Carolyn L. Abitbol

Histomorphometric Analysis of Postnatal Glomerulogenesis in Extremely Preterm Infants

Until now oligonephropathy to indicate “too few nephrons” has been associated with intrauterine growth restriction and experimentally induced abnormalities of renal development. The purpose of this study was to determine whether there is evidence of abnormal postnatal glomerulogenesis in extremely low birth weight preterm infants. Renal autopsy tissue was studied by computer-assisted morphometry from 56 extremely premature infants (birth weight ≤ 1000 g) and 10 fullterm infants as controls. Preterm infants were divided into two groups (short survival < 40 days vs. long survival ≥40 days). Each group was subdivided into those with renal failure (RF) and those with normal renal function. Forty-two of 56 preterm infants (75%) were adequate for gestational age. Glomerulogenesis as measured by radial glomerular counts (RGC) was markedly decreased in all preterm infants as compared to term controls and correlated significantly with gestational age (r = 0.87; P < 0.001). Active glomerulogenesis with “basophilic S-shaped bodies” was absent in longer surviving preterm and all term infants. RGC of preterm infants surviving ≥40 days with RF were significantly less than RGC of those with long survival and no RF (P < 0.001). Only this latter group demonstrated increased glomerular size as measured by mesangial tuft area and Bowman’s capsule area compared to all other groups (P < 0.001). The kidney continues to form postnatally in preterm neonates, but glomerulogenesis ceases after 40 days. Moreover, it is further inhibited by RF. Compensatory mechanisms in longer surviving preterm infants include glomerular hypertrophy and mesangial proliferation that could lead to hyperfiltration.

Renal Disease in Children with the Acquired Immunodeficiency Syndrome

Abstract Of 155 children with the acquired immunodeficiency syndrome (AIDS) whom we evaluated during a 6 1/2-year period, 12 were found to have proteinuria. Histologic studies of tissue from these 12 patients revealed a wide spectrum of renal disease: focal glomerulosclerosis in 5, mesangial hyperplasia in 5, segmental necrotizing glomerulonephritis in 1, and minimal change disease in 1. In addition, 6 had tubulointerstitial infiltrates, and 10 had glomerular dense deposits. All 10 renal specimens studied by electron microscopy contained endothelial tubuloreticular inclusions. The mean age (±SD) of the five patients with focal glomerulosclerosis when this condition was identified was 27±19 months. All five had severe renal failure within a year and died of other causes during the following year. The mean age of the five patients with mesangial hyperplasia was 38±31 months. Although none of them went on to have renal failure, four died within 8±7 months. Ten of the 12 patients with proteinuria died during ...

Comparative renal histomorphometry: A case study of oligonephropathy of prematurity

Children born with very low birth weight have a decreased nephron number. Low nephron mass is associated with adult hypertension, proteinuria, and diabetes mellitus. The histomorphometry and radial glomerular count (RGC) of a total nephrectomy from a child with renal disease associated with extreme prematurity was compared with the kidney from a full-term age-matched child of normal gestation with chronic renal failure due to focal and segmental glomerulosclerosis (FSGS) and to a child without renal disease. Bowman’s space area, mesangium and mesangial tuft area were determined in 50 glomeruli of each specimen by computer-assisted morphometry. RGC was 4 in the ex-preterm child, 8 in the patient with FSGS, and 9 in normal control. The patient with FSGS had larger glomerular area expressed as square micrometers (μm2) of Bowman’s capsule, the mesangium and the mesangial tuft area measurements than the normal control and the child born preterm who subsequently developed renal failure had significantly larger Bowman’s capsule and mesangium than the two controls. This case report begins to identify important pathologic findings of decreased nephron numbers and glomerulomegaly associated with preterm birth.

Twenty-five Years of Infant Dialysis: A Single Center Experience

OBJECTIVE To perform a retrospective analysis of the long-term outcome of infants with end-stage kidney disease (ESKD) treated at our center during the past 25 years. STUDY DESIGN The total cohort (n = 52) was divided into era 1 (1983-1995; n = 23) and era 2 (1996-2008; n = 29). Dialysis morbidity, transplantation, and long-term survival rates were assessed and compared between the 2 eras. RESULTS Average age at initiation of dialysis was 4.4 +/- 5.3 months (range, 0.5-18 months), with 96% begun on peritoneal dialysis. The predominant diagnoses were dysplasia/obstructive uropathy and autosomal recessive polycystic kidney disease. The overall survival rate is 46%, with current age of survivors ranging from 1.5 to 25 years. Mortality rates in the 2 eras were not significantly different. The predominant mortality occurred within the first year. Twenty-four patients received an initial renal transplant at 2.6 +/- 1.7 years of age. Six patients (25%) required a second renal allograft. Increased risk for mortality included African-American ethnicity, oligoanuria, autosomal recessive polycystic kidney disease, and co-morbid diagnoses. CONCLUSIONS Long-term survival is possible in infants with ESKD, although mortality and morbidity remain high. Technical innovations are needed to accommodate smaller infants undergoing dialysis. Early initiation of dialysis treatment is preferable because prognostic indicators remain poorly defined.

