prevalence of hypertension and albuminuria in pediatric

Original Investigation | Pediatrics

Prevalence of Hypertension and Albuminuria in Pediatric Type 2 DiabetesA Systematic Review and Meta-analysisMilena Cioana, BHSc; Jiawen Deng; Maggie Hou, BHSc; Ajantha Nadarajah, BHSc; Yuan Qiu, BHSc; Sondra Song Jie Chen, BHSc; Angelica Rivas, BHSc;Laura Banfield, MLIS, MHSc; Rahul Chanchlani, MD, MSc; Allison Dart, MD, MSc; Brandy Wicklow, MD, MSc; Haifa Alfaraidi, MD; Ahlam Alotaibi, MD;Lehana Thabane, PhD; M. Constantine Samaan, MD, MSc

Abstract

IMPORTANCE Hypertension and albuminuria are markers of diabetes-related nephropathy andimportant factors associated with kidney outcomes in pediatric type 2 diabetes. However, theirprevalence in these patients is unknown.

OBJECTIVE To measure the prevalence of hypertension and albuminuria in pediatric patients withtype 2 diabetes and to evaluate the association of sex and race/ethnicity with these conditions.

DATA SOURCES MEDLINE, Embase, CINAHL, Cochrane Library, Web of Science, the gray literature,and references of the screened articles were searched for human studies from date of databaseinception to February 20, 2020.

STUDY SELECTION Observational studies with at least 10 participants reporting the prevalence ofhypertension and/or albuminuria in pediatric patients with type 2 diabetes were included. Threeteams of 2 independent reviewers screened 7614 papers, of which 60 fulfilled the eligibility criteria.

DATA EXTRACTION AND SYNTHESIS Three teams of 2 independent reviewers performed dataextraction, risk of bias analysis, and level of evidence analyses. The meta-analysis was conductedusing a random-effects model and followed the Meta-analysis of Observational Studies inEpidemiology (MOOSE) guidelines.

MAIN OUTCOMES AND MEASURES The primary outcomes included the pooled prevalence rates(percentages with 95% CI) for hypertension and albuminuria. The secondary outcomes assessedpooled prevalence rates by sex and racial/ethnic group.

RESULTS Sixty studies were included in the systematic review. Diabetes duration varied frominclusion at diagnosis to 15.0 years after diagnosis, and the reported mean age at diagnosis rangedfrom 6.5 to 21.0 years. Hypertension prevalence among 3463 participants was 25.33% (95% CI,19.57%-31.53%). Male participants had higher hypertension risk than female participants (odds ratio[OR], 1.42 [95% CI, 1.10-1.83]), with Pacific Islander and Indigenous youth having the highestprevalence of all racial/ethnic groups (Pacific Islander youth: 26.71% [95% CI, 14.54%-40.72%];Indigenous youth: 26.48% [95% CI, 17.34%-36.74%]; White youth: 20.95% [95% CI,12.65%-30.57%]; African American youth: 19.04% [95% CI, 12.01%-27.23%]; Hispanic/Latino youth:15.11% [95% CI, 6.56%-26.30%]; Asian youth: 18.37% [95% CI, 9.49%-29.23%]). Albuminuriaprevalence among 2250 participants was 22.17% (95% CI, 17.34%-27.38%). Pacific Islander youth,Indigenous youth, and Asian youth had higher prevalence rates than White youth (Pacific Islanderyouth: 31.84% [95% CI, 11.90%-55.47%]; Indigenous youth: 24.27% [95% CI, 14.39%-35.73%]; Asianyouth: 23.00% [95% CI, 18.85%-27.41%]; White youth: 12.59% [95% CI, 7.75%-18.33%]), with no

(continued)

Key PointsQuestion What is the prevalence of

hypertension and albuminuria in

children and adolescents with type 2

diabetes?

Findings This systematic review and

meta-analysis of 60 studies found that

25% of children and adolescents with

type 2 diabetes had hypertension and

22% had albuminuria. Pacific Islander

and Indigenous youth had a higher risk

of these conditions than children from

other racial groups.

Meaning In this study, the burden of

hypertension and albuminuria in

pediatric type 2 diabetes was

substantial, especially among Pacific

Islander and Indigenous youth.

+ Supplemental content

Author affiliations and article information arelisted at the end of this article.

Open Access. This is an open access article distributed under the terms of the CC-BY License.

JAMA Network Open. 2021;4(4):e216069. doi:10.1001/jamanetworkopen.2021.6069 (Reprinted) April 30, 2021 1/27

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Abstract (continued)

sex differences (OR for male vs female participants, 0.68 [95% CI, 0.46-1.01]). Heterogeneity washigh among studies, with a low to moderate risk of bias.

CONCLUSIONS AND RELEVANCE In this study, markers of diabetes-related nephropathy werecommonly detected in pediatric patients with type 2 diabetes, with a disproportionate burden notedamong Pacific Islander and Indigenous youth. Personalized management strategies to target kidneyoutcomes are urgently needed in pediatric patients with type 2 diabetes to alleviate the burden ofthis condition on the kidneys.

JAMA Network Open. 2021;4(4):e216069. doi:10.1001/jamanetworkopen.2021.6069

Introduction

The global increase in obesity has driven the emergence of type 2 diabetes in children.1,2 Pediatrictype 2 diabetes is an aggressive disease with greater risk of end-organ damage and comorbiditiesthan pediatric type 1 diabetes or adult-onset type 2 diabetes.1-5 The kidneys are notable early targetsof type 2 diabetes–associated organ damage, and diabetes-related nephropathy commonlymanifests as hypertension and albuminuria.6-8 If untreated, hypertension is associated withcardiovascular anomalies, including increased carotid intima-media thickness and left ventricularhypertrophy.9,10 These subclinical adverse outcomes are known risk factors for future cardiovasculardisease and mortality.9,10 Similarly, microalbuminuria is the first sign of diabetes-related nephropathyand can progress to chronic kidney disease and end-stage kidney disease if untreated.11

To ensure early detection and treatment of nephropathy in the pediatric type 2 diabetespopulation, current screening guidelines recommend measuring blood pressure (BP) and urinealbumin-to-creatine ratio (ACR) at type 2 diabetes diagnosis and annually thereafter.9,12,13 Withadequate glycemic and blood pressure control, the onset of end-stage kidney disease can bedelayed, and the risk of microvascular and macrovascular complications can be reduced, making themanagement of hypertension and albuminuria crucial to improving outcomes in patients withpediatric type 2 diabetes.11,14 However, the full burden of diabetes-related nephropathy in pediatricpatients with type 2 diabetes is not well established. There has also been some evidence suggestingthat the rate of type 2 diabetes complications differs by sex and race/ethnicity.15-17 Determining howsex and race/ethnicity are associated with hypertension and albuminuria prevalence is an importantstep toward identifying at-risk groups and can inform future personalized screening and treatmentstrategies.

Thus, this systematic review aimed to determine the prevalence of hypertension andalbuminuria in pediatric patients with type 2 diabetes and to explore the association of sex and race/ethnicity with prevalence.

Methods

Systematic Review Protocol and RegistrationThis systematic review has been registered with PROSPERO (CRD42018091127).18 The study isreported according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE)reporting guideline.19

Search StrategiesSearch strategies were developed by a senior health sciences librarian and conducted in MEDLINE,Embase, CINAHL, Cochrane Central Register of Controlled Trials, and Cochrane Database ofSystematic Reviews from database inception to February 20, 2020, without language restrictions

JAMA Network Open | Pediatrics Prevalence of Hypertension and Albuminuria in Pediatric Type 2 Diabetes




https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=91127

https://www.equator-network.org/reporting-guidelines/meta-analysis-of-observational-studies-in-epidemiology-a-proposal-for-reporting-meta-analysis-of-observational-studies-in-epidemiology-moose-group/

(eTables 1-5 in the Supplement). The gray literature, including ClinicalTrials.gov and Web of Science:Conference Proceedings Citation Index–Science, was searched. We combined concepts of pediatricsand type 2 diabetes with terms for hypertension, albuminuria, prevalence, and epidemiologic studydesign. We also searched the references of included articles. If a conference abstract was deemedeligible, we sought a full-text publication and contacted the corresponding author if a publishedarticle could not be located or did not report the relevant data set for this analysis.

Eligibility CriteriaWe included studies with observational designs, including retrospective and prospective cohortstudies as well as cross-sectional studies. The eligibility criteria included studies involving humanparticipants with a sample size of at least 10 that reported on hypertension and/or albuminuriaprevalence in patients with type 2 diabetes who were 18 years of age or younger. For studies withserial reporting of data, we included the report with the largest sample size. We excluded studiesreporting participants with gestational diabetes.

To be as comprehensive as possible, we included studies reporting on all definitions ofhypertension and albuminuria for our prevalence estimate. In the meta-analysis, we only pooledstudies with similar definitions. Hypertension was defined as systolic and/or diastolic BP levels in the95th percentile or greater for sex, age, and height.20 Most studies used BP reference values basedon the National Heart, Lung, and Blood Institute data, whereas some used reference values based onthe European guidelines.20-25 Urine ACR of 30 mg/g or greater defined albuminuria.9,12,13,26

Microalbuminuria was defined as an ACR of 30 or greater to 300 mg/g, and macroalbuminuria wasdefined as an ACR of greater than 300 mg/g. Persistent albuminuria, microalbuminuria, ormacroalbuminuria were defined as 2 of 3 samples with levels greater than the corresponding ACRthreshold over 6 months. If not specified, it was assumed that measurements were taken only once.Studies using other definitions of hypertension or albuminuria were removed in the sensitivityanalysis.

Study Selection, Data Abstraction, and Quality AppraisalThree teams of 2 independent reviewers (M.C., M.H., A.N., Y.Q., S.J.J.C., A.R.) screened titles,abstracts, and full-text articles and completed data abstraction, risk of bias assessments, and level ofevidence assessments. Reviewers resolved disagreements through discussion, and a third reviewer(M.C.S.) resolved persistent disagreements.

A data abstraction form was designed and piloted specifically for this study. We extracted dataon study design, age at diabetes diagnosis, age at study enrollment, duration of diabetes, samplesize, sex, and race. We also extracted hypertension and albuminuria definitions and prevalence withsex-specific and race-specific data, if reported.

