| Abstract|| |
To determine the patterns in children with nephrotic syndrome (NS) in our region, we retrospectively studied 25 nephrotic patients evaluated and followed-up in the hospitals of the Aljouf region in Saudi Arabia. The male to female ratio was 2:1. The incidence of idiopathic NS was two to six cases per 100,000 children/year, while the prevalence was 12 cases per 100,000 children. Five patients presented with hypertension, seven (28%) with respiratory tract infection, three (12%) with tender abdomen, two (8%) with gross hematuria, one (4%) with thrombosis of renal veins with seizure and shock and the remaining seven presented to the hospital without complications. Twenty-three (92%) patients were sensitive to the first steroid course and two (8%) patients were steroid resistant, and both of them proved to have focal segmental glomerulosclerosis (FSGS) on biopsy. Of those who responded, six (24%) patients remained in remission, while 17 (68%) patients became steroid dependant. Of those who were diagnosed as steroid dependent, three patients were biopsied and one of them was diagnosed as FSGS, while the remaining two had minimal change glomerulonephritis. Regarding steroid-dependent patient relapses, seven (41%) patients showed infrequent relapses and ten (59%) patients had frequent relapses. We conclude that the patterns of NS and the response to treatment observed in this study did not differ significantly from studies from other places in the world.
|How to cite this article:|
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
|How to cite this URL:|
Alhassan A, Mohamed WZ, Alhaymed M. Patterns of childhood nephrotic syndrome in Aljouf region, Saudi Arabia. Saudi J Kidney Dis Transpl [serial online] 2013 [cited 2020 Jan 21];24:1050-4. Available from: http://www.sjkdt.org/text.asp?2013/24/5/1050/118096
| Introduction|| |
Nephrotic syndrome (NS) is a common type of kidney disease seen in children.  In the first few years of life, children with this condition often show periorbital swelling with or without generalized edema.  By far, idiopathic nephrotic syndrome (INS) is the most common type of this disease during childhood.  Minimal change nephrotic syndrome (MCNS) is the most common form of INS in children, and its prevalence is inversely proportional to the age (i.e., the younger the child, the more likely the incidence of MCNS). Racial predilection to NS may affect the incidence and prevalence of this disease in different geographical areas. ,,,,
Before the introduction of antibiotics, corticosteroids and other immunosuppressive the rapies, NS was associated with mortality as high as 67%, usually following infections. The introduction of adrenocorticotropic hormone and cortisone in the 1950s contributed to a great decrease in the mortality to 9%. 
We aimed in this study to determine the incidence and prevalence of the different patterns of NS in children of our region in Saudi Arabia and their response to therapy.
| Methods and Patients|| |
We studied children with NS diagnosed and treated from 2005 to 2010 at the Maternity and Children Hospital and Dawmat Aljandal General Hospital. All patients' parents consented for the study. All medical records of children were subjected to comprehensive data collection, with a focus on criteria required to diagnose NS, including edema, massive proteinuria (>40 mg/m 2 /hr or a urine protein/creatinine ratio >2.0 mg/mg) and hypoalbuminemia (<2.5 g/dL). ,
On presentation, medical history and clinical examination were performed to rule out secondary causes of NS. Laboratory investigations included check for proteinuria in urinalysis and 24-h urine and hematuria. In addition, we obtained the serum total protein and albumin, serum creatinine, cholesterol and serological tests for hepatitis B and C and HIV.
Patients with secondary NS, e.g. secondary to diabetes, systemic lupus or amyloid disease were excluded from the study.
Treatment plans were reviewed in all patients according to the following definitions:
- Remission was characterized by a marked reduction in proteinuria (to <4 mg/m 2 /hr or urine albumin dipstick of 0 to trace for three consecutive days) in association with resolution of edema and normalization of serum albumin to at least 3.5 g/dL. ,
- Relapse was defined as recurrence of massive proteinuria (>40 mg/m 2 /hr, urine protein/creatinine ratio >2.0 mg/mg or urine albumin dipstick >2+ on three consecutive days), most often in association with recurrence of edema. ,
- Patients who achieved remission in response to corticosteroid treatment alone were referred to as having steroid-sensitive nephrotic syndrome.
- Patients who failed to enter remission after 8 weeks of corticosteroid treatment were referred to as having steroid-resistant nephrotic syndrome (SRNS). ,,,
- Patients were labeled as steroid-dependent NS if they responded initially to corticosteroid treatment by achieving complete remission but developed a relapse either while still receiving steroids or within 2 weeks of discontinuation of treatment. 