Linear growth and anthropometric and nutritional measurements in children with mild to moderate renal insufficiency: A report of the growth failure in children with renal diseases study

During the control period of the Growth Failure in Children With Renal Diseases Study, investigators at 23 centers were able to observe and characterize growth and to make anthropometric and nutritional measurements in 82 children with mild to moderate renal insufficiency. As a multicenter, controlled clinical trial designed to study the relative efficacy of 1,25-dihydroxyvitamin D3 and dihydrotachysterol in the treatment of renal osteodystrophy, no prior vitamin D exposure and a creatinine clearance of 25 to 75 ml/min/1.73 m2 were criteria for entrance into the clinical trial. Ages ranged from 18 months to 11 years (mean 5.6 +/- 3.1 years), and distribution by age category was as follows: 38%, 1 to 3 years; 28%, 4 to 6 years; and 34%, 7 to 10 years. There was a 3:1 male/female ratio; 72% of the patients had congenital disease by the International Classification of Diseases (ninth revision). Mean creatinine clearance was 49.5 +/- 20 ml/min/1.73 m2. The C-terminal parathyroid hormone values (1121 +/- 1562 pg/ml) were well above 2 SD of the mean of a normal growing population of similar age. Parathyroid hormone values correlated with degree of renal insufficiency (r = -0.57) and with height by bone age but not with chronologic height or growth velocity. The bone age/height age ratio, a predictor of growth potential in normal children, was low for the entire series of patients (0.88 +/- 0.35) but failed to correlate with growth velocity and was negatively correlated with rising parathyroid hormone levels. Average values for height, weight, triceps skin fold, mid-arm muscle circumference, and body mass index were within 2 SD of the mean of the normal population, although measurements for the 1- to 3-year age group were significantly less than those of the older patients. Total energy intake averaged less than 86% of the recommended dietary allowances; total protein intake was more than 161% of the allowance. Nitrogen balance in 23 patients was positive and correlated most significantly with increasing energy intake (r = 0.6). Growth velocity, calculated from the interval gain during the month control period, averaged +0.3 SD, with the highest growth velocity z scores recorded for those with acquired disease. A growth velocity index, expressed as the slope of the regression between change in height SD and growth velocity z score, was used to describe the growth accomplished in the control period by age category.(ABSTRACT TRUNCATED AT 400 WORDS)

A prospective double-blind study of growth failure in children with chronic renal insufficiency and the effectiveness of treatment with calcitriol versus dihydrotachysterol

Because controlled trials in adults have shown accelerated deterioration of renal function in a small number of patients receiving calcitriol for renal osteodystrophy, we initiated a prospective, randomized, double-blind study of the use of calcitriol versus dihydrotachysterol in children with chronic renal insufficiency. We studied children aged 1½ through 10 years, with a calculated glomerular filtration rate between 20 and 75 ml/min per 1.73 m 2 , and with elevated serum parathyroid hormone concentrations. Ninety-four patients completed a mean of 8.0 months of control observations and were randomly assigned to a treatment period; 82 completed the treatment period of at least 6 months while receiving a calcitriol dosage (mean±SD) of 17.1±5.9 ng/kg per day or a dihydrotachysterol dosage of 13.8±3.3 μg/kg per day. With treatment the height z scores for both calcitriol- and dihydrotachysterol-treated groups showed no differences between the two groups. In relation to cumulative dose, there was a significant decrease in glomerular filtration rate for both calcitriol and dihydrotachysterol; for calcitriol the rate of decline was significantly steeper ( p =0.0026). The treatment groups did not differ significantly with respect to the incidence of hypercalcemia (serum calcium concentration >2.7 mmol/L (>11 mg/dl)). We conclude that careful follow-up of renal function is mandatory during the use of either calcitriol or dihydrotachysterol because both agents were associated with significant declines in renal function. There was no significant difference between calcitriol and dihydrotachysterol in promoting linear growth or causing hypercalcemia in children with chronic renal insufficiency. Dihydrotachysterol, the less costly agent, can be used with equal efficacy.

