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Biomedical subjects

E N Ellis

Publications and source records attributed to E N Ellis.

At least 19 recordsLinked to original sources

The impact of supplemental feeding in young children on dialysis: a report of the North American Pediatric Renal Transplant Cooperative Study.

Supplemental feedings are commonly recommended for young children on dialysis but their effect on growth parameters and mortality has not been well documented. We report the results of a North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) survey on the impact of supplemental feedings on growth and mortality in children < 6 years of age at dialysis initiation. Sixty-four nonsurvivors (NonS) were matched with 110 survivors (S) for age at dialysis initiation, primary renal disease, and year of entry into the NAPRTCS database. Questionnaires were completed by participating centers on 137 patients (51 NonS, 86 S). Supplemental feedings were given to 70% of patients and more commonly given to patients < 2 years of age compared to those 2-5 years of age at dialysis initiation (P < 0.001). Supplemental feedings were also more commonly given to patients with nonrenal disease in addition to renal disease compared to those with renal disease only (P < 0.001). In patients receiving supplemental feedings, the method of supplemental feeding was most commonly by nasogastric tube in patients < 2 years of age compared to those 2-5 years of age (P = 0.027). Supplemental feeding use was not different in S compared to NonS. There were no differences in height standard deviation score (SDS), weight SDS, or change in height or weight SDS in patients receiving supplemental feedings compared to those who did not. The height and weight SDS did not improve over time on supplemental feeds. In summary, despite the common use of supplemental feedings in young patients on dialysis, height, weight, and mortality remain unaffected. Prospective long-term evaluation of this therapy is needed to determine the effectiveness of supplemental feeding.

Body Height↗

The use of short-acting nifedipine in pediatric patients with hypertension.

OBJECTIVE: To evaluate the use of short-acting nifedipine for treatment of severe hypertension in children. STUDY DESIGN: A retrospective chart review of 520 nifedipine doses given for severe hypertension in 117 pediatric patients was completed. Nifedipine dose, systolic and diastolic blood pressures before and within 2 hours of the dose, and side effects were recorded. Pre- and post-dose mean arterial pressure (MAP) and percent reductions in MAP and systolic and diastolic blood pressure were calculated. Age, dose, primary diagnosis, and use of other antihypertensive agents were examined with respect to blood pressure reduction. RESULTS: Of the doses received, 35% were associated with > or =25% reduction in MAP, a degree of MAP reduction previously associated with hypertension treatment complications. MAP percent reduction was correlated with nifedipine dose adjusted for weight (r = 0.24, P<.001). Mean nifedipine doses per kilogram were larger in patients who had > or =25% MAP reduction compared with those who had <25% MAP reduction (0.26 +/- 0.12 mg/kg vs. 0.21 +/- 0.11 mg/kg, F = 29.01, P <.001). Adolescents received lower nifedipine doses per kilogram and had lower percent reduction in blood pressure compared with younger children. No clinically significant side effects were noted after administration of nifedipine. CONCLUSION: Precipitous reductions in blood pressure are ameliorated by decreasing the initial nifedipine dose to < or =0.25 mg/kg in pediatric patients. Short-acting nifedipine use in pediatric patients with hypertension in a hospital setting is safe.

Adolescent↗

Risk factors for mortality in infants and young children on dialysis.

The factors associated with a greater mortality risk in infants and young children undergoing dialysis have not been clearly determined. We report the results of a North American Pediatric Renal Transplant Cooperative Study designed to assess risk factors in patients aged younger than 6 years at initiation of dialysis therapy. Sixty-four nonsurvivors were matched with 110 survivors for age at dialysis initiation, primary renal disease, and year of entry onto the database. Questionnaires on 137 patients (51 nonsurvivors, 86 survivors) were completed by participating centers. Seventy-five percent (103 of 137 patients) of the patients were aged younger than 2 years at dialysis initiation; 42% (58 of 137 patients) had renal aplasia, dysplasia, and/or hypoplasia or obstructive uropathy; 62% were boys; and 62% were white. One-year patient survival rates were 83% in infants beginning dialysis at younger than 3 months of age, 89% in 3- to 23-month-olds, and 95% in 2- to 5-year-olds (P = 0.001). Comorbid nonrenal disease occurred in 37 of 51 nonsurvivors (74%) versus 46 of 84 survivors (55%; P = 0.027). Nonsurvivors had pulmonary disease and/or hypoplasia more often (14 of 37 nonsurvivors; 37.8% versus 8 of 46 survivors; 17.4%; P = 0.04). Oliguria or anuria was present in 23 of 33 nonsurvivors (70%) aged younger than 2 years versus 26 of 64 survivors (41%; P = 0.007). Infection accounted for 15 of 51 deaths (29.4%). In summary, these results suggest that age at dialysis initiation; presence of nonrenal disease, particularly pulmonary disease and/or hypoplasia; and oliguria or anuria in children aged younger than 2 years are identifiable as risk factors for mortality in these young patients.

