Nigerian Journal of Paediatrics

3Influence of disease remission on renal dimensions in childhood nephrotic syndrome in Ibadan South West Nigeria

Niger J Paediatr 2016; 43 (3):170 – 174

ORIGINAL

Afolabi OS

Influence of disease remission on

Atalabi O

Asinobi AO

renal dimensions in childhood

Adebowale DA

nephrotic syndrome in Ibadan,

South West Nigeria

DOI:http://dx.doi.org/10.4314/njp.v43i3.3

Accepted: 26th April 2016

Abstract : Background: The hall-

dinal, anteroposterior, transverse

mark of Nephrotic syndrome is

dimensions and volume were

Afolabi OS

(

)

massive proteinuria, with associ-

higher in cases compared to the

Department of Radiology,

ated enlarged kidneys. However

controls, bilaterally (p <0.001).

University College Hospital, Ibadan

Nigeria

the association between remission

The mean difference in values of

Email: afolabios@yahoo.com

status and size of the kidneys in

the measured parameters between

patients with nephrotic syndrome

the cases in remission and those

Atalabi O

is not known. This study is aimed

yet to attain remission was not

Department of Radiology,

at determining the dimensions of

significant. The bipolar dimension

College of Medicine/University College

the kidneys of children with

of the left kidney showed positive

Hospital, Ibadan Nigeria

nephrotic syndrome and to com-

correlation with duration of dis-

pare kidney dimensions in pa-

ease (r= 0.290, p=0.035). The

Asinobi AO, Adebowale DA

tients with nephrotic syndrome

study was also able to demonstrate

Department of Paediatrics,

College of Medicine/University College

who were in remission compared

high incidence of nephromegaly,

Hospital, Ibadan Nigeria

with the dimensions in patients

in 52.8%, 62.3% and 67.9% re-

who were not in remission.

spectively for the right kidney, left

Subjects and Methods: This is a

kidney and combined.

case-control study, where fifty-

Conclusion: Despite a comparative

three children with diagnosis of

global enlargement in the kidney

Nephrotic syndrome and fifty-

dimensions

children

with

seven age matched healthy con-

nephrotic syndrome compared

trols were analysed. The kidneys

with controls and the general

of both cases and controls were

population, the remission status

scanned using the B- mode ultra-

does not seem to be a significant

sound and the kidneys Bipolar,

factor.

anteroposterior and

transverse

dimensions and volume were de-

Keywords: Nephrotic syndrome,

termined.

renal dimensions, ultrasonography,

Results: The mean renal longitu-

nephromegaly, paediatric.

Introduction

little is known about the relationship of the renal

enlargement and disease remission.

Nephrotic syndrome is a leading cause of chronic renal

Ultrasonography is a recognised investigative tool in

disease, with subsequent morbidity and mortality among

assessing the kidneys of the patients with nephrotic syn-

the paediatric age group. It is defined by the presence

1 – 5

drome, especially the renal size. Ultrasound is also

of massive proteinuria, hypoalbuminaemia, and ana-

important as an adjunct procedure to localize the kid-

neys when performing renal biopsy.

sarca. It is thus technically defined as defined as the

presence of nephrotic- range proteinuria (>40mg/m /hr),

or urine protein to creatinine ratio of >2-3mg/mg, hypo-

albuminaemia (<2.5-3.0g/dl) and oedema.

There is usually an associated nephromegaly.

Materials and methods

Proteinuria being a major yardstick in nephrotic syn-

This is a prospective study

drome, its absence would also signify disease resolution.

This is termed remission, which is dipstix proteinuria of

Ethical approval was obtained from the University of

<1+ for three consecutive days. Thus, attaining remis-

Ibadan / University College Hospital ethical review

sion is an important goal in the management of the dis-

committee, as the study spanned through twelve months

ease.

(July 2013 to July 2014).

Fifty- five cases with known diagnosis of nephrotic syn-

Despite a series of publications emphasizing the renal

drome were recruitedfrom the Children emergency ward

enlargement seen in nephrotic syndrome,

6,8

however

and Children outpatient clinic of the University College

171

Hospital, Ibadan. Two were eventually dropped because

The ultrasound low frequency (2-5KHz) transducer of

they defaulted and could not be traced. Fifty- seven

Mindray M7, 2010 by Shenzhen Mindray bio- medical

healthy controls were also recruited to give a total of one

electronics company limited ultrasound machine was

hundred and twelve subjects for the study. The control

used. The subjects were scanned in supine, lateral

subjects were children of members of staff and friends.

oblique and prone positions.