For longitudinal studies, we extracted the prevalence values closest to the time of type 2diabetes diagnosis because we wanted to define the prevalence closest to the time of hypertensionor albuminuria diagnosis. For unreported data, we contacted the corresponding authors to retrievethe information specific to our study question. Several studies reported on cohorts that includedparticipants older than 18 years. We contacted the study authors to retrieve pediatric-specific data.When we did not receive the data, we included studies if most participants were 18 years or youngerand no participants were older than 25 years.

Risk of bias was evaluated for each study using a validated tool for prevalence studiesdeveloped by Hoy et al.27 The tool assesses methodological quality across 10 items addressingstudies’ external and internal validity.27 Each criterion was given a score of 0 if unaddressed orunclear and 1 if it was met.27 External validity criteria included whether the target population wasrepresentative of the national population, the sampling frame was representative of the targetpopulation, random selection or a census was used, and whether there was limited evidence ofnonresponse bias.27 Internal validity criteria included whether data were collected directly fromparticipants, an acceptable case definition was used, reliable and valid tools were used to assess





prevalence, data were collected using the same method for all participants, the length of the shortestprevalence period for the parameter of interest was appropriate, and, if appropriate, numerators anddenominators were used to assess prevalence.27 The overall risk of bias was rated as low (score >8),moderate (score 6-8), or high (score �5).27 The overall level of evidence was assessed according tothe Oxford Centre for Evidence-Based Medicine criteria (OCEBM).28

Statistical AnalysisA random-effects model meta-analysis was performed when 2 or more studies of similar design,populations, methods, and outcomes were available.29,30 The primary outcomes of this reviewincluded the pooled prevalence of hypertension and albuminuria (reported as a percentage with95% CIs) across all study designs. Because it was expected that some reports would have a smallnumber of events, we transformed all prevalence estimates using the Freeman-Tukey double arcsinemethod30 and converted the results back to prevalence estimates for reporting.31,32 Inconsistencyindex (I2) and χ2 test P values were used to quantify heterogeneity among studies, and an I2 greaterthan 75% and P < .10 defined significant heterogeneity.33 Prespecified subgroup, sensitivity,metaregression, and publication bias assessments were performed if at least 10 studies wereincluded in the meta-analysis for a given outcome.33 Subgroup analyses were performed by sexand race.

We also did a meta-analysis with studies comparing the prevalence between male and femaleparticipants and calculated odds ratios with 95% CIs. We used the National Institutes of Healthdefinitions to categorize racial groups.34 We used the term Indigenous to report data fromIndigenous populations in North America.

We also performed a random-effects metaregression to determine the association of obesityprevalence with hypertension and albuminuria. We performed sensitivity analyses by removingconference abstracts, studies with a sample size smaller than 50 patients, patients older than 18years, or studies that used different or unspecified definitions of hypertension or albuminuria. Afunnel plot was used to investigate publication bias with the Egger test and visual inspection toassess plot asymmetry.35 The prevalence meta-analyses were conducted using the metafor packagein RStudio version 1.1.383, R version 3.4.3 (R Project for Statistical Computing).36-38 The sex-basedforest plots for ORs were generated using Review Manager Version 5.3 (Cochrane Collaboration).39

Results

Search ResultsThe searches yielded 7614 unique records, and 60 eligible studies were included in the review(eFigure 1 in the Supplement). Most articles were removed, as they were irrelevant to the researchquestion, reported on adult type 2 diabetes, or did not assess hypertension and/or albuminuriaprevalence in children and adolescents with type 2 diabetes.

HypertensionStudy CharacteristicsForty-six studies reported hypertension prevalence (Table 1).4,15,17,40-82 The reported age atdiagnosis of type 2 diabetes ranged from 7.1 to 20.0 years,46,47,49,72 and the duration of diabetesranged from inclusion at diagnosis40,41,43,51,52,55,56,60,65,66,75,76,81 to 7.8 years after diagnosis.71 While26 studies (57%) had a cross-sectional design,15,17,40-58,75-78,82 13 (28%) were retrospective cohortstudies,59-69,79,80 and 7 (15%) were prospective cohort studies.4,70-74,81

Pooled Prevalence of HypertensionThirty-one studies including 4363 patients with type 2 diabetes reported on the prevalence ofhypertension defined as BP in the 95th percentile or greater for age, sex, and height or systolic BP130 to 140 mm Hg or greater and diastolic BP of 80 to 90 mm Hg or greater.4,15,17,40-45,51-69,72-74 The





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Tabl

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fric

an/

Carib

bean

,As

ian,

H,

Mid

dle

East

ern)

:14

.3(1

3.7-

14.9

)f

Cana

dian

Abor

igin

al:

12.9

(12.

4-13

.4)f ,

Whi

te:1

4.4

(13.

8-15

.1)f ,

othe

r(A

fric

an/

Carib

bean

,As

ian,

H,

Mid

dle

East

ern)

:14

.3(1

3.7-

14.9

)f

061 (2

7.8)

221

M:9

1(4

1.2)

;F:

130

(58.

8)Ca

nadi

anAb

orig

inal

:10

0(4

5.2)

;Whi

te:5

7(2

5.8)

;oth

er(A

fric

an/C

arib

bean

,As

ian,

H,M

iddl

eEa

ster

n):6

4(2

9.0)

Cana

dian

Abor

igin

al:2

7(2

7.3)

;Whi

te:1

6(2

8);o

ther

(Afr

ican

/Ca

ribbe

an,A

sian

,H

,Mid

dle

East

ern)

:18

(28)

NR

NR

211

(95.

3)

Amut

haet

al,5

320

12In

dia

CSN

R16

.1(2

.5)

22.2

(9.7

)47 (2

3.7)

198

M:8

1(4

0.9)

;F:

117

(59.

1)So

uth

Indi

an:1

98(1

00.0

)dM

:22

(27)

;F:2

5(2

1.4)

;Sou

thIn

dian

:47

(23.

7)

BP≥1

30/8

5m

mH

gN

RN

R

Drut

elan

dPa

ulo,

54

2014

g

Unite

dSt

ates

CSN

Rra

nge,

3-18

NR

73 (27.

8)26

3N

RN

RN

RN

RN

RN

R

Klin

gens

mith

etal

,55

2016

Unite

dSt

ates

CS13

.1(2

.3)b

13.1

(2.3

)b0

44 (29.

3)15

0N

RN

RN

RBP

≥95t

hpe

rcen

tile

fora

gean

dhe

ight

NR

315

(62.

6)b

Zabe

enet

al,5

620

16Ba

ngla

desh

CSAg

e9-

10y:

11(1

4.3%

);ag

e11

-14

y:46

(59.

7%);

age

15-1

7y:

20(2

6.0%

)

Age

9-10

y:11

(14.

3%);

age

11-1

4y:

46(5

9.7%

);ag

e15

-17

y:20

(26.

0%)

025

(32)

77M

:26

(34)

;F:5

1(6

6)Ba

ngla

desh

i:77

(100

)dBa

ngla

desh

i:25

(32)

BP≥9

5th

perc

entil

efo

rage

and

sex

NH

LBIS

econ

dTa

skFo

rce

Repo

rt2

2

45(5

8)

Aulic

het

al,5

720

19Au

stra

liaCS

NR

15.1

(1.9

)1.

8(0

.3-3

.3)c

6(1

9)31

NR

NR

NR

BP≥9

5th

perc

entil

efo

rage

and

sex

for

patie

nts<

18y,

≥140

/90

mm

Hg

forp

atie

nts≥

18y,

orre

leva

ntm

edic

alth

erap

y

NH

LBIS

econ

dTa

skFo

rce

Repo

rt2

2

24(7

5)b

Khal

ilet

al,5

820

19Eg

ypt

CS18

.0(2

.0)

19.8

(1.1

)2.

5(2

.0)

1(8

)13

M:6

(46)

;F:7

(54)

Egyp

tian:

13(1

00)d

M:1

(17)

;F:0

;Eg

yptia

n:0

Syst

olic

BP≥1

40m

mH

gor

dias

tolic

BP≥8

0m

mH

gor

taki

ngan

tihyp

erte

nsiv

em

edic

atio

n

NR

NR

Scot

tet

al,5

920

04N

ewZe

alan

dRC

NR

mea

n,19

.6;

rang

e,14

-23

1.7

5(3

9)13

M:7

(54)

;F:6

(46)

Mao

ri:7

(54)

;Eu

rope

an:4

(30)

;PI:

1(8

);As

ian

Indi

an:1

(8)

NR

Syst

olic

BP>1

30m

mH

gor

dias

tolic

BP>8

0m

mH

g

NR

13(1

00)

Zdra

vkov

icet

al,6

020

04Ca

nada

RC13

.5(2

.2)

[ran

ge,

8.8-

17.5

]

13.5

(2.2

)[r

ange

,8.

8-17

.5]

04

(10)

41M

:15

(37)

;F:2

6(6

3)So

uth/

East

Asia

n:19

(46)

;Afr

ican

Cana

dian

:11

(27)

;N

HW

:6(1

5);H

:4(1

0);F

N:1

(2)

NR

BP≥9

5th

perc

entil

efo

rage

and

sex

NH

LBIU

pdat

eon

Seco

ndTa

skFo

rce

Repo

rt2

3

33(8

0)

Pére

z-Pe

rdom

oet

al,6

120

05

Puer

toRi

coRC

NR

Age

≤17

y:35

(80%

);ag

e18

-19

y:9

(20%

)

NR

5(1

1)44

NR

NR

NR

NR

NR

69(8

0)b

(con

tinue

d)




Tabl

e1.

Char

acte

ristic

sofI

nclu

ded

Stud

iesR

epor

ting

onPr

eval

ence

ofH

yper

tens

ion

inPe

diat

ricTy

pe2

Dia

bete

s(co

ntin

ued)

Sour

ceCo

untr

ySt

udy

desi

gn

Age

atdi

agno

sis,

mea

n(S

D),y

Age

aten

rollm

ent,

mea

n(S

D),y

Diab

etes

dura

tion,

mea

n(S

D),y

Case

s,N

o.(%

)Sa

mpl

esi

ze,N

o.Se

xdi

strib

utio

nN

o.(%

)Ra

cial

grou

pdi

strib

utio

n,N

o.(%

)

Case

sby

sex

and/

orra

cial

grou

p,N

o.(%

)H

yper

tens

ion

defin

ition

Refe

renc

eva

lues

sour

ce

Prev

alen

ceof

obes

ity,

No.

