Health-Related Quality of Life in Children with Steroid-Resistant Nephrotic Syndrome

Summary

Objectives:

Nephrotic syndrome (NS) is considered as a major global health concern, and a higher proportion of children with NS have steroid resistance (SR). This study aimed to assess the health-related quality of life (HRQoL) of children with SRNS.

Methods:

This case-control study was conducted from January to June 2023 at University Children's Hospital, Minia, Egypt. There were 160 participants in total who were divided into 3 groups: 60 participants with SRNS and 2 control groups (one of which had steroid-sensitive NS) that were matched appropriately. Each participant's QoL was assessed using the Pediatric Quality of Life Inventory (PedsQL 4.0 Generic Core Scales).

Results:

Children with SRNS had the lowest mean scores across all domains of the PedsQL (P<0.001) with duration of the illness and high cumulative glucocorticoids being significant in the prediction of low QoL in those children (P = 0.01 each).

Conclusions:

To properly evaluate and improve the QoL for children with SRNS, coordinated efforts involving paediatric nephrologists and psychiatrists are required.

1. Introduction

Nephrotic syndrome (NS) is characterised by severe proteinuria that causes hypoalbuminemia, which in turn causes hyperlipidaemia, oedema and numerous other complications. The management of NS may encounter several difficulties, such as frequent relapses, dependency on or resistance to steroids, resistance to other immunosuppressive medications and adverse effects associated with treatment.¹ Children diagnosed with steroid-resistant NS (SRNS), particularly those attributed to focal segmental glomerulosclerosis, have the potential to progress to end-stage kidney disease (ESKD) with associated risks of renal replacement therapy.² NS is considered a serious health concern and there an increasing prevalence of recently identified cases in children as well as a growing percentage of children experiencing a steroid-resistant course.³

The Pediatric Quality of Life Inventory (PedsQL) is a tool that has been tested on the basis of classical test theory to evaluate individuals' emotional, physical, social and school functioning.^4,5

The chronic and recurring nature of NS, together with the demands of therapy and the potential consequences of prognosis, may have adverse physical and psychosocial effects on both affected children and their families.² To ensure the provision of the most effective therapy for children with chronic kidney disease (CKD), it is essential to include psychological considerations that facilitate a seamless transition into adulthood.⁶ Therefore, optimising the quality of life of these children is considered essential and has emerged as a primary objective in the comprehensive care of their condition. The precise determination of variables that impact the quality of life (QoL) of children with NS has the potential to enhance the treatment of this condition and help them better follow the medical instructions they require.^6,7 By comprehending the health-related QoL (HRQoL) in children diagnosed with NS, valuable insights may be gained into their self-perception and well-being. This understanding can then inform and enhance the guidance provided for their treatment.⁷

Numerous studies have demonstrated a diminished QoL among children with CKD and ESKD who regularly receive haemodialysis or peritoneal dialysis.^{8,9,10,11,12,13,14} However, research on QoL in children with idiopathic NS (INS) in general, particularly in developing nations, is scarce.^15,16,17,18 Nevertheless, to the best of the authors knowledge the assessment of HRQoL has not been previously investigated in the context of children diagnosed with SRNS. Given the shortage of research conducted on children with SRNS, the purpose of this research was to assess the HRQoL of children with SRNS. This was achieved by utilising the PedsQL™ 4.0 to assess the HRQoL of children with SRNS compared with those with SSNS, along with healthy controls.

