The clinical usefulness of serial assays of urinary N-acetyl-β-D-glucosaminidase (NAG), γ-glutamyltransferase (GGT) and β2-microglobulin (β2M) were tested to evaluate and follow up the nephrotoxicity resulting from the prolonged administration of ciclosporin (CS). Three groups of patients were studied for 18 months: group A: functioning renal transplant patients (n = 13) on maintenance therapy from 12-31 months with CS and prednisone; group B: functioning renal transplant patients (n = ll) treated with prednisone and azathioprine; group C: patients (n = 10) affected by autoimmune steroid-unsensitive uveitis, free from previous renal disorder and treated with CS (for 8-16 months) at progressively decreasing doses. In groups A and B, the urinary enzymes and β2M underwent overlapping increases, so that these parameters cannot be considered reliable indices of CS-induced nephrotoxicity. This is due to the fact that transplanted kidneys are already altered by concomitant or preexisting affections, or by persistent immunologic injury. Conversely, in patients with uveitis, the serial assays of such urinary parameters prove to be quite reliable to evidence clinically yet unrecognizable kidney involvement due to prolonged CS administration. High enzymuria has been shown to be an earlier marker of nephrotoxicity only in nephropathy-free patients; on the other hand, the regression of elevated β2Muria into normal ranges indicates complete tubule cell recovery.
The recovery of tubules after relief of obstructive nephropathy may be investigated through serial assessment of the urinary excretion of tubular enzymes alpha-glucosidase, gamma-glutamyl-transferase and N-acetyl glucosaminidase as well as of the microprotein beta-2-microglobulin. We studied 21 patients in whom obstructive nephropathy was relieved by operative or nonoperative methods. Anuria persisted from 2 to 14 days. In these patients urinary excretion of alpha-glucosidase, gamma-glutamyl-transferase, N-acetyl glucosaminidase and beta-2-microglobulin, as well as the serum creatinine were assessed weekly. Serum creatinine was the earliest index to return to normal (within 9 to 26 days). Enzymuria returned to normal within 35 to 45 days, whereas normal urinary excretion of beta-2-microglobulin occurred more than 100 days after relief of obstructive nephropathy. N-acetyl glucosaminidase and gamma-glutamyl-transferase proved to be more reliable than alpha-glucosidase in detecting recovery of the luminal membrane of the proximal tubule. The return to normal of urinary beta-2-microglobulin levels has been shown to occur later, since more specific and complex intracellular functions underlie this index. The pathophysiological aspects of recovery of obstructive nephropathy may be considered similar to those observed in ischemic acute renal failure, since in both instances hemodynamic changes are involved.
Four coagulation indices [fibrinopeptide A (FpA), X degradation products (XDPs), platelet factor (PF4), β-thromboglobulin (β-TG)] were assessed in 38 patients affected by large bowel cancer at different stages before surgery, 7 and 30 days after it, to evaluate the capacity of such neoplasia to influence coagulation. The reported study showed that (1) FpA levels were elevated in nearly all cases both before and after surgery (thus it is a useful index for the diagnosis of such neoplasia, although its levels are not influenced by the presence of metastases), (2) increased levels of XDPs were found in a significantly (p < 0.05) higher percent of patients 7 days after surgery (no significant differences were observed in relation to the cancer stage), (3) PF4 levels were in the normal range throughout the study, and (4) β-TG levels were increased throughout the study in a high percentage of cases. It may be inferred that large bowel cancers may affect coagulation in either way(s), by triggering platelet activation and/or fibrinolysis. The most useful index for the diagnosis and follow-up of this neoplasia is FpA, although its levels are unaffected by the presence of metastases. The comprehensive evaluation of the four above-mentioned coagulation indices may give rise to the suspicion of large bowel cancer.
The ultrastructure of human renin granules has been studied from a case of Bartter’s syndrome. Renin bodies present roundish (R), lobulated (L) or sharply angulated (SA) shapes. The latter are indicative of the highest rates of renin synthesis and thereby of the greatest concentrations of the pressor enzyme. Their singular shape is consistent with the form monoclinic crystals assume when they grow in an isotropic medium. R granules form owing to filling of Golgian vesicles by renin. R bodies may then coalesce for giving rise to transient L forms. Renin is released through leak from the containing granules into the intracellular space.
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