(%)

Scot

tet

al,6

220

06N

ewZe

alan

dRC

NR

20.0

(0.4

)3.

0(0

.3)

21 (20.

0)10

5N

RM

aori/

PI/o

ther

:66

(62.

9);E

urop

ean:

39(3

7.1)

NR

BP>1

30/8

5m

mH

gN

R10

5(1

00)

Bala

sant

hira

net

al,6

320

12Un

ited

King

dom

RC15

.2(3

.3)

21.2

(3.2

)5.

4(3

.1)

9(2

1)44

M:1

7(3

9);F

:27

(61)

Bang

lade

shi:

11(2

5);

Paki

stan

i:9

(20)

;In

dian

:7(1

6);W

hite

Briti

sh:6

(14)

;Bla

ckAf

rican

:4(9

);Bl

ack

Carib

bean

:4(9

);un

clea

r:3

(7)

NR

BPpe

rsis

tent

ly>1

30/8

5m

mH

gN

R23

(59)

b,e

Osm

anet

al,6

420

13Su

dan

RCAg

e<1

1y:

3(8

%);

age

11-1

8y:

35(9

2%)

NR

NR

22(5

8)38

M:1

7(4

5);F

:21

(55)

Arab

:32

(84)

;m

ultir

acia

l:4

(11)

;no

n-Ar

ab:2

(5)

NR

BP≥9

5th

perc

entil

efo

rage

and

sex

on>1

occa

sion

NR

29(7

6)

Dart

etal

,65

2014

Cana

daRC

13.5

(2.2

)13

.5(2

.2)

034

(9.9

)34

2M

:129

(37.

8);F

:21

3(6

2.2)

NR

NR

Elev

ated

BPfo

rag

e,se

x,an

dhe

ight

NH

LBIF

ourt

hRe

port

20

NR

Hay

nes

etal

,66

2014

g

Aust

ralia

RC13

.3(2

.0)b

13.3

(2.0

)b0

15(2

0)75

NR

NR

NR

NR

NR

82(6

0.7)

b

Yafi,

67

2019

gUn

ited

Stat

esRC

rang

e,8-

15N

RN

R1

(5)

25M

:11

(44)

;F:1

4(5

6)H

:15

(60)

;oth

er:1

0(4

0)N

RN

RN

RN

R

Yeow

etal

,68

2019

Mal

aysi

aRC

14.3

(3.5

)20

.7(3

.7)

6.5

(2.8

)3

(13)

24M

:10

(42)

;F:1

4(5

8)M

alay

:12

(50)

;Ch

ines

e:11

(46)

;As

ian

Indi

an:1

(4)

NR

BP≥9

5th

perc

entil

efo

rage

and

sex

for

patie

nts<

17y;

BP≥1

40/9

0m

mH

gfo

rpat

ient

s≥1

7y

NH

LBIF

ourt

hRe

port

20

;N

HLB

ISev

enth

Repo

rt2

4

10(4

2)

Curr

anet

al,6

920

20Au

stra

liaRC

All

part

icip

ants

<10

All

part

icip

ants

,<1

6

NR

3(2

7)11

NR

PI:1

1(1

00)

PI:3

(27)

NR

NR

11(1

00)

Eppe

nset

al,4

2006

Aust

ralia

PC13

.2(1

1.6-

15.0

)b,c

15.3

(13.

6-16

.4)b

,c1.

3(0

.6-3

.1)b

,c21

(36)

58N

RN

RN

RSy

stol

icor

dias

tolic

BP>9

5th

perc

entil

efo

rage

and

sex

NH

LBIU

pdat

eon

Seco

ndTa

skFo

rce

Repo

rt2

3

36(5

6)b

Shie

ldet

al,7

020

09Un

ited

King

dom

and

Repu

blic

ofIr

elan

d

PCm

ean,

13.6

;ra

nge,

9.9-

16.8

b

mea

n,14

.5;

rang

e,10

.8-1

7.8b

mea

n,1b

19(3

2)59

M:2

4(4

1);F

:35

(59)

NR

M:7

(29)

;F:1

2(3

4)Sy

stol

icor

dias

tolic

BP≥9

8th

perc

entil

efo

rage

and

sex

UKRe

fere

nce

Valu

es2

561

(80)

b

Ruha

yel

etal

,71

2010

Aust

ralia

PC13

.4(r

ange

,9.

2-17

.4)a,

cM

:16.

0(1

3.6-

18.2

);F:

15.6

(11.

7-19

.8)a,

c

M:2

.2(0

.0-

7.8)

;F:2

.3(0

.1-7

.4)a,

c

9(3

0)30

NR

NR

NR

BP>9

8th

perc

entil

efo

rage

and

sex

UKRe

fere

nce

Valu

es2

523

(70)

b

Jeff

erie

set

al,7

220

12N

ewZe

alan

dPC

12.9

(1.8

)[r

ange

,7.

1-15

.5]

NR

NR

27(5

2)52

M:1

7(3

3);F

:35

(67)

PI/M

aori:

47(9

0);

othe

r:5

(10)

NR

BP≥9

5th

perc

entil

efo

rsex

and

age

NR

NR

Schm

idt

etal

,73

2012

Germ

any

and

Aust

ria

PC13

.5(3

.4)

15.3

(3.0

)N

R20

2(2

9.5)

684

M:2

61(3

8.2)

;F:

423

(61.

8)Ge

rman

/Aus

tria

n:48

2(7

0.5)

;oth

er:2

02(2

9.5)

NR

BP>9

5th

perc

entil

efo

rage

,se

x,an

dhe

ight

NH

LBIF

ourt

hRe

port

20

NR

Dart

etal

,74

2019

Cana

daPC

All

part

icip

ants

<18

15 (13.

3-16

.8)c

2.3

(0.9

-4.1

)c15

5(8

2.9)

187

M:6

2(3

3.2)

;F:

125

(66.

8)In

dige

nous

:179

(95.

7);o

ther

:8(4

.3)

NR

BP≥9

5th

perc

entil

efo

rage

,se

xan

dhe

ight

NH

LBIF

ourt

hRe

port

20

NR (c

ontin

ued)




Tabl

e1.

Char

acte

ristic

sofI

nclu

ded

Stud

iesR

epor

ting

onPr

eval

ence

ofH

yper

tens

ion

inPe

diat

ricTy

pe2

Dia

bete

s(co

ntin

ued)

Sour

ceCo

untr

ySt

udy

desi

gn

Age

atdi

agno

sis,

mea

n(S

D),y

Age

aten

rollm

ent,

mea

n(S

D),y

Diab

etes

dura

tion,

mea

n(S

D),y

Case

s,N

o.(%

)Sa

mpl

esi

ze,N

o.Se

xdi

strib

utio

nN

o.(%

)Ra

cial

grou

pdi

strib

utio

n,N

o.(%

)

Case

sby

sex

and/

orra

cial

grou

p,N

o.(%

)H

yper

tens

ion

defin

ition

Refe

renc

eva

lues

sour

ce

Prev

alen

ceof

obes

ity,

No.

(%)

Syst

olic

hype

rten

sion

Upch

urch

etal

,75

2003

Unite

dSt

ates

CS13

.6(2

.3)b

13.6

(2.3

)b0

41(4

9)83

NR

NR

NR

Syst

olic

BP≥9

5th

perc

entil

efo

rage

,se

x,an

dhe

ight

NR

91(9

3)b

Wei

etal

,76

2003

Taiw

anCS

M:1

3.7

(2.5

);F:

13.0

(2.5

)a,b

M:1

3.7

(2.5

);F:

13.0

(2.5

)a,b

049 (3

9.2)

125

M:4

7(3

7.6)

;F:7

8(6

2.4)

NR

M:2

3(4

9);F

:26

(33)

Syst

olic

BP≥8

5th

perc

entil

eof

sex

and

age

base

don

popu

latio

nin

the

stud

y

NR

63(4

8.1)

b

Cruz

etal

,77

2004

Mex

ico

CSAl

lpa

rtic

ipan

ts<1

8

13.8

(1.8

)m

ean,

0.9;

rang

e,0.

08-3

2(5

)44

M:2

0(4

6);F

:24

(54)

Mex

ican

:44

(100

)dM

exic

an:2

(5)

NR

NR

NR

Hot

uet

al,7

820

04N

ewZe

alan

dCS

mea

n,15

;ra

nge,

11-1

9N

RN

R5

(28)

18M

:9(5

0);F

:9(5

0)M

aori/

PI:1

8(1

00)

M:3

(33)

;F:2

(22)

;Mao

ri/PI

:5(2

8)

Syst

olic

BP>9

5th

perc

entil

efo

rage

,se

xan

dhe

ight

NH

LBIU

pdat

eon

Seco

ndTa

skFo

rce

Repo

rt2

3

NR

Rodr

igue

zet

al,1

720

10Un

ited

Stat

esCS

12.9

(2.1

)14

.8(2

.0)

1.6

(1.5

)10

6(2

5.9)

410

M:1

52(3

7.1)

;F:

258

(62.

9)AA

:130

(31.

7);H

:99

(24.

1);N

HW

:84

(20.

5);A

I:56

(13.

7);

API:

37(9

.0);

othe

r:4

(1.0

)

NR

Syst

olic

BP>9

5th

perc

entil

efo

rage

,se

xan

dhe

ight

NH

LBIF

ourt

hRe

port

20

332

(81.

0)

Selle

rset

al,7

920

07Ca

nada

RCm

ean,

13.1

;ra

nge,

9-17

mea

n,15

.3;

rang

e,9-

18N

R13

(13)

99M

:42

(42)

;F:5

7(5

8)FN

/Met

is:9

4(9

5);

othe

r:5

(5)

M:5

(12)

;F:8

(14)

Syst

olic

BP>9

5th

perc

entil

efo

rage

and

gend

er

NH

LBIF

ourt

hRe

port

20

38(3

8)

Pelh

amet

al,8

020

18Un

ited

Stat

esRC

NR

15.2

(2.7

)2.