2. Methods

This case-control study was conducted at University Children's Hospital, Minia, Egypt, in the paediatric nephrology unit from January to June 2023. Participants included in this study were divided into 3 groups: (1) patients diagnosed with SRNS and were between the ages of 8 and 18 (i.e. cases); (2) a control group with participants with SSNS; and (3) a control group of healthy children. They were diagnosed and treated according to kidney disease improving global outcomes (KDIGO) guidelines of childhood NS.¹⁹

SRNS was defined as the inability to achieve complete remission following a 6-week course of daily corticosteroid administration at the recommended dosage. There are 3 subtypes of steroid sensitive NS: steroid-dependent NS (SDNS), frequent relapsing NS (FRNS) and infrequent relapsing NS (IFRNS). SDNS was characterised by any recurrence of the condition throughout the course of alternate day therapy or during a 2-week period after the completion of maintenance steroid therapy, irrespective of dosage. FRNS was defined as experiencing 2 or more relapses within 6 months. IFRNS was characterised by 1 relapse during the first 6 months of the preliminary response or 1–3 relapses within a 12-month span.¹⁹

To qualify to be included in the case group, the participants had to have a 1-year minimum duration of illness and normal renal function, as measured by an estimated glomerular filtration rate (eGFR) of more than 90 mL/min/1.73 m². The eGFR was determined via the modified Schwartz formula. The formula is:

GFR = kL/Pcr

Where L represents body length in cm, Pcr represents plasma creatinine concentration in mg per dL and k is a constant of proportionality that reflects the relationship between urinary creatinine excretion and units of body size. The value of k varies as a function of age and sex is 0.55 in children and adolescent girls, and 0.70 in adolescent boys.²⁰ Children who had been previously diagnosed with mental or physical disabilities, psychiatric disorders, or obesity prior to developing NS were excluded.

For the healthy controls, children who visited the general outpatient paediatric clinic were included. These children had no history or clinical signs indicating the presence of kidney problems or any other chronic illnesses with age and sex matching to SRNS patients. To gain a more comprehensive understanding of the distinct impact of SRNS as a medical condition with different pathology and genetic predisposition and still unknown pathogenesis on HRQoL scores, a supplementary control group consisting of children diagnosed with SSNS was included in the study. The SSNS controls were randomly selected from 850 SSNS children using a systematic random sampling technique at a sampling interval of 5; these children were age and sex matched to the SRNS children.

For every gram increase in cumulative glucocorticoid (CGC) dose, the probability of any glucocorticoid-related side event increased considerably.²¹ A prior study by Eid et al. found that children with NS were divided into 2 groups based on the children's cumulative glucocorticoid dose over the previous year: high cumulative glucocorticoid dose (>1 g/kg) and low cumulative glucocorticoid dose (<1 g/kg).¹⁸

The current study assessed the disease's complications as well as the complications of immunosuppressive medications as follows: body mass index Z-score ≥95th percentile based on Egyptian growth curves was used to identify obesity;²² Cushingoid characteristics included moon facies, acne, acanthosis nigricans, facial plethora, fine downy hair, violaceous striae and supraclavicular fat pads;²³ bone complications were assessed using either a history of prior pathological fractures, avascular necrosis of the femoral head or low bone mineral density (BMD), which was identified by dual x-ray absorptiometry scans when clinically indicated as a BMD Z-score of less than -2;²⁴ alopecia caused by chemotherapy that resulted in significant hair loss or thinning;²⁵ hirsutism was assessed using the modified Ferriman-Gallwey score (a score of 8 or higher is regarded as hirsutism);²⁶ gum hyperplasia was diagnosed clinically when the expanded gingival tissues cover the teeth, making it difficult to maintain good oral hygiene and allowing plaque to build up as well as a granular appearance or “cobble stones” aspect to the gingival tissues; features of overgrown gingiva included erythematous or normal coloration;²⁷ finally, severe infections including respiratory infections, peritonitis and central nervous system infections were encountered.

HRQoL was assessed with the PedsQoL 4.0 Generic Core Scales. A questionnaire that includes child self-report and parent-report. Child self-report includes ages 5–7, 8–12 and 13–18 years. Parent proxy-report includes ages 2–4 years (toddler), 5–7 years (young child), 8–12 years (child) and 13–18 years (adolescent) and assesses parent's perceptions of their child's HRQOL.⁵ It takes 4–5 minutes to administer the scale.²⁸ This instrument had 23-items that were designed to measure the core dimensions of health as delineated by the World Health Organization: (1) physical functioning (8 items), (2) emotional functioning (5 items), (3) social functioning (5 items) and (4) school functioning (5 items). The assessment of the PedsQoL includes evaluations of its reliability, responsiveness, validity and practicality in diverse paediatric groups, including those who are physically well and those affected by chronic and acute health issues. The self-reported PedsQoL data revealed a high level of internal consistency and reliability, with a coefficient approaching 0.90.^5,29,30 The scores for each dimension were consistent with the suggested methodology and were computed in the following manner: the mean score in the current study was determined by dividing the total number of items by the total number of questions answered. The raw scores were then converted into standardised scores, ranging from 0 to 100, where higher scores indicate higher levels of functioning.

