Subclinical First Trimester Renal Abnormalities Are Associated With Preeclampsia in Normoalbuminuric Women With Type 1 Diabetes

Clare B Kelly; Michelle B Hookham; Jeremy Y Yu; Alicia J Jenkins; Alison J Nankervis; Kristian F Hanssen; Satish K Garg; James A Scardo; Samar M Hammad; M Kathryn Menard; Christopher E Aston; Timothy J Lyons

doi:10.2337/dc17-1635

Subclinical First Trimester Renal Abnormalities Are Associated With Preeclampsia in Normoalbuminuric Women With Type 1 Diabetes

Clare B Kelly, Michelle B Hookham, Jeremy Y Yu, Alicia J Jenkins, Alison J Nankervis, Kristian F Hanssen, Satish K Garg, James A Scardo, Samar M Hammad, M Kathryn Menard, Christopher E Aston, Timothy J Lyons

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Abstract

OBJECTIVE: This study was conducted to determine the utility of tubular (urinary/plasma neutrophil gelatinase-associated lipocalin [NGAL] and urinary kidney injury molecule 1 [KIM-1]) and glomerular (estimated glomerular filtration rate [eGFR]) biomarkers in predicting preeclampsia (PE) in pregnant women with type 1 diabetes mellitus (T1DM) who were free of microalbuminuria and hypertension at the first trimester.

RESEARCH DESIGN AND METHODS: This was a prospective study of T1DM pregnancy. Maternal urinary and plasma NGAL urinary KIM-1 (ELISA of frozen samples), and eGFR (Chronic Kidney Disease Epidemiology Collaboration equation) were determined at three study visits (V1: 12.4 ± 1.8; V2: 21.7 ± 1.4; V3: 31.4 ± 1.5 weeks' gestation [mean ± SD]) in 23 women with T1DM with subsequent PE (DM+PE+), 24 who remained normotensive (DM+PE-), and, for reference, in 19 normotensive pregnant women without diabetes (DM-). The groups with diabetes were matched for age, diabetes duration, HbA1c, and parity. All subjects were normotensive and free of microalbuminuria or albuminuria at V1. All study visits preceded the onset of PE.

RESULTS: Urinary creatinine-corrected NGAL (uNGALcc, ng/mg) was significantly elevated at V1 in DM+PE+ versus DM+PE- women (P = 0.01); this remained significant after exclusion of leukocyte-positive samples (5 DM+PE+ and 2 DM+PE-) (P = 0.02). Accounting for BMI, HbA1c, and total daily insulin dose, a doubling of uNGALcc at V1 conferred a sevenfold increase in risk for PE (P = 0.026). In contrast, neither plasma NGAL nor urinary KIM-1 predicted PE. Also at V1, eGFR was elevated in DM+PE+ versus DM+PE- (P = 0.04).

CONCLUSIONS: Early tubular and glomerular dysfunction may predict PE in first trimester women with T1DM, even if free of microalbuminuria. These data suggest that subclinical renal tubular and glomerular injury, if present early in pregnancy, may predispose women with T1DM to PE.

Original language	English
Pages (from-to)	1-8
Journal	Diabetes Care
Volume	40
Issue number	11
Early online date	09 Nov 2017
DOIs	https://doi.org/10.2337/dc17-1635
Publication status	Early online date - 09 Nov 2017

Keywords

Journal Article

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Subclinical First Trimester Renal Abnormalities Are Associated With Preeclampsia in Normoalbuminuric Women With Type 1 Diabetes
© 2017 The American Diabetes Association. This work is made available online in accordance with the publisher’s policies. Please refer to any applicable terms of use of the publisher.
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Kelly, C. B., Hookham, M. B., Yu, J. Y., Jenkins, A. J., Nankervis, A. J., Hanssen, K. F., Garg, S. K., Scardo, J. A., Hammad, S. M., Menard, M. K., Aston, C. E., & Lyons, T. J. (2017). Subclinical First Trimester Renal Abnormalities Are Associated With Preeclampsia in Normoalbuminuric Women With Type 1 Diabetes. Diabetes Care, 40(11), 1-8. https://doi.org/10.2337/dc17-1635

Kelly, Clare B ; Hookham, Michelle B ; Yu, Jeremy Y ; Jenkins, Alicia J ; Nankervis, Alison J ; Hanssen, Kristian F ; Garg, Satish K ; Scardo, James A ; Hammad, Samar M ; Menard, M Kathryn ; Aston, Christopher E ; Lyons, Timothy J. / Subclinical First Trimester Renal Abnormalities Are Associated With Preeclampsia in Normoalbuminuric Women With Type 1 Diabetes. In: Diabetes Care. 2017 ; Vol. 40, No. 11. pp. 1-8.