7(1

.7)

34(3

7)93

M:2

7(2

9);F

:66

(71)

NR

NR

Syst

olic

BP≥9

5th

perc

entil

efo

rage

,ge

nder

,and

heig

ht

NH

LBIF

ourt

hRe

port

20

NR

Shie

ldet

al,7

020

09Un

ited

King

dom

and

Repu

blic

ofIr

elan

d

PCm

ean,

13.6

;ra

nge,

9.9-

16.8

b

mea

n,14

.5;

rang

e,10

.8-1

7.8b

mea

n,1b

4(7

)59

M:2

4(4

1);F

:35

(59)

NR

M:1

(4);

F:3

(9)

Syst

olic

BP≥9

8th

perc

entil

efo

rage

and

sex

UKRe

fere

nce

Valu

es2

561

(80)

b

Cand

ler

etal

,81

2018

Unite

dKi

ngdo

man

dRe

publ

icof

Irel

and

PC14

.3(7

.9-1

6.9)

h14

.3(7

.9-1

6.9)

h0

22 (20.

8)10

6M

:35

(33.

0);F

:71

(67.

0)N

HW

:47

(44.

3);

Asia

n/As

ian

Briti

sh:

36(3

4.0)

;BAC

BB:1

4(1

3.2)

;oth

er:5

(4.7

);un

cert

ain:

4(3

.8)

NR

Syst

olic

BP≥9

5th

perc

entil

efo

rsex

,ag

ean

dhe

ight

NH

LBIF

ourt

hRe

port

20

86(8

1.1)

Dias

tolic

hype

rten

sion

Upch

urch

etal

,75

2003

Unite

dSt

ates

CS13

.6(2

.3)b

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M:2

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perc

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Char

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pooled prevalence of hypertension was 25.33% (95% CI, 19.57%-31.53%) (Figure 1). Highheterogeneity was noted across studies (I2 = 94%; P < .001).

Another 15 studies that reported on the prevalence of hypertension were not included in themeta-analysis. Two studies had a higher cutoff for hypertension (BP �98th percentile) and reporteda prevalence of 30% among 30 participants and 32% among 59 participants, respectively.70,71 Fivestudies presented racial subgroup data46-50 of another included study.17 Eight studies were onlyincluded in the analysis of isolated systolic or diastolic hypertension.75-82

When pooling only the studies with hypertension definition of BP in 95th percentile or greaterfor age, sex, and height (2763 participants), the prevalence was significantly higher at 34.00% (95%CI, 24.00%-45.00%; I2 = 97%; P < .001) (eTable 6 in the Supplement).4,15,17,42-44,55-57,60,64,68,72-74

The metaregression analysis revealed no significant association between hypertension prevalenceand obesity prevalence.

Figure 1. Forest Plot Showing Pooled Prevalence of Hypertension in Pediatric Type 2 Diabetes

0 60 10040 80Prevalence, % (95% CI)

20

Weight, %Study

Cross-sectional studies

CasesNo.

TotalPrevalence, %(95% CI)

Khalil et al,58 2019Aulich et al,57 2019Zabeen et al,56 2016Klingensmith et al,55 2016Drutel et al,54 2014Amutha et al,53 2012Amed et al,52 2012Copeland et al,15 2011Rodriguez et al,17 2010Urakami et al,51 2009Unnikrishnan et al,45 2008Eppens et al,44 2006Reinehr et al,43 2005Ettinger et al,42 2005Scott et al,41 1997Pinhas-Hamiel et al,40 1996

162544734761969713164815149

1331771502631982217044101123626516264454

7.69 (0.00-30.13)19.35 (7.05-35.39)32.47 (22.41-43.39)29.33 (22.30-36.90)27.76 (22.50-33.34)23.74 (18.05-29.93)27.60 (21.89-33.70)13.64 (11.20-16.27)23.66 (19.66-27.90)11.61 (6.25-18.27)2.78 (0.00-11.54)24.15 (19.48-29.50)50.00 (25.40-74.60)57.69 (38.07-76.20)31.82 (18.76-46.43)16.67 (7.75-27.93)

2.43.03.43.63.63.63.63.73.73.53.13.62.52.93.23.3

Total (95% CI) 2620 23.14 (18.51-28.10) 52.7Heterogeneity: τ2 = 0.0092; χ2 = 98.16, df = 15 (P < .001); I2 = 85%

Retrospective cohort studies

Curran et al,69 2020Yeow et al,68 2019Yafi,67 2019Haynes et al,66 2014Dart et al,65 2014Osman et al,64 2013Balasanthiran et al,63 2012Scott et al,62 2006Pérez-Perdomo et al,61 2005Zdravkovic et al,60 2004Scott et al,59 2004

331153422921545

112425753423844105444113

27.27 (4.39-57.92)12.50 (1.73-29.28)4.00 (0.00-16.38)20.00 (11.63-29.89)9.94 (6.98-13.35)57.89 (41.76-73.25)20.45 (9.65-33.80)20.00 (12.85-28.24)11.36 (3.37-22.70)9.76 (2.20-21.07)38.46 (13.47-66.73)

2.22.82.93.43.73.13.23.53.23.12.4


Prospective cohort studies

Dart et al,74 2019Schmidt et al,73 2012Jefferies et al,72 2012Eppens et al,4 2006

1552022721

1876845258

82.89 (77.13-87.97)29.53 (26.17-33.01)51.92 (38.25-65.46)36.21 (24.25-49.06)

3.63.73.33.3


Total (95% CI) 4363 25.33 (19.57-31.53) 100Heterogeneity: τ2 = 0.0310; χ2 = 527.45, df = 30 (P < .001); I2 = 94%





Pooled Prevalence of Systolic and Diastolic Hypertension in Type 2 DiabetesIsolated systolic hypertension prevalence across 6 studies with 747 participants was 24.79% (95%CI, 14.04%-37.31%; I2 = 90%; P < .001) (eFigure 2 in the Supplement).17,75,77-80 Two additionalstudies using different definitions reported a prevalence of 39.2% among 125 participants(hypertension definition, BP �85th percentile)76 and 7% among 59 participants (hypertensiondefinition, BP �98th percentile).70 Another study determined a prevalence of 20.8% among 106participants; because it was the only prospective cohort study, it was not included in themeta-analysis.81

Isolated diastolic hypertension prevalence across 6 studies with 740 participants was 11.65%(95% CI, 6.41%-18.04%; I2 = 75%; P = .001) (eFigure 3 in the Supplement).17,75,77,79,80,82 Twoadditional studies using different definitions reported a prevalence of 42.4% among 125 participants(diastolic hypertension, BP �85th percentile)76 and 19% among 59 participants (diastolichypertension, BP �98th percentile).70

Sex and Race Associations With HypertensionFour studies reported hypertension prevalence in 600 male participants of 23.81% (95% CI, 18.56%-29.47%; I2 = 58%; P = .07) and 977 female participants of 18.56% (95% CI, 12.25%-25.82%;I2 = 85%; P < .001) with an OR of 1.42 (95% CI, 1.10-1.83; I2 = 0%; P for heterogeneity = .65)(eFigure 4 and eFigure 5 in the Supplement).15,17,44,53 In contrast, 1 study with hypertension definitionof BP in the 98th percentile or greater reported a prevalence of 29% in 24 male participants and 34%in 35 female participants.70

When assessing the prevalence of hypertension in different racial groups, Indigenous andPacific Islander youth had the highest rates of hypertension when compared with other groups(Pacific Islander youth17,69: 48 participants; prevalence, 26.71% [95% CI, 14.54%-40.72%]; I2 = 0%;P = .92; Indigenous youth15,47,52: 205 participants; prevalence, 26.48% [95% CI, 17.34%-36.74%];I2 = 58%, P = .09; White youth15,43,46,52,58: 330 participants; prevalence, 20.95% [95% CI, 12.65%-30.57%]; I2 = 66%; P = .02; African American youth15,50: 434 participants; prevalence, 19.04% [95%CI, 12.01%-27.23%]; I2 = 76%; P = .04; Hispanic/Latino youth15,48: 409 participants; prevalence,15.11% [95% CI, 6.56%-26.30%]; I2 = 85%; P < .001; Asian youth45,49,51,53,56: 452 participants;prevalence, 18.37% [95% CI, 9.49%-29.23%]; I2 = 84%, P < .001) (eFigure 6 in the Supplement).

AlbuminuriaStudy CharacteristicsThirty-nine studies reported on albuminuria prevalence(Table 2).4,8,15,16,42,44-46,50,52,53,57-59,62,64-69,71-74,78,81,83-94 The age at type 2 diabetes diagnosisranged from 6.5 to 21.0 years,90,93 and type 2 diabetes duration ranged fromdiagnosis52,65,66,71,81,83,85,89,94 to more than 15.0 years after diagnosis.50,53 Nineteen studies (49%)were cross-sectional studies,15,16,42,44-46,50,52,53,57,58,78,83,84,86-90 14 (36%) were retrospectivecohort studies,8,59,62,64-69,85,91-94 and 6 (15%) were prospective cohort studies.4,71-74,81

Pooled Prevalence of Albuminuria and Persistent Albuminuria in Type 2 DiabetesPooled albuminuria prevalence in 14 studies of 2250 patients with type 2 diabetes was 22.17% (95%CI, 17.34%-27.38%) (Figure 2).16,42,52,53,67-69,71,73,74,78,81,83,85 There were high levels of heterogeneity(I2 = 82%; P < .001).

Four studies were not included in the meta-analysis. One used a definition of albuminuria of24-hour urine protein excretion of greater than 500 mg, and found no patients with this outcome.45

Another study did not report the sample size or the definition of albuminuria but reported aprevalence of 23%.84 Two other studies46,50 reported the prevalence in specific racial groups, andthe data were captured by another included study.16 Removing studies with 678 patients older than18 years lowered the estimate to 17.00% (95% CI, 9.00%-27.00%; I2 = 86%;








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Char

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Tabl

e2.

Char

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ristic

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nclu

ded

Stud

iesR

epor

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onth

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ofAl

bum

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Pedi

atric

Type

2D

iabe

tes(

cont

inue

d)

Sour

ceCo

untr

ySt

udy

desi

gn

Age

atdi

agno

sis,

mea

n(S

D),y

Age

atst

udy

enro

llmen

tor

mea

sure

men

t,m

ean

(SD)

,y

Dura

tion

ofdi

abet

es,

mea

n(S

D),y

Case

s,N

o.(%

)Sa

mpl

esi

zeSe

xdi

strib

utio

n,N

o.(%

)

Raci

algr

oup

dist

ribut

ion,

No.