Before the surveys were utilised, a user agreement was executed with the MAPI Research Institute in Lyon, France, after free registration from their website.⁵ The forward translation into Arabic of all the PedsQL corresponding versions was conducted by El-Beh et al. and its reliability and validity in Egyptian children were justified.³¹ The participants were requested to respond to the questionnaire at their scheduled routine appointments. The parent-reports included ages 8–12 and 13–18 years were administrated by one of the authors (M.W.E.A.) for all cases and controls' parents or caregivers.

The data were generated and analysed using Statistical Package for Social Sciences (SPSS) software, Version 22 (IBM Corp., Armonk, New York, USA). Patients' characteristics were expressed in percentages, means and standard deviations. To assess QoL, many measures were used, including the total score for HRQoL, as well as scores pertaining to physical, emotional, social and school functioning. These scores were reported in terms of their mean values and standard deviations. The statistical methods used in this study to investigate the associations between HRQoL and demographic/clinical variables included Chi-square analysis and t- tests. Non-parametric evaluations were used when the data did not exhibit a normal distribution. Univariate and multivariate regression analyses were used to investigate the variables that impact the QoL experienced by children diagnosed with SRNS. Forward selection was used to choose variables in multivariate regression analysis.

3. Results

A total of 160 children (40 with SRNS, 60 with SSNS and 60 healthy controls) were included in this study. The average age of the children was 10.1±2.3, 10.5±2.1 and 10.7±1.4 years for the SRNS, SSNS and healthy controls, respectively. The mean duration of NS was 31.8±16.5 and 22±14.4 months in the SRNS and SSNS groups, respectively. The clinical types of the SSNS group included 25 (41.7%) infrequent relapses, 15 (25%) frequent relapses and 20 (33.3%) steroid-dependent NS. Compared with the SSNS group, the SRNS group presented significantly greater rates of complications and medication use [Table 1].

Table 1.

Characteristics of the included children with steroid-resistant and steroid-sensitive nephrotic syndrome as well as healthy controls (N = 160).

