ESPN 50th Annual Meeting

ESPN 2017


 
First-year Profile of Biomarkers for Early Detection of Renal Injury in Healthy Infants
DUSAN KOSTIC 1 GLENDA PRISCILA NEVES DOS SANTOS BEOZZO 1 ANDRE HENRIQUE TERUAKI KATO 1 VERA LUCIA JORNADA KREBS 1 VICTOR BUNDUKI 2 MARCELO ZUGAIB 2 VERA HERMINA KALIKA KOCH 1

1- CHILDRENS INSTITUTE - UNIVERSITY OF SAO PAULO
2- HOSPITAL DAS CLINICAS - UNIVERSITY OF SAO PAULO
 
Introduction:

To analyze first-year profiles of two serum renal biomarkers: creatinine and cystatin C; and five urinary renal biomarkers: Neutrophil gelatinase-associated lipocalin (NGAL), Kidney Injury Molecule-1 (KIM-1), Transforming growth factor beta 1 (TGF-β1), Retinol-binding protein (RBP) and Cystatin C (CyC) in a cohort of healthy infants.

Material and methods:

In this longitudinal, prospective and pilot study 24 healthy infants were followed from birth up to one year of age, in a quaternary healthcare institution, by nephrology pediatrics, neonatology and obstetrics team. All of the subjects were free of gestational or delivery complications with normal glomerular and tubular function parameters and normal renal ultrasound findings. The blood samples were collected from the umbilical cord at birth and subsequently, between 3th- 7th day, at 6th and 12th months of age. The urine samples were obtained in the period between 3th- 7th day, at 1st, 2nd, 3rd, 6th, 9th and 12th month of age. Anthropometric parameters and blood pressure were obtained during follow-up. Serum and urine samples were stored at -70ºC, and thereafter analyzed by quantitative enzymatic immunoassay (ELISA).

Results:

The cohort is characterized by homogeneous distribution of sex (58.3% boys, 47.1% girls), race and gestational age. 24/45 (53.3%) newborns completed the follow-up, in period from 2011 until 2016. Demographic distributions, main renal function parameters and mean values of renal biomarkers during the first year of life are presented in table 1.

Table 1. Demographic characteristics, main renal function parameters and Mean values of renal biomarkers during the first year of life in healthy infants.

Cohort Characteristics

Mean/SD

 

Gestational age (weeks)

38.4 ± 1.4

 

Birth weight (grams)

3105 ± 401.5

 

Weight at 12 months – boys (grams)

9820 ± 1005.8

 

Weight at 12 months – girls (grams)

9433.5 ± 1144.2

 

Stature at 12 months – boys (cm)

76 ± 1.8

 

Stature at 12 months – girls (cm)

74.9 ± 3.8

 

Systolic blood pressure (mmHg)

88.3 ± 1.08

 

Diastolic blood pressure (mmHg)

53.4 ± 2.99

 

Biomarker

Mean / SD

p value

Albuminuria (mg/g urine creatinine)

23.06 ± 3.77

p=0.33(1)

GFR by creatinine (ml/min/1.73m2)

 

p=0.068(2)

Neonatal period (3rd to 7th day of life)

69.87 ± 32.33

 

6 months

142.21 ± 23.64

 

12 months

135.75 ± 35.15

 

GFR by cystatin C (ml/min/1.73m2)

 

p=0.105(2)

Neonatal period (3rd to 7th day of life)

71.66 ± 24.55

 

6 months

97.64 ± 26.49

 

12 months

96.7 ± 19.49

 

Serum Creatinine (mg/dl)

 

p=0.21(2)

Umbilical cord

0.62 ± 0.20

 

Neonatal period (3rd to 7th day of life)

0.38 ± 0.17

 

6 months

0.22 ± 0.04

 

12 months

0.27 ± 0.07

 

Serum Cystatin C (μg/dl)

 

p=0.47(2)

Umbilical cord

2.55 ± 0.75

 

Neonatal period (3rd to 7th day of life)

1.65 ± 0.55

 

6 months

1.20 ± 0.57

 

12 months

1.13 ± 0.25

 

RBPu (normalized by urine creatinine, in ng/g)

 

p=0.034(2)

Neonatal period (3rd to 7th day of life)

23.79 ± 67.27

 

1st month

1.77 ± 1.66

 

2nd month

1.18 ± 1.37

 

3rd month

0.74 ± 0.56

 

6th month

1.12 ± 1.28

 

9th month

2.12 ± 3.11

 

12th month

2.48 ± 6.13

 

NGALu (normalized by urine creatinine, in ng/g)

1.09 ± 1.51

p=0.43(2)

CyCu (normalized by urine creatinine, in ng/g)

 

p=0.023(2)

Neonatal period (3rd to 7th day of life)

61.51 ± 58.99

 

1st month

10.73 ± 9.34

 

2nd month

8.22 ± 5.77

 

3rd month

10.87 ± 10.64

 

6th month

13.78 ± 14.26

 

9th month

22.15 ± 24.86

 

12th month

17.74 ± 18.68

 

TGFβ1u (normalized by urine creatinine, in pg/g)

1.5 ± 1.5

p=0.06(2)

KIM-1u (normalized by urine creatinine, in ng/g)

2.01 ± 1.8

p=0.12(2)

GFR – Glomerular filtration rate; (1) t-Student Test. (2) Test F (ANOVA) by Tukey’s comparisons, statistical significance: p<0.05; RBP – Retinol-Binding Protein; NGALu – Urine Neutrophil Gelatinase-Associated Lipocalin, CyCu – Urine Cystatin C, TGFβ1u – Urine Transforming Growth Factor Beta 1 (TGF-β1); KIM-1u – Urine Kidney Injury Molecule-1;

 

 

Conclusions:

In healthy infants, the evolution of biomarkers values during the first year of life represents, as expected, renal maturation. KIM-1, TGFβ-1 and NGAL maintained low values throughout the observation period confirming absence of renal impairment. Further studies with more participants are necessary in order to validate these biomarkers for their future use in early renal impairment detection.