Obesidad y Microalbuminuria

7/28/2019 Obesidad y Microalbuminuria

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BRIEF REPORT

Limited value of routine microalbuminuria assessment

in multi-ethnic obese children

Nalini N. E. Radhakishun & Mariska van Vliet &

Ines A. von Rosenstiel & Jos H. Beijnen &

Michaela Diamant

Received: 28 November 2012 /Revised: 11 February 2013 /Accepted: 22 February 2013# IPNA 2013

AbstractBackground To determine the prevalence of microalbuminuria

and its association with cardiometabolic risk factors in a multi-

ethnic cohort of overweight and obese children.

Case-Diagnosis/Treatment A retrospective analysis of pro-

spectively collected data was performed using data from 408

overweight and obese children (age 319 years). In addition to

administering an oral glucose tolerance test, we measured

anthropometric variables, plasma lipid levels, alanine amino-

transferase and the urinary albumin/creatinine ratio (ACR).

Microalbuminuria was defined as an ACR of between 2.5 and

25 mg/mmol in boys and 3.5 and 25 mg/mmol in girls. In

total, only 11 (2.7 %) of the children analyzed presented withmicroalbuminuria, with no differences between ethnic groups,

sex or in the prevalence of hypertension compared to the

children with normoalbuminuria. After adjustment for con-

founders, the body mass index Z-score tended to be different

between the group with microalbuminuria versus that without

(3.6 vs. 3.2, respectively; P=0.054). ACR was not associated

with hypertension, impaired glucose tolerance, high triglycer-ides or low high-density lipoprotein-cholesterol.

Conclusions In a large multi-ethnic cohort of overweight and

obese children, we found a low prevalence of microalbuminuria

(11 children, 2.7 %), and in this small number of individuals,

we found no association with any of the cardiometabolic

risk factors assessed. Therefore, our data do not support the

routine measurement of microalbuminuria in asymptomatic

overweight and obese children and adolescents.

Keywords Albumin/creatinine ratio . Cardiometabolic risk

factors . Body mass index . Metabolic syndrome .

Albuminuria . Prevalence

Introduction

The increasing numbers of obese children give rise to a wide

spectrum of cardiovascular risk factors and obesity-associated

diseases. One such complication is renal injury, which clinically

manifests as (micro)albuminuria [1]. Microalbuminuria has

also proven to be an independent predictor of atherosclerotic

cardiovascular disease and mortality in adults [2].

The available literature on pediatric obesity shows a large

variation in the prevalence of microalbuminuria, ranging from

0.3 to 23.9 % [35]. Moreover, the association between

microalbuminuria and cardiometabolic risk factors in children

remains unclear [4]. Therefore, we determined the prevalence

of microalbuminuria and its association with other

cardiometabolic risk factors in a cohort of overweight and

obese children. Our hypotheses were: (1) overweight and

obese children have a high prevalence of microalbuminuria

and (2) microalbuminuria is associated with other

cardiometabolic risk factors, such as hypertension.

N. N. E. Radhakishun (*) : I. A. von Rosenstiel

Department of Pediatrics, Slotervaart Hospital, Louwesweg 6,

1066 EC Amsterdam, The Netherlands

e-mail: [email protected]

M. van Vliet

Department of Internal Medicine, Slotervaart Hospital,

Amsterdam, The Netherlands

J. H. Beijnen

Department of Pharmacy & Pharmacology, Slotervaart Hospital,

Amsterdam, The Netherlands

M. Diamant

Department of Endocrinology/Diabetes Center, VU University

Medical Center (VUmc), Amsterdam, The Netherlands

Pediatr Nephrol

DOI 10.1007/s00467-013-2451-6


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Patients and methods

Children who visited the pediatric obesity outpatient clinic for

a general obesity screening from 2007 to 2011 were selected.

Blood pressure, height, weight and waist circumference (WC)

were measured and pubertal stage was determined (according

to Tanner). Each child underwent an oral glucose tolerance

test, and fasting blood samples were drawn for the assessmentof insulin, lipid levels and alanine aminotransferase (ALT). A

morning urine sample was also taken. Parents and child were

instructed to collect the childs first urine sample after waking

up and, if necessary, store it in the refrigerator before bringing

it to the hospital on the same day. Each child was instructed to

avoid exercise 24 h prior to sampling. Girls were asked not to

collect urinary samples during their menstruation. The study

was conducted according to the guidelines of the Declaration

of Helsinki and approved by the Research Ethics Committee.

Microalbuminuria was defined using the International So-

ciety for Pediatric and Adolescent Diabetes guidelines, name-

ly, an albumin/creatinine ratio (ACR) of 2.525 mg/mmol forboys and 3.525 mg/mmol for girls [6]. Body mass index

(BMI) and WC values were standardized using Z-scores

according to Dutch reference values [7, 8]. A child with a

BMI Z-score ranging from 1.1 to 2.3 was classified as over-

weight, and a BMI Z-score of 2.3 indicated obesity [7].