Every consecutive child, whose parents consented to the

The kidney sizes were measured in centimetres while

study, was recruited. These cases met the diagnostic

the subject lied in prone position, as the measurements

criteria (Nephrotic-range proteinuria of >40mg/m /hr, or

were taken from the back. The renal dimensions

Urinary protein to Creatinine ratio of >2, hypoalbu-

(Bipolar length, Width, Thickness and Volume) were

minaemia of <2.5g/dl and oedema).

3,10

The average age

derived by using the in-built electronic callipers of the

of the NS cases was 126.24 ± 40.11months, with a ma-

machine. The callipers were placed at the edges of the

jority (56.6%) in the 10 – 15yearsage brackets. The

kidneys in craniocaudal, anteroposterior, and transverse

mean age of the control subjects is slightly lower

planes to estimate the bipolar length, thickness and

((117.63± 38.11months).

width respectively of the kidneys. The measurements

were standardized for consistency. To obtain the bipolar

Complete remission was defined as protein negative or

length, the upper and lower poles of the kidney were

trace on urine dipstick for 3 consecutive days while re-

marked and the maximal value obtained at the midsagit-

lapse was defined as proteinuria of ≥ 3+ on urine dip-

tal plane. The anteroposterior dimension was also ob-

stick for 3 consecutive days. Infrequent relapse was de-

tained from the same midsagittal image. The transverse

fined as one relapse within 6 months of initial response,

scan was obtained perpendicular to the axis of the mid-

or one to three relapses in any 12-month period. Fre-

sagittal plane, and measurement for the transverse di-

quent relapse was two or more relapses within 6 months

mension made at about 1cm point from the hilum. Each

of initial response, or four or more relapses in any 12-

subject was scanned once. No variability expected, as

month period. Steroid dependent nephrotic syndrome

ultrasound was done by single Radiologist. The renal

referred to two consecutive relapses during corticoster-

volume was derived by the machine’s in -built algorithm,

oid therapy, or within 14 days of ceasing therapy. Ster-

using the ellipsoid formula (Bipolar length(LS) x

breadth (AP) x width (TS) x 0.523).

oid sensitive nephrotic syndrome included patients who

achieved remission with steroid therapy and had not

recordedany relapse as well as infrequent relapsers, fre-

The presence of nephromegaly was determined by com-

quent relapser and patients with steroid dependent

paring the kidney sizes of each of the cases with age and

sex matched population from a previous study.

nephrotic syndrome. Steroid sensitive nephrotic syn-

drome included infrequent relapsers, frequent relapsers

Statistical Analysis was done with SPSS version 17. The

and steroid dependent nephrotic syndrome. Steroid re-

mean value ± standard deviation of the kidney dimen-

sistance was defined as failure to achieve complete re-

sions (Length, breadth, width, and volume), were de-

mission after 8 weeks of corticosteroid therapy.

picted in tables. The mean renal dimensions in cases and

Patients with nephrotic syndrome were initially man-

controls as well as in those in remissions versus those

aged with per oral (p.o) prednisolone 60mg/m daily for

who were not in remission were compared by independ-

4-6 weeks and 40mg/m /day for 2-4 weeks to make at

ent student t- test.

least 8 weeks of prednisolone therapy.

The correlation between disease duration and renal di-

Patients who attained remission went on to receive 4

mensions in the nephrotic cases were determined by

additional months of tapering doses of p.o prednisolone

Pearson’s correlation.

in the initial episode. While first relapse of nephrotic

syndrome and infrequent relapsers were managed with

p.o prednisolone 60mg/m until remission and 40mg/m

on alternate day for 4 weeks. Steroid resistant nephrotic

Results

syndrome was usually managed with monthly intrave-

nous (i.v) Cyclophosphamide (2mg/kg/d) for 6 months,

A total of One hundred and twelve children were re-

p.o prednisolone, and angiotensin converting enzyme

cruited for the study, out of which fifty- five (49.1%)

inhibitors.

were the primary cases with nephrotic syndrome and the

remaining fifty- seven (50.9%) were controls. However,

A consent form was filled and signed by the parents of

two of the recruited cases were dropped from analysis

the proposed subjects. Likewise, a verbal assent was

due to incomplete data as they were lost to follow up.

also obtained from each child old enough to do same.

