Thromboprophylaxis in congenital nephrotic syndrome: 15-year experience from a national cohort.

INTRODUCTION: Congenital nephrotic syndrome (CNS) is an ultra-rare disease associated with a pro-thrombotic state and venous thromboembolisms (VTE). There is very limited evidence evaluating thromboprophylaxis in patients with CNS. This study aimed to determine the doses and duration of treatment required to achieve adequate thromboprophylaxis in patients with CNS. METHODS: From 2005 to 2018 children in Scotland with a confirmed genetic or histological diagnosis of CNS were included if commenced on thromboprophylaxis. The primary study endpoint was stable drug monitoring. Secondary outcomes included VTE or significant haemorrhage. RESULTS: Eight patients were included; all initially were commenced on low-molecular weight heparin (enoxaparin). Four patients maintained therapeutic anti-Factor Xa levels (time 3-26 weeks, dose 3.2-5.07 mg/kg/day), and one patient developed a thrombosis (Anti-Factor Xa: 0.27 IU/ml). Four patients were subsequently treated with warfarin. Two patients maintained therapeutic INRs (time 6-11 weeks, dose 0.22-0.25 mg/kg/day), and one patient had two bleeding events (Bleed 1: INR 6, Bleed 2: INR 5.5). CONCLUSIONS: Achieving thromboprophylaxis in CNS is challenging. Similar numbers of patients achieved stable anticoagulation on warfarin and enoxaparin. Enoxaparin dosing was nearly double the recommended starting doses for secondary thromboprophylaxis. Bleeding events were all associated with supra-therapeutic anticoagulation.

Bilateral ureteric obstruction secondary to renal papillary necrosis.

A 2-year-old male presented to hospital with a 5-day history of vomiting and pyrexia. He was initially treated with non-steroidal medication as an anti-pyretic. Initial investigations demonstrated a raised urea and creatinine and he was treated with intravenous fluids. Within 24 h he became anuric with progressive renal insufficiency. Ultrasound scan demonstrated minimal bilateral hydronephrosis with debris in the lower pole calyces. The bladder was empty. Cystoscopy and retrograde contrast imaging revealed bilateral ureteric obstruction. Double J stents were inserted and his renal function returned to normal within 4 days. We believe the aetiology to be renal papillary necrosis and bilateral ureteric obstruction secondary to the administration of ibuprofen in association with dehydration.

Vascular access survival in children and young adults receiving long-term hemodialysis.

BACKGROUND: The delivery of long-term hemodialysis therapy in children is complicated by smaller vascular caliber and the potential lifelong requirement for hemodialysis access. Various factors have resulted in the increased use of cuffed central venous catheters (CVLs) in preference to autologous arteriovenous fistulae (AVFs) and arteriovenous synthetic grafts (AVGs). The aim of this study is to compare CVL, AVF, and AVG survival and determine factors affecting their survival. METHODS: A 20-year retrospective study was undertaken of pediatric patients receiving long-term hemodialysis therapy. Age, height, weight, body mass index, and sex were noted at each procedure, in addition to the presence of hypoalbuminemia, underlying diagnosis, type and site of vascular access, and effect of previous access surgery. The grade of operator also was noted. RESULTS: Three hundred four vascular access procedures were performed on 114 patients, with a median age at initial access formation of 12.0 years (range, 4 weeks to 21.9 years). The most common procedure was CVL insertion (182 procedures) and then AVF formation (107 procedures), with only 15 AVGs created. Median censored survival was 3.14 years (95% confidence interval, 1.22 to 5.06) for AVFs and 0.6 years (95% confidence interval, 0.20 to 1.00) for CVLs. Factors adversely affecting vascular access survival were younger age, trainee operator, presence of hypoalbuminemia, and type of access undertaken, with AVF better than CVL. CONCLUSION: This study shows increased survival of AVFs over CVLs and AVGs. Vascular access in children and adolescents may impact on future dialysis accessibility and should be undertaken by those most experienced in each technique.

Renal transplant biopsy specimen adequacy in a paediatric population.