Age Factors↗

Risk factors for bone mineral density loss in pediatric renal transplant patients.

Bone mineral density (BMD) is decreased in both adult and pediatric renal transplant recipients. To investigate the risk factors associated with this decrease in BMD post-renal transplant, we studied 33 children, aged 7-22 yr, who had received a renal transplant from 0.3 to 10 yr prior to this study. BMD analysis of the total body, spine, and femur was carried out by using dual-energy X-ray absorptiometry (DEXA). Age, weight, Tanner stage, time on dialysis prior to transplantation, cumulative corticosteroid dosage, and cyclosporin A (CsA) dosage since transplantation, and use of corticosteroid therapy prior to transplantation, were recorded. Spine, femur, and total body BMD Z-scores were greater than two standard deviations (2 SD) below the mean in 45%, 42%, and 17% of patients, respectively. Age correlated inversely with total body and spine BMD Z-scores (p = 0.001 and p = 0.008); no child under 14 yr of age had a total body or spine BMD Z-score greater than 2 SD below the mean for age. Patients at a Tanner stage of 4 or 5 had lower total body and spine BMD Z-scores than did patients at Tanner stages 1-3 (p = 0.043). Time post-transplant correlated inversely with both spine and total body BMD Z-score (p = 0.013 and p = 0.023). Only total body BMD Z-score correlated inversely with cumulative corticosteroid dose (in g, p = 0.045). BMD did not correlate with cumulative CsA dose. Black patients tended to have decreased total body BMD compared with Caucasian patients. In pediatric renal transplant patients, decreases in BMD start in adolescence. Risk factors for BMD loss in these patients include increasing age, time post-transplant, increasing Tanner stage, and ethnicity. Longitudinal studies in these patients and strategies to improve BMD are needed.

Absorptiometry, Photon↗

Acute rejection-associated tubular basement membrane defects and chronic allograft nephropathy.

BACKGROUND: Acute rejection is a major risk factor for chronic allograft nephropathy, although the link(s) between these events is not understood. The hypothesis of this study is that alterations in tubular basement membranes (TBMs) that occur during acute rejection may be irreversible and thereby play a role in the development of chronic allograft nephropathy. METHODS: Fourteen renal transplant patients were selected, each having had two or more biopsies performed (42 total). All biopsies were scored for acute and chronic rejection using Banff 1997 criteria. The initial biopsy showed only acute interstitial rejection (type I rejection). No biopsies contained significant chronic arterial lesions of chronic vascular rejection. The entire cortex was examined on Jones methenamine silver-stained sections at x400 for interruption in TBM staining. The number of tubules with TBM abnormalities was counted, and the renal cortical area was measured by image analysis. Periodic acid-Schiff/immunoperoxidase stain was performed on 12 acute rejection biopsies stained for laminin, cytokeratin 7, CD3, CD20, and CD68. Controls consisted of 11 biopsies (8 negative for rejection and 3 acute tubular necrosis). RESULTS: Numerous TBM alterations in silver staining were identified as being associated with acute rejection and tubulitis, consisting of abrupt TBM discontinuities and/or extreme attenuation with segmental or complete absence of TBM. A loss of TBM matrix proteins was confirmed by absent laminin staining in areas of acute rejection and tubulitis. There was herniation of tubular cells into the interstitium through TBM defects confirmed by cytokeratin staining. The TBM defects were spatially associated with inflammatory cells, particularly macrophages. When the biopsies were divided into two groups, <10 and> 10 TBM breaks/mm2, there were statistically significant morphologic and clinical correlations. The number of TBM disruptions correlated with the serum creatinine at the time of biopsy, a combined Banff t + i score, the difference in tubular atrophy between the initial and most recent biopsy and the difference between the nadir creatinine and most recent creatinine. CONCLUSION: Damage to TBM develops in acute rejection as a consequence of interstitial inflammation and tubulitis. These lytic events correlate with the later development of clinical and morphologic evidence of chronic injury in the absence of arterial injury of chronic rejection. We suggest that chronic allograft nephropathy may have an inflammatory interstitial origin.

