Glomerular hemodynamics in experimental diabetes mellitus

Abstract

Micropuncture studies were performed in three groups of euvolemic male Munich-Wistar rats: 8 control rats, 7 severely hyperglycemic rats made diabetic with streptozotocin (60 mg/kg, i.v.), and 6 moderately hyperglycemic rats made diabetic by the same method but given 2 U of NPH insulin daily. Glucose concentrations at the time of micropuncture study averaged 115 +/- (sem) 10, 565 +/- 12, and 375 +/- 23 mg/dl, respectively. Single nephron GFR (SNGFR) values were significantly lower (28.8 +/- 1.9nl/min) in severely hyperglycemic rats than they were in controls (48.9 +/- 3.8). This reduction in SNGFR was due mainly to a fall in glomerular plasma flow rate ((Q(A)). In contrast, moderately hyperglycemic rats exhibited glomerular hyperfiltration, with SNGFR values averaging 69.0 +/- 8.0 nl/min. This hyperfiltration, with resulted from elevations in values for Q(A) and glomerular transcapillary hydraulic pressure difference (delta P) to levels significantly above control. These alterations in SNGFR in severely hyperglycemic and moderately hyperglycemic rats, relative to controls, were paralleled by changes in whole kidney GFR and mimic the changes in GFR observed in diabetic patients with analogous degrees of hyperglycemia. Measurements of blood volumes in separate groups of control, severely, and moderately hyperglycemic rats revealed equivalent absolute blood volumes in all three conditions and increased blood volumes, relative to body weight, in both groups of hyperglycemic rats. Thus, SNGFR is increased in diabetic rats with moderate hyperglycemia but decreased in those with severe hyperglycemia, and these changes are not simply related to variations in circulating blood volume.

Sorbinil does not prevent hyperfiltration, elevated ultrafiltration pressure and albuminuria in streptozotocin-diabetic rats

“…If any clinical conclusions are to be drawn from experimental studies, the rats used in such a study should have a well-defined state of diabetes [5,14]. The rats in this study were under daily supervision with regard to blood glucose control, insulin administration and body weight.…”

“…Evidence has been presented which both supports and rejects this hypothesis. Variations in the severity of diabetes and variations in diabetic control may have contributed to the inconsistencies in the results [5].Such inconsistencies in previous reports indicate the need for a study with a well-standardized experimental protocol. This need is emphasized by the fact that numerous clinical studies have recently been started to test the effects of aldose reductase inhibitors on the various complications of diabetes in humans.…”

“…Evidence has been presented which both supports and rejects this hypothesis. Variations in the severity of diabetes and variations in diabetic control may have contributed to the inconsistencies in the results [5].…”

“…It has been shown that in experimental diabetes, elevations in single nephron glomerular filtration rate (SNGFR) result from concomitant elevations in ultrafiltration pressure and glomerular plasma flow [5]. It has been suggested that these early glomerular haemodynamic abnormalities, and in particular the elevated ultrafiltration pressure, constitute the major pathogenetic factor in the progressive glomerular sclerosis that eventually develops in a substantial number of Type 1 diabetic patients [6].…”

Diabetic Glomerulopathy

“…Both hemo-and peritoneal dialysis limit social life, leisure, and sexual activity. (Hostetter TH, 1981) Patients with diabetes may manifest uremic symptoms at a relatively less-advanced degree of renal insufficiency than their nondiabetic counterparts. (Hostetter TH, 1982) …”