Characteristic	SRNS (n = 40)	SSNS (n = 60)	Healthy controls (n = 60)	P value
Gender				0.91
Male	24 (60)	36 (60)	34 (56.6)
Female	16 (40)	24 (40)	26 (43.4)
Mean age at enrolment in years±SD	10.1±2.3	10.5±2.1	10.7±1.4	0.80
Mean age at diagnosis in years±SD	7.5 ±1.3	8.1±1.6	–	0.06
Mean duration of illness in months ±SD	31.8±16.5	22±14.4	–	0.02
Educational status				0.57
No education	2 (5)	4 (6.7)	8 (13.3)
Primary	26 (65)	36 (60)	28 (46.7)
Preparatory	8 (20)	14 (23.3)	16 (26.7)
Secondary	4 (10)	6 (10)	8 (13.3)
Residence				0.52
Rural	24 (60)	38 (63.3)	32 (53.3)
Urban	16 (40)	22 (36.7)	28 (46.7)
Family size				0.17
<5	22 (55)	44 (73.3)	40 (66.7)
≥5	18 (45)	16 (26.7)	20 (33.3)
Family status				0.66
Living together	22 (55)	40 (66.7)	32 (53.3)
Parents divorced	5 (12.5)	6 (10)	10 (16.7)
One parent dead	6 (15)	8 (13.3)	10 (16.7)
One parent overseas	7 (17.5)	6 (10)	8 (13.3)
Mean annual household income in Egyptian pounds × 1,000±SD	29.2 ±8.2	33 ±11.8	14.1±2.2	0.06
Mean number of hospital admissions per year ±SD	2.5 ± 0.7	1.4 ± 0.6	–	0.001
Clinical type of SSNS				–
Infrequent relapses	–	25 (41.7)	–
Frequent relapses	–	15 (25)	–
Steroid-dependent	–	20 (33.3)	–
Complication
Persistent hypertension	18 (45)	6 (10)	–	0.008
Bone complications	2 (5)	0 (0)	–	0.001
Cushingoid manifestations	8 (20)	16 (26.7)	–	0.44
Obesity	15 (37.5)	16 (26.7)	–	0.73
Hypertrichosis	10 (25)	0 (0)	–	0.001
Gum hyperplasia	4 (10)	0 (0)	–	0.001
Alopecia	4 (10)	0 (0)	–	0.001
Serious infection	4 (10)	2 (3.3)	–	0.16
Previous/current medication
Levamisole	2 (5)	16 (26.7)		0.006
Cyclosporine	26 (65)	18 (30)		0.001
Mycophenolate mofetil	22 (55)	18 (30)		0.01
Cyclophosphamide	6 (15)	8 (13.3)		0.81
CGC grade				0.86
High	26 (65)	40 (66.7)
Low	14 (35)	20 (33.3)

SRNS = steroid-resistant nephrotic syndrome; SSNS = steroid-sensitive nephrotic syndrome; SD = standard deviation; CGC = cumulative glucocorticoid.

The mean physical score was 71.6 ±10.8 for the SRNS children, 81.4 ±5.5 for the SSNS children and 87.3 ±4.6 for the healthy controls, which was significantly different (P <0.001 each). The emotional score was 61.7± 8.6 for the SRNS children, 75.8± 6.6 for the SSNS controls and 82.5± 5.1 for the healthy controls (P <0.001 each). The social score was significantly lower in the SRNS group (74.8± 6) than in both the SSNS (81.1± 6.3) and healthy control (90± 6.2) group (P <0.001 each). The mean school achievement score was 70± 5.6 in the SRNS group, 79± 6.1 in the SSNS control group, and 85.2± 4.7 in the healthy control group which was also statistically significant (P <0.001 each). Similarly, the mean total QoL score was statistically significant at 69.5± 5 in the SRNS group, 79.3± 2.9 in the SSNS group and 86.2± 3.1 in the healthy group (P <0.001) [Table 2].

Table 2.

Pediatric quality of life inventory scores of the included children.

PedsQL subscale	SRNS cases (n = 40)	SSNS controls (n = 60)	Healthy controls (n = 60)	P value	Post hoc analysis
Mean physical score ±SD	71.6 ±10.8	81.4 ±5.5	87.3 ±4.6	<0.001	P1: <0.001
(range)	(54–89)	(71–91)	(79–97)		P2: <0.001
					P3: <0.001
Mean emotional score ±SD	61.7± 8.6	75.8± 6.6	82.5± 5.1	<0.001	P1: <0.001
(range)	(49–78)	(61–89)	(73–91)		P2: <0.001
					P3: <0.001
Mean social score ±SD	74.8± 6	81.1± 6.3	90± 6.2	<0.001	P1: <0.001
(range)	(64–83)	(71–92)	(81–99)		P2: <0.001
					P3: <0.001
Mean school score ±SD	70± 5.6	79± 6.1	85.2± 4.7	<0.001	P1: <0.001
(range)	(59–82)	(71–89)	(71–91)		P2: <0.001
					P3: <0.001
Mean total score ±SD	69.5± 5	79.3± 2.9	86.2± 3.1	<0.001	P1: <0.001
(range)	(59–79)	(72.5–84.5)	(81–92)		P2: <0.001
					P3: <0.001

PedsQL = Pediatric Quality of Life Inventory; SRNS = steroid-resistant nephrotic syndrome; SSNS = steroid-sensitive nephrotic syndrome; SD = standard deviation; P1 = mean P value between SRNS and SSNS; P2 = mean P value between SRNS and control; P3 = mean P value between SSNS and control.