Updated guidelines on the diagnosis of acute allograft rejection including criteria for biopsy specimen adequacy were published in 1999. We sought to determine the adequacy of specimens in paediatric transplant patients and identify factors influencing adequacy. All renal transplant biopsies performed between 1998 and 2003 were classified as adequate (n =25), minimal (n =19) or inadequate (n =27) in accordance with the Banff 97 criteria, and the histological diagnoses were documented. The effect on specimen adequacy of grade of operator, method of sedation, age of child, needle gauge, number of cores and total core length was then investigated. Overall, a minimal or adequate specimen was obtained in 62% of cases. No histological diagnosis could be made in 30% of all specimens, just over half of which were inadequate. Higher rates of rejection were found in adequate (52%) than inadequate (33%) samples. The grade of operator (p =0.498), the age of the child at the time of biopsy (p =0.815) and type of sedation (p =0.188) did not affect adequacy. More than one core was obtained in 38 (54%) cases, and this was significantly associated with specimen adequacy (p <0.0005) as was longer total core length (p =0.002). Clinical features in isolation are not sufficient for the diagnosis of acute allograft rejection. Renal biopsy remains the gold standard and relies on adequate specimen collection. Our data shows that specimen adequacy according to the Banff 97 guidelines is achievable in children and that more than one core at the time of sampling significantly improves this achievement. Adequate sampling reduces the risk of an inconclusive histological diagnosis.

Body composition and nutritional intake in children with chronic kidney disease.

The aim of this study was to assess body composition in children with chronic renal failure (CRF) and post renal transplantation (Tx), and to compare it to body mass index (BMI) and nutritional intake. Dietary assessment using 3-day diaries, total and regional body composition assessment by dual x-ray energy absorptiometry of 50 CRF children (29M, 21F), median age 8.9 yrs and 50 Tx children (32M, 18F), median age 12.9 yrs. BMI, percentage fat mass (%FM) and lean mass (LM) were corrected for height and expressed as SDS (HSDS). In both groups, BMIHSDS was lower than %FMHSDS and higher than LMHSDS (p<0.05). In the Tx group, there were associations on bivariate analysis between energy & protein intake and BMIHSDS & %FMHSDS (r,0.5, p<0.05), and between LMHSDS and protein intake (r,0.5, p<0.05). On multivariate analysis, there was an association between LMHSDS and time since transplantation (r,-0.4, p<0.05). Children in the CRF and Tx groups had a high percentage predicted trunk:leg FM ratio of 148% and 157%, respectively. Children with CRF and Tx have discordant body composition with a relatively high FM and low LM, which is not reflected by BMI. In addition, they appear to have an increased level of central adiposity that may predispose them to increased morbidity in later life.

Bone mineral content, corrected for height or bone area, measured by DXA is not reduced in children with chronic renal disease or in hypoparathyroidism.

