Verna Yiu

IgA nephropathy and thin basement membrane disease in association with Crohn disease.

Abstract.  There have been a wide variety of reported renal parenchymal diseases associated with inflammatory bowel disease, ranging from interstitial nephritis to amyloidosis to immune complex glomerulonephritis. Two pediatric cases of renal parenchymal pathology in association with Crohn disease are presented. The first is an 11-year-old child who presented with recurrent bouts of gross hematuria, biopsy-proven IgA nephropathy, and later developed Crohn disease 4 years after the initial presentation. Her renal function is normal with persistent isolated microscopic hematuria. The second case is that of a 9-year-old male who presented with the classic gastrointestinal manifestations of Crohn disease, later developed hematuria and proteinuria, and was found on a renal biopsy to have thin basement membrane disease. There have been several reported cases of IgA nephropathy associated with inflammatory bowel disease; but to our knowledge, this is the first case of thin basement membrane disease occurring in conjunction with Crohn disease. Discussion focuses on the relationship of IgA nephropathy with inflammatory bowel disease with additional comments on thin basement membrane disease.

Clinical practice guidelines for pediatric peritoneal dialysis.

Peritoneal dialysis (PD) continues to be an important modality of treatment for children with end-stage renal disease. The Canadian Association of Pediatric Nephrologists recognized the need nationally to review the literature on the delivery of PD in children to provide optimal standardized care. This resulted in the development of the Canadian Clinical Practice Guidelines for pediatric PD. Clinical practice guidelines are a useful adjunct to clinical care. The present review includes recommendations for catheter placement and types, requirement for prophylactic omentectomy, initiation and adequacy of dialysis, PD prescription, and solute clearance. It provides physicians with updated evidence-based recommendations that include consideration towards practicality with the major goal of improved and standardized patient care.

Deletions in 16q24.2 are associated with autism spectrum disorder, intellectual disability and congenital renal malformation

Background The contribution of copy-number variation (CNV) to disease has been highlighted with the widespread adoption of array-based comparative genomic hybridisation (aCGH) and microarray technology. Contiguous gene deletions involving ANKRD11 in 16q24.3 are associated with autism spectrum disorder (ASD) and intellectual disability (ID), while 16q24.1 deletions affecting FOXF1 are associated with congenital renal malformations, alveolar capillary dysplasia, and various other abnormalities. The disease associations of deletions in the intervening region, 16q24.2, have only been defined to a limited extent. Aim To determine whether deletions affecting 16q24.2 are correlated with congenital anomalies. Methods 35 individuals, each having a deletion in 16q24.2, were characterised clinically and by aCGH and/or SNP-genotyping microarray. Results Several of the 35 16q24.2 deletions identified here closely abut or overlap the coding regions of FOXF1 and ANKRD11, two genes that have been previously associated with the disease. 25 patients were reported to have ASD/ID, and three were found to have bilateral hydronephrosis. 14 of the deletions associated with ASD/ID overlap the coding regions of FBXO31 and MAP1LC3B. These same genes and two others, C16orf95 and ZCCHC14, are also included in the area of minimal overlap of the three deletions associated with hydronephrosis. Conclusions Our data highlight 16q24.2 as a region of interest for ASD, ID and congenital renal malformations. These conditions are associated, albeit without complete penetrance, with deletions affecting C16orf95, ZCCHC14, MAP1LC3B and FBXO31. The function of each gene in development and disease warrants further investigation.

Renal interstitial fibrosis in children treated with FK506 for nephrotic syndrome

BACKGROUND Steroid-dependent, steroid-resistant or frequently relapsing nephrotic syndrome carries a poor prognosis, including progression to renal failure. There are a number of studies confirming the efficacy of FK506 in steroid-resistant or steroid-dependent nephrotic syndrome. Although the use of this medication is becoming more common, we know very little about the potential nephrotoxicity when used in nephrotic syndrome. METHOD We retrospectively reviewed the characteristics and biopsy findings of 11 children with steroid-dependent or frequently relapsing nephrotic syndrome treated with FK506. Two sequential biopsies were evaluated for the change in interstitial fibrosis, measured by a quantitative stereological method, and the change in arteriolar hyaline thickening, tubular atrophy and interstitial fibrosis, graded according to Banff criteria. RESULTS There was an increase in interstitial fibrosis (P = 0.005), with a median absolute change in the per cent volume density between initial and follow-up biopsies of 1.8% [interquartile range (IQR) 3.9%]. Median percentage change in volume density of interstitial fibrosis, relative to volume density of interstitial fibrosis prior to initiating FK506, was 93% (IQR 138%). Banff scores for interstitial fibrosis and tubular atrophy also increased following tacrolimus therapy (P = 0.04 for both). Average FK506 trough level over the treatment period was significantly associated with change in fibrosis (Spearmans rho = 0.67 and P = 0.02). CONCLUSIONS This is some of the first histological data concerning tacrolimus nephrotoxicity in childhood nephrotic syndrome. Although the role of the natural progression of the underlying disease in the observed change is not definitively clear, the changes seen are in keeping with the known nephrotoxic effects of FK506 demonstrated in renal transplant. This increase is small when presented as a median change. However, there were a number of children who had a larger change in fibrosis. The factors predictive of interstitial fibrosis while on FK506 are not well defined; the findings from this study suggest that FK506 level may be a factor. Given the observations and limitations of the few published studies, there is an obvious need for further study in a large multicenter prospective trial.

High-calorie nutrition for infants with chronic renal disease

Abstract Objective : This report describes the administration of high-calorie formula (HCF), with caloric densities between 40 kcal/oz and 60 kcal/oz, to children with renal disease and severe fluid restrictions. Design : Retrospective Descriptive Analyses. Setting : Childrens Hospital, Harvard Medical School, Boston, Massachusetts. Patients : Records of all infants with chronic renal disease treated at Childrens Hospital between 1984 and 1991 and who received supplemental formulas with a minimal caloric density of 40 kcal/oz were reviewed. Intervention : Commercial formulas were modified with glucose polymers and corn oil to attain caloric densities of 40 kcal/oz to 60 kcal/oz. The target caloric density for each patient was selected based on each infants fluid restrictions and recommended daily allowance requirements. Patients were evaluated monthly for compliance, and formula changes were adjusted to ensure adequate caloric intake and fluid balance. Main outcome measures : Patient tolerance of the HCF was defined by the absence of noninfectious diarrhea and vomiting while receiving the HCF. Progression of formula advancement (either in volume or concentration) required the stools be tested negative for reducing substances. The review was discontinued when the following occurred: fluid liberalization, transplantation, or death. Results : Seventeen infants given the HCF were reviewed. Sixteen infants required nasogastric feedings (usually given continuously at night). The mean average daily caloric intake achieved was 113.2 kcal/kg/d. Fifty-nine percent of the patients were tolerant of the HCF. The type and duration of dialysis did not affect tolerance of the HCF. Conclusion : The HCF was well tolerated with minimal side effects and should be considered for any infant with severe fluid restrictions.