Impaired glucose metabolism was diagnosed when impaired

fasting glucose (IFG; fasting glucose 5.6 mmol/L), impaired

glucose tolerance (IGT, 2-h glucose 7.8 mmol/L) or both

were found. Insulin resistance was determined according to

the homeostasis model assessment for insulin resistance

(HOMA-IR): fasting plasma insulin (IU/L) fasting glucose

(mmol/L)/22.5 3.5 [9]. The metabolic syndrome (MetS;

[10]) was diagnosed when obesity was present in addition to

two or more of the following criteria: IGT; triglyceride level

95th percentile for age and sex [11]; high-density lipoprotein

(HDL)-cholesterol level 30 IU/L, suggesting the presence of fatty liver.

Children who used glucose- or lipid-lowering drugs

and/or anti-hypertensive medication and children with ne-

phropathy, diabetes mellitus, genetic syndromes, hypo- or

hyperthyroidism were excluded from the study.

Plasma glucose levels, total cholesterol, triglycerides and

HDL-cholesterol were measured by standardized validated

methods (SYNCHRON LX20; Beckman Coulter, Brea, CA;

MODULAR ANALYTICS EVO solution; Roche Diagnos-

tics, Vilvoorde, Belgium). LDL-cholesterol was calculated

by the Friedewald formula. Plasma insulin levels were mea-

sured by an immunoluminometric assay (Immulite 200 sys-

tem; Diagnostics Products Corp, Los Angeles, CA; intra-

assay variation 36 %; inter-assay variation 35 %). Urinary

albumin concentrations were measured with an immuno-

chemistry system (Beckman Coulter; intra-assay variation

1.21.6 %; inter-assay variation 3.36.5 %). Urinary creat-

inine levels were measured by standardized validated

methods (SYNCHRON LX20; Beckman Coulter; intra-

assay variation


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Discussion

In this study, we found a low prevalence of microalbuminuria

(2.7 %) in a large multi-ethnic pediatric overweight/obese

cohort. Similar to our results, Savino et al. reported a low

prevalence of 4.7 % in 107 obese Caucasian children (mean

age 11.72.9 years) [4]. Moreover, the National Health

a n d Nu trit ion E x amin atio n S u rv e y (NHANE S), a

population-based study including 2,515 adolescents (age

range 1219 years), reported a microalbuminuria prevalence

of 0.3 % in overweight adolescents compared to 8.7 % in non-

overweight ones [3]. A possible explanation for this finding is

that normal-weight children are more likely to exercise 24 h

pr ior to ur in e co ll ec tion , lea di ng to ph ys iol og ica l

microalbuminuria [6].

In adults, African Americans have a higher risk of devel-

oping end-stage renal disease, which is partly explained by a

higher prevalence of hypertension and albuminuria [13]. In

contrast, Nguyen et al. [3] reported no association between

ethnicity and microalbuminuria in 2,515 non-overweight

and overweight adolescents (26.7 % Whites, 31.4 % African

American and 38.8 % Hispanic) from the NHANES cohort.

Similarly, we also did not find any difference in the preva-

lence of microalbuminuria between the ethnic groups; in

Table 1 Baseline characteristics stratified according to micro- or normoalbuminuria

Baseline characteristics Total Microalbuminuria Normoalbuminuria Pvaluea

n (%) 408 (100) 11 (2.7) 397 (97.3)

Boys, n (%) 204 (50.0) 5 (45.5) 199 (50.1) n.s.

Pubertal, n (%) 223 (54.7) 5 (45.5) 218 (54.9) n.s.

Obese, n (%) 394 (96.6) 11 (100) 383 (96.7) n.s.

Age (years) 10.63.3 11.43.2 10.63.3 n.s.

BMI (kg/m2) 27.45.0 30.24.5 27.35.0 n.s.

BMI Z-score 3.2 0.6 3.60.7 3.20.6 0.047

WC Z-score 3.8 1.8 3.90.9 3.71.4 n.s.

Systolic blood pressure (mmHg) 11312 10611 11412 n.s.

Diastolic blood pressure (mmHg) 7010 678.0 7010 n.s.

Fasting glucose (mmol/L) 5.2 0.4 5.20.2 5.20.4 n.s.

2-h glucose (mmol/L) 5.9 1.0 6.00.9 5.91.0 n.s.

HbA1C (%) 5.3 0.3 5.30.3 5.3 0.3 n.s.

Fasting insulin (pmol/L) 119 (77169) 139 (100237) 118 (76168) n.s.

HOMA-IR 3.8 (2.45.4) 4.4 (3.17.7) 3.8 (2.45.4) n.s.

Total cholesterol (mmol/L) 4.3 0.8 4.30.8 4.30.8 n.s.

HDL-cholesterol (mmol/L) 6.9 0.4 1.00.1 1.1 0.4 n.s.

LDL-cholesterol (mmol/L) 2.8 0.7 2.80.6 2.8 0.7 n.s.

Triglycerides (mmol/L) 0.9 (0.61.2) 1.0 (0.71.7) 0.9 (0.61.2) n.s.

