalized children, its etiologies are shifting, and new treatment modalities are evolving; however, diarrhea-associated hemolytic uremic syndrome (D+HUS) remains the most common primary disease causing AKI in young children. Little has been published about acute renal replacement therapy (ARRT) and its challenges in this population. We describe our single centers experience managing 134 pediatric patients with D+HUS out of whom 58 (43%) required ARRT over the past 16 years. In our cohort, all but one patient were started on peritoneal dialysis (PD). Most patients, 47 (81%), received acute PD on a pediatric inpatient ward. The most common recorded complications in our cohort were peritoneal fluid leaks 13 (22%), peritonitis 11 (20%), and catheter malfunction 5 (9%). Nine patients (16%) needed surgical revision of their PD catheters. There were no bleeding events related to PD despite a mean platelets count of 40.9 (±23.5) × 103/mm3 and rare use of platelets infusions. Despite its methodological limitations, this paper adds to the limited body of evidence supporting the use of acute PD as the primary ARRT modality in children with D+HUS.

Ambulatory Blood Pressure Monitoring in a Cohort of Children Referred with Suspected Hypertension: Characteristics of Children with and without Attention Deficit Hyperactivity Disorder

Childhood hypertensions increasing prevalence has generally been linked to the obesity epidemic. We observed that a significant proportion of children referred to our pediatric center with documented office hypertension are nonobese and have a history of attention deficit hyperactivity disorder (ADHD). To define the extent of this anecdotal observation, we performed a retrospective analysis of ambulatory blood pressure monitoring (ABPM) tests which in our center are routinely performed in newly referred children suspected of hypertension. Twenty-one percent (48 of 227 new referrals) had a history of ADHD, and 81% of them were treated with psychostimulant medications at the time of their ABPM test. Children in this group had a significantly lower average BMI z-score compared with the rest of the children (0.18 versus 0.75) and were significantly more likely to have abnormally elevated wake systolic loads on ABPM (38% versus 4%). The overall proportion of children with any abnormality on ABPM was comparable in both groups (46% versus 40%). Conclusion. A significant proportion of children suspected of hypertension have ADHD which may be related to higher wake systolic BP values. The prevalence of hypertension among children with ADHD will have to be determined in prospective studies.

A longitudinal retrospective analysis of left ventricular mass in a cohort of pediatric kidney transplant recipients

Childhood end‐stage kidney disease is associated with increased risk for early adulthood cardiovascular (CV) morbidity and mortality. Increased LVM is an early indicator of CV disease. Previous studies have suggested that LVM decreases after kidney transplantation; however, trends have been inconsistent. A single center retrospective longitudinal cohort analysis of LVM, documented annually, starting before kidney transplantation for up to 10 yr after transplantation was performed. BP documented by annual 24‐h ambulatory monitoring studies, and BMI values were also reviewed. Twenty‐seven children followed for a mean period of 5.3 yr were included. Depending on definition of LVH, its prevalence pretransplant and in the first years post‐transplant was up to 33% dropping to 0–25% thereafter. Individual longitudinal LVM z‐score trends were highly variable but generally trended toward the mean immediately after transplant and toward negative values in the following years. BP was stable during the follow‐up period while mean annual BMI increased in the first‐year post‐transplant but declined thereafter. In a cohort of pediatric renal transplant recipients, prevalence of LVH decreased after transplant; however, individual longitudinal LVM trends were highly variable among patients. Prospective studies are needed to correlate individual LVM trends with outcomes.