|Year : 2018 | Volume
| Issue : 2 | Page : 74-77
Long-term outcome of childhood steroid-sensitive nephrotic syndrome
Nada Kalakattawi1, Halimah Alghamdi2, Najlaa Alotaibi1, Khalid A Alhasan3, Jameela A Kari1
1 Department of Paediatrics, Faculty of Medicine; Department of Pediatric Nephrology Center of Excellence, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia
2 Department of Pediatric Nephrology Center of Excellence, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia
3 Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia
|Date of Web Publication||27-Dec-2018|
prof Jameela A Kari
Department of Pediatrics, Pediatric Nephrology Center of Excellence, King Abdulaziz University, P. O. Box 80215, Jeddah 21589
Kingdom of Saudi Arabia
Source of Support: None, Conflict of Interest: None
Background: The long-term outcome of childhood steroid-sensitive nephrotic syndrome (SSNS) needs further evaluation. In this study, In this study, we report the long-term outcome of childhood SSNS at our center. Patients and Methods: This is a retrospective review of cohort of children with SSNS followed by cross-sectional follow-up evaluation. We included all children aged ≥16 years with a history of childhood SSNS. Of 45 children diagnosed with SSNS and contacted for follow-up, only 9 children were available for evaluation of long-term outcome. Demographic, socioeconomic, and disease history data were collected through a questionnaire. All the patients were examined and had their urine and blood samples collected for investigations. The data were analyzed using SPSS. Results: The mean age at onset for the 45 children was 7.3 ± 3.9 years. Follow-up revealed that 65.1% had frequent relapsing or steroid-dependent nephrotic syndrome and 34.9% had infrequent relapses. Of nine patients were included in the follow-up study for a median (range) duration of 11 (5–18) years, 2 of the patients were relapsing at the time of the study and two had one or more relapses during the previous year. Estimated glomerular filtration rate (eGFR) declined in two children and the mean eGFR for the whole group was lower at the time of last follow-up than at baseline (P = 0.032). Conclusion: Children with SSNS need careful long-term monitoring of disease activity and kidney function. A larger prospective study is required.
Keywords: Pediatric, long-term, minimal change disease, focal segmental glomerulosclerosis
|How to cite this article:|
Kalakattawi N, Alghamdi H, Alotaibi N, Alhasan KA, Kari JA. Long-term outcome of childhood steroid-sensitive nephrotic syndrome. Asian J Pediatr Nephrol 2018;1:74-7
|How to cite this URL:|
Kalakattawi N, Alghamdi H, Alotaibi N, Alhasan KA, Kari JA. Long-term outcome of childhood steroid-sensitive nephrotic syndrome. Asian J Pediatr Nephrol [serial online] 2018 [cited 2019 Nov 12];1:74-7. Available from: http://www.ajpn-online.org/text.asp?2018/1/2/74/248639
| Introduction|| |
Childhood idiopathic nephrotic syndrome (NS) is chief steroid responsive.,,, However, most affected children experience relapses and a considerable percentage develops a troublesome disease course characterized by frequent relapses or steroid dependent pattern. These observations might vary among children from differing ethnic backgrounds. While steroid sensitive NS (SSNS) is more common in Asian children, relapses were reported to be more frequent among Caucasian children.
Recent long-term studies showed that the prognosis of SSNS is not as good,,,, as it was reported before. Esfahani et al. from Iran reported that more than one-third of children with SSNS experience frequent relapses, which continued to adulthood despite the combination of multiple immunosuppressive medications. This is similar to a report by Fakhouri et al. who found that more than 40% of SSNS patients experience relapses in adulthood.
The complications and outcomes of long-term SNSS remain largely unknown for patients from the middle East due to limited number of region specific studies. This is a retrospective review of cohort of children with SSNS, including cross-sectional follow-up, that evaluated the long-term outcome of these children.
| Patients and Methods|| |
Based on computerized records, we identified all children who fulfilled the following inclusion criteria: diagnosed with SSNS, born before 2001 (aged 16 or older at the time of assessment), followed up at our center and with normal kidney function at the time of SSNS diagnosis. Children with syndromic disease or congenital NS were excluded. Ethical approval was obtained from the Biomedical Ethics Research Committee of the Faculty of Medicine at King Abdulaziz University and written informed consent was obtained from the participants. The study adhered to the principles of the Declaration of Helsinki.
Forty-five children fulfilled the inclusion criteria and were contacted for reassessment; however, only nine children were available to be re-evaluated. The reasons for non-availability were various, including change of contact information or expatriates returning to their country of origin.
We prepared a structured questionnaire, which included questions regarding demographic data, age at diagnosis of SSNS, age at last relapse, age at menarche or puberty, medications received, medication adverse effects, and renal biopsy status. The data were obtained and recorded by a trained researcher.