(%)

Case

sby

sex

orra

cial

grou

p,N

o.(%

)Al

bum

inur

iade

finiti

on

Prev

alen

ceof

obes

ity,

No.

(%)

Yafi,

67

2019

eUn

ited

Stat

esRC

rang

e,8-

15N

RN

R3

(12)

25M

:11

(44)

;F:

14(5

6)H

:15

(60)

;oth

er:

10(4

0)N

RN

RN

R

Yeow

etal

,68

2019

Mal

aysi

aRC

14.3

(3.5

)20

.7(3

.7)

6.5

(2.8

)7

(29)

24M

:10

(42)

;F:

14(5

8)M

alay

:12

(50)

;Ch

ines

e:11

(46)

;As

ian

Indi

an:1

(4)

Asia

n:7

(29)

M:A

CR>2

.5m

g/m

mol

,F:

ACR

>3.5

mg/

mm

ol10

(42)

Curr

anet

al,6

920

20Au

stra

liaRC

All

part

icip

ants

<10

Allp

artic

ipan

ts,

<16

NR

2(1

8)11

NR

PI:1

1(1

00)

PI:2

(18)

NR

11(1

00)

Ruha

yel

etal

,71

2010

Aust

ralia

PC13

.4(9

.2-1

7.4)

a,d

M:1

6.0

(13.

6-18

.2;F

:15

.6(1

1.7-

19.8

)a,d

M:2

.2(0

.0-

7.8;

F:2.

3(0

.1-7

.4)a,

d

9(4

5)20

NR

NR

NR

ACR

>3.5

mg/

mm

ol23

(70)

a

Schm

idt

etal

,73

2012

Germ

any

and

Aust

riaPC

13.5

(3.4

)15

.3(3

.0)

NR

170

(24.

9)68

4M

:261

(38.

2);

F:42

3(6

1.8)

Germ

an/A

ustr

ian:

482

(70.

5);

othe

r:20

2(2

9.5)

NR

NR

NR

Cand

ler

etal

,81

2018

Unite

dKi

ngdo

man

dRe

publ

icof

Irel

and

PC14

.3(7

.9-1

6.9)

d14

.3(7

.9-1

6.9)

d0

3(2

.8)

106

M:3

5(3

3.0)

;F:

71(6

7.0)

NH

W:4

7(4

4.3)

;As

ian/

Asia

n-Br

itish

:36

(34.

0);

BACB

B:14

(13.

2);o

ther

:5(4

.7);

unce

rtai

n:4

(3.8

)

NR

NR

86(8

1.1)

Dart

etal

,74

2019

Cana

daPC

All

part

icip

ants

<18

15(1

3.3-

16.8

)b2.

3(0

.9-4

.1)b

47(2

5.1)

187

M:6

2(3

3.2)

;F:

125

(66.

8)In

dige

nous

:179

(95.

7);o

ther

:8(4

.3)

NR

ACR

>2m

g/m

mol

NR

Pers

iste

ntal

bum

inur

ia

Yoo

etal

,86

2004

Kore

aCS

12.8

(1.5

)18

.4(4

.3)

5.5

(3.9

)5

(23)

22M

:8(3

6);M

:14

(64)

Kore

an:2

2(1

00)

Kore

an:5

(23)

AER

>20

μg/m

inon

sam

ples

3m

oap

art

NR

Fara

het

al,8

720

06Un

ited

Stat

esCS

NR

rang

e,10

-21

mea

n,1.

8;ra

nge,

<2-5

9(2

7)33

NR

NR

NR

ACR

>30

mg/

gon

2sa

mpl

esw

ithin

3-6

mo

29(7

3)a

Cope

land

etal

,15

2011

Unite

dSt

ates

CSra

nge,

10-1

714

.0(2

.0)

0.7

(0.5

)92

(13.

0)70

4M

:247

(35.

1);

F:45

7(6

4.9)

H:2

89(4

1.1)

;N

HB:

222

(31.

5);

NH

W:1

38(1

9.6)

;AI

:43

(6.1

);As

ian:

12(1

.7)

M:2

6(1

0.6)

;F:6

5(1

4.3)

;H:4

1(1

4.1)

;N

HB:

25(1

1.2)

;NH

W:

20(1

4.6)

;AI:

3(8

)

ACR

≥30m

g/g

on2

of3

sam

ples

durin

g3-

mo

perio

d

NR

Selle

rset

al,8

820

16Ca

nada

CSAl

lpa

rtic

ipan

ts<1

8

NR

NR

50(5

.1)

976

NR

NR

NR

M:A

CR>2

mg/

mm

ol,F

:AC

R>2

.8m

g/m

mol

on2

occa

sion

sdur

ing

6-m

ope

riod

NR

Aulic

het

al,5

720

19Au

stra

liaCS

NR

15.1

(1.9

)1.

8(0

.3-3

.3)b

6(3

0)20

NR

NR

NR

AER

≥20

μg/m

inin

≥2of

3sa

mpl

esor

mea

nAC

R,M

:≥3.

5m

g/m

mol

;F:≥

4m

g/m

mol

from

3fir

stm

orni

ngco

llect

ions

24(7

5)a

Khal

ilet

al,5

820

19Eg

ypt

CS18

.0(2

.0)

19.8

(1.1

)2.

5(2

.0)

0(0

)13

M:6

(46)

;F:7

(54)

Egyp

tian:

0cEg

yptia

n:0

ACR

≥30m

g/g

on2

sam

ples

with

in3-

6m

oN

R

Scot

tet

al,5

920

04N

ewZe

alan

dRC

NR

mea

n,19

.6;r

ange

,14

-23

1.7

2(1

5)13

M:7

(54)

;F:6

(46)

Mao

ri:7

(54)

;Eu

rope

an:4

(30)

;PI

:1(8

);As

ian

Indi

an:1

(8)

NR

M:A

CR>2

.5m

g/m

mol

;F:

ACR

>3.5

mg/

mm

olon

≥2oc

casi

ons

13(1

00)

(con

tinue

d)




Tabl

e2.

Char

acte

ristic

sofI

nclu

ded

Stud

iesR

epor

ting

onth

ePr

eval

ence

ofAl

bum

inur

iain

Pedi

atric

Type

2D

iabe

tes(

cont

inue

d)

Sour

ceCo

untr

ySt

udy

desi

gn

Age

atdi

agno

sis,

mea

n(S

D),y

Age

atst

udy

enro

llmen

tor

mea

sure

men

t,m

ean

(SD)

,y

Dura

tion

ofdi

abet

es,

mea

n(S

D),y

Case

s,N

o.(%

)Sa

mpl

esi

zeSe

xdi

strib

utio

n,N

o.(%

)

Raci

algr

oup

dist

ribut

ion,

No.

(%)

Case

sby

sex

orra

cial

grou

p,N

o.(%

)Al

bum

inur

iade

finiti

on

Prev

alen

ceof

obes

ity,

No.

(%)

Scot

tet

al,6

220

06N

ewZe

alan

dRC

NR

20.0

(0.4

)3.

0(0

.3)

76(7

2.4)

105

NR

Mao

ri/PI

/oth

er:

66(6

2.9)

;Eu

rope

an:3

9(3

7.1)

NR

M:A

CR>2

.5m

g/m

mol

;F:

ACR

>3.5

mg/

mm

olon

≥2oc

casi

ons

105

(100

)

Dart

etal

,65

2014

Cana

daRC

13.5

(2.2

)13

.5(2

.2)

093

(27.

1)34

2M

:129

(37.

8);

F:21

3(6

2.2)

NR

NR

ACR

>3m

g/m

mol

orAE

R>3

0mg/

24h

on≥2

of3

mea

sure

men

ts1

mo

apar

t

NR

Eppe

nset

al,4

2006

Aust

ralia

PC13

.2(1

1.6-

15.0

)a,b

15.3

(13.

6-16

.4)a,

b1.

3(0

.6-3

.1)a,

b10

(28)

36N

RN

RN

RAE

R≥2

0μg

/min

in≥2

of3

sam

ples

orAC

R≥2

.5m

g/m

mol

36(5

6)a

Jeff

erie

set

al,7

220

12N

ewZe

alan

dPC

mea

n,12

.9;

rang

e,7.

1-15

.5

NR

NR

18(3

5)52

M:1

7(3

3);F

:35

(67)

PI/M

aori:

47(9

0);o

ther

:5(1

0)

NR

ACR

≥2.5

mg/

mm

olon

≥2of

3sa

mpl

esdu

ring

6-m

ope

riod

NR

Dart

etal

,74

2019

Cana

daPC

All

part

icip

ants

<18

15(1

3.3-

16.8

b2.

3(0

.9-4

.1)b

57(3

0.5)

187

M:6

2(3

3.2)

;F:

125

(66.

8)In

dige

nous

:179

(95.

7);o

ther

:8(4

.3)

M:1

5(2

4);F

:42

(33.

6);I

ndig

enou

s:56

(31.

3)

ACR

>2m

g/m

mol

on2

of3

sam

ples

durin

ga

6-m

ope

riod

NR

Mic

roal

bum

inur

ia

Hot

uet

al,7

820

04N

ewZe

alan

dCS

mea

n,15

(11-

19N

RN

R5

(42)

12M

:6(5

0);F

:6(5

0)M

aori/

PI:1

2(1

00)

M:3

(50)

;F:2

(33)

;M

aori/

PI:5

(42)

ACR

≥30-

300m

g/g

NR

Ettin

ger

etal

,42

2005

Unite

dSt

ates

CSN

R15

.0(1

.9)

1.5

(1.0

)10

(40)

25M

:12

(46)

;F:

14(5

4)a

H:1

5(5

8);N

HB:

8(3

1);o

ther

:2(7

);m

ultir

acia

l:1

(4)a

NR

AER

≥30m

gal

bum

in/2

4h

NR

Eppe

nset

al,4

420

06W

este

rnPa

cific

CS12

.0(1

0.7-

13.5

)a,b

14.9

(13.

2-16

.4)a,

b2.

3(1

.4-3

.6)a,

b20

(8.0

)25

1N

RN

RN

RAE

R30

-300

mg/

24h

or>2

0μg

/min

orAC

R>2

.5m

g/m

mol

106

(32.

