Single-dose rATG induction at renal transplantation: Superior renal function and glucoregulation with less hypomagnesemia

R. Brian Stevens, James T. Lane, Brian P Boerner, Clifford D Miles, Theodore H. Rigley, John P. Sandoz, Kathleen J. Nielsen, Jill Y. Skorupa, Anna J. Skorupa, Bruce Kaplan, Lucile E. Wrenshall

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background: Rabbit anti-thymocyte globulin (rATG) induction reduces reperfusion injury and improves renal function in kidney recipients by means of properties unrelated to T-cell lysis. Here, we analyze intensive rATG induction (single dose, rATG S, vs. divided dose, rATG D) for improved renal function and protection against hyperglycemia. Methods: Patients without diabetes (n=98 of 180) in a prospective randomized trial of intensive rATG induction were followed for sixmonths for the major secondary composite end point of impaired glucose regulation (hyperglycemia and new-onset diabetes after transplantation, NODAT). Prospectively collected data included fasting blood glucose and HbA 1c. Serum Mg ++ was routinely collected and retrospectively analyzed. Results: Induction with rATG S produced less impaired glucose regulation (p=0.05), delayed NODAT development (p=0.02), less hyperglycemia (p=0.02), better renal function (p=0.04), and less hypomagnesemia (p=0.02), a factor associated with a lower incidence of NODAT. Generalized linear modeling confirmed that rATG S protects against a synergistic interaction between tacrolimus and sirolimus that otherwise increased hypomagnesemia (p=0.008) and hyperglycemia (p=0.03). Conclusions: rATG S initiated before renal reperfusion improved early renal function and reduced impaired glucose regulation, an injury by diabetogenic maintenance agents (tacrolimus and sirolimus).

Original languageEnglish (US)
Pages (from-to)123-132
Number of pages10
JournalClinical Transplantation
Volume26
Issue number1
DOIs
StatePublished - Jan 1 2012

Fingerprint

Antilymphocyte Serum
Kidney Transplantation
Rabbits
Kidney
Hyperglycemia
Transplantation
Tacrolimus
Sirolimus
Glucose
Reperfusion Injury
Reperfusion
Blood Glucose
Fasting
Maintenance
T-Lymphocytes
Incidence
Wounds and Injuries
Serum

Keywords

  • Hyperglycemia
  • Hypomagnesemia
  • Kidney transplantation
  • Magnesium
  • New-onset diabetes after transplantation
  • Rabbit anti-thymocyte globulin

ASJC Scopus subject areas

  • Transplantation

Cite this

Single-dose rATG induction at renal transplantation : Superior renal function and glucoregulation with less hypomagnesemia. / Stevens, R. Brian; Lane, James T.; Boerner, Brian P; Miles, Clifford D; Rigley, Theodore H.; Sandoz, John P.; Nielsen, Kathleen J.; Skorupa, Jill Y.; Skorupa, Anna J.; Kaplan, Bruce; Wrenshall, Lucile E.

In: Clinical Transplantation, Vol. 26, No. 1, 01.01.2012, p. 123-132.

Research output: Contribution to journalArticle

Stevens, RB, Lane, JT, Boerner, BP, Miles, CD, Rigley, TH, Sandoz, JP, Nielsen, KJ, Skorupa, JY, Skorupa, AJ, Kaplan, B & Wrenshall, LE 2012, 'Single-dose rATG induction at renal transplantation: Superior renal function and glucoregulation with less hypomagnesemia', Clinical Transplantation, vol. 26, no. 1, pp. 123-132. https://doi.org/10.1111/j.1399-0012.2011.01425.x
Stevens, R. Brian ; Lane, James T. ; Boerner, Brian P ; Miles, Clifford D ; Rigley, Theodore H. ; Sandoz, John P. ; Nielsen, Kathleen J. ; Skorupa, Jill Y. ; Skorupa, Anna J. ; Kaplan, Bruce ; Wrenshall, Lucile E. / Single-dose rATG induction at renal transplantation : Superior renal function and glucoregulation with less hypomagnesemia. In: Clinical Transplantation. 2012 ; Vol. 26, No. 1. pp. 123-132.
@article{2e27f1dd90334c8086cedce6f53503a5,
title = "Single-dose rATG induction at renal transplantation: Superior renal function and glucoregulation with less hypomagnesemia",
abstract = "Background: Rabbit anti-thymocyte globulin (rATG) induction reduces reperfusion injury and improves renal function in kidney recipients by means of properties unrelated to T-cell lysis. Here, we analyze intensive rATG induction (single dose, rATG S, vs. divided dose, rATG D) for improved renal function and protection against hyperglycemia. Methods: Patients without diabetes (n=98 of 180) in a prospective randomized trial of intensive rATG induction were followed for sixmonths for the major secondary composite end point of impaired glucose regulation (hyperglycemia and new-onset diabetes after transplantation, NODAT). Prospectively collected data included fasting blood glucose and HbA 1c. Serum Mg ++ was routinely collected and retrospectively analyzed. Results: Induction with rATG S produced less impaired glucose regulation (p=0.05), delayed NODAT development (p=0.02), less hyperglycemia (p=0.02), better renal function (p=0.04), and less hypomagnesemia (p=0.02), a factor associated with a lower incidence of NODAT. Generalized linear modeling confirmed that rATG S protects against a synergistic interaction between tacrolimus and sirolimus that otherwise increased hypomagnesemia (p=0.008) and hyperglycemia (p=0.03). Conclusions: rATG S initiated before renal reperfusion improved early renal function and reduced impaired glucose regulation, an injury by diabetogenic maintenance agents (tacrolimus and sirolimus).",
keywords = "Hyperglycemia, Hypomagnesemia, Kidney transplantation, Magnesium, New-onset diabetes after transplantation, Rabbit anti-thymocyte globulin",
author = "Stevens, {R. Brian} and Lane, {James T.} and Boerner, {Brian P} and Miles, {Clifford D} and Rigley, {Theodore H.} and Sandoz, {John P.} and Nielsen, {Kathleen J.} and Skorupa, {Jill Y.} and Skorupa, {Anna J.} and Bruce Kaplan and Wrenshall, {Lucile E.}",
year = "2012",
month = "1",
day = "1",
doi = "10.1111/j.1399-0012.2011.01425.x",
language = "English (US)",
volume = "26",
pages = "123--132",
journal = "Clinical Transplantation",
issn = "0902-0063",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Single-dose rATG induction at renal transplantation