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title = "Subclinical First Trimester Renal Abnormalities Are Associated With Preeclampsia in Normoalbuminuric Women With Type 1 Diabetes",

abstract = "OBJECTIVE: This study was conducted to determine the utility of tubular (urinary/plasma neutrophil gelatinase-associated lipocalin [NGAL] and urinary kidney injury molecule 1 [KIM-1]) and glomerular (estimated glomerular filtration rate [eGFR]) biomarkers in predicting preeclampsia (PE) in pregnant women with type 1 diabetes mellitus (T1DM) who were free of microalbuminuria and hypertension at the first trimester.RESEARCH DESIGN AND METHODS: This was a prospective study of T1DM pregnancy. Maternal urinary and plasma NGAL urinary KIM-1 (ELISA of frozen samples), and eGFR (Chronic Kidney Disease Epidemiology Collaboration equation) were determined at three study visits (V1: 12.4 ± 1.8; V2: 21.7 ± 1.4; V3: 31.4 ± 1.5 weeks' gestation [mean ± SD]) in 23 women with T1DM with subsequent PE (DM+PE+), 24 who remained normotensive (DM+PE-), and, for reference, in 19 normotensive pregnant women without diabetes (DM-). The groups with diabetes were matched for age, diabetes duration, HbA1c, and parity. All subjects were normotensive and free of microalbuminuria or albuminuria at V1. All study visits preceded the onset of PE.RESULTS: Urinary creatinine-corrected NGAL (uNGALcc, ng/mg) was significantly elevated at V1 in DM+PE+ versus DM+PE- women (P = 0.01); this remained significant after exclusion of leukocyte-positive samples (5 DM+PE+ and 2 DM+PE-) (P = 0.02). Accounting for BMI, HbA1c, and total daily insulin dose, a doubling of uNGALcc at V1 conferred a sevenfold increase in risk for PE (P = 0.026). In contrast, neither plasma NGAL nor urinary KIM-1 predicted PE. Also at V1, eGFR was elevated in DM+PE+ versus DM+PE- (P = 0.04).CONCLUSIONS: Early tubular and glomerular dysfunction may predict PE in first trimester women with T1DM, even if free of microalbuminuria. These data suggest that subclinical renal tubular and glomerular injury, if present early in pregnancy, may predispose women with T1DM to PE.",

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author = "Kelly, {Clare B} and Hookham, {Michelle B} and Yu, {Jeremy Y} and Jenkins, {Alicia J} and Nankervis, {Alison J} and Hanssen, {Kristian F} and Garg, {Satish K} and Scardo, {James A} and Hammad, {Samar M} and Menard, {M Kathryn} and Aston, {Christopher E} and Lyons, {Timothy J}",

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Subclinical First Trimester Renal Abnormalities Are Associated With Preeclampsia in Normoalbuminuric Women With Type 1 Diabetes. / Kelly, Clare B; Hookham, Michelle B; Yu, Jeremy Y; Jenkins, Alicia J; Nankervis, Alison J; Hanssen, Kristian F; Garg, Satish K; Scardo, James A; Hammad, Samar M; Menard, M Kathryn; Aston, Christopher E; Lyons, Timothy J.

In: Diabetes Care, Vol. 40, No. 11, 09.11.2017, p. 1-8.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Subclinical First Trimester Renal Abnormalities Are Associated With Preeclampsia in Normoalbuminuric Women With Type 1 Diabetes