The age and sex distribution of the cases and healthy

The kidneys of the cases, as well as that of the age-

controls were demonstrated in table 1. The subjects were

matched controlswere scanned. The control group had

predominantly males in both the cases and control

urinalysis to rule out any subclinical proteinuria. They

group. Thirty- two (60.4%) of the analyzed cases were

were also screened by the B mode ultrasound to ensure

male, while there were thirty- four (59.6%) males

they had normal parenchymal echogenicity and pre-

among the controls. The average age of the cases was

served corticomedullary differentiation, so as to exclude

126.24 ± 40.11months. The mean age of the controls is

those with abnormal parenchymal echogenicity. These

slightly lower (117.63± 38.11months). The mean differ-

were done in the department of Radiology by the Radi-

ence in age between the cases and control group was not

ologist.

statistically significant (p= 0.44). The mean ages of the

172

cases in remission and those not in remission were

combined (figure 2).

118.6months and 125.3months respectively. This is also

of no statistical significance (p= 0.61)

Fig 2: A column showing a higher number of the cases dem-

The duration of illness ranged from 1week to 87months

onstrating nephromegaly

(7.25years) with a mean of 20.29monthsand most of the

cases (71.7%) hadduration of illness less than 2years

(Table 2).

Table 1: Age and sex distribution of the cases and controls

Nephrotic cases

Controls

(n=53)

(n=57)

Age (months)

Males

122.2 ± 39.9(p= 0.78)

114.0 ± 37.4(p= 0.40)

Female

125.6 ± 45.3

123.0 ± 39.3

Sex

Males

32 (60.4%)

34 (59.6%)

The mean LS, AP and TS dimensions in the cases were

Females

21 (39.6%)

23 (40.4%)

significantly greater than in the control subjects (p<

0.001) (Table 3).In addition, the left kidney was gener-

No statistical significance between mean ages of the cases and controls

ally larger in its mean LS, AP and TS dimensions in

(p=0.44)

both the cases and controls.

Table 2: Duration of disease in the cases

Table 3: Comparison of the dimensions of both kidneys for

Duration

the cases and controls

(months)

Number

Measured

Cases

Controls

<2years

71.7

parameters

Mean ± sd

p- Value

2-<4years

11.3

Right kidney

4- < 6years

9.4

Longitudinal

9.82 ± 1.23

8.30 ± 1.05

6.785

<0.001

Anteroposterior

4.39 ± 0.85

3.66 ± 0.42

5.558

<0.001

≥ 6years

7.5

Transverse

4.45 ± 0.77

3.69 ± 0.42

6.301

<0.001

Volume

102.32± 45.72

56.05 ± 16.15

6.829

<0.001

Left kidney

Forty of the fifty- three of the recruited cases were clas-

Longitudinal

10.28 ± 1.53

8.60 ± 1.88

6.205

<0.001

sified based on response to steroid therapy. The other

Anteroposterior

4.75 ± 0.84

3.71 ± 0.46

7.720

<0.001

children are still within the 4- 8weeks steroid trial, thus

Transverse

4.88 ± 0.97

3.95 ± 0.46

6.170

<0.001

Volume

126.66± 56.67

63.53± 21.39

7.407

<0.001

they could not be classified. However, of the classified

cases, majority (37, 70%) were steroid sensitive

p value <0.05 is significant

nephrotic syndrome as shown in figure 1.

However, the comparison of the mean values of the re-

Fig 1: 3D pie chart showing the clinical classification of the

nal dimensions of the children who were not in remis-

children with nephrotic syndrome based on the response to

sion and those in remission only showed marginal, but

steroid therapy. Majority of the cases were of the steroid sensi-

non-significant increase in the LS, AP and TS dimen-

tive (SSNS) subtype, while the least occurring subtype is the

sions, as well as volume of both kidneys in the former.

FRNS.

(Table 4).

