Abstract
Background:
Nephrotic syndrome (NS) as a glomerular basal membrane disease has different outcomes. The current study aimed at evaluating epidemiologic status in NS and its correlation with the outcome in children.Methods:
The current hospital based study evaluated the patients of pediatric clinic at Amir-Kabir hospital. Demographic information was obtained by interviewing both the physicians and patients. Also, to determine the sesitivityto steroid drugs, children were given prednisolone (2 mg/kg/day with maximum dose of 60 mg/day) for four weeks and syndromes were determined based on children responses to the drug. Patients were divided into four groups of 25. At the end, data were transfered to SPSS program and the correlations between epidemiological information and different types of NS were investigatedResults:
Results of the current study showed that steroid responded children with frequent relapse as well as steroid dependent children had better epidemiological and socioeconomic status compared with the steroid resistance ones (P < 0.05).Conclusions:
Prognosis of NS or medication responses was related to epidemiological status of children.Keywords
1. Background
Nephrotic syndrome (NS) as glioblastoma multiforme (GBM), in medicine and urology has a set of clinical manifestations due to increased glomerular membrane permeability, which occur due to high protein excretion (1, 2). Since non-nephrotic kidney has a low urinary protein excretion (Up/Cr < 0.2 or < 4 mg/m2/hour), excretion increases and reaches more than 2.0 U PR/Cr or 40 mg/m2/hour, which leads to some clinical manifestations including edema hypoproteinemia, and lipoproteins (3, 4). In children and young adults, this is almost invariably the continuum clinical counterpart of glomerular diseases in minimal change disease (MCD) and mesangial proliferative GN (MesGN) (5).
This syndrome, based on outcome, is divided into transient, persistent, asymptomatic, symptomatic, orthostatic, and fixed in types (6, 7). Syndrome treatment, independent of the underlying renal pathology, is by continuously taking prednisone for four weeks, as the basic approach of treatment, which in approximately 90% of children with MCD and 20% - 60% of those with focal segmental glomerulosclerosis (FSGS) achieves remission (8, 9). However, after steroid tapering or withdrawal, 60% - 70% of patients relapsed and most of them required repeated prednisone courses to achieve remission. Based on the relapse rate, the patients were classified as frequently relapsing or steroid-dependent; that is patients in most urgent, effective, and safer treatment (7, 10). The current study aimed at evaluating the epidemiological factors and their correlation with nephritic syndrome outcomes including steroid-dependent, frequently relapsing, and steroid resistance.
2. Methods
2.1. Study Setting
It was as a case series study conducted in pediatric clinic of Amirkabir hospital.
2.2. Ethical Considerations
Authors completely observed ethical issues (double publication, including plagiarism, and data fabrication. (In addition, the ethical committee of Arak University of Medical Sciences approved the study protocol.
2.3. Study Population
The patients were selected by representative sampling from children < 15 years old with nephritic syndrome diagnosis. The study data were obtained from patient-physician interviews. The current study considered 100 children with NS diagnosis. To determine the drug responses, each child was given prednisolone (2 mg/kg/day with maximum dose of 60 mg/day) for four weeks; based on their responses to corticosteroids in one month, children were divided into four groups as steroid responded, steroid resistant, frequent relapse, and steroid dependent.
2.4. Statistical Analysis
Data analysis was conducted by chi-square test with SPSS at a significant level of < 0.05.
2.5. Measurements
Epidemiological and clinical information were obtained by physician-patient interviews on admission to hospital.
2.6. Inclusion and Exclusion Criteria
Age less than 15 years, consent to participate in the research project, and absence of another congenital kidney disease were considered as inclusion criteria; in addition, presence of severe liver, kidney, or cardiac diseases, and dissatisfied with personal data utilization in the current study were considered as exclusion criteria.
3. Results
Epidemiological and clinical information of children with NS are shown in Table 1. In some of the variables such as gender (P = 0.004), gestational age (P = 0.001), diabetic nephropathy (P = 0.007), prerenal azotemia (P = 0.001), allergies (P = 0.001), microscopic hematuria (P = 0.001), delivery type (P = 0.001), passive smoking (P = 0.001), child’s body mass index (BMI) (P = 0.001), and neonatal jaundice (P = 0.001) a statistically significant difference was observed among the groups (P = 0.007).