Acute Disease↗

Use of pump-assisted hemofiltration in children with acute renal failure.

In critically ill children, acute renal failure (ARF) is associated with a high mortality. To assess the outcome and complications of pump-assisted hemofiltration (PAHF) using a standard volumetric pump to regulate blood flow, we retrospectively reviewed our experience in 52 patients with ARF treated with PAHF from 1989 to 1995. These patients ranged in age from < 1 month to 19 years and in weight from 2 to 125 kg. The most common underlying diagnoses were congenital heart disease and infection. The duration of PAHF averaged 9 +/- 8 days (range 24 h to 43 days). Hemodiafiltration for solute control was required in 40 patients. Total fluid intake while on PAHF was 136 +/- 95 ml/kg per day, while urine output and ultrafiltration averaged 15 +/- 24 ml/kg per day and 89 +/- 58 ml/kg per day, respectively. Management of laboratory abnormalities was efficient with only 4 patients requiring 1 or 2 additional treatments of hemodialysis for control of uremia. Complications included hyponatremia in 13 patients, hypokalemia in 14 patients, hypovolemia in 8 patients, hyperglycemia in 6 patients, and bleeding in 9 patients. No complications specifically related to use of the volumetric infusion pump for PAHF were noted. PAHF using a volumetric infusion pump for blood flow regulation in critically ill children with ARF is a practical and efficient therapy.

Acute Kidney Injury↗

Renal structural-functional relationships in early diabetes mellitus.

To define the earliest renal morphological changes in patients with type I diabetes, we studied renal function and morphometric analysis of renal biopsies in 59 patients with diabetes for 5-12 years and normal blood pressure, normal creatinine clearance (CCr), and negative dipstick urinary protein. Arteriolar hyalinization and intimal fibrous thickening were noted in 43%. Glomerular basement membrane thickness and fractional mesangial volume were increased in 51% and 56%, respectively. The pre-pubertal and post-pubertal years of diabetes were associated with similar degrees of renal structural changes, but during the pre-pubertal years normal urinary albumin excretion (UAE) was seen. Principal factor analysis of morphometric structural parameters yielded four clusters of variables: "glomerular size" correlated with patient age, CCr, and UAE; "peripheral capillary decrease" correlated with glycosylated hemoglobin, diastolic blood pressure, glomerular filtration rate, and UAE; "mesangial increase" correlated with UAE; and "interstitial scarring" correlated with diastolic blood pressure. This study provides unique documentation of renal structural abnormalities which precede clinically evident renal functional abnormalities and documents that these early structural abnormalities are present in the pre-pubertal years of diabetes as well as postpuberty, and are associated with each other in constellations that correspond to postulated mechanisms in diabetic nephropathy.

Adolescent↗

Spectrum of disease associated with anti-neutrophil cytoplasmic autoantibodies in pediatric patients.

Anti-neutrophil cytoplasmic autoantibodies (ANCA) are usually determined during the diagnostic evaluation of systemic vasculitis and glomerulonephritis syndromes in adult patients, but few pediatric patients with ANCA have been reported. We describe five pediatric patients with ANCA and glomerulonephritis, with and without upper or lower respiratory tract disease. We compared these five patients and six previously described patients to affected adults; the spectrum of ANCA-associated disease appears to be similar in adults and children, but a female predominance may exist in the pediatric patients. Pediatric patients often had end-stage renal disease within 1 year after onset. We conclude that ANCA is a useful diagnostic tool in both pediatric and adult patients with systemic vasculitis and glomerulonephritis.

Adolescent↗

Resistance to glomerular injury in the diabetic biobreeding rat.

This study was designed to determine whether the diabetic BioBreeding rat develops significant renal injury following long-term moderate to severe hyperglycaemia. Diabetic and control rats were followed from the onset of diabetes (2-4 months) to 18 months of age. Frank proteinuria and/or albuminuria were always absent. Glomerular filtration rate, measured by inulin clearance (ml min-1 (100 g body weight)-1), was significantly higher in diabetic rats than in controls at 10, 12 and 18 months of age. Advanced glycosylation end-product cross-links assessed by percentage solubility of tail tendon collagen were moderately increased in diabetic compared with control animals. Urinary excretion of advanced glycosylation end-products in unfractionated urine and in urine fractionated for low molecular mass peptides (< 10 kDa) was 11-fold greater in the diabetic rats than in the control group. Urinary excretion of nitric oxide metabolites (nmol NO2- and NO3- (24 h)-1) were significantly (P < 0.05) greater in diabetic rats than in controls after 8 months of age. Mild histopathology resembling human diabetic nephropathy, including increased mesangial volume and glomerular basement membrane thickness, was detected at 18 months of age. The findings of hyperfiltration and mild glomerular morphological changes in diabetic BioBreeding rats are similar to the abnormalities seen in stage 2 human diabetic nephropathy. We hypothesize that two factors which may contribute to the resistance or tolerance to renal injury in the BioBreeding diabetic rat are increased nitric oxide production and the decreased accumulation of advanced glycosylation end-products.