AU - Kelly, Clare B

AU - Hookham, Michelle B

AU - Yu, Jeremy Y

AU - Jenkins, Alicia J

AU - Nankervis, Alison J

AU - Hanssen, Kristian F

AU - Garg, Satish K

AU - Scardo, James A

AU - Hammad, Samar M

AU - Menard, M Kathryn

AU - Aston, Christopher E

AU - Lyons, Timothy J

PY - 2017/11/9

Y1 - 2017/11/9

N2 - OBJECTIVE: This study was conducted to determine the utility of tubular (urinary/plasma neutrophil gelatinase-associated lipocalin [NGAL] and urinary kidney injury molecule 1 [KIM-1]) and glomerular (estimated glomerular filtration rate [eGFR]) biomarkers in predicting preeclampsia (PE) in pregnant women with type 1 diabetes mellitus (T1DM) who were free of microalbuminuria and hypertension at the first trimester.RESEARCH DESIGN AND METHODS: This was a prospective study of T1DM pregnancy. Maternal urinary and plasma NGAL urinary KIM-1 (ELISA of frozen samples), and eGFR (Chronic Kidney Disease Epidemiology Collaboration equation) were determined at three study visits (V1: 12.4 ± 1.8; V2: 21.7 ± 1.4; V3: 31.4 ± 1.5 weeks' gestation [mean ± SD]) in 23 women with T1DM with subsequent PE (DM+PE+), 24 who remained normotensive (DM+PE-), and, for reference, in 19 normotensive pregnant women without diabetes (DM-). The groups with diabetes were matched for age, diabetes duration, HbA1c, and parity. All subjects were normotensive and free of microalbuminuria or albuminuria at V1. All study visits preceded the onset of PE.RESULTS: Urinary creatinine-corrected NGAL (uNGALcc, ng/mg) was significantly elevated at V1 in DM+PE+ versus DM+PE- women (P = 0.01); this remained significant after exclusion of leukocyte-positive samples (5 DM+PE+ and 2 DM+PE-) (P = 0.02). Accounting for BMI, HbA1c, and total daily insulin dose, a doubling of uNGALcc at V1 conferred a sevenfold increase in risk for PE (P = 0.026). In contrast, neither plasma NGAL nor urinary KIM-1 predicted PE. Also at V1, eGFR was elevated in DM+PE+ versus DM+PE- (P = 0.04).CONCLUSIONS: Early tubular and glomerular dysfunction may predict PE in first trimester women with T1DM, even if free of microalbuminuria. These data suggest that subclinical renal tubular and glomerular injury, if present early in pregnancy, may predispose women with T1DM to PE.

AB - OBJECTIVE: This study was conducted to determine the utility of tubular (urinary/plasma neutrophil gelatinase-associated lipocalin [NGAL] and urinary kidney injury molecule 1 [KIM-1]) and glomerular (estimated glomerular filtration rate [eGFR]) biomarkers in predicting preeclampsia (PE) in pregnant women with type 1 diabetes mellitus (T1DM) who were free of microalbuminuria and hypertension at the first trimester.RESEARCH DESIGN AND METHODS: This was a prospective study of T1DM pregnancy. Maternal urinary and plasma NGAL urinary KIM-1 (ELISA of frozen samples), and eGFR (Chronic Kidney Disease Epidemiology Collaboration equation) were determined at three study visits (V1: 12.4 ± 1.8; V2: 21.7 ± 1.4; V3: 31.4 ± 1.5 weeks' gestation [mean ± SD]) in 23 women with T1DM with subsequent PE (DM+PE+), 24 who remained normotensive (DM+PE-), and, for reference, in 19 normotensive pregnant women without diabetes (DM-). The groups with diabetes were matched for age, diabetes duration, HbA1c, and parity. All subjects were normotensive and free of microalbuminuria or albuminuria at V1. All study visits preceded the onset of PE.RESULTS: Urinary creatinine-corrected NGAL (uNGALcc, ng/mg) was significantly elevated at V1 in DM+PE+ versus DM+PE- women (P = 0.01); this remained significant after exclusion of leukocyte-positive samples (5 DM+PE+ and 2 DM+PE-) (P = 0.02). Accounting for BMI, HbA1c, and total daily insulin dose, a doubling of uNGALcc at V1 conferred a sevenfold increase in risk for PE (P = 0.026). In contrast, neither plasma NGAL nor urinary KIM-1 predicted PE. Also at V1, eGFR was elevated in DM+PE+ versus DM+PE- (P = 0.04).CONCLUSIONS: Early tubular and glomerular dysfunction may predict PE in first trimester women with T1DM, even if free of microalbuminuria. These data suggest that subclinical renal tubular and glomerular injury, if present early in pregnancy, may predispose women with T1DM to PE.

KW - Journal Article

U2 - 10.2337/dc17-1635

DO - 10.2337/dc17-1635

M3 - Article

C2 - 29122892

VL - 40

SP - 1

EP - 8

JO - Diabetes Care

JF - Diabetes Care

SN - 0149-5992

IS - 11

ER -

Subclinical First Trimester Renal Abnormalities Are Associated With Preeclampsia in Normoalbuminuric Women With Type 1 Diabetes

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