Persistence of behavioral abnormalities following corticosteroid therapy in children with initial episode of idiopathic nephrotic syndrome: a prospective longitudinal observation

Singh, Parichay; Mishra, Om P.; Upadhyay, Shashi K.; Prasad, Rajniti; Singh, Ankur; Abhinay, Abhishek; Mishra, Akash; Schaefer, Franz

doi:10.1590/2175-8239-JBN-2021-0043

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Brazilian Journal of Nephrology

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Original Articles • Braz. J. Nephrol. 44 (1) • Jan-Mar 2022 • https://doi.org/10.1590/2175-8239-JBN-2021-0043 copy

Persistence of behavioral abnormalities following corticosteroid therapy in children with initial episode of idiopathic nephrotic syndrome: a prospective longitudinal observation

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Introduction:

Treatment of nephrotic syndrome with corticosteroid can cause several side- effects including behavioral abnormalities. The objectives of the study were to observe the proportion of non-relapsers having persistence of behavioral abnormalities after completion of treatment of initial episode and compare the abnormalities with relapsers, and to determine risk factors for persistence.

Methods:

Seventy-five children with a first episode of idiopathic nephrotic syndrome and 60 normal children were rated by parents for behavioral problems using the Child Behavior Checklist. The Parenting Stress Index was also evaluated. The children were rated before treatment and 12 and 36 weeks after.

Results:

Both relapsers and non-relapsers showed abnormalities in internalizing and externalizing domains at 12 weeks of steroid therapy. Non-relapsers had abnormal scores in the internalizing domain in 63.5 % and externalizing domain in 48.1% of cases at 36 weeks. Relapsers had abnormal scores in all the three behavior domains, but a significantly higher proportion of relapsers had abnormal scores regarding total behavior (65.2% vs 28.8%, p<0.01) and child domains (100% vs 57.7%, p<0.001) of Parenting Stress Index in comparison to non-relapsers at 36 weeks. Occurrence of relapse increased the risk (odds ratio 5.76, 95% CI 1.35-10.76, p< 0.001) for persistence of abnormal total behavior at 36 weeks follow-up.

Conclusion:

Persistence of abnormalities was observed not only in relapsers but also in non-relapsers. Relapse was found to be a significant risk factor for persistence of abnormal behaviors in these patients.

Keywords:
Child Behavior Disorders; Child; Adrenal Cortex Hormones; Nephrotic Syndrome

Behavioral domains	(A) Controls (n=30)	(B) Pre-treatment (n=26)	(C) Post-treatment at 12 weeks (n=26)	(D) Post -treatment at 36 weeks (n=26)	p
Emotionally reactive	51.33	51.77	62.92***	61.73***
Emotionally reactive	±1.60	±2.06	±3.61	±3.23	<0.001
Anxious/ depressed	52.23	53.50^* * P< 0.05; B vs C:	66.00***	64.62***
Anxious/ depressed	±1.59	±2.37	±3.29	±2.98	<0.001
Somatic complaints	56.17	58.50^* * P< 0.05; B vs C:	58.65	57.81
Somatic complaints	±3.05	±3.67	±3.60	±3.67	0.611
Withdrawn/ depressed	56.50	57.27	59.73^ P<0.01,	58.27
Withdrawn/ depressed	±2.92	±2.84	±3.03	±2.22	<0.01
Sleep problems	51.87	52.00	52.96	52.92
Sleep problems	±1.98	±2.37	±2.97	±2.58	0.293
Attention problems	53.60	53.19	56.42^ P<0.01,	54.73
Attention problems	±2.84	±2.61	±3.81	±2.91	<0.01
Aggressive behavior	54.40	54.27	60.92***	60.08***
Aggressive behavior	±2.40	±2.62	±2.51	±3.21	<0.001

Behavioral domains	Controls (n=30)	(B) Pre-treatment (n=26)	(C) Post-treatment at 12 weeks (n=26)	(D) Post-treatment at 36 weeks (n=26)	p
Anxious/ depressed	54.43	53.65	56.38**	55.31*
Anxious/ depressed	±2.62	±2.37	±2.28	±2.62	<0.001
Withdrawn/ depressed	56.43	55.85	56.69	55.96
Withdrawn/ depressed	±3.16	±2.36	±2.15	±2.13	0.289
Somatic complaints	58.90	58.23	59.50	57.46
Somatic complaints	±3.57	±3.36	±3.20	±3.73	0.110
Social problems	54.80	54.69	56.12	55.58
Social problems	±2.51	±2.91	±2.44	±2.18	0.164
Thought problems	54.03	54.15	55.92*	55.69*
Thought problems	±2.77	±2.98	±2.41	±2.72	<0.05
Attention problems	53.57	52.88	53.46	53.19
Attention problems	±1.57	±1.07	±1.39	±1.63	0.328
Rule breaking behavior	56.93	56.46	60.88**	59.31**
Rule breaking behavior	±3.19	±2.66	±2.44	±2.89
Aggressive behavior	55.47	55.04	60.8**	59.92**	<0.001
Aggressive behavior	±1.99	±2.01	±2.33	±2.35