Epidemiological Information of Children with NS
| Variable | Steroid Responded | Steroid Dependent | Steroid Resistant | Frequent Relapse | P Value |
|---|---|---|---|---|---|
| Gender | 0.004 | ||||
| Male | 24 | 76 | 52 | 52 | |
| Female | 76 | 24 | 48 | 48 | |
| Gestational age | 0.001 | ||||
| Term | 78 | 40 | 26 | 20 | |
| Preterm | 12 | 48 | 72 | 80 | |
| Post-term | 12 | 12 | 0 | 0 | |
| Diabetic nephropathy | 0.007 | ||||
| Negative | 100 | 100 | 88 | 76 | |
| Positive | 0 | 0 | 12 | 24 | |
| Hematological disease | 0.387 | ||||
| Negative | 100 | 100 | 100 | 100 | |
| Positive | 0 | 0 | 0 | 0 | |
| Pre-renal azotemia | 0.001 | ||||
| Positive | 12 | 56 | 80 | 76 | |
| Negative | 88 | 44 | 20 | 24 | |
| Allergies | 0.001 | ||||
| Positive | 0 | 44 | 48 | 76 | |
| Negative | 100 | 56 | 52 | 24 | |
| UTI | 0.133 | ||||
| Positive | 24 | 36 | 36 | 56 | |
| Negative | 76 | 64 | 64 | 44 | |
| Microscopic hematuria | 0.001 | ||||
| Positive | 8 | 68 | 76 | 64 | |
| Negative | 92 | 32 | 24 | 36 | |
| Delivery type | 0.001 | ||||
| Natural | 64 | 76 | 52 | 72 | |
| Cesarean | 36 | 24 | 48 | 28 | |
| Passive smoker | 0.001 | ||||
| Positive | 12 | 40 | 72 | 4 | |
| Negative | 88 | 60 | 28 | 96 | |
| Children BMI | 0.001 | ||||
| Obesity | 4 | 20 | 52 | 16 | |
| Overweight | 20 | 28 | 20 | 44 | |
| Normal | 56 | 40 | 24 | 8 | |
| Underweight | 20 | 12 | 4 | 32 | |
| Neonatal jaundice | 0.007 | ||||
| Positive | 16 | 40 | 64 | 36 | |
| Negative | 84 | 60 | 36 | 64 |
Also, about epidemiological and clinical information of children families, indicated in Table 2, a statistically significant difference was observed among the groups in some factors including economic status (P = 0.001), mother’s BMI (P = 0.011), mother’s pregnancy age (P = 0.04), preeclampsia (P = 0.04), gestational hypertension (P = 0.001), consanguineous marriage (P = 0.001), and passive smoking of mothers (P = 0.001). The results showed a better status of the steroid responded group compared with the other groups.
Familial Epidemiological Information of Children with NS
| Variable | Steroid Responded | Steroid Dependent | Steroid Resistant | Frequent Relapse | P Value |
|---|---|---|---|---|---|
| Father’s occupation | 0.062 | ||||
| Unemployed | 4 | 0 | 8 | 16 | |
| Self-employed | 4 | 8 | 4 | 24 | |
| Worker | 16 | 28 | 36 | 24 | |
| Employee | 76 | 64 | 52 | 36 | |
| Mother’s occupation | 0.064 | ||||
| Unemployed | 20 | 28 | 16 | 12 | |
| Self-employed | 0 | 0 | 8 | 32 | |
| Worker | 16 | 12 | 32 | 12 | |
| Employee | 64 | 60 | 44 | 44 | |
| Father’s education | 0.470 | ||||
| Under diploma | 0 | 16 | 28 | 16 | |
| Diploma | 8 | 24 | 20 | 20 | |
| Associate | 20 | 8 | 4 | 8 | |
| Bachelor | 52 | 40 | 32 | 40 | |
| Master’s degree and higher | 20 | 12 | 16 | 16 | |
| Mother’s education | 0.194 | ||||
| Diploma | 28 | 32 | 28 | 28 | |
| Associate | 8 | 8 | 4 | 0 | |
| Bachelor | 44 | 36 | 32 | 36 | |
| Master’s degree and higher | 20 | 16 | 4 | 24 | |
| Economic status, US$ | 0.001 | ||||
| < 250 | 12 | 0 | 4 | 8 | |
| 250 - 500 | 0 | 24 | 28 | 12 | |
| > 500 | 88 | 76 | 68 | 80 | |
| Maternal BMI, kg/m2 | 0.011 | ||||
| Obesity | 4 | 44 | 48 | 40 | |
| Overweight | 16 | 8 | 20 | 16 | |
| Normal | 68 | 44 | 20 | 32 | |
| Underweight | 12 | 4 | 12 | 12 | |
| Maternal pregnancy age, y | 0.004 | ||||
| 18 > | 0 | 0 | 4 | 4 | |
| 18 - 24 | 44 | 4 | 4 | 12 | |
| 25 - 29 | 48 | 28 | 12 | 0 | |
| 30 - 34 | 8 | 52 | 44 | 32 | |
| 35 < | 0 | 16 | 36 | 52 | |
| Preeclampsia | 0.004 | ||||
| Positive | 4 | 4 | 52 | 52 | |
| Negative | 96 | 56 | 48 | 48 | |
| Eclampsia | 0.432 | ||||
| Positive | 12 | 0 | 4 | 4 | |
| Negative | 88 | 100 | 96 | 96 | |
| Diabetes | 0.118 | ||||
| Pre-gestational | 8 | 24 | 40 | 20 | |
| Gestational | 24 | 24 | 36 | 32 | |
| No diabetes | 68 | 52 | 24 | 48 | |
| Gestational HTN | 0.001 | ||||
| Positive | 8 | 32 | 76 | 68 | |
| Negative | 92 | 68 | 24 | 32 | |
| Chronic HTN | 0.058 | ||||
| Positive | 20 | 52 | 56 | 52 | |
| Negative | 80 | 48 | 44 | 48 | |
| Consanguineousmarriage | 0.001 | ||||
| Positive | 12 | 40 | 76 | 72 | |
| Negative | 88 | 60 | 24 | 28 | |
| Living place | 0.572 | ||||
| City | 76 | 52 | 68 | 60 | |
| Village | 24 | 48 | 32 | 40 | |
| Mother’s passive smoking | 0.001 | ||||
| Positive | 20 | 52 | 80 | 72 | |
| Negative | 80 | 48 | 20 | 28 |
4. Discussion
The current study investigated the epidemiological and clinical information of children in different types of NS outcomes.