0)a

Kim

etal

,83

2010

Unite

dSt

ates

CSN

R14

.5(3

.0)

mea

n,1.

3(0

-2.1

19(1

8.5)

103

M:4

0(3

8.8)

;F:

63(6

1.2)

Pim

aIn

dian

:103

(100

.0)

Pim

aIn

dian

:19

(18.

5)AC

R≥3

0-30

0mg/

gN

R

Amut

haet

al,5

320

12In

dia

CS16

.1(2

.5)

22.2

(9.7

)Ag

e≤5

y:21

9(5

9.5%

);ag

e>5

to≤1

0y:

67(1

8.2%

);ag

e>1

0to

≤15

y:21

(5.7

%);

age

>15

y:61

(16.

6%)

54(1

4.7)

368

M:1

68(4

5.7)

;F:

200

(54.

3)So

uth

Indi

an:3

68(1

00)c

Sout

hIn

dian

:54

(14.

7)AC

R≥3

0-29

9mg/

gN

R

Zabe

enet

al,8

920

16e

Bang

lade

shCS

13.0

(11.

0-15

.0)d

13.0

(11.

0-15

.0)d

014

(10.

0)14

4N

RBa

ngla

desh

i:14

4(1

00)c

Bang

lade

shi:

14(1

0.0)

ACR

≥30-

300m

g/g

NR

Nam

bam

etal

,90

2017

Unite

dSt

ates

CSAl

lpa

rtic

ipan

ts<2

1

16.0

(14.

0-17

.7)b

2.0

(0.7

-4.2

)b36

(6.0

)59

8M

:218

(36.

5);

F:38

0(6

3.5)

H:3

29(5

5.0)

;AA

:179

(30.

0);

NH

W:4

8(8

.0);

othe

r/m

ultir

acia

l:42

(7.0

)

NR

NR

472

(85.

0)a

Le etal

,91

2013

Unite

dSt

ates

RC13

.8(2

.4)a

14.2

(2.4

)N

R11

(17)

64M

:20

(31)

;F:

44(6

9)AA

:52

(81)

;N

HW

:12

(19)

AA:1

1(2

1);N

HW

:0f

ACR

≥30-

299

mg/

gN

R

Osm

anet

al,6

420

13Su

dan

RCAg

e<1

1y:

3(7

.9%

);ag

e11

-18

y:35

(92.

1%)

NR

NR

7(1

8)38

M:1

7(4

5);F

:21

(55)

Arab

:32

(84)

;m

ultir

acia

l:4

(11)

;non

-Ara

b:2

(5)

NR

NR

29(7

6)

Hay

nes

etal

,66

2014

eAu

stra

liaRC

13.3

(2.0

)a13

.3(2

.0)a

011

(18)

61N

RN

RN

RN

R82

(60.

7)a

(con

tinue

d)




Tabl

e2.

Char

acte

ristic

sofI

nclu

ded

Stud

iesR

epor

ting

onth

ePr

eval

ence

ofAl

bum

inur

iain

Pedi

atric

Type

2D

iabe

tes(

cont

inue

d)

Sour

ceCo

untr

ySt

udy

desi

gn

Age

atdi

agno

sis,

mea

n(S

D),y

Age

atst

udy

enro

llmen

tor

mea

sure

men

t,m

ean

(SD)

,y

Dura

tion

ofdi

abet

es,

mea

n(S

D),y

Case

s,N

o.(%

)Sa

mpl

esi

zeSe

xdi

strib

utio

n,N

o.(%

)

Raci

algr

oup

dist

ribut

ion,

No.

(%)

Case

sby

sex

orra

cial

grou

p,N

o.(%

)Al

bum

inur

iade

finiti

on

Prev

alen

ceof

obes

ity,

No.

(%)

Cala

gua

Qui

spe

etal

,92

2015

e

Peru

RC12

.6(2

.3)

NR

3.7

(2.4

)9

(43)

20M

:10

(50)

;F:

10(5

0)N

RN

RN

RN

R

New

ton

etal

,93

2015

eN

ewZe

alan

dRC

rang

e,6.

5-17

Allp

artic

ipan

ts,

<17

NR

6(5

5)11

NR

NR

NR

NR

22(9

6)a

Son

etal

,94

2015

Kore

aRC

NR

15.4

(12.

6-17

.4)b

0.9

(0.0

-3.0

)b8

(44)

18M

:4(2

2);F

:14

(78)

Kore

an:1

8(1

00)c

Kore

an:8

(44)

ACR

≥30-

300m

g/g

NR

Yeow

etal

.,68

2019

Mal

aysi

aRC

14.3

(3.5

)20

.7(3

.7)

6.5

(2.8

)7

(29)

24M

:10

(42)

;F:

14(5

8)M

alay

:12

(50)

;Ch

ines

e:11

(46)

;As

ian

Indi

an:1

(4)

Asia

n:7

(29)

M:A

CR>2

.5m

g/m

mol

,F:

ACR

>3.5

mg/

mm

ol10

(42)

Ruha

yel

etal

,71

2010

Aust

ralia

PC13

.4(9

.2-1

7.4)

a,d

M:1

6.0

(13.

6-18

.2);

F:15

.6(1

1.7-

19.8

)a,d

M:2

.2(0

.0-

7.8)

;F:2

.3(0

.1-7

.4)a,

d

9(4

5)20

NR

NR

NR

ACR

>3.5

mg/

mm

ol23

(70)

a

Schm

idt

etal

,73

2012

Germ

any

and

Aust

riaPC

13.5

(3.3

)15

.3(3

.0)

NR

154

(22.

5)68

4M

:261

(38.

2);

F:42

3(6

1.8)

Germ

an/A

ustr

ian:

482

(70.

5);

othe

r:20

2(2

9.5)

NR

NR

NR

Pers

iste

ntm

icro

albu

min

uria

Yoo

etal

,86

2004

Kore

aCS

12.8

(1.5

)18

.4(4

.3)

5.5

(3.9

)4

(18)

22M

:8(3

6);M

:14

(64)

Kore

an:2

2(1

00)

Kore

an:4

(18)

AER

>20

μg/m

inon

sam

ples

3m

oap

art

NR

Fara

het

al,8

720

06Un

ited

Stat

esCS

NR

rang

e,10

-21

mea

n,1.

8;ra

nge,

<2-5

9(2

7)33

NR

NR

NR

ACR

>30m

g/g

on2

sam

ples

with

in3-

6m

o29

(73)

a

Cope

land

etal

,15

2011

Unite

dSt

ates

CSra

nge,

10-1

714

.0(2

.0)

0.7

(0.5

)92

(13.

0)70

4M

:247

(35.

1);

F:45

7(6

4.9)

H:2

89(4

1.1)

;N

HB:

222

(31.

5);

NH

W:1

38(1

9.6)

;AI

:43

(6.1

);As

ian:

12(1

.7)

M:3

5(1

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Figure 2. Forest Plot Showing Pooled Prevalence of Albuminuria and Persistent Albuminuriain Pediatric Type 2 Diabetes

0 60 10040 80Prevalence, % (95% CI)

20

0 60 10040 80Prevalence, % (95% CI)

20

Weight, %Study


CasesNo.


Amutha et al,53 2012Amed et al,52 2012Kim et al,83 2010Maahs et al,16 2007Ettinger et al,42 2005Hotu et al,78 2004

85322283107

3682211033742512

23.10 (18.93-27.55)14.48 (10.12-19.45)21.36 (13.93-29.85)22.19 (18.12-26.55)40.00 (21.46-60.04)58.33 (29.01-85.10)

10.19.68.410.14.93.1



Curran et al,69 2020Yeow et al,68 2019Yafi,67 2019Sellers et al,85 2009

27326

11242590

18.18 (0.47-47.35)29.17 (12.42-49.17)12.00 (1.65-28.20)28.89 (19.94-38.73)

3.04.84.98.2

Total (95% CI) 150 24.04 (16.36-32.57) 20.9Heterogeneity: τ2 = 0.0012; χ2 = 3.43, df = 3 (P = .33); I2 = 12%


Dart et al,74 2019Candler et al,81 2018Schmidt et al,73 2012Ruhayel et al,71 2010

4731709

18710668420

25.13 (19.16-31.62)2.83 (0.35-7.05)24.85 (21.68-28.17)45.00 (23.57-67.36)

9.48.510.54.4



AlbuminuriaA

Weight, %Study


CasesNo.


Khalil et al,58 2019Aulich et al,57 2019Sellers et al,88 2016Copeland et al,15 2011Farah et al,87 2006Yoo et al,86 2004

06509295

13209767043322

0.00 (0.00-12.82)30.00 (11.56-52.18)5.12 (3.82-6.60)13.07 (10.67-15.66)27.27 (13.23-43.91)22.73 (7.22-42.89)

6.87.59.49.48.27.6



Dart et al,65 2014Scott et al,62 2006Scott et al,59 2004

93762

34210513

27.19 (22.60-32.04)72.38 (63.39-80.55)15.38 (0.37-40.99)

9.39.06.8



Dart et al,74 2019Jefferies et al,72 2012Eppens et al,4 2006

571810

1875236

30.48 (24.07-37.29)34.62 (22.20-48.15)27.78 (14.18-43.70)

9.28.68.3

Total (95% CI) 275 30.77 (25.37-36.44) 26.0Heterogeneity: τ2 = 0; χ2 = 0.5, df = 2 (P = .78); I2 = 0%


Persistent albuminuriaB




P < .001),42,52,67,69,74,81,83 suggesting that albuminuria worsens with age in this population (eTable 7in the Supplement).

Pooled prevalence of persistent albuminuria across 12 studies with 2503 participants was24.04% (95% CI, 13.50%-36.33%; I2 = 97%; P < .001) (Figure 2).4,15,57-59,62,65,72,74,86-88 Removingstudies using different definitions of albuminuria lowered the pooled estimate to 17.00% (95% CI,7.00%-29.00%; I2 = 92%; P < .001) (eTable 8 in the Supplement).