T2 - Superior renal function and glucoregulation with less hypomagnesemia

AU - Stevens, R. Brian

AU - Lane, James T.

AU - Boerner, Brian P

AU - Miles, Clifford D

AU - Rigley, Theodore H.

AU - Sandoz, John P.

AU - Nielsen, Kathleen J.

AU - Skorupa, Jill Y.

AU - Skorupa, Anna J.

AU - Kaplan, Bruce

AU - Wrenshall, Lucile E.

PY - 2012/1/1

Y1 - 2012/1/1

N2 - Background: Rabbit anti-thymocyte globulin (rATG) induction reduces reperfusion injury and improves renal function in kidney recipients by means of properties unrelated to T-cell lysis. Here, we analyze intensive rATG induction (single dose, rATG S, vs. divided dose, rATG D) for improved renal function and protection against hyperglycemia. Methods: Patients without diabetes (n=98 of 180) in a prospective randomized trial of intensive rATG induction were followed for sixmonths for the major secondary composite end point of impaired glucose regulation (hyperglycemia and new-onset diabetes after transplantation, NODAT). Prospectively collected data included fasting blood glucose and HbA 1c. Serum Mg ++ was routinely collected and retrospectively analyzed. Results: Induction with rATG S produced less impaired glucose regulation (p=0.05), delayed NODAT development (p=0.02), less hyperglycemia (p=0.02), better renal function (p=0.04), and less hypomagnesemia (p=0.02), a factor associated with a lower incidence of NODAT. Generalized linear modeling confirmed that rATG S protects against a synergistic interaction between tacrolimus and sirolimus that otherwise increased hypomagnesemia (p=0.008) and hyperglycemia (p=0.03). Conclusions: rATG S initiated before renal reperfusion improved early renal function and reduced impaired glucose regulation, an injury by diabetogenic maintenance agents (tacrolimus and sirolimus).

AB - Background: Rabbit anti-thymocyte globulin (rATG) induction reduces reperfusion injury and improves renal function in kidney recipients by means of properties unrelated to T-cell lysis. Here, we analyze intensive rATG induction (single dose, rATG S, vs. divided dose, rATG D) for improved renal function and protection against hyperglycemia. Methods: Patients without diabetes (n=98 of 180) in a prospective randomized trial of intensive rATG induction were followed for sixmonths for the major secondary composite end point of impaired glucose regulation (hyperglycemia and new-onset diabetes after transplantation, NODAT). Prospectively collected data included fasting blood glucose and HbA 1c. Serum Mg ++ was routinely collected and retrospectively analyzed. Results: Induction with rATG S produced less impaired glucose regulation (p=0.05), delayed NODAT development (p=0.02), less hyperglycemia (p=0.02), better renal function (p=0.04), and less hypomagnesemia (p=0.02), a factor associated with a lower incidence of NODAT. Generalized linear modeling confirmed that rATG S protects against a synergistic interaction between tacrolimus and sirolimus that otherwise increased hypomagnesemia (p=0.008) and hyperglycemia (p=0.03). Conclusions: rATG S initiated before renal reperfusion improved early renal function and reduced impaired glucose regulation, an injury by diabetogenic maintenance agents (tacrolimus and sirolimus).

KW - Hyperglycemia

KW - Hypomagnesemia

KW - Kidney transplantation

KW - Magnesium

KW - New-onset diabetes after transplantation

KW - Rabbit anti-thymocyte globulin

UR - http://www.scopus.com/inward/record.url?scp=79960983881&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79960983881&partnerID=8YFLogxK

U2 - 10.1111/j.1399-0012.2011.01425.x

DO - 10.1111/j.1399-0012.2011.01425.x

M3 - Article

C2 - 21401720

AN - SCOPUS:79960983881

VL - 26

SP - 123

EP - 132

JO - Clinical Transplantation

JF - Clinical Transplantation

SN - 0902-0063

IS - 1

ER -