- Patients who developed relapses four or more times in any 12-month period were referred to as having frequent relapsing nephrotic syndrome. 
| Statistical Analysis|| |
Standard descriptive statistical tests were performed as indicated using SPSS (Statistics Program for Social Sciences) version 16.0 (SPSS Inc., Chicago, IL, USA).
| Results|| |
We studied 25 children with INS, 17 (68%) male and eight (32%) female, with a mean age of onset of the disease of 6.44 ± 3.44 years (range: 2-12 years; 20 patients between 1 and 10 years and five patients aged more than 10 years, [Table 1].
|Table 1: Age and sex distribution of 25 patients with nephrotic syndrome.|
Click here to view
All patients on presentation met the diagnosis of NS by generalized edema, ascites, albumin in urine dipstick > +++, low serum albumin (mean: 1.57 g/dL) and high cholesterol (mean: 353 mg/dL). The annual incidence of INS in the Aljouf region, Saudi Arabia, was estimated as two to six cases per 100,000 children and the prevalence was estimated as 12 cases per 100,000 children.
Five (20%) patients presented with hypertension, seven (28%) with respiratory tract infection, three (12%) with tender abdomen that was diagnosed as peritonitis, two (8%) with gross hematuria and one (4%) with thrombosis of renal veins with seizure and shock. The remaining seven (28%) patients presented to the hospital without complications [Table 2] [Figure 1]. All the patients received prednisolone 2 mg/kg/day daily dose and 23 (92%) patients were sensitive to the first steroid course and two (8%) were steroid resistant; both patients underwent kidney biopsy and proved to have focal segmental glomerulosclerosis (FSGS). Of those who responded, six (24%) patients remained in remission while 17 (68%) patients became steroid dependent. Of those who were diagnosed as steroid dependent, three patients underwent kidney biopsy; one of them was diagnosed as FSGS and the remaining two were diagnosed as minimal change disease (MCGN). Seven (41%) of the steroid-dependent patients showed infrequent relapses and ten (59%) patients showed frequent relapses.
| Discussion|| |
The results of our study showed that the male to female ratio is 2.1:1 in children with INS. Other studies also disclosed a male preponderance among young children with this disease, at a male to female ratio of 1.6 to 2.76/1, ,,, although this gender disparity disappears by adolescence, making the incidence in adolescents and adults equal among males and females. ,,,
In our study, the incidence and prevalence of INS in the Aljouf region, Saudi Arabia, were comparable to those published data from most countries in the western hemisphere that estimated the annual incidence of INS to range from two to seven new cases per 100,000 children ,,, and a prevalence of about 16 cases per 100,000 children. 
In our report, the mean age of the patients at the onset of INS was 6.44 ± 3.44 years, while in the study by Kumar et al, in India, the mean age of the patients at onset of NS was 7.9 ± 5.1 years,  and it was 4.3 ± 3.1 years in other studies in Saudi Arabia. 
Hypertension was found in 20% of our patients, which is comparable to the reports from the International Study of Kidney Disease in Children (ISKDC) in young children with biopsy-confirmed MCGN. 
Systemic infection was found in 28% of our patients at presentation as respiratory tract infection and peritonitis, in contrast with the recent review by McIntyre and Craig that stated a relatively uncommon incidence of serious infection complications associated with INS. 
Gross hematuria was found in 8% of our patients, but the ISKDC stated that although gross hematuria is unusual in NS, microscopic hematuria may be seen in up to 23% of the patients with MCGN and in a higher percentage of patients with other histologic variants. 
Renal vein thrombosis was found in 4% of our patients, which was comparable to that found by other studies in children with NS, which is estimated as 1.8-5%. 
Regarding treatment of patients in our study, the initial response rate to steroids was nearly similar to that reported in the ISKDC (78.1%).  Other studies have shown a variable cortico-steroid sensitivity of 76-87%. ,,,
Significant discrepancies exist in the literature about the definition of SRNS according to doses and duration of therapy. , Although these discrepancies make direct comparison of reports of the efficacy of newer treatments for NS more difficult, the most important implication for patients who have been given the label SRNS is that they are at a significantly higher risk for development of complications of the disease as well as progression of the disease to chronic kidney disease or end-stage renal disease (ESRD). According to a report on the outcomes of 75 pediatric patients with FSGS who were followed up for nearly 5 years, 37% had persistent proteinuria, 23% progressed to chronic renal insufficiency and 21% developed ESRD. 
We conclude that the patterns of NS and the response to treatment did not differ significantly from other places in the world.
| References|| |
|1.||Arneil GC. The nephrotic syndrome. Pediatr Clin North Am 1971;18:547-59. |
|2.||Arneil GC, Lam CN. Long-term assessment of steroid therapy in childhood nephrosis. Lancet 1966;2:819-21. |
|3.||Niaudet P. Steroid-sensitive idiopathic neph-rotic syndrome. In: Avner ED, Harmon WE, Niaudet P, eds. Pediatric nephrology. 5 th ed. Philadelphia: Lippincott Williams and Wilkins; 2004. p. 545-73. |
|4.||Burgstein JM. Nephrotic syndrome. In: Behrman RE, Kliegman RM, Jenson HB, eds. Nelson Textbook of pediatrics. 18 th ed. Philadelphia: Saunders WB; 2008. p. 243. |
|5.||Churg J, Habib R, White RH. Pathology of the Nephrotic syndrome in children: A report from the International Study of Kidney Disease in Children. Lancet 1970;5:1799-802. |
|6.||Falk JR, Jennette JC, Nachman PH. Primary glomerular disease. In: Brenner BM, Levine SA, eds. The Kidney. 7 th ed. Philadelphia: Saunders WB; 2004. p. 1295-307. |
|7.||Hawkins P. Nephrotic syndrome. In: McMillan JA, Angelis CD, Feigin RD, eds. Oski pediatrics principles and practice. 3 rd ed. Philadelphia: Lippincott Williams and Wilkings; 2000. p. 1590-9 |
|8.||ISKDC: The primary nephrotic syndrome in children. Identification of patients with minimal change nephrotic syndrome from initial response to prednisone. J Pediatr 1981;98:561-4. |
|9.||Niaudet P. Steroid-resistant idiopathic nephrotic syndrome in children. In Avner ED, Harmon WE, Niaudet P, eds: Pediatric nephrology. Philadelphia: Lippincott Williams & Wilkins; 2004. |
|10.||ISKDC: Primary nephrotic syndrome in children: Clinical significances of histopathologic variants of minimal change, Kidney Int 1981; 20:765-71. |
|11.||Niaudet P, Gagnadoux MF, Broyer M. Treatment of childhood steroid-resistant idiopathic nephrotic syndrome. Adv Nephrol Necker Hosp 1998;28:43-61. |
|12.||Schulman SL, Kaiser BA, Polinsky MS, Srinivasan R, Baluarte HJ. Predicting the response to cytotoxic therapy for childhood nephrotic syndrome: Superiority of response to corticosteroid therapy over histopathologic patterns. J Pediatr 1988;113:996-1001. |
|13.||Cameron JS. The nephrotic syndrome: A historical review. In: Cameron JS, Glassock RJ, Whelton A, eds. The nephritic syndrome. Vol. 8. New York: Marcel Dekker, Inc; 1988. p. 3-56. |
|14.||Ozkaya N, Cakar N, Ekim M, Kara N, Akkok N, Yalcinkaya F. Primary nephritic syndrome during childhood in Turkey. Pediatr Int 2004; 46:436-8. |
|15.||Bircan Z, Yilmaz AY, Katar S, Yildrim M. Childhood idiopathic nephotic syndrome in turkey. Pediatr Int 2002;44:608-13. |
|16.||Madani AB. Clinicopathologic and drug response in children with idiopathic nephrotic syndrome in pediatric medical center. J Tehran Univ Med Sci 2003;1:71-9. |
|17.||Sorkhi HA. Steroid response in children with nephrotic syndrome in Amirkola hospital. J Babol Univ Med Sci 2002;3:39-42. |
|18.||Bonilla-Felix M, Parra C, Dajani T, et al. Changing patterns in the histopathology of Idiopathic nephrotic syndrome in children. Kidney Int 1999;55:1885-90. |
|19.||Kari JA. Changing trends of histopathology in childhood nephritic syndrome in western Saudi Arabia. Saudi Med J 2002;23:317-21. |
|20.||Eddy AA, Symons JM. Nephrotic syndrome in childhood. Lancet 2003;362:629-39. |
|21.||Filler G, Young E, Geier P, Carpenter B, Drukker A, Feber J. Is there really an increase in non-minimal change nephrotic syndrome in children? Am J Kidney Dis 2003;42:1107-13. |
|22.||Srivastava T, Simon SD, Alon US. High incidence of focal segmental glomerulosclerosis in nephrotic syndrome of childhood. Pediatr Nephrol 1999;13:13-8. |
|23.||Hogg RJ, Portman RJ, Milliner D, Lemley KV, Eddy A, Ingelfinger J. Evaluation and management of proteinuria and nephrotic syndrome in children: Recommendations from a pediatric nephrology panel established at the National Kidney Foundation Conference on Proteinuria, Albuminuria, Risk, Assessment, Detection, and Elimination (PARADE). Pediatrics 2000;105: 1242-9. |
|24