CYP3A5 *1 allele associated with tacrolimus trough concentrations but not subclinical acute rejection or chronic allograft nephropathy in Japanese renal transplant recipients

Abstract We compared the diagnostic validity of five urinary enzymes--alanine aminopeptidase (EC 3.4.11.2), alkaline phosphatase (EC 3.1.3.1), gamma-glutamyltransferase (EC 2.3.2.2), N-acetyl-beta-D-glucosaminidase (EC 3.2.1.30), and lysozyme (EC 3.2.1.17)--as indicators of acute rejection crises in renal-transplant recipients. In 82 patients (group A), the excretion of each of these five enzymes was measured daily from transplantation until discharge from hospital. In another 69 patients (group B), enzyme determinations were made when the patient came for regular checkups (about every four to eight weeks). We used an "activity ratio" (the activity measured at a particular time compared with the activity on the preceding determination) value of 1.5 as the decision point. In group A, use of this discrimination point for alanine aminopeptidase, gamma-glutamyltransferase, and N-acetyl-beta-D-glucosaminidase yielded a specificity and sensitivity of about 90%. In group B, only alanine aminopeptidase had a greater diagnostic sensitivity than creatinine alone. Evidently, measurement of alanine aminopeptidase can be a helpful indicator of acute rejection crises, when interpreted in combination with other available relevant clinical, biochemical, and immunological data.

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Effect of Ethnicity on Tacrolimus (Adoport) Trough Concentrations in Renal Transplant Recipients. A Single Centre Retrospective Study

Transplantation Journal ◽

10.1097/01.tp.0000543472.72552.71 ◽

2018 ◽

Vol 102 ◽

pp. S589

Author(s):

Binay BG Gurung ◽

Shafiq Chughtai ◽

Shakeeb SK Khan ◽

Ahmed AA Ali

Keyword(s):

Retrospective Study ◽

Renal Transplant ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Single Centre ◽

Trough Concentrations

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Persistence of De Novo Donor Specific Antibodies Results in Higher Rates of Acute Rejection and Graft Loss in Renal Transplant Recipients With Stable Renal Function.

Transplantation Journal ◽

10.1097/00007890-201407151-00376 ◽

2014 ◽

Vol 98 ◽

pp. 122-123

Author(s):

J. DeVos ◽

R. Knight ◽

S. Patel ◽

A. Islam ◽

L. Teeter ◽

...

Keyword(s):

Renal Function ◽

Renal Transplant ◽

Acute Rejection ◽

De Novo ◽

Graft Loss ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Specific Antibodies ◽

Stable Renal Function ◽

Donor Specific Antibodies

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Steady-state concentration of cyclosporin G (OG37-325) and its metabolites in renal transplant recipients

Clinical Chemistry ◽

10.1093/clinchem/40.4.613 ◽

1994 ◽

Vol 40 (4) ◽

pp. 613-616 ◽

Cited By ~ 3

Author(s):

L J Langman ◽

A B Leichtman ◽

W F Weitzel ◽

R W Yatscoff

Keyword(s):

Steady State ◽

Renal Transplant ◽

Secondary Metabolites ◽

Whole Blood ◽

Relative Concentration ◽

Cross Reactivity ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Dosing Interval ◽

Trough Concentrations

Abstract The steady-state concentrations of cyclosporin G (OG37-325) (CsG) and six of its metabolites (GM1, GM9, GM4N, GM1c, GM1c9, GM19) were measured throughout the 12-h dosing interval in six renal transplant recipients receiving CsG as prophylaxis against acute cellular rejection. The mean 12-h whole-blood trough concentrations (micrograms/L) were CsG, 131 +/- 26; GM1, 79 +/- 55; GM9, 110 +/- 114; GM4N, 28 +/- 18; GM1c, 31 +/- 18; GM1c9, 216 +/- 145; and GM19, 303 +/- 217. The relative concentration of the primary metabolites (GM1, GM9, GM4N) remained stable with respect to CsG throughout the dosing interval, whereas that of the secondary metabolites increased. The secondary metabolites GM19 and GM1c9 exhibited extensive between-patient variation. We investigated the effect of these metabolites on commercially available monoclonal antibody-based fluorescence polarization immunoassays (FPIA) and RIAs adapted for measurement of CsG. The 12-h whole-blood trough concentrations measured by FPIA and RIA exceed those measured by HPLC by 19% and 36%, respectively. These measured biases corresponded closely with the calculated biases (FPIA 19%, RIA 28%) based on the known cross-reactivities of CsG metabolites and their concentrations. These results suggest that cross-reactivity with metabolites account for a large part of the bias observed in immunoassays of CsG.

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