NS was defined as urine protein excretion >40 mg/m2/hr and hypoalbuminemia (serum albumin <2.5 g/L). Remission of NS was characterized by urine protein excretion reduction to normal level, (i.e., <4 mg/m2/hr or albumin dipstick of nil for three consecutive days), edema resolution, and serum albumin level normalization. SSNS was defined as patients who exhibited remission in response to prednisolone within 4 weeks. A relapse was determined by 300 mg/dl on urine dipstick for 3 consecutive days.
Body mass index (BMI) was calculated using the equation: weight/height2 (kg/cm2). Laboratory examinations were requested, including urine analysis and blood tests for serum albumin, renal function, bone profile, parathyroid hormone, and 25-hydroxy vitamin D3 level. In addition, hand X-ray was performed to determine bone age. Estimated glomerular filtration rate (eGFR) was calculated at assessment and presentation using the modified Schwartz formula.
Data were analyzed using the IBM SPSS statistical for window (IBM Corp. Released 2012; version 21.0 Armonk, NY). Continuous data are represented as the mean ± standard deviation (SD) whereas categorical data are presented as percentages. Significance between steroid sensitivity and some variables was determined using the chi-square test for categorical data, and the t-test for continuous variables. A value of P < 0.05 was considered statistically significant.
| Results|| |
Baseline data were collected for 45 children, of which only 9 (15.6%) were available for follow-up data. Of the 45 children, 26 (57.8%) were male [Table 1]. The mean age at presentation was 7.3 ± 3.9 years (median, 6 years). [Table 1] shows various parameters at baseline, including the mean height, height SD score and eGFR. More than half of the children 26 (57.8%) were Saudi, and most were of Middle Eastern ethnicity (n = 38; 86.4%). Five children (11.4%) were from African origin, and one child (2.3%) was Asian.
|Table 1: Baseline characteristics of all (45 children) and follow-up sample (9 children)|
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Course of nephrotic syndrome
Records were available for 45 patients at baseline [Table 1]. Of these, frequent relapses or steroid-dependent NS pattern was the disease course in 30 (65.1%) patients, while 15 (34.9%) had infrequent relapses.
Only nine patients (15.5%) were available for follow-up, whereas the remaining cases (n = 38; 84.4%) were to lost to follow-up. The former were followed up for a median (range) duration of 11 (5–18) years.
Two of the nine patients who had follow-up were identified to be in relapse at the time of re-evaluation; these patients had proteinuria, with a urine albumin/creatinine ratio >300 mg/g and hypoalbuminemia of <25 g/L. Another two patients had experienced relapses within the last year, i.e., a total of four patients had active disease. The remaining five patients did not have relapse for more than 1 year at last follow up. The mean height at the time of the evaluation was 158.00 ± 9.35 cm at a median age of 18 years. The mean eGFR was significantly lower (P = 0.032) and mean serum creatinine was insignificantly higher than at baseline [Table 2]; two patients had low eGFR of 80.73 and 60 ml/min/1.73 m2. The two children with low eGFR were treated with both - cyclosporine and angiotensin-converting enzyme inhibitor.
These patients had normal serum calcium of 2.2 ± 0.14 mmol/L (2.1–2.6) and phosphate 1.1 ± 0.4 mmol/L (0.85–1.2) levels All nine children had low vitamin D level with mean ± SD of 20.1 ± 14.2 ng/ml (75–125) and low serum albumin of 30.8 ± 9.9 g/L (35–45). Seven children had no proteinuria while two children had nephrotic range proteinuria at re-evaluation. Eight of them required the use of other immunosuppression medications during their illness.
| Discussion|| |
We have observed that more than 40% of patients with SSNS had active disease at early adulthood. This is similar to previous reports of disease activity in 30%–40% of patients approaching adulthood., However, a lower proportion of relapses have been reported by other authors. Skrzypczyk et al., observed relapses in 13.5% of their patients. Fakhouri et al., observed that the activity of childhood SSNS at adulthood was associated with the age at onset, with younger age at presentation associated with a higher risk of relapse during adulthood. Similarly, severe disease and multiple relapses requiring immunosuppression during childhood were associated with a higher risk of relapse during adulthood.
The present study showed that 57.8% of the patients were boys. Similarly, other studies found a male predominance among young children with the disease., In our report, the mean age of the patients was 7.3 ± 3.9 years, which is consistent with the results of Alhassan et al., who found that the mean age of children with SSNS in the AlJouf region of Saudi Arabia was 6.4 ± 3.4 years. A study conducted in France reported onset age at 4.1 years. Previous studies have also observed that patients with early age at onset of NS were more likely to be show steroid sensitive disease course than those who develop the disease at a later age.
The increase in serum creatinine during follow up in our patients may have been confounded by increasing muscle mass with age. However, eGFR in children with SSNS is expected to be normal at presentation and stay stable during follow-up. Two children in our study had eGFR below normal, which could be due to prolonged use of cyclosporine.