Characteristics	Non-relapsers (n= 52)		Relapsers (n= 23)		p
Age group (years)	n	%	n	%
1.5-5	26	50	13	56.5	0.602
6-15	26	50	10	43.5	0.602
Gender
Male	34	65.4	11	47.8	0.152
Female	18	34.6	12	52.2	0.152
Residence
Rural	38	73.1	20	87.0	0.186
Urban	14	26.9	03	13.0	0.186
Socioeconomic status
Upper	5	9.6	2	8.7	0.953
Middle	39	75.0	18	78.3
Lower	8	15.4	3	13.0
Child domains at 12 weeks
High ≥60%	35	67.3	17	73.9	0.567
Low <60%	17	32.7	6	26.1	0.567
Parent domains at 12 weeks
High ≥60%	7	13.5	0	0.0	0.093
Low <60%	45	86.5	23	100	0.093
Child domains at 36 weeks
High ≥60%	30	57.7	23	100	<0.001
Low <60%	22	42.3	0	0.0	<0.001
Parent domains at 36 weeks
High ≥60%	8	15.4	6	26.1	0.273
Low <60%	44	84.6	17	73.9	0.273
Hemoglobin (g/dL)	11.5 ±1.5		11.7± 1.7		0.836
Systolic BP (mm Hg)	98.5 ±10.4		96.3± 9.6		0.410
Diastolic BP (mm Hg)	61.2 ±7.9		59.9± 7.8		0.508
Cumulative steroid dose (mg/m²)	2937.3 ± 303.2		4095.2±.440.3		<0.001

Behavioral domains	Non-relapsers (n= 52)		Relapsers (n= 23)		p
	n	%	n	%
Internalizing behavior score at pre-treatment
Abnormal ≥60	3	5.8	1	4.3
Normal <60	49	94.2	22	95.7	1.000
Externalizing behavior score at pre-treatment
Abnormal ≥60	1	1.9	0	0
Normal <60	51	98.1	23	100	1.000
Total behavior score at pre-treatment
Abnormal ≥60	0	0	0	0
Normal <60	52	100	23	100	-
Internalizing behavior score at 12 weeks
Abnormal ≥60	39	75.0	16	69.6
Normal <60	13	25.0	7	30.4	0.624
Externalizing behavior score at 12 weeks
Abnormal ≥60	39	75.0	19	82.6
Normal <60	13	25.0	4	17.4	0.468
Total behavior score at 12 weeks
Abnormal ≥60	20	38.5	12	52.8
Normal <60	32	61.5	11	48.2	0.268
Internalizing behavior score at 36 weeks
Abnormal ≥60	33	63.5	17	73.9
Normal <60	19	36.5	6	26.1	0.376
Externalizing behavior score at 36 weeks
Abnormal ≥60	25	48.1	15	65.2
Normal <60	27	51.9	8	34.8	0.170
Total behavior score at 36 weeks
Abnormal ≥60	15	28.8	15	65.2
Normal <60	37	71.2	8	34.8	<0.01

	Internalizing behavior at 36 weeks					Externalizing behavior at 36 weeks					Total behavior at 36 weeks
Parameters	Abnormal (≥ 60) n=50		Normal (<60) n=25		P	Abnormal (≥ 60) n=40		Normal (<60) n= 35		p	Abnormal (≥ 60)n=30		Normal (<60) n=45		p
	n	%	n	%		n	%	n	%		n	%	n	%
Gender
Male	29	58	16	64	0.617	22	55	23	65.7	0.345	18	60	27	60	1.000
Female	21	42	09	36	0.617	18	45	12	34.3	0.345	12	40	18	40	1.000
Residence
Rural	12	24	05	20	0.697	10	25	7	20	0.606	8	26.7	9	20	0.499
Urban	38	76	20	80	0.697	30	75	28	80	0.606	22	73.3	36	80	0.499
Relapse status
Relapser	17	34	06	24	0.376	15	37.5	8	22.9	0.170	15	50	8	17.8	<0.01
Non-Relapser	33	66	19	76	0.376	25	62.5	27	77.1	0.170	15	50	37	82.2	<0.01
Child
domains
Abnormal	34	68	18	72	0.723	29	72.5	23	65.7	0.525	19	63.3	33	73.3	0.358
Normal	16	32	07	28	0.723	11	27.5	12	34.3	0.525	11	36.7	12	26.7	0.358
Parent
domains
Abnormal	05	10.0	02	8	1.000	3	7.5	4	11.4	0.853	3	10	4	8.9	1.000
Normal	45	90.0	23	92	1.000	37	92.5	31	88.6	0.853	27	90	41	91.1	1.000
Socioeconomic status
Upper	5	10	2	8	1.000	6	15	1	2. 8	0.113	4	13.3	3	6.7	0.427
Middle	34	68	23	92		28	70	29	42.9		197	63.3	38	84.4
Lower	11	22	0	0		6	15	5	14.3			23.3	4	8.9
Hemoglobin (g/dL)	11.6 ±1.6		11.4±1.6		0.383	11.4±1.5		11.9±1.6		0.185	11.4± 1.6		11.7± 1.6		0.467
Systolic blood
pressure (mmHg)	102.7±6.9		95.7±10.9		<0.01	98.5±10.1		96.9±10.2		0.506	100.0± 10.1		94.4±9.3		<0.05
Cumulative
steroid dose	3481.3		3197.9		0.070	3389.9		3310.9		0.160	3310.9		3280.0		0.840
at 36 weeks (mg/m²)	±608.4		±640.7		0.070	±652.2		±616.8		0.160	±646.7		±643.0		0.840

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[1] Correspondence to: Om P. Mishra. E-mail: opmpedia@yahoo.co.uk