Microalbuminuria pooled prevalence across 16 studies with 2441 participants was 21.57% (95%CI, 15.59%-28.16%; I2 = 90%; P < .001) (eFigure 7 in the Supplement).42,44,53,64,66,68,71,73,78,83,89-94

Removing studies with 50 participants or fewer changed the estimate to 14.00% (95% CI,9.00%-20.00%; I2 = 92%; P < .001; 2273 participants),44,53,66,73,83,89-91 as this resulted in theelimination of Pacific Islander group from the analysis; this group had the highest microalbuminuriaprevalence (eTable 9 in the Supplement). Ten studies with 1345 participants reported persistentmicroalbuminuria pooled prevalence of 29.19% (95% CI, 16.85%-43.21%; I2 = 95%; P < .001)(eFigure 8 in the Supplement).4,8,15,57,59,62,72,86,87,94 Similarly, removing studies with patients olderthan 18 years or those using different definitions of microalbuminuria reduced the prevalence andheterogeneity estimates to 23.00% (95% CI, 14.00%-34.00%; I2 = 88%; P < .001) and 24.00%(95% CI, 11.00%-39.00%; I2 = 84%; P < .001), respectively, because this resulted in the exclusion ofa study reporting a very high microalbuminuria prevalence of 72% among 105 participants in asample with a high proportion of Pacific Islander and Indigenous patients (eTable 10 in theSupplement).62

Macroalbuminuria pooled prevalence from 4 studies with 730 participants was 3.85% (95% CI,0.02%-11.63%; P < .001) (eFigure 9 in the Supplement).44,53,78,83 Another study reported aprevalence of 2.4% among 684 participants,73 but it was the only prospective cohort study, so it wasnot included in the meta-analysis. In addition, the prevalence of persistent macroalbuminuria was5% among 22 participants in 1 cross-sectional study86 and 4.7% among 342 participants in anotherretrospective cohort study.8 Metaregression analysis revealed no statistically significant correlationbetween obesity prevalence and albuminuria, persistent albuminuria, microalbuminuria, orpersistent microalbuminuria prevalence.

Sex and Racial Group Associations With AlbuminuriaOne study reported that albuminuria in 140 male participants (20.7%) was lower than in 234 femaleparticipants (23.1%).16 Similarly, persistent microalbuminuria prevalence was higher in 247 maleparticipants (14.3%) than in 457 female participants (10.6%) in another study.15 Persistentalbuminuria prevalence across 2 studies in 309 male participants was 16.14% (95% CI,5.05%-31.65%; I2 = 86%; P < .001) and 22.90% (95% CI, 7.08%-44.22%; I2 = 95%; P < .001) in 582female participants (OR, 0.68 [95% CI, 0.46-1.01]; I2 = 0%; P for heterogeneity = .78) (eFigure 10and eFigure 11 in the Supplement).15,74

Albuminuria prevalence was assessed by racial group, and White youth had lower rates ofalbuminuria than other groups. The pooled prevalence among 158 White participants was 12.59%(95% CI, 7.75%-18.33%; I2 = 0%; P = .58)46,52 compared to 23.00% (95% CI, 18.85%-27.41%;I2 = 0%; P = .46) in 392 Asian participants,53,68 24.27% (95% CI, 14.39%-35.73%; I2 = 79%; P < .01)in 295 Indigenous participants,16,52,83 and 31.84% (95% CI, 11.90%-55.47%; I2 = 58%; P = .09) in 48Pacific Islander participants16,69,78 (eFigure 12 in the Supplement). Single studies found analbuminuria prevalence of 14.1% in 212 African American participants50 and 23% in 64 Hispanic/Latino participants.16

Individual studies reported a prevalence of persistent albuminuria of 11.2% in 222 AfricanAmerican participants,15 14.1% in 289 Hispanic/Latino participants,15 and 23% in 22 Koreanparticipants.86 Two studies reported a prevalence of 6.96% (95% CI, 0.00%-25.91%; I2 = 70%;P = .07) in 150 White participants15,58 and 19.06% (95% CI, 2.27%-45.67%; I2 = 91%; P < .001) in 217Indigenous participants (eFigure 13 in the Supplement).15,74














For microalbuminuria, the pooled prevalence was 18.98% (95% CI, 9.98%-29.87%; I2 = 80%;P = .002) in 554 Asian participants (eFigure 14 in the Supplement).53,68,89,94 Individual studies founda prevalence of microalbuminuria of 0% in 12 White participants,91 21% in 52 African Americanparticipants,91 18.5% in 103 Indigenous participants,83 and 42% in 12 Pacific Islander participants.78

Finally, for persistent microalbuminuria, the pooled prevalence 22.31% (95% CI,10.22%-37.01%; I2 = 0%; P = .48) in 40 Asian participants (eFigure 15 in the Supplement).86,94 Onestudy reported a prevalence of 14.1% in 289 Hispanic/Latino participants, 11.2% in 222 AfricanAmerican participants, 14.6% in 138 White participants, and 8% in 43 Indigenous participants.15

Publication BiasPublication bias was found for the prevalence of microalbuminuria based on the funnel plot andEgger test. It was not found for hypertension, albuminuria, persistent albuminuria, or persistentmicroalbuminuria (eFigures 16-20 in the Supplement).

Risk of Bias and Overall Quality of EvidenceThe included studies had either a low (n = 27)8,15-17,40,44-48,50,53,55,56,60,64,65,69,70,72,76,78,79,81,85,89,90

or moderate (n = 33)4,41-43,49,51,52,54,57-59,61-63,66-68,71,73-75,77,80,82-84,86-88,91-94 risk of bias (eTable 11and eFigure 21 in the Supplement). Some studies did not have a nationally representative sample,which limits their generalizability.4,8,40-43,46-51,53,54,56-60,63-68,71,72,74,75,77-80,82,83,85-87,89,91-94 Thesampling frame of some studies was not representative of their targetpopulation,41,42,44,51,52,54,61,63,67,74,75,77,80,82,86-88,91,92,94 and some did not take a random or censussample.15,41,42,51,52,54,57,67,75,82,86,87,92,94 Some studies also had missing data of greater than 25%,potentially leading to nonresponse bias.4,43,49,57,58,61,62,66,68,71,73,75,83,84,91,93 In 3 studies, thedefinition used to diagnose hypertension or albuminuria was unspecified,67,69,92 and in some studiesit was unclear that all participants were examined using the samemethods.45,52,55,59,61,62,70,73,81,84,88,90

Based on the OCEBM criteria,28 29 studies(48%)8,16,17,40,44,46-48,50,53,55,56,62,65,66,70,72-74,76,79-81,83,85,88-91 had an evidence level of 1; 17 studies(28%)4,43,45,49,58-61,63,64,68,69,71,77,78,84,93, 2; and 14 studies (23%),15,41,42,51,52,54,57,67,75,82,86,87,92,94

3 (eTable 11 in the Supplement). Nearly half of the studies thus provide the highest level of evidenceto answer the prevalence question we posed, although a significant portion of studies did not use arandom sample or census to estimate prevalence.

Discussion

The rates of type 2 diabetes in children and adolescents are increasing globally, and this rise isassociated with the obesity epidemic.95 Type 2 diabetes is associated with rapid progression ofkidney complications, and early detection and treatment are crucial to avoid end-stage kidneydisease, cardiovascular morbidities, and mortality.7,8,11,14 Current clinical guidelines on themanagement of pediatric type 2 diabetes are informed by independent studies with variablesample sizes.9,12,13

This systematic review investigated the prevalence of hypertension and albuminuria, markersof diabetes-related nephropathy and important predictors of kidney outcomes, in pediatric type 2diabetes. Approximately 1 in 4 pediatric patients with type 2 diabetes had hypertension. Althoughmore female patients had type 2 diabetes than male patients,9 male patients appeared to be morelikely to develop hypertension than female patients. Pacific Islander and Indigenous youth had ahigher burden of hypertension than other racial groups.

While most studies followed the National Heart, Lung, and Blood Institute guidelines forassessing hypertension in children and adolescents4,17,42,44,46-50,56,57,60,68,73,74 (ie, BP �95thpercentile for age, sex, and height20), 6 studies used the adult definition of hypertension of systolicBP level of 130 to 140 mm Hg or greater and diastolic BP level of 80 to 90 mm Hg or









greater.51,53,58,59,62,63 The different definitions of hypertension across studies were partlyresponsible for the noted heterogeneity, and using adult definitions might underestimatehypertension prevalence in children and adolescents.

Updated National Heart, Lung, and Blood Institute guidelines were released in 2017 thatlowered BP thresholds for hypertension, as they were based on only children with weight in thereference range, whereas older guidelines also included children with overweight and obesity.96

While no studies reported using the 2017 guidelines, it is possible that hypertension prevalence willbe higher if assessing data from existing studies against the 2017 guidelines.

Obesity is an important contributor to hypertension risk, with an estimated 6% increased riskof hypertension per unit of body mass index increase.6 Conversely, the metaregression analysisrevealed that obesity was not associated with the prevalence of hypertension. However, obesityprevalence and severity were not available in all studies, and it is probable that obesity maycontribute indirectly to the risk of hypertension in pediatric type 2 diabetes. On a mechanistic level,obesity-driven insulin resistance and hyperinsulinemia increases sodium reabsorption from the renaltubules.97 In addition, hyperglycemia can lead to hypervolemia, increased sympathetic activity,97

and the activation of the renin-angiotensin-aldosterone system, which increases cardiac output andperipheral vascular resistance, leading to hypertension.97 The associations between obesity andhypertension in pediatric type 2 diabetes require further study.

This review also demonstrated that between 1 in 5 and 1 in 4 pediatric patients with type 2diabetes had albuminuria. While no sex differences were identified, Pacific Islander, Indigenous, andAsian youth had higher rates of albuminuria than White youth. While macroalbuminuria occurred in4% of participants, fewer studies reported the persistence of albuminuria, despite the need forconfirmation of persistence being a key criterion for albuminuria diagnosis.9,12,13 Persistentalbuminuria is associated with macrovascular disease98 and predicts the progression to end-stagekidney disease.9,99 Prospective studies are needed to assess persistent albuminuria in pediatric type2 diabetes. When studies of adult patients with type 2 diabetes were excluded, the albuminuriapooled prevalence estimate decreased from 22.17% (95% CI, 17.34%-27.38%) to 17.00% (95% CI,9.00%-27.00%), and these results corroborate current evidence that albuminuria increases with ageand duration of diabetes.6,53

These data have several important implications. Type 2 diabetes–related nephropathy exerts amuch higher burden than that seen in children with type 1 diabetes.16,100 For example, the SEARCHfor Diabetes in Youth study reported elevated urine ACR of 9.2% in children with type 1 diabetes vs22.2% in those with type 2 diabetes,16 and youth with type 2 diabetes had 4-fold higher rates ofkidney failure compared with youth with type 1 diabetes.8 In addition, a study including Pima Indians,an Indigenous group with high rates of type 2 diabetes, found that those who developed type 2diabetes before 20 years of age had a 5-fold increased risk of end-stage kidney disease by middle ageand higher mortality rates compared with patients with adult-onset type 2 diabetes.7 Ongoingintensive screening and intervention strategies are warranted to reduce mortality and end-stagekidney disease in pediatric patients with type 2 diabetes.

