The Value of Glycated Albumin for Monitoring Graft Function in the Non-Human Primate Porcine Islet Transplantation Model

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Abstract

Background

The development of a precise and simple-to-use monitoring tool for islet graft function is important in clarifying the causes of graft loss, identifying appropriate therapy, and ensuring graft survival in the nonhuman primate (NHP) model of porcine islet transplantation (PITx). Glycated albumin (GA) is an indicator of intermediate-term changes in blood glucose control and is useful in clinical diabetes management. The validity of GA for monitoring graft function in NHP recipients of PITx was evaluated using a retrospective analysis of cohort samples.

Methods

Data from a total of 23 PITxs performed in 20 recipients (3 were re-transplanted) were included in this study. Islet clusters purified from adult wild-type pigs were transplanted via the intraportal route into streptozotocin-induced diabetic rhesus monkeys with immune suppression. Blood samples were obtained once per week from the recipients until they lost insulin-independence (Ins-Ind). Blood was also obtained from 69 non-diabetic monkeys that served as a control group. The levels of GA and albumin in stored plasma aliquots were measured using each enzymatic method, and the GA result was expressed as the percentage of GA level to the total albumin level.

Results

The median level of GA in the recipients on the day of PITx (median 18.6%, 95% confidence interval [CI] 16.7-20.4%) was significantly higher than that of healthy controls (median 9.14%, 95% CI 9.0-9.3%, P < 0.0001). However, the level decreased after PITx and remained low or increased depending on the extent of residual graft function. The GA level at a nadir (median 11.6%, 95% CI 10.8-13.0%) and the time to reach a nadir (median 43 days, 95% CI 21.7-69.3 days) correlated with Ins-Ind duration (rho [ρ] = -0.605, P = 0.0028 and ρ = 0.662, P = 0.0008, respectively]. The GA level strongly correlated with KG, the glucose disappearance rate during intravenous glucose tolerance testing (ρ = -0.76, P < 0.0001). The GA levels at post-transplant week (PTW) 3 and at PTW 4 in recipients with long-term Ins-Ind (>90 days) were significantly lower than those with short-term Ins-Ind, revealing excellent performance for prediction of long-term Ins-Ind, similar to that of porcine C-peptide (historic data).

Conclusions

As a surrogate indicator for graft function, serial measurement of GA may provide supplemental information to conventional monitoring techniques for graft function in assessing porcine islet grafts in NHP models.

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