Survival and complications of cuffed catheters in children on chronic hemodialysis

Abstract Central venous catheters are being increasingly used as hemodialysis vascular access. We evaluated catheter survival, outcome predictors, and complications in a total of 36 catheters used in 13 children and young adults undergoing chronic maintenance hemodialysis through catheter for a duration of 10.4±5.6 months. Reasons for catheter failure were: thrombosis 12 of 36 (33%), infection 6 of 36 (17%), and extrusion 2 of 36 (5.4%). Catheters were lost to infection and thrombosis at 1.1 and 2.2 episodes per 1,000 catheter days, respectively. Symptomatic infections, Gram-negative and polymicrobial sepsis increased the risk of catheter failure. Most of the thrombotic episodes occurred in patients with inherent thrombotic tendency. The survival of the 36 catheters was 62% at 1 year. The survival of 13 randomly chosen catheters, 1 from each patient, was 85% at 1 year. The time from insertion to first complication correlated significantly with the outcome (P<0.03). We conclude that central venous catheters are still associated with a high rate of failure and may be a regular access choice only in a selected patient population with no inherent thrombotic tendency and no other option available for long-term hemodialysis.

Rationale of the growth failure in children with renal diseases study

The Growth Failure in Children With Renal Diseases Study was organized to evaluate linear growth in children with chronic; moderate renal failure who are being treated with 1,25-dihydroxyvitamin D 3 or di.hydrotachysterol in a randomized, double-blind, controlled clinical trial. This study was also prompted in 1980 by the need to compare the results (efficacy and safety) of long-term 1,25-dihydroxyvitamin D3 therapy with those in a control group of children with chronic moderate renal failure, with particular attention given to the rate of progression of renal failure, to confirm or refute reports that this therapy may accelerate deterioration of renal function.

The Kidney in Sickle Cell Disease

Sickle cell disease (SCD) and trait (SCT) are acknowledged as existing in North America and Africa but often overlooked is the fact that they also are found in Central America and northern South America, primarily in those areas into which blacks were brought from Africa. Hemoglobin A is the normal hemoglobin which has a glutamic acid in position 6, while hemoglobin S is the characteristic hemoglobin of sickle cell disease and has a valine in position 6 (1). In an SCD or SCT patient in crisis, hemoglobin gels and leads to the formation of the classically sickled shape red blood cell (RBC); when hemoglobin S remains in its gel status, the RBC’s become irreversibly (or permanently) sickled (2).

Incidence and outcomes of neonatal acute kidney injury (AWAKEN): a multicentre, multinational, observational cohort study

Background Single-center studies suggest that neonatal acute kidney injury (AKI) is associated with poor outcomes. However, inferences regarding the association between AKI, mortality, and hospital length of stay are limited due to the small sample size of those studies. In order to determine whether neonatal AKI is independently associated with increased mortality and longer hospital stay, we analyzed the Assessment of Worldwide Acute Kidney Epidemiology in Neonates (AWAKEN) database. Methods All neonates admitted to 24 participating neonatal intensive care units from four countries (Australia, Canada, India, United States) between January 1 and March 31, 2014, were screened. Of 4273 neonates screened, 2022 (47·3%) met study criteria. Exclusion criteria included: no intravenous fluids ≥48 hours, admission ≥14 days of life, congenital heart disease requiring surgical repair at <7 days of life, lethal chromosomal anomaly, death within 48 hours, inability to determine AKI status or severe congenital kidney abnormalities. AKI was defined using a standardized definition —i.e., serum creatinine rise of ≥0.3 mg/dL (26.5 mcmol/L) or ≥50% from previous lowest value, and/or if urine output was <1 mL/kg/h on postnatal days 2 to 7. Findings Incidence of AKI was 605/2022 (29·9%). Rates varied by gestational age groups (i.e., ≥22 to <29 weeks =47·9%; ≥29 to <36 weeks =18·3%; and ≥36 weeks =36·7%). Even after adjusting for multiple potential confounding factors, infants with AKI had higher mortality compared to those without AKI [(59/605 (9·7%) vs. 20/1417 (1·4%); p< 0.001; adjusted OR=4·6 (95% CI=2·5–8·3); p=<0·0001], and longer hospital stay [adjusted parameter estimate 8·8 days (95% CI=6·1–11·5); p<0·0001]. Interpretation Neonatal AKI is a common and independent risk factor for mortality and longer hospital stay. These data suggest that neonates may be impacted by AKI in a manner similar to pediatric and adult patients. Funding US National Institutes of Health, University of Alabama at Birmingham, Cincinnati Children’s, University of New Mexico.