In a study by Chanchlani et al., on ethnic differences in NS, they reported that drug responses in NS outcomes varied with ethnicity (11). In another study by Huttunen et al., on Finnish type of congenital NS, they observed slight increases in blood urea nitrogen in 14 cases and 50% death of the children before six months without frank uremia developed before death (12). A study on the epidemiology of renal failure (RF) expressed high incidence of RF at PUHC-CDG of Ouagadougou (13). Takahashi et al., conducted a study on relapse triggers in children with steroid dependency; they observed 442 relapses in 2499 patients (14). Yousefichaijan et al., observed no statistically significant correlation between children with attention deficit hyperactivity disorder (ADHD) and steroid-dependent nephrotic syndrome (SDNS), and their healthy counterparts (15), which was not investigated in the current study. Sreenivasa et al., concluded that urinary tract infections (UTIs) are a common infection, which can lead to NS (16). In Feehally et al., concluded that NS was more preponderant in children living in the Leicester city (17). Mangia et al., observed that RF was associated with a wide range of different etiologies and different levels of morbidity, and consequently influenced the outcome of disease (18). Ruggenenti et al., concluded that Rituximab reduces immunosuppression needs in steroid-dependent or frequently relapsing nephrotic syndrome (19). The current study limitation was defective epidemiologic questionnaire completion by parents; after explaining to parents about the effect of NS on kidney and other body systems they agreed to cooperate. Furthermore, it is recommended to confirm the results by further studies.
4.1. Conclusion
Steroid resistant, frequent relapsing, and steroid dependent outcomes of NS in children increased with particular distribution related to epidemiologic factors including gender, gestational age, diabetic nephropathy, prerenal azotemia, allergies, etc. Based on this epidemiological status, modification can influence and increase NS outcomes.
Acknowledgements
References
-
1.
Yousefichaijan P, Rezagholizamenjany M, Dorreh F, Shariatmadari F, Ghandi Y, Alinejad S. Serum Vitamin D Status in reflux nephropathy. Sch J App Med. 2016;4(12):4325-7.
-
2.
Teeninga N, Kist-van Holthe JE, van den Akker EL, Kersten MC, Boersma E, Krabbe HG, et al. Genetic and in vivo determinants of glucocorticoid sensitivity in relation to clinical outcome of childhood nephrotic syndrome. Kidney Int. 2014;85(6):1444-53. [PubMed ID: 24429396]. https://doi.org/10.1038/ki.2013.531.
-
3.
Buscher AK, Beck BB, Melk A, Hoefele J, Kranz B, Bamborschke D, et al. Rapid Response to Cyclosporin A and Favorable Renal Outcome in Nongenetic Versus Genetic Steroid-Resistant Nephrotic Syndrome. Clin J Am Soc Nephrol. 2016;11(2):245-53. [PubMed ID: 26668027]. [PubMed Central ID: PMC4741047]. https://doi.org/10.2215/CJN.07370715.
-
4.
Rezagholi-Zamnjany M, Yousefichaijan P. An overview on peritoneal dialysis. Ann Res Dial. 2016;1(1).
-
5.
Guitard J, Hebral AL, Fakhouri F, Joly D, Daugas E, Rivalan J, et al. Rituximab for minimal-change nephrotic syndrome in adulthood: predictive factors for response, long-term outcomes and tolerance. Nephrol Dial Transplant. 2014;29(11):2084-91. [PubMed ID: 24920841]. https://doi.org/10.1093/ndt/gfu209.