The comparison between SRNS and other clinical phenotypes of SSNS revealed that, compared with the FRNS, SDNS and IFRNS groups, the children with SRNS had the lowest mean scores across all domains of the PedsQL (P<0.001) [Table 3].

Table 3.

Comparison of pediatric quality of life inventory 4.0 generic core scale scores across nephrotic syndrome clinical phenotypes.

PedsQL subscale	SRNS (n = 40)	SDNS (n = 20)	FRNS (n = 15)	IFRNS (n = 25)	P value
Physical	71.6 ±10.8	80 ± 6.2*	81 ± 5.1*	84.5 ± 3.4*	<0.001
Emotional	61.7± 8.6	73 ± 6.8*†	77 ± 6.1*	79.4 ± 4.7*	<0.001
Social	74.8± 6	80.3 ± 7*	81.1 ± 6*	82.7 ± 5.2*	<0.001
School	70± 5.6	75.8 ± 4.6*†	79.9 ± 5.7*	83.8 ± 5.9*	<0.001
Total	69.5± 5	77.4 ± 2.4*†	79.6 ± 2.1*	82.6 ± 1.9*	<0.001

SRNS = steroid-resistant nephrotic syndrome; SDNS = steroid-dependent nephrotic syndrome; FRNS = frequent relapsing nephrotic syndrome; IFRNS = infrequent relapsing nephrotic syndrome.

^* Significant with SRNS.

^† Significant with IFRNS.

Regression analysis revealed that age, duration of the disease, number of hospital admissions, number of medications, high CGCs, cushingoid facies, hypertension, obesity, bone complications, gum hyperplasia, hypertrichosis and alopecia were all risk factors for low total PedsQL score (P<0.05 each). Multivariate linear regression showed a significant role for the duration of the disease and high CGCs in prediction of low QoL in SRNS children [Table 4].

Table 4.

Univariate and multivariate linear regression analysis of factors predicting total Pediatric Quality of Life Inventory scores in steroid-resistant nephrotic syndrome children.

Parameter	Standardised coefficient Beta (95% CI)	P value
Univariate linear regression analysis
Age at enrolment/year	–0.38 (–1.5–0.15)	0.01
Age at diagnosis/year	–0.16 (–1.8–0.58)	0.30
Female gender	–0.02 (–3.6–3.1)	0.85
Duration of illness	–0.52 (–0.24– –0.07)	0.001
Rural versus urban	0.06 (–2.7–4)	0.69
Family size above 5	–0.09 (–4.2–2.3)	0.56
Household income	0.05 (–0.16–0.23)	0.74
Number of hospital admissions	–0.43 (–4.9– –1.7)	<0.006
Number of medications	–0.63 (–5.6– –1.8)	<0.001
CGCs (high versus low)	–0.50 (–8.2– –2.3)	<0.001
Cushingoid facies	–0.61 (–10.9– –4.4)	<0.001
Hypertension	–0.39 (–7– –0.93)	0.01
Obesity	–0.39 (–6.3– –0.96)	0.01
Bone complications	–0.31 (–10.5–0.12)	0.04
Gum hyperplasia	–0.33 (–10.7– –0.43)	0.03
Hypertrichosis	–0.39 (–8– –1)	0.01
Alopecia	–0.33 (–10.7– –0.43)	0.03
Receiving cyclosporine	–0.18 (–5.3– –1.4)	0.25
Receiving levamisole	0.10 (–1.4–4.9)	0.29
Receiving cyclophosphamide	–0.27 (–7.9– –0.97)	0.12
Receiving mycophenolate mofetil	–0.24 (–5.6–0.72)	0.12
Multivariate linear regression analysis
Duration of illness	–0.62 (–0.34– –0.03)	0.01
CGCs (high versus low)	–0.35 (–6.7– –0.90)	0.01

CI = confidence interval; CGCs = cumulative glucocorticoids.

