PATHOGENESIS OF CHRONIC-RENAL-FAILURE IN PRIMARY GLOMERULOPATHIES

Comparative analysis of renal biopsy findings and clinical status in p atients with different types of glomerulopathy (primary glomerulonephr itis, 1747; diabetic glomerulosclerosis, 488; renal AA and AL amyloido sis, 225) was undertaken to investigate the pathogenesis of chronic re nal failure in these diseases. Morphometric, cytological and electron- microscopic investigations were undertaken and yielded the following r esults: 1. Disease of the renal corpuscles alone, even if it is very s evere, does not lead to renal insufficiency or even elevation of the s erum creatinine concentration. 2. Chronic renal insufficiency develops only in those cases of glomerulopathy in which the postglomerular cap illaries in the renal cortex exhibit chronic inflammation that causes such severe narrowing of these vessels as to impair glomerular perfusi on. 3. The passage of basement membrane material from the glomerular c apillaries into the primary urine may play a critical role in the path ogenesis of some forms of chronic renal failure, since this material c an be reabsorbed by the tubules and is probably presented as an autoan tigen to intraepithelial T lymphocytes by proximal tubular epithelial cells that express distinct HLA class II antigens and ICAM-1. 4. The p resentation of these autoantigens to intraepithelial T lymphocytes lea ds in genetically predisposed individuals to an autoimmune response wi th a consequent marked increase in numbers of T lymphocytes and an inc rease in macrophages/monocytes, fibroblasts/fibrocytes and plasma cell s, and increased production of extracellular matrix by fibroblasts/fib rocytes. 5. The increase in extracellular matrix leads to obliteration of the postglomerular capillaries. 6. Progressive renal insufficiency can also develop in any case of glomerulopathy if acute renal failure develops. even if this is only transient, since the cortical intersti tial oedema often seen with this complication can develop into interst itial fibrosis with progressive obliteration of the postglomerular cap illaries. Thus. patients with glomerulopathy who develop acute renal f ailure generally have a worse long-term prognosis; that is, they often exhibit a rise in serum creatinine concentration that progresses to u raemic levels.