Animals↗

Outcome of infants on chronic peritoneal dialysis.

To assess the outcome of infants on chronic peritoneal dialysis (PD), we retrospectively reviewed 21 patients who began PD prior to one year of age. Mean age at first dialysis was 56 +/- 56 days with mean weight of 3.6 +/- 1.6 kg. Seventeen infants were male and 17 were Caucasian. The most common primary renal diagnosis was renal hypoplasia/dysplasia, occurring in 7 infants. Mean time on PD was 10 +/- 10 months. Eleven infants had oliguria, and 10 infants had adequate urine output. All but 1 infant received tube feedings; mean caloric intake was 453 +/- 92 kJ/kg/day. Despite nutritional management, weight, height, and head circumference was at or above the fifth percentile in only 10, 4, and 5 infants, respectively. Nonrenal abnormalities were present in 12 of 21 infants with lung, heart, and central nervous system abnormalities occurring most often. Outcome included 7 receiving renal transplants, 1 who recovered renal function, 4 who continued on PD, and 9 who died. Seven infants with oliguria died, while only 2 infants with adequate urine output died. No infant with isolated renal disease died, while 9 of 12 patients with renal plus nonrenal abnormalities died. Thus mortality in infants less than one year of age on PD appears to be associated with the presence of oliguria and nonrenal abnormalities.

Female↗

Pump-assisted hemofiltration in infants with acute renal failure.

Hemofiltration is accepted management for acute renal failure in critically ill patients. However, in infants, obtaining arterial access or adequate flow through the access is often difficult. We report our technique and experience with pump-assisted hemofiltration (PAHF) in ten infants with acute renal failure. In five patients, double-lumen venous catheters provided access, while two catheters at separate sites were used in the remaining patients. In all patients, hemofilters were used with standard intravenous tubing added to pre-filter tubing and placed through a standard volumetric infusion pump for regulation of blood flow. The infants, aged 5-575 days, weighed from 2.8 to 11.4 kg and had primary diagnoses of post-operative congenital heart disease in five, sepsis in four, and renal dysplasia in one. The duration of PAHF averaged 158 +/- 115 h (range 20-332 h). Complications included bleeding at a catheter or surgical site in one patient each and asymptomatic hyponatremia in five patients. Thus, with adequate nurse training, PAHF using a volumetric infusion pump for blood regulation can be acceptable therapy in acute renal failure in infants.

Acute Kidney Injury↗

Renal disease in adolescents with type I diabetes mellitus: a report of the Southwest Pediatric Nephrology Study Group.

Although 30% to 40% of patients with type I diabetes mellitus develop diabetic nephropathy, the usual signs of clinical nephropathy are often thought to be delayed until adulthood. We studied 13 adolescents with type I diabetes mellitus for 5 to 14 years who had renal biopsies completed because of clinical problems, including proteinuria, hematuria, or hematuria plus proteinuria. Changes typical of diabetes were seen by light and immunofluorescence microscopy; evidence of other renal diseases was not noted. On electron microscopy evaluation, glomerular basement membrane width was increased in 11 patients. In seven patients, mesangial volume was elevated above the normal range. Peripheral capillary filtration surface density was diminished below the normal range in five patients. Thus, several of these adolescents had severe glomerular lesions that were indicative of overt diabetic nephropathy. Within 2 to 3 years after biopsy, at least two patients were dialysis dependent. Thus, the adolescent diabetic patient with a relatively short duration of diabetes may be developing progressive diabetic renal lesions, and the clinical signs and symptoms at presentation may not be those typically seen in diabetic nephropathy.

Adolescent↗

Diminished glomerular capillary hydraulic conductivity precedes morphologic changes in experimental diabetes mellitus in the rat.