Height SD score was much lower at re-evaluation compared with the value at presentation. The difference did not reach significance, possibly because of small number of children studied. Reduced height velocity could be explained by excessive use of steroids in those children. The low 25-hydroxy vitamin D level in all nine patients, with a median of 17 ng/mL (mean ± SD, 20.1 ± 14.2 ng/mL), is consistent with regional findings.,
There are several limitations in our study, including small number of studied children at a single center and a high rate of attrition, which may have resulted in selective reporting of patients at with severe disease during follow up. We have evaluated only kidney function and disease activity of NS, but did not look at immunosuppression related side effects such as bone health, cataract, fertility and psycho-social parameters such as educational, employment, and marital status.
| Conclusion|| |
Long-term follow-up is recommended in children with SSNS. Larger studies with prolonged follow up and low attrition rates are needed to investigate the long-term effects of SSNS on renal function and disease activity.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Dossier C, Lapidus N, Bayer F, Sellier-Leclerc AL, Boyer O, de Pontual L, et al.
Epidemiology of idiopathic nephrotic syndrome in children: Endemic or epidemic? Pediatr Nephrol 2016;31:2299-308.
Ladapo TA, Esezobor CI, Lesi FE. High steroid sensitivity among children with nephrotic syndrome in South Western Nigeria. Int J Nephrol 2014;2014:350640.
Alhassan A, Mohamed WZ, Alhaymed M. Patterns of childhood nephrotic syndrome in Aljouf region, Saudi Arabia. Saudi J Kidney Dis Transpl 2013;24:1050-4.
] [Full text]
Alharthi AA. Patterns of childhood steroid-sensitive and steroid-resistant nephrotic syndrome in Saudi children. Clin Pediatr (Phila) 2017;56:177-83.
Hahn D, Hodson EM, Willis NS, Craig JC. Corticosteroid therapy for nephrotic syndrome in children. Cochrane Database Syst Rev 2015;3:CD001533. doi:10.1002/14651858.CD001533.pub5.
Banh TH, Hussain-Shamsy N, Patel V, Vasilevska-Ristovska J, Borges K, Sibbald C, et al.
Ethnic differences in incidence and outcomes of childhood nephrotic syndrome. Clin J Am Soc Nephrol 2016;11:1760-8.
Esfahani ST, Madani A, Asgharian F, Ataei N, Roohi A, Moghtaderi M, et al.
Clinical course and outcome of children with steroid-sensitive nephrotic syndrome. Pediatr Nephrol 2011;26:1089-93.
Fakhouri F, Bocquet N, Taupin P, Presne C, Gagnadoux MF, Landais P, et al.
Steroid-sensitive nephrotic syndrome: From childhood to adulthood. Am J Kidney Dis 2003;41:550-7.
Kyrieleis HA, Löwik MM, Pronk I, Cruysberg HR, Kremer JA, Oyen WJ, et al.
Long-term outcome of biopsy-proven, frequently relapsing minimal-change nephrotic syndrome in children. Clin J Am Soc Nephrol 2009;4:1593-600.
Ishikura K, Yoshikawa N, Nakazato H, Sasaki S, Nakanishi K, Matsuyama T, et al.
Morbidity in children with frequently relapsing nephrosis: 10-year follow-up of a randomized controlled trial. Pediatr Nephrol 2015;30:459-68.
Skrzypczyk P, Panczyk-Tomaszewska M, Roszkowska-Blaim M, Wawer Z, Bienias B, Zajgzkowska M, et al.
Long-term outcomes in idiopathic nephrotic syndrome: From childhood to adulthood. Clin Nephrol 2014;81:166-73.
Trompeter RS, Lloyd BW, Hicks J, White RH, Cameron JS. Long-term outcome for children with minimal-change nephrotic syndrome. Lancet 1985;1:368-70.
Mian AN, Schwartz GJ. Measurement and estimation of glomerular filtration rate in children. Adv Chronic Kidney Dis 2017;24:348-56.
Downie ML, Gallibois C, Parekh RS, Noone DG. Nephrotic syndrome in infants and children: Pathophysiology and management. Paediatr Int Child Health 2017;37:248-58.
Gulati S, Sural S, Sharma RK, Gupta A, Gupta RK. Spectrum of adolescent-onset nephrotic syndrome in Indian children. Pediatr Nephrol 2001;16:1045-8.
Alsaidi S, Wagner D, Grisaru S, Midgley J, Hamiwka L, Wade A, et al.
Glomerular filtration rate trends during follow-up in children with steroid-sensitive nephrotic syndrome. Can J Kidney Health Dis 2017;4:2054358117709496. doi: 10.1177/2054358117709496.
Ribeiro D, Zawadynski S, Pittet LF, Chevalley T, Girardin E, Parvex P, et al.
Effect of glucocorticoids on growth and bone mineral density in children with nephrotic syndrome. Eur J Pediatr 2015;174:911-7.
Chakhtoura M, Rahme M, Chamoun N, El-Hajj Fuleihan G. Vitamin D in the Middle East and North Africa. Bone Rep 2018;8:135-46.
Mansour MM, Alhadidi KM. Vitamin D deficiency in children living in Jeddah, Saudi Arabia. Indian J Endocrinol Metab 2012;16:263-9.
[Table 1], [Table 2]