-
6.
Bazzi C, Rizza V, Casellato D, Tofik R, Berg AL, Gallieni M, et al. Fractional excretion of IgG in idiopathic membranous nephropathy with nephrotic syndrome: a predictive marker of risk and drug responsiveness. BMC Nephrol. 2014;15:74. [PubMed ID: 24886340]. [PubMed Central ID: PMC4018618]. https://doi.org/10.1186/1471-2369-15-74.
-
7.
Inaba A, Hamasaki Y, Ishikura K, Hamada R, Sakai T, Hataya H, et al. Long-term outcome of idiopathic steroid-resistant nephrotic syndrome in children. Pediatr Nephrol. 2016;31(3):425-34. [PubMed ID: 26335197]. https://doi.org/10.1007/s00467-015-3174-7.
-
8.
Lombel RM, Gipson DS, Hodson EM, Kidney Disease: Improving Global O. Treatment of steroid-sensitive nephrotic syndrome: new guidelines from KDIGO. Pediatr Nephrol. 2013;28(3):415-26. [PubMed ID: 23052651]. https://doi.org/10.1007/s00467-012-2310-x.
-
9.
Yousefichaijan P, Rezagholizamenjany M, Dorreh F, Rafiei M, Taherahmadi H, Niyakan Z, et al. Comparison of development indicators, according to ages and stages questionnaires in children with pollakiuria compared to healthy children. Nephrourol Mon. 2017;9(4). https://doi.org/10.5812/numonthly.45898.
-
10.
Kamei K, Ogura M, Sato M, Sako M, Iijima K, Ito S. Risk factors for relapse and long-term outcome in steroid-dependent nephrotic syndrome treated with rituximab. Pediatr Nephrol. 2016;31(1):89-95. [PubMed ID: 26341251]. https://doi.org/10.1007/s00467-015-3197-0.
-
11.
Chanchlani R, Parekh RS. Ethnic Differences in Childhood Nephrotic Syndrome. Front Pediatr. 2016;4:39. [PubMed ID: 27148508]. [PubMed Central ID: PMC4835686]. https://doi.org/10.3389/fped.2016.00039.
-
12.
Huttunen NP. Congenital nephrotic syndrome of Finnish type. Study of 75 patients. Arch Dis Child. 1976;51(5):344-8. [PubMed ID: 938078]. [PubMed Central ID: PMC1545982]. https://doi.org/10.1136/adc.51.5.344.
-
13.
Gérard C, Hamidou S, Evariste BB, Roger KA, Fla K, Manan HK, et al. Epidemiology of renal failure in children at the pediatric university hospital charles De-Gaulle of Ouagadougou (Burkina Faso). Open J Pediatr. 2016;6(1):141-8. https://doi.org/10.4236/ojped.2016.61021.
-
14.
Takahashi S, Wada N, Murakami H, Funaki S, Inagaki T, Harada K, et al. Triggers of relapse in steroid-dependent and frequently relapsing nephrotic syndrome. Pediatr Nephrol. 2007;22(2):232-6. [PubMed ID: 17043884]. https://doi.org/10.1007/s00467-006-0316-y.
-
15.
Yousefichaijan P, Salehi B, Rafiei M, Dahmardnezhad M, Naziri M. The correlation between attention deficit hyperactivity disorder and steroid-dependent nephrotic syndrome. Saudi J Kidney Dis Transpl. 2015;26(6):1205-9. [PubMed ID: 26586060]. https://doi.org/10.4103/1319-2442.168624.
-
16.
Sreenivasa B, Murthy CS, Raghavendra K, Basavanthappa S, Pejaver R, Jadala HV. Urinary tract infection at presentation of nephrotic syndrome: A clinical evaluation. Indian J Child Health. 2015;2(1):1-4.
-
17.
Feehally J, Kendell NP, Swift PG, Walls J. High incidence of minimal change nephrotic syndrome in Asians. Arch Dis Child. 1985;60(11):1018-20. [PubMed ID: 4073934]. [PubMed Central ID: PMC1777627]. https://doi.org/10.1136/adc.60.11.1018.
-
18.
Mangia C, Andrade M. Epidemiological aspects of kidney failure in hospitalized children in Brazil. J Nephrol Ther. 2015;6(245):2161-70.
-
19.
Ruggenenti P, Ruggiero B, Cravedi P, Vivarelli M, Massella L, Marasa M, et al. Rituximab in steroid-dependent or frequently relapsing idiopathic nephrotic syndrome. J Am Soc Nephrol. 2014;25(4):850-63. [PubMed ID: 24480824]. [PubMed Central ID: PMC3968490]. https://doi.org/10.1681/ASN.2013030251.