Glomerular ultrafiltration coefficient, Kf, is diminished in established diabetic nephropathy. To determine whether Kf is decreased because of a decrease in capillary area, A, and or in hydraulic conductivity, Lp, glomerular Kf and morphometric parameters were measured, and Lp was calculated in glomeruli of young rats with STZ-induced DM and in control rats. STZ was administered to Fischer 344 rats that weighted 50-75 g; glomeruli were examined after 3 or 5 mo of DM, and their structure and function was compared with that of control rats. The effects of insulin or of an ACEI, enalapril, also were assessed after 3 or 5 mo. Growth of DM rats was markedly impaired, and their ratio of kidney weight to body weight was increased. Ccr was proportional to rat weight, and the ratio of Ccr to body weight was not different in DM and control rats. At 3 mo, average volume of glomeruli isolated from DM rats was less than that of glomeruli from control rats. In contrast, glomerular volume after 5 mo was equal in DM and control rats. No increase in GBM thickness or mesangial volume was observed, nor was any decrease seen in GBM area in DM rats at 5 mo. Kf was lower in DM rats than controls after 3 mo, but not after 5 mo. The Lp of DM and control glomeruli did not differ at 3 mo, but was lower in DM at 5 mo. Insulin therapy improved somatic growth and increased kidney and glomerular size in DM rats; the kidney weight/body weight ratio remained elevated.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗

Prevention of glomerular basement membrane thickening by aminoguanidine in experimental diabetes mellitus.

The etiology of diabetic glomerulopathy appears to be related, at least in part, to the degree of hyperglycemia, the resultant nonenzymatic glycosylation of proteins, and the eventual formation of advanced glycosylation end products in long-lived structural proteins. To investigate the relationship between the glomerular basement membrane (GBM) changes of diabetic nephropathy and the formation of advanced glycosylation end products, we studied control rats, diabetic rats, and control and diabetic rats who received aminoguanidine, a compound that pharmacologically inhibits formation of advanced glycosylation end products. After 9 months, rat weight was smaller and kidney weight larger in both diabetic groups compared with both control groups. GBM width was increased in the diabetic group compared with the control group. Aminoguanidine administration to diabetic rats ameliorated this increase in GBM. Thus, aminoguanidine administration from the onset of experimental diabetes prevented the widening of the GBM that is typical of diabetes.

Animals↗

Glomerulopathy in patient with Donohue syndrome (leprechaunism).

OBJECTIVE: To evaluate renal structure in a child with Donohue syndrome (leprechaunism), who at 10 yr of age was noted to have hypertension, microalbuminuria, and enlarged kidneys, a renal biopsy was performed. RESEARCH DESIGN AND METHODS: The renal biopsy tissue was evaluated by light and electron microscopy with standard stereological techniques to measure glomerular volume, glomerular basement membrane width, fractional mesangial volume, and peripheral capillary filtering surface density. RESULTS: On renal biopsy, there was a marked increase in glomerular volume, glomerular basement width, and mesangial volume, findings similar to those seen in patients with diabetic nephropathy. CONCLUSIONS: This patient with marked insulin resistance associated with Donohue syndrome demonstrates renal and glomerular enlargement and morphometric glomerular changes similar to those seen in patients with diabetic nephropathy. In unusual syndromes with hyperglycemia and hyperinsulinemia, renal structural and functional changes typical of traditional diabetes mellitus may be seen.

Adolescent↗

Use of the peritoneal equilibration test in pediatric dialysis patients.

The peritoneal equilibration test (PET) has been used in adult peritoneal dialysis (PD) patients to determine PD efficiency and optimal dialysis prescription. To investigate its usefulness in pediatric PD patients, we performed the PET in 10 patients divided into 2 groups: 3 patients less than 2 years of age (group 1) and 7 patients aged 5 to 17 years (group 2). The PET was performed after an overnight dwell by standard protocol with an overnight dialysate sample and 6 dialysate samples during the 4 hour test. Dialysate to plasma (D/P) ratios were calculated for creatinine (Cr), urea, and protein. D/PCr over time was similar in both pediatric groups compared to adults. D/P urea over time was lower in both pediatric groups compared to published adult data. D/P protein over time was markedly increased in both pediatric groups and was highest in the smallest patients. D/P ratios are different in pediatric PD patients compared to adults. In order to be used to assess dialysis efficiency, normal values for the PET test in children need to be established.

Adolescent↗

Ultrasonographic findings in congenital nephrotic syndrome.

This report documents a case of biopsy-proven congenital nephrotic syndrome, Finnish type (CNF), which was initially misdiagnosed as infantile polycystic kidney disease based on ultrasonographic findings. We report this to further describe ultrasonographic features of CNF, and to point out that these two diseases may have similar features on ultrasound.

Biopsy↗