Usefulness of the Assessment of Urinary Enzymes and Microproteins in Monitoring Ciclosporin Nephrotoxicity

Abstract

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.

Cell-Specific Biomarkers in Renal Medicine and Research

“…Published human studies include antibiotics (20,79), cyclosporin (94,95), contrast media (80), and anaesthetics (94,96,97). As a general rule, specific biomarkers are released in advance of changes in serum creatinine.…”

Cyclosporine Nephrotoxicity and Rejection Crisis: Diagnosis by Urinary Enzyme Excretion

“…Since the introduction of cylosporine (CsA) as a main tenance immunosuppressive drug in clinical renal trans plantation, the 1-year graft survival rate has been im proved [13,14]; however, in renal transplant recipients undergoing CsA therapy, physical signs and clinical symp toms of an allograft AR crisis may be overshadowed [15,16], Moreover, nephrotoxicity is the most troublesome side effect of CsA therapy [17], Hence, when an acute renal impairment occurs in those patients, the differential diagnosis between CsA acute nephrotoxicity (CsAN) and AR crisis is difficult, mainly in the early post-transplant period [16,17], On the other hand, CsA has been reported to affect the renal proximal tubular epithelium, raising the possibility that increased enzymuria might be an indica tor of CsAN [18].…”

Pathological Release of Urinary Endopeptidase 24.11 Early after Renal Transplantation

“…Alanine aminopeptidase, y-glutamyltransferase and the lysosomal N-acetyl-ß-D-glucosaminidase are the main renal en zymes studied for several years [16,17], Pathological enzymuria has been detected in several diseases associated with tubular inju ry, such as drug-induced nephrotoxicity [18,19], renal artery stenosis hypertension [20] and kidney graft rejection [21]. Our data show that urinary endopeptidase 24.11 could also be used as a marker of tubular injury in renal transplantation, but further studies are needed to assess the clinical situ ations in which this type of enzymuria could be a useful diagnostic tool.…”