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Biomedical subjects

E D Avner

Publications and source records attributed to E D Avner.

98 records · Page 6Linked to original sources

Diabetic nephropathy in adolescence: appearance during improved glycemic control.

Two girls, aged 15 and 14 years, with poorly controlled insulin-dependent diabetes (IDD) of 9 and 7 years duration, respectively, developed overt and persistent proteinuria shortly after rapid increases in insulin therapy and improved glycemic control. Renal biopsies showed diffuse diabetic glomerulosclerosis. Both patients maintained normal or increased creatinine clearances. Direct ophthalmoscopy and fluorescein retinal angiography demonstrated nonproliferative diabetic retinopathy in the first patient, which deteriorated after 6 weeks of strict metabolic control; the second patient had normal retinas. The appearance of clinical proteinuria during this brief period of good glycemic control suggests that the latter may have unmasked a preexisting condition. Possible pathophysiologic mechanisms initiating the proteinuria in these patients are reviewed.

Adolescent↗

Development of renal basement membrane glycoproteins in metanephric organ culture.

Because of the importance of renal basement membrane glycoproteins in normal and abnormal tubular and glomerular morphogenesis, structure, and function, the sequential development of fibronectin, GP-2, and entactin was studied in vivo and in a newly developed, serum-free mouse metanephric organ culture system. The organ culture system permits advanced tubular differentiation and glomerular epithelial development of whole metanephros without perfusion or urine formation. Affinity-purified antibodies and immunohistologic techniques were used, and the ontogeny of basement membrane glycoproteins was characterized in vivo and in vitro. It was thus possible to characterize the pattern of normal renal basement membrane glycoprotein production and to comparatively study renal glomerular and tubular basement membrane formation in the presence and the absence of endothelial and/or mesangial influences. Both in vivo and in vitro undifferentiated mesenchyme expressed fibronectin but not GP-2 or entactin. Further, both in vivo and in vitro, all three glycoproteins developed in the basement membranes of the earliest recognizable tubular and glomerular forms. Because of the sharp parallel between in vivo and in vitro basement membrane glycoprotein production we conclude that the whole organ metanephric culture system is a useful model for the study of renal basement membrane development. Further, based on the pattern of in vitro basement membrane production, it may be concluded that tubular and glomerular epithelial cells are capable of producing basement membrane glycoproteins in the absence of endothelial or recognizable mesangial cells following initial embryonic induction.

Animals↗

Metanephric development in serum-free organ culture.

A new mouse metanephric organ culture system has been developed to study mammalian renal development. The system permits in vitro organotypic differentiation in a serum-free, hormone supplemented medium consisting of Dulbecco's minimal essential medium (MEM) and Ham's F12 medium supplemented with insulin, 5 microgram/ml; PGE1, 25 ng/ml; T3, 3.2 pg/ml; hydrocortisone, 5 microgram/ml; and transferrin, 5 microgram/ml. In this system, metanephric development continues morphologically beyond the S-shaped tubule stage. A well differentiated proximal tubule forms with a well defined brush border, specialized intercellular connections, and an apical endocytic network. In addition, a unique devascularized glomerulus, with highly differentiated podocytes surrounding areas of basement membrane, forms entirely from epithelial elements. The present organ culture model goes beyond the limitations of previously described systems in that it does not require separation of nephrogenic blastema from ureteric bud, nor require animal serum or nonspecific tissue extracts for metanephric development. The model is thus suited for morphological, biochemical, and endocrinological study of normal and abnormal renal organogenesis.

Animals↗

Mortality of chronic hemodialysis and renal transplantation in pediatric end-stage renal disease.

The long-term mortality of chronic hemodialysis and renal transplantation was analyzed in all children treated for end-stage renal disease at Children's Hospital Medical Center over the pase 8 1/2 years. A total of 216 transplantation or dialysis courses in 120 patients were studied. No patients were excluded from treatment or analysis. Overall actuarial survival was 92% at six months, 90% at 12 months, and 89% at five years. When actuarial survival for each form of treatment was examined, patient survival was 100% at six months and 95% at five years for chronic hemodialysis; 92% at six months and five years for living related transplantation; and 88% at six months and 85% at five years for cadaveric transplantation. We conclude that most children with end-stage renal disease can be kept alive with current treatment programs, and that the mortality of chronic hemodialysis in children is comparable to that of renal transplantation.

Adolescent↗

Effects of improved glycemic control on microalbuminuria in adolescents with insulin-dependent diabetes mellitus.

The effect of improved glycemic control on microalbuminuria was evaluated longitudinally in 13 adolescents with insulin-dependent diabetes mellitus (IDDM) of 8.4 +/- 0.8 years duration. Glycemic control and microalbuminuria were assessed under three treatment regimens: conventional therapy (Period A); after 6 weeks of intensified conventional therapy (Period B); and at three periods during continuous subcutaneous insulin infusion (CSII) (Period C = 10-14 days, Period D = 2-4 months, and Period E = 6-8 months, of CSII). Although euglycemia was not achieved, there was a decrease in mean 24-hour blood glucose concentrations measured hourly in the hospital, with values averaging 239 mg/dl in Period A, 202 mg/dl in Period B, and 156-184 mg/dl in Periods C to E. This was accompanied by significant reductions in the values for whole blood, and to a lesser extent, in stable glycosylated hemoglobin A1 (GHbA1) (p less than 0.05), but not in creatinine clearance, albumin clearance, or in albumin excretion rate. Significant correlations were found between whole blood GHbA1 levels and albumin clearance in each of Periods B to E and between albumin clearance and albumin excretion in Periods B to D (p less than 0.05) but not in Period A. Our data suggests that the degree of improvement in glycemic control obtained in our adolescent population with IDDM using either intensive conventional therapy or CSII does not reduce the microalbuminuria. If modulation of microalbuminuria is achievable it may require euglycemia or may involve other factors which have a more direct effect on the transit of albumin across the glomerular basement membrane.

Adolescent↗