PubMed Health⌕ Search

Biomedical subjects

E N Ellis

Publications and source records attributed to E N Ellis.

At least 19 recordsLinked to original sources
PubMed2000

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1990

Concepts of fluid therapy in diabetic ketoacidosis and hyperosmolar hyperglycemic nonketotic coma.

Despite many advances in the overall treatment of type I diabetes mellitus during the last few years, no major advance has been made in decreasing the mortality rate of diabetic ketoacidosis or hyperosmolar hyperglycemic nonketotic coma. A major concern in both of these disease states is the development of cerebral edema during treatment. The guiding principles of therapy in both disease states are rehydration, electrolyte replacement, insulin therapy, and treatment of any underlying illnesses. If the patient is hypotensive, therapy begins with colloid or normal saline administration to support blood pressure. Fluid and electrolyte deficits should be calculated and replaced during 48 hours. Low-dose insulin therapy is employed for treatment of hyperglycemia. Neurologic function should be carefully monitored and mannitol administered if a change in neurologic function occurs.

Child↗
PubMed1989

Glomerular lesions and urinary albumin excretion in type I diabetes without overt proteinuria.

Since several studies have suggested that a slight increase in urinary albumin excretion (microalbuminuria) is predictive of nephropathy in patients with diabetes mellitus, we studied the relation of albumin excretion to renal structure in patients with insulin-dependent (Type I) diabetes. Renal biopsy specimens were evaluated with light- and electron-microscopical morphometric techniques in 48 patients who had had diabetes for 5 to 40 years and who excreted less than 200 mg of urinary albumin per 24 hours. Patients in Group I (n = 26) had normal urinary albumin excretion, creatinine clearance, and blood pressure; those in Group II (n = 10) had increased urinary albumin excretion but normal creatinine clearance and blood pressure; those in Group III (n = 12) had increased urinary albumin excretion and hypertension, decreased creatinine clearance, or both. Glomerular structure varied similarly, ranging from normal to abnormal in Groups I and II, but was consistently abnormal in Group III. The thickness of the glomerular basement membrane, the fractional volume of the mesangium, and the mesangial volume per glomerulus in Group III exceeded the corresponding values in the other groups significantly. Thus, microalbuminuria, when present with hypertension, decreased creatinine clearance, or both, indicates established abnormalities of glomerular structure. Normal albumin excretion, or microalbuminuria without these other functional abnormalities, does not accurately predict the severity of the underlying glomerular lesions in patients with Type I diabetes.

Adolescent↗
PubMed1989

Glomerular capillary morphology in normal humans.

Knowledge of quantitative glomerular structure in normal man is limited. At the time of renal transplantation, 28 living-related normal kidney donors had renal biopsies performed. Tissue was processed for light and electron microscopy using standard techniques. Standard stereologic techniques were used to determine mean glomerular volume, capillary length density, fractional volumes of mesangium and capillary lumen, surface densities of the peripheral capillary, mesangial-epithelium interface, and the lumenal-mesangial interface. Volume of total mesangium/glomerulus, capillary lumenal volume/glomerulus, peripheral capillary filtration surface/glomerulus, capillary mesangial-epithelial surface/glomerulus, capillary lumenal-mesangial surface/glomerulus, capillary length/glomerulus, and average capillary diameter were calculated. There were no significant differences between males and females in any structural parameter. There were no significant correlations between age or body surface area and any structural parameter. In comparison with these normal values, previously reported diabetic patients with clinical nephropathy demonstrate markedly expanded mesangial volume/glomerulus and a diminished filtration surface/glomerulus. The availability of these normal values will allow comparison with functional data in normal humans and greater understanding of human glomerular disease.

Adult↗
PubMed1987

Observations of glomerular epithelial cell structure in patients with type I diabetes mellitus.

Overt proteinuria is a hallmark of diabetic nephropathy while microalbuminuria is thought to be a predictor of later onset of diabetic nephropathy. Yet the mechanisms for abnormal urinary protein leak in diabetes have not been defined. We studied 28 patients with type I diabetes for 7 to 33 years. Creatinine clearance, urinary albumin excretion rate (UAE), and multiple blood pressures were obtained in each patient. A renal biopsy was performed in each patient and in 28 normal subjects. Quantitative stereology was used to determine foot process (FP) width, filtration slit length density (FSLV) and filtration slit length/glomerulus (FSLG). FP width was slightly wider than normal in diabetic patients with UAE less than 250 mg/24 hr while FP was significantly wider than both of these groups in diabetics with UAE greater than 250 mg/24 hr. FSLV and FSLG were similar in normals and diabetics with UAE less than 250 mg/24 hr but both were reduced in diabetics with UAE greater than 250 mg/24 hr. UAE correlated with FP width (P less than 0.05), FSLG (P less than 0.01) and most precisely and FSLV (P less than 0.001). Diabetics with microalbuminuria had values for all the structural parameters measured here not different from diabetics with UAE in the normal range. Perturbations of epithelial cell structure are present in diabetes mellitus especially in patients with nephropathy. The exact relationships between albuminuria and epithelial cell structure remains to be elucidated.

Adult↗