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The value of glycated albumin for the prediction of graft outcome in the non‐human primate porcine islet transplantation model
Author(s) -
Kang Hee Jung,
Lee Haneulnari,
Park Eun Mi,
Kim JongMin,
Shin JunSeop,
Park ChungGyu
Publication year - 2018
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1111/xen.12384
Subject(s) - islet , medicine , transplantation , albumin , diabetes mellitus , urology , confidence interval , streptozotocin , endocrinology , gastroenterology
Background The development of a precise and easy‐to‐use tool for monitoring 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 ( PIT x). 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 PIT x was evaluated using a retrospective analysis of cohort samples. Methods Data from a total of 23 PIT xs performed in 20 recipients (3 were retransplanted) 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. Blood samples were 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 PIT x (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 < .0001). However, the level decreased after PIT x 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) both correlated with the duration of insulin‐independence (rho [ρ] = −.605, P = .0028 and ρ = .662, P = .0008, respectively). The GA level strongly correlated with K G , the glucose disappearance rate during intravenous glucose tolerance testing (ρ = −.76, P < .0001). At post‐transplant week ( PTW ) 3 and at PTW 4, the GA levels in recipients with long‐term insulin‐independence (>90 days) were significantly lower than those with short‐term insulin‐independence, which revealed the excellent performance for the prediction of long‐term insulin‐independence that is comparable to that of porcine C‐peptide (historic data). Conclusions As a surrogate indicator for graft function, serial measurement of GA may provide Supporting Information to that obtained from conventional monitoring techniques of graft function for assessing porcine islet grafts in NHP models.