4. Discussion

Most research conducted on chronic illnesses in children, including NS, has focused on improving clinical outcomes and developing new treatment modalities without considering their impact on the QoL of these children. However, children's QoL may affect their compliance with treatment protocols, increase the quality of care and improve the outcome of those children.³⁰

This study's results revealed that all domains of the PedsQL (physical, emotional, social, school performance and total HRQoL scores) in SRNS were significantly lower than both the SSNS and healthy control groups. There are limited data available concerning the HRQoL in children with SRNS. To the best of the authors' knowledge, this research is the first attempt to assess the HRQoL specifically in children with SRNS rather than viewing it just as a clinical phenotype of primary NS. Furthermore, the mean scores of the PedsQL domains in the SSNS group were significantly greater than those in the SRNS group but were significantly lower than those in the healthy control group.

The poor PedsQL scores observed may be attributed to the chronic nature of NS, clinical characteristics, including severe oedema and hypertension and the use of corticosteroids and other immunosuppressive drugs as calcineurin inhibitors with its various side effects (e.g., obesity, gingival hypertrophy and hypertrichosis), in addition to frequent hospitalisations and absences from school. The lower scores, especially in the physical domain, may be attributed to obesity, which is frequent in SRNS children and may affect physical activity. Also, lower scores in the social domain might be attributed to a lack of social support in the context of integrated therapy of children with chronic illnesses in underdeveloped countries.

The decreased PedsQL scores in participants with SSNS were comparable to several studies in developed countries which showed an effect of the social domain mainly.^16,17,32 In developing countries, 2 studies showed impairments across all dimensions of the PedsQL compared to healthy children; however, the NS group had higher PedsQL scores than the non-renal chronic disease group.^18,33 The possible differences in these studies' results could be explained by differences in the selection criteria, the used questionnaires, different treatment protocols and resource availability between industrialised and poor countries.

The current study's findings concerning the impact of the steroid response on PedsQL, differed from those of Agrawal et al. and Selewski et al. who found no significant differences in QoL scores among the different clinical phenotypes of NS.^15,16 However, Eid et al. reported that the group with SRNS had worse scores in all areas than children with other clinical phenotypes of NS.¹⁸ This discrepancy may be due to the percentage of each clinical phenotype, as the SRNS children in those studies were randomly included as having INS and were not studied as a different group. The current study has the advantage of being an integrated study of SRNS.

After assessing the possible risk factors for lower values of the total PedsQL score in SRNS, univariate analysis showed that age, duration of illness, number of hospital admissions, number of medications, high CGCs, cushingoid facies, hypertension, obesity, bone complications, gum hyperplasia, hypertrichosis and alopecia may have a possible negative impact on PedsQL scores. Multivariate analysis showed that the duration of illness and high CGCs are independent risk factor for low QoL scores in SRNS children. These findings are consistent with those of previous studies that have shown a significant association between prolonged illness duration, increased recurrence rates and worse HRQoL scores in children with NS.^16,34,35 This finding also aligns with the results of Eid et al., who similarly documented the effects of steroid treatment, greater CGCs and associated complications on PedsQL scores.¹⁸ Furthermore, they showed a significant correlation between poor PedsQL scores and the administration of cyclosporine, a medication often prescribed to children with SRNS. However, Roussel et al. examined the impact of drugs utilised for NS on PedsQL scores and did not observe any significant alteration in QoL based on the specific drug administered.¹⁷

Given the strong evidence that SRNS children's QoL has decreased, attention must be directed toward improvements. Addressing the underlying causes enhances QoL, influences clinical treatment and produces better results overall. Raising awareness of the issue and implementing a thorough care plan that includes both medical and non-medical approaches are the first steps in addressing these challenges. Medical strategies including (1) ensuring the family receives the most effective evidence-based management and (2) reducing the uncertainty caused by conflicting physician opinions are very important strategies that can be implemented by medical teams while adhering to standard guidelines. Additionally, keeping a nephrotic diary and monitoring urine protein at home, being aware of possible side effects and consequences, minimising the use of steroids and having recent vaccinations is beneficial.³⁶ Non-medical approaches should include consistent exercise, interacting with peers, appropriate diet, family education, support groups, supporting school attendance or online learning and engaging in artistic hobbies.³⁶

Maintaining regular physical activity is crucial for improving QoL and needs to be promoted even in oedematous children. Children with SRNS have difficulty with moderate or strenuous activities, such as running, sports and swimming, due to their pain and tendency to become tired rapidly. Playing team sports can improve mood and foster relationships with peers.