The specific renal pathology that drives proteinuria and hypertension in pediatric type 2diabetes is unknown. While studies of kidney biopsies in youth with type 2 diabetes are limited, mostanomalies found on kidney ultrasounds have been classified as congenital.88 Kidney biopsies frompatients describe immune complex disease and glomerulosclerosis, findings that are notcharacteristic of typical diabetes-related nephropathy, which are considered non–diabetes-drivenpathologies.85 However, these observations are based on a small sample of Indigenous youth andmay not be generalizable to all children and adolescents with type 2 diabetes. Further studies areurgently needed to assess renal histopathology in type 2 diabetes across different sexes and racialgroups to define the exact mechanisms of nephropathy in this population.




LimitationsThis study has limitations, including the high heterogeneity among studies. Some studies did notachieve a high quality rating (n = 31) because of small sample sizes (n = 17) or the lack of clarity as towhether the results were based on a randomized sample or census (n = 14). Moreover, a largeproportion of the studies did not have a nationally representative sample, as they were based in asingle center or clinic. As such, larger studies across multiple centers are needed to assessprevalence. In addition, obesity severity data, which could confound hypertension and proteinuriaprevalence, were also not available. While the results should be interpreted with this information inmind, this report presents all current data available to assess hypertension and albuminuria inpediatric patients with type 2 diabetes.

Conclusions

In this study, hypertension and albuminuria were frequent comorbidities of pediatric type 2 diabetes,and Pacific Islander and Indigenous youth had a disproportionately higher burden of these conditionsthan youth from other racial groups. There is a critical need for personalized screening and treatmentstrategies to provide renoprotection from prolonged hyperglycemia and obesity to preventend-stage kidney disease, future cardiovascular disease, and improve life expectancy. The exactetiopathogenetic mechanisms driving nephropathy in youth with type 2 diabetes need to beelucidated. These data are relevant for health care professionals and policy makers, as clinicalservices treating pediatric patients with type 2 diabetes need to be resourced to track kidneyscreening and treatments to improve outcomes.

ARTICLE INFORMATIONAccepted for Publication: February 24, 2021.

Published: April 30, 2021. doi:10.1001/jamanetworkopen.2021.6069

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Cioana Met al. JAMA Network Open.

Corresponding Author: M. Constantine Samaan, MD, MSc, Department of Pediatrics, McMaster University,1200 Main St W, 3A-57, Hamilton, ON L8N 3Z5, Canada ([email protected]).

Author Affiliations: Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada (Cioana, Deng,Hou, Nadarajah, Qiu, Chen, Rivas, Chanchlani, Samaan); Division of Pediatric Endocrinology, McMaster Children’sHospital, Hamilton, Ontario, Canada (Cioana, Deng, Hou, Nadarajah, Qiu, Chen, Rivas, Samaan); Health SciencesLibrary, McMaster University, Hamilton, Ontario, Canada (Banfield); Division of Pediatric Nephrology, McMasterChildren’s Hospital, Hamilton, Ontario, Canada (Chanchlani); Department of Pediatrics and Child Health, Universityof Manitoba, Winnipeg, Manitoba, Canada (Dart, Wicklow); Children’s Hospital Research Institute of Manitoba,University of Manitoba, Winnipeg, Manitoba, Canada (Dart, Wicklow); College of Medicine, King Saud binAbdulaziz University for Health Sciences, Division of Endocrinology, Department of Pediatrics, Ministry of theNational Guard Health Affairs, Riyadh, Saudi Arabia (Alfaraidi); Department of Pediatrics, Division of PediatricEndocrinology, King Abdullah bin Abdulaziz University Hospital, Princess Noura University, Riyadh, Saudi Arabia(Alotaibi); Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton,Ontario, Canada (Thabane, Samaan); Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada(Thabane); Centre for Evaluation of Medicines, St Joseph’s Health Care, Hamilton, Ontario, Canada (Thabane);Biostatistics Unit, St Joseph’s Healthcare, Hamilton, Ontario, Canada (Thabane); Michael G. De Groote School ofMedicine, McMaster University, Hamilton, Ontario, Canada (Qiu, Rivas, Samaan).

Author Contributions: Ms Cioana and Dr Samaan had full access to all of the data in the study and takeresponsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Cioana, Dart, Thabane, Samaan.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Cioana, Thabane, Samaan.





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mailto:[email protected]

Critical revision of the manuscript for important intellectual content: Cioana, Deng, Hou, Nadarajah, Qiu, Chen,Rivas, Banfield, Chanchlani, Dart, Wicklow, Alfaraidi, Alotaibi, Samaan.

Statistical analysis: Cioana, Deng, Dart, Thabane, Samaan.

Administrative, technical, or material support: Hou, Qiu, Banfield, Wicklow, Samaan.

Supervision: Chanchlani, Thabane, Samaan.

Conflict of Interest Disclosures: None reported.

Meeting Presentation: Data were presented as an oral presentation at the Diabetes Canada Meeting; October29, 2020.

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SUPPLEMENT.eTable 1. Search Strategy, MEDLINEeTable 2. Search Strategy, EmbaseeTable 3. Search Strategy, CINAHLeTable 4. Search Strategy, Cochrane Library: Cochrane Central Register of Controlled Trials and Cochrane Databaseof Systematic ReviewseTable 5. Search Strategy, Web of Science: Conference Proceedings Citation Index-ScienceeTable 6. Results of Sensitivity Analysis for Prevalence of Hypertension in Pediatric Type 2 Diabetes Meta-analysis




https://dx.doi.org/10.1007/s00592-014-0583-1

https://dx.doi.org/10.1542/peds.2009-1230

https://dx.doi.org/10.1111/dme.12665_8







https://dx.doi.org/10.4158/EP13016.OR


https://dx.doi.org/10.6065/apem.2015.20.1.13

https://dx.doi.org/10.6065/apem.2015.20.1.13

https://dx.doi.org/10.1007/s00125-013-2915-z

https://dx.doi.org/10.1542/peds.2017-1904

https://dx.doi.org/10.1038/s41440-018-0034-4

https://dx.doi.org/10.1016/S0140-6736(12)61350-6

https://dx.doi.org/10.1056/NEJM198402093100605


eTable 7. Results of Sensitivity Analysis for Prevalence of Albuminuria in Pediatric Type 2 Diabetes Meta-analysiseTable 8. Results of Sensitivity Analysis for Prevalence of Persistent Albuminuria in Pediatric Type 2 DiabetesMeta-analysiseTable 9. Results of Sensitivity Analysis for Prevalence of Microalbuminuria in Pediatric Type 2 Diabetes Meta-analysiseTable 10. Results of Sensitivity Analysis for Prevalence of Persistent Microalbuminuria in Pediatric Type 2Diabetes Meta-analysiseTable 11. Risk of Bias and OCEBM Level of Evidence of Included StudieseFigure 1. Study Flow DiagrameFigure 2. Forest Plot Showing Pooled Prevalence of Systolic Hypertension in Pediatric Type 2 DiabeteseFigure 3. Forest Plot Showing Pooled Prevalence of Diastolic Hypertension in Pediatric Type 2 DiabeteseFigure 4. Forest Plot Showing Pooled Prevalence of Hypertension in Pediatric Type 2 Diabetes by SexeFigure 5. Forest Plot Showing Pooled Odds Ratio of Hypertension in Male vs Female Participants with PediatricType 2 DiabeteseFigure 6. Forest Plot Showing Pooled Prevalence of Hypertension Across Different Racial Groups with PediatricType 2 DiabeteseFigure 7. Forest Plot Showing Pooled Prevalence of Microalbuminuria in Pediatric Type 2 DiabeteseFigure 8. Forest Plot Showing Pooled Prevalence of Persistent Microalbuminuria in Pediatric Type 2 DiabeteseFigure 9. Forest Plot Showing Pooled Prevalence of Macroalbuminuria in Pediatric Type 2 DiabeteseFigure 10. Forest Plot Showing Pooled Prevalence of Persistent Albuminuria in Pediatric Type 2 Diabetes by SexeFigure 11. Forest Plot Showing Pooled Odds Ratio of Persistent Albuminuria in Male vs Female Participants withPediatric Type 2 DiabeteseFigure 12. Forest Plot Showing Pooled Prevalence of Albuminuria across Different Racial Groups with PediatricType 2 DiabeteseFigure 13. Forest Plot Showing Pooled Prevalence of Persistent Albuminuria across Different Racial Groups withPediatric Type 2 DiabeteseFigure 14. Forest Plot Showing Pooled Prevalence of Microalbuminuria in Asian Patients with Pediatric Type 2DiabeteseFigure 15. Forest Plot Showing Pooled Prevalence of Persistent Microalbuminuria in Asian Patients with PediatricType 2 DiabeteseFigure 16. Funnel Plot Examining Publication Bias for Pooled Prevalence of Hypertension OutcomeeFigure 17. Funnel Plot Examining Publication Bias for Pooled Prevalence of Albuminuria OutcomeeFigure 18. Funnel Plot Examining Publication Bias for Pooled Prevalence of Persistent Albuminuria OutcomeeFigure 19. Funnel Plot Examining Publication Bias for Pooled Prevalence of Microalbuminuria OutcomeeFigure 20. Funnel Plot Examining Publication Bias for Pooled Prevalence of Persistent MicroalbuminuriaOutcomeeFigure 21. Distribution of Risk of Bias Sources in the Included StudieseAppendix. List of Studies Excluded at the Full-Text Screening StageeReferences.




prevalence of hypertension and albuminuria in pediatric

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