Showing papers by "Helmut G. Rennke published in 1985"

Control of glomerular hypertension limits glomerular injury in rats with reduced renal mass.

Abstract: Micropuncture and morphologic studies were performed in four groups of male Munich-Wistar rats after removal of the right kidney and segmental infarction of two-thirds of the left kidney. Groups 1 and 3 received no specific therapy. Groups 2 and 4 were treated with the angiotensin I converting enzyme inhibitor, enalapril, 50 mg/liter of which was put in their drinking water. All rats were fed standard chow. Groups 1 and 2 underwent micropuncture study 4 wk after renal ablation. Untreated group 1 rats exhibited systemic hypertension and elevation of the single nephron glomerular filtration rate (SNGFR) due to high average values for the mean glomerular transcapillary hydraulic pressure difference and glomerular plasma flow rate. In group 2 rats, treatment with enalapril prevented systemic hypertension and maintained the mean glomerular transcapillary hydraulic pressure gradient at near-normal levels without significantly compromising SNGFR and the glomerular capillary plasma flow rate, as compared with untreated group 1 rats. Groups 3 and 4 were studied 8 wk after renal ablation. Untreated group 3 rats demonstrated persistent systemic hypertension, progressive proteinuria, and glomerular structural lesions, including mesangial expansion and segmental sclerosis. In group 4 rats, treatment with enalapril maintained systemic blood pressure at normal levels over the 8-wk period and significantly limited the development of proteinuria and glomerular lesions. These studies suggest that control of glomerular hypertension effectively limits glomerular injury in rats with renal ablation, and further support the view that glomerular hemodynamic changes mediate progressive renal injury when nephron number is reduced.

Predominance of hemodynamic rather than metabolic factors in the pathogenesis of diabetic glomerulopathy.

Abstract: Six groups of Munich-Wistar rats underwent micropuncture study 2-10 weeks and morphologic studies 11-13 months after induction of streptozotocin diabetes or after sham treatment. Diabetic rats received diets containing 6% (group D6), 12% (D12), or 50% protein (D50) and were maintained under similar conditions of moderate hyperglycemia by daily injections of ultralente insulin. Age- and weight-matched normal control rats were also given 6% (Group N6), 12% (N12), or 50% protein (N50). Kidney weight, whole-kidney and single-nephron glomerular filtration rate, glomerular plasma flow, and mean glomerular transcapillary hydraulic pressure difference were higher in D50 rats than in all other groups and predisposed this group to marked and progressive albuminuria. Likewise, histological examination of the kidneys disclosed areas of sclerosis in 19.6% of glomeruli in D50 rats; the frequency of such lesions was less than 2.5% in all other groups. These findings indicate that the metabolic disorder seen in stable, moderately hyperglycemic diabetic rats does not lead to glomerulopathy as long as elevations in glomerular pressures and flows are prevented.

Antibody-induced glomerular injury.

Abstract: Although an immunological mechanism had been suspected for many glomerular diseases in humans since the early descriptions by Schick and von Pirquet [54, 62], it was not until the advent of immunofluorescence microscopic techniques that the central role of humoral factors, and in particular the participation of antibodies, was clearly established. During the last three decades, a number of investigators have clarified many aspects of the mechanisms of immune-mediated injury by using various disease models induced in experimental animals. These studies have clearly defined the influence of molecular determinants of participating antigens, the characteristics of specific immunoglobulins, and the role played by other mediators such as the complement system, polymorphonuclear neutrophils, macrophages, the coagulation system, and hemodynamic factors in the pathogenesis of acute and chronic glomerulonephritides. In spite of such major advances in this field, there remain a considerable number of unanswered questions, particularly related to the participation of T cells and their secretory products in the development of glomerular capillary damage. It is for this reason that the emphasis of this brief review is focused exclusively on antibody-induced glomerular injury in the experimental animal. A summary of the meMediators of Giomerular Injury