Table 4: Comparision of the mean kidney dimensions in the

nephrotic children in remission and those not in remission

Parameters meas-

Not in Remis-

ured

In remission

sion

P Value

RK- Bipolar Length

9.59 ± 1.34

9.87 ± 1.22

0.667

0.513

RK- Anteroposterior

4.12 ± 0.91

4.47 ± 0.81

1.230

0.234

RK- Transverse

4.24 ± 0.60

4.52 ± 0.80

1.333

0.193

RK- Volume

90. 76 ± 51.54

105.21 ± 43.52

0.909

0.375

LK- Bipolar Length

10.01 ± 1.92

10.34 ± 1.41

0.549

0.589

LK- Anteroposterior

4.52 ± 1.00

4.80 ± 0.79

0.948

0.355

Only about one-fourth (14, 26,4%) of the cases were in

LK- Transverse

4.74 ± 1.10

4.91 ± 0.94

0.511

0.615

remission, as at the time of this study. The remaining

LK- Volume

120.05 ± 76.18

127.12 ± 49.55

0.324

0.750

(39, 73.6%)were either in relapse or yet to attain remis-

Mean (in cm), Volume (in cm ), RK is Right kidney, LK is Left kid-

sion. A high occurrence of relapse was also reported in

ney.

27 (67.5%) of the cases. A third (14, 35%) of which also

demonstrated proteinuria level of 3+.

The duration of disease showed significant positive cor-

There is a high prevalence of nephromegaly in the cases.

relation with the bipolar dimension of the left kidney

This is demonstrated by more than a half (28, 52.8%),

only (r= 0.290) (p= 0.035). Thus, the longer the duration

almost two-thirds (33, 62.3%), more than two-thirds (36,

of disease, the longer the bipolar length, as shown in

67.9%) respectively by the right kidney, left kidney and

table 5.

173

Table 5: Relationship between the duration of disease and

resistance was also documented. Similarly, Nammarlwar

dimensions of both kidneys in the cases

et al also reported a high incidence (65.2%) of steroid

Measured

Right kidney

Left kidney

resistance among the Indian children.

parameters

p- Value

Longitudinal

0.141

0.317

0.290

0.035

There is presence of nephromegaly, just as reported in a

Anteroposterior

-0.065

0.645

0.074

0.600

previous study by Gersen et al in the United States

Transverse

-0.064

0.650

0.091

0.519

where 42% of the paediatric cases demonstrated

nephromegaly.

Volume

-0.046

0.744

0.153

0.275

There was a trend toward a higher kidney dimensions in

p <0.05 is significant, r = Pearson’s correlation

nephrotic syndrome patients who were not in remission

compared to values in patients who were in remission.

In addition, a comparison of renal dimensions in the

different remission statuses is also difficult due to non-

Discussion

availability of previous publications. Larger studies are

however needed to confirm the finding that remission

The mean age of the children with nephrotic syndrome

status does not significantly influence the size of the

in this study is higher than that from other regions where

kidneys in patients with nephrotic syndrome. A search

mean ages of 5.3 years and 3.8years in Kuwait and

through the literature also revealed paucity of studies on

Saudi Arabia have been reported.

13,14

This may be due to

the association between duration of nephrotic syndrome

geographic factors.

and kidney dimensions.

The relative low rate of patients in remission is in con-

trast to the high occurrence in Enugu (63.9%)

and

Benin city (51.7%)

in Nigeria, as well as in Kuwait

(84%) and in Finland (82.5%) . This is probably also

Conclusion

due to the rarity of minimal change disease in our envi-

ronment and also difference ethnic genetic makeup.

A comparative global enlargement of all the renal di-

Despite the relative low remission rate in the cases, quite

mensions in nephrotic syndrome was confirmed by this

a high proportion was classified as steroid sensitive. The

study. There was a trend towards larger mean bipolar,

low proportion of patients in remission may also be due

anteroposterior and transverse kidney dimensions in

to high relapse rate at the time of this study as it was

nephrotic syndrome patients who were not in remission

documented in previous local studies. Anochie et al (in

as compared with patients who were, but the difference

Port Harcourt) and Ibadin et al (in Benin) reported an

was not significant. Larger studies are however needed

initial steroid response of 80% and 51.7%, with subse-

to confirm influence of disease remission status on renal

quent high relapse of 75% and 43.4% respectively. Asi-

dimensions. This may per- haps be able to demonstrate

nobi et al in Ibadan also reported an initial steroid re-

serial kidney dimensions as an adjunct to urinary protein

sponse of 60%. Olowu et al

21,22

in Ile- Ife also reported

in assessing disease remission.

initial remission of 57.1% and 64.1% in separate publi-

cations, yet with a high relapse of 64.1% in the initially

Conflict of interest: None

sensitive patients. A high incidence (46.3%) of steroid

Funding: None

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