The combination of poor growth and parathyroid and mineral disorders complicates the diagnosis of renal bone disease in children with chronic renal insufficiency (CRI), and the role of dual X-ray absorptiometry (DXA) is unclear. We aimed to examine the role of DXA in assessing variation in size-adjusted bone mineral content (BMC) in children with CRI and compare it with a cohort with hypoparathyroidism (HPT) and pseudo-hypoparathyroidism (PHPIa). In 29 patients with CRI (21 male) with a median age of 11 years (10th, 90th centiles 4.4, 14.6) and 10 patients with HPT and PHPIa (three male), with a median age of 13.7 years (7, 16) lumbar spine (LS) and total body (TB) BMC were measured by DXA. Age-, gender- and height-matched data allowed calculation of percentage predicted bone area for age and gender (pBAr) and percentage predicted BMC for bone area and height. In the CRI group, the median glomerular filtration rate (GFR) was 27.4 ml/min per 1.73 m2 (7.1, 69.5), and the median duration of illness was 9.3 years (2.1, 12.1). Median height standard deviation score (Ht SDS) was -1.6 (-3.0, 0.3), and, as expected, median LS and TB pBAr were low at 82% (68, 974) and 76% (63, 92), respectively. LS and TB predicted BMC (pBMC) SDS (corrected for bone size) were generally high, with a median value of 0.4 (-0.9, 1.4) and 0.4 (-0.1,0.9), respectively. Analysis of the prepubertal subset of children (n=15) showed that median percentage predicted LS BMC for height was 104% (80, 116), whereas the median TB BMC for height was 96% (74, 108). Median Ht SDS of the HPT and PHPIa cohort was -0.3 (-2.9, 0.3) and median LS and TB pBAr were 90% (66, 100) and 91% (76, 98), respectively. Median LS and TB pBMC SDS were 0.6 (-0.4, 1.8) and 0.7 (0.3, 1.1), respectively. Median percentage predicted LS and TB BMC for height were 102% (82, 114) and 102% (92, 122). There was no relationship between pBMC SDS and duration of illness, GFR, vitamin D dose, serum intact parathyroid hormone (PTH), serum calcium/phosphate product or serum total alkaline phosphatase (ALP) in the CRI or the HPT cohort. However, one of the highest pBMC SDSs was recorded in a child with PHPIa before she started on any treatment. In children with CRI, BMC, when adjusted for co-existing growth retardation, is similar to that observed in children with hypoparathyroidism. The correct reading of BMC needs a correction for bone size.

Glomerular basement membrane thickness in children: a stereologic assessment.

BACKGROUND: Stereologic methods have emerged as the technique of choice in assessing glomerular basement membrane (GBM) thickness, following conceptual modeling comparing the stereologic technique of harmonic mean of the orthogonal intercept estimation (Th) with the model based method of arithmetic mean estimation (ATH), with no direct comparison undertaken. We undertook to establish the gold standard for GBM estimation and use this technique to establish a range for GBM thickness in children. METHODS: Intra-observer and inter-glomerular variation was estimated in 34 cases with (presumed) normal GBM thickness, using Th, ATH and a rapid direct measurement technique, with intra-observer variation measured in 35 cases with GBM attenuation. A total of 34,011 measurements were undertaken to establish a range for Th in children on 212 biopsies from 199 patients (127 male) demonstrating minimal change nephropathy (N = 153), focal segmental glomerulosclerosis (24), no abnormality (24), and acute tubular necrosis (8), which were used as surrogates for normals. RESULTS: Th demonstrated less variation than ATH in both the normal and attenuated groups. GBM thickness increased throughout childhood, from 194 +/- 6.5 nm (mean +/- SE) at one year to 297 +/- 6.0 nm at 11 years, with a reduced rate of increase after age 11 years. CONCLUSION: Stereologic methods are superior to model based techniques in estimating GBM thickness and should be regarded as the technique of choice in this area. GBM thickness was observed to increase during childhood with no gender effect demonstrable as a main effect or interaction.

Skeletal disproportion in children with chronic renal disease.

OBJECTIVES: To assess stature and skeletal disproportion in children with chronic renal disease. METHODS: Cross-sectional study of height (HT), sitting height (SH), subischial leg length (SILL), sitting height/height ratio (SH:HT) and disproportion score (SH SDS minus SILL SDS) in 56 children (M:35) with median age 11.4 years (range 4.5,18.7) with chronic renal disease. RESULTS: There were 19 children with chronic renal insufficiency, 6 receiving peritoneal dialysis and 31 after renal transplant. The median HTSDS for the whole group was -1.21 (-2.8, 0.35). The median SH:HT ratio in non-transplanted children and renal transplant were 0.51 (0.49, 0.53) and 0.50 (0.48, 0.53), respectively (p = 0.02). The median disproportion score of the whole group was -3.2 (-4.8, -1.8). There was a significant correlation between disproportion score and SH:HT (r = 0.5, p = 0.005). SH:HT ratio was negatively related to duration of illness (r = 0.4, p = 0.005). CONCLUSION: Children with chronic renal disease have significant body disproportion and this may be due to a disproportionately greater effect of disease and treatment on spinal growth.