Support groups can provide counselling that enhances psychosocial well-being. Support groups can be helpful as they allow children with SRNS and their families to interact with other children or families experiencing similar issues.³⁶ Counselling and education for families is essential to managing illness. In this chronic condition, reducing anxiety can be achieved by identifying prognostic markers such age at onset and disease severity, as well as by advising the family about long-term prognosis. The goal should be to maintain normalcy in the child's life as possible much as possible so that they don't feel like they have a physical or mental disability as they grow up.

Special schools that provide home attendance choices and online learning may reduce absenteeism. Youngsters may be encouraged to participate in artistic pastimes such as painting, drawing and crafts as well as indoor games like chess. They must be supported in order to realise their full potential and healthy parenting ought to be given first priority.³⁶

There may be an increased amount of travel required for the healthcare needs of patients with chronic diseases. Building ties between paediatric nephrologists and family physicians, teaching and sharing current NS treatment protocols and advising families to see nearby physicians for follow-up are some strategies to overcome this obstacles. Following COVID and telemedicine's legalisation as a consultation method, this approach can assist to reduce travel-time and would not only save money but also guarantee attendance at school and time for everyday activities. All of these could contribute to these childrens' improved QoL.³⁶

The current study has several strengths as it is the first study to assess QoL in children with SRNS. The design of differed in that it included 2 control groups, a healthy control group and a SSNS control group, which may lead to a better understanding of the impact of SRNS as a clinical phenotype with different pathogenesis on HRQoL. Additionally, this study investigated many demographic and clinical characteristics and complications related to the disease itself or its treatment regimen. However, this study was subject to certain limitations. One of the limitations is that this is a single-centre study which may limit the generalisability of the findings. Also, the cross-sectional nature of the study does not allow for longitudinal HRQoL evaluation over time and thus, limiting the capability to set causality. In the future, large confirmatory studies should be conducted to shed light on the role of QoL assessment in children with SRNS as well as more longitudinal studies to be able to use the results in the clinical practice. Future research directions should include testing new comprehensive care models and conducting similar studies in diverse settings to validate the current study's findings.

5. Conclusion

NS is a curable disease, but it can societally, academically, emotionally and physically affect all aspects of life. The presence of SRNS has the potential to negatively impact the QoL of children with NS across different domains of functioning. A comprehensive approach, including the collaboration of paediatric nephrologists and psychiatrists, is necessary for the effective assessment and enhancement of the QoL in children with SRNS. Furthermore, parents should be included in the proposed comprehensive approach, as they play a critical role in enhancing their children's QoL.

Authors' Contribution

Mohamed Mahgoob: Conceptualization, Methodology, Formal Analysis, Writing - Original Draft, Writing - Review & Editing. Marwa W.E. Ali: Conceptualization, Investigation, Data Curation, Formal Analysis, Writing - Original Draft, Writing - Review & Editing.

Ethics Statement

The study was performed as per the Helsinki principles and the study protocol received approval from Minia University Hospital's Institutional Review Board and Medical Ethics Committee (No: 513/2022). The research protocol was thoroughly described to the children's caregivers and a signed consent form was provided by the children's parents or authorised caregiver. Before consent was obtained, assurances were given about the confidentiality of the data and a comprehensive description of the study objectives was given.

Conflict of Interest

The authors declare no conflicts of interest.

Funding

No funding was received for this study.

Data Availability

Data is available upon reasonable request from the corresponding author.