摘要：

A comparative analysis of renal biopsy findings (morphometric, cytological, and electronmicroscopic) and clinical findings in patients with various types of primary glomerulopathy, renal vasculopathy, and chronic interstitial nephritis revealed the following: (1) In all the primary glomerulopathies except rapidly progressive glomerulonephritis, there is a significant positive correlation between the relative volume of the cortical interstitium and the serum creatinine concentration, and a significant negative correlation between the relative cortical capillary volume and the serum creatinine concentration. (2) In secondary malignant nephrosclerosis, the gradient of the line computed for the relationship between the renal cortical interstitial volume and the serum creatinine concentration is greater than in the primary glomerulopathies and decompensated benign nephrosclerosis, which indicates that the serum creatinine concentration in this disease is determined not only by postglomerular, but also by preglomerular and glomerular changes. (3) In decompensated benign nephrosclerosis, this gradient is the same as in focal sclerosing glomerulonephritis. (4) In the chronic interstitial nephritides, as in the primary glomerulopathies, there is a significant positive correlation between the relative volume of the renal cortical interstitium and the serum creatinine concentration, and a significant negative correlation between the relative cortical capillary volume and the serum creatinine concentration, indicating that the hypothesis of Spuhler and Zollinger that the uremia in these disorders is due to obliteration of the postglomerular capillaries is correct. (5) Isolated disease of the renal corpuscles, regardless of its severity, does not lead to renal failure, or even to elevation of the serum creatinine concentration. (6) The pathogenesis of chronic renal failure in the primary glomerulopathies, decompensated benign nephrosclerosis and secondary malignant nephrosclerosis involves the passage of basement membrane material from the glomerular capillaries into the primary urine, and its reabsorption and presentation as auotantigen to interstitial lymphocytes and macrophages by proximal tubular epithelial cells that express HLA class II antigens. (7) It is also possible that immunoglobulins in the glomerular filtrate in nonselective proteinuria may become autoantigens after tubular reabsorption and processing. (8) It is postulated that the presentation of these autoantigens by the tubular cells leads, in genetically predisposed individuals, to proliferation of fibroblasts and fibrocytes, among other cells, and thus to increased production of extracellular matrix (including collagen type III) and eventually to obliteration of the postglomerular capillaries, resulting in a progressive-fall in the glomerular filtration rate. (9) Progressive renal failure may develop in any of the primary glomerulopathies and renal vasculopathies if acute renal failure occurs, because the interstitial edema of the renal cortex often seen in this complication may develop into interstitial fibrosis with progressive obliteration of the postglomerular capillaries. (10) It is thought that cortical interstitial fibrosis causing progressive renal failure may also develop in diabetes as a result of increased production of extracellular matrix associated with hyperglycemia.

展开