ALT (IU/L) 2617 2819 2617 n.s.

ACR (mg/mmol) 0.8 1.3 6.45.3 0.6 0.4 0.005

The metabolic syndrome, n (%) 108 (26.5) 2 (18.2) 106 (26.7) n.s.

Impaired glucose metabolism, n (%) 73 (17.9) 2 (18.2) 71 (18.5) n.s.

Insulin resistance, n (%) 227 (55.6) 7 (63.6) 220 (55.4) n.s.

High total cholesterol, n (%) 51 (12.5) 1 (9.1) 50 (12.6) n.s.

Low HDL-cholesterol, n (%) 135 (33.1) 3 (27.3) 132 (33.2) n.s.

High LDL-cholesterol, n (%) 70 (17.2) 1 (9.1) 69 (17.4) n.s.

High triglycerides, n (%) 81 (19.8) 4 (36.4) 77 (19.4) n.s.Hypertension, n (%) 99 (24.7) 1 (9.1) 98 (25.1) n.s.

ALT >30 IU/L, n (%) 87 (21.3) 2 (18.2) 85 (21.4) n.s.

BMI Z-score, Standard deviation score of BMI;WC Z-score, standard deviation score of waist circumference; HbA1C, glycosylated hemoglobin;

HOMA-IR, homeostasis model assessment for insulin resistance; HDL, high density lipoprotein; LDL, low density lipoprotein; ALT, alanine

aminotransferase; ACR, albumin/creatinine ratio; n.s., not significant;

Data are expressed as the mean with the percentage (in parenthesis) or standard deviation (SD) or, as in the case of variables with a skewed

distribution, as the median with the interquartile range (IQR) in parenthesisaDifferences were tested by t tests for continuous variables and with 2 tests for categorical data

Pediatr Nephrol


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fact, none of the Black Surinamese children and adolescents

(whose original descent is from the same region as African

Americans) presented with microalbuminuria. However, in

contrast to our results but similar to data reported on the

adult population [14], Nguyen et al. [3] did find a significant

association between hypertension and microalbuminuria in

overweight adolescents. The authors hypothesized that hy-

pertension may cause endothelial dysfunction, leading tomicroalbuminuria [3]. Since 24-h ambulatory blood pres-

sure measurements were not performed in our study, we

may have underestimated the frequency of hypertension as

well as its potential correlation with microalbuminuria.

Obesity is associated with glomerular hyperperfusion

and hyperfiltration from physiological maladaptation [1],

which may lead to renal injury [1]. In agreement with

this, we found a higher BMI Z-score in those children

with microalbuminuria. Microalbuminuria has proven to

be an independent predictor of atherosclerotic cardiovas-

cular disease and mortality in adults [2]. In the pediatric

pop ula tion, how eve r, dat a fro m lon git udi nal studi esassessing the cardiovascular morbidity and mortality in

healthy and obese children with microalbuminuria are lack-

ing. Although studies show conflicting results with respect to

the association between microalbuminuria and cardiometabolic

risk factors, associations with IFG, IGT, insulin resistance,

hypertension, dyslipidemia and the MetS have been

reported in obese children [3, 4]. Given the low prevalence

of microalbuminuria, a lack of power could be the reason

that we did not detect such associations. The pathophysio-

logical mechanisms underlying the association between

microalbuminuria and cardiometabolic risk factors are not

fully understood. One of the hypotheses is that insulin

interferes at several points in the reninangiotensinaldoste-

rone system, increasing its activity despite a state of sodi-

um retention and volume expansion [14]. Through this

route, reduced insulin sensitivity (leading to higher plasma

insulin levels) may lead to vascular damage and renal

injury [14]. We hypothesize that a longer exposure to

obesity and insulin resistance is needed before any impair-

ment of renal function develops.

Our study has many strong points, most notably the

relatively large size of the cohort and its multi-ethnic nature.

However, several limitations must be acknowledged. These

include the lack of a normal-weight control group, which

precludes generalization of our results, although, as indicat-

ed, previous studies have found a higher prevalence of

microalbuminuria in normal-weight children. A second lim-

itation is the cross-sectional nature of the study, as renal

injury may develop over time. Moreover, the collection of

only one morning sample may have led to a sample error

because albuminuria can be transient and induced by factors

such as fever, exercise or exposure to extreme cold. How-

ever, the ACR used for the spot urine sample correlates very

well with the 24-h urine collection [15]. In addition, ortho-

static or postural proteinuria is common in adolescents; thus,

the true prevalence of microalbuminuria may be even lower

than we reported.

I n c o n c l u s i o n , w e f o u n d a l o w p r e v a l e n c e o f

microalbuminuria in a large cohort of overweight and

obese children and adolescents. After adjustment for

confounding factors, ACR was not associated with any of thecardiometabolic risk factors assessed. Therefore, our data do

not support the routine measurement of microalbuminuria in

asymptomatic multi-ethnic overweight and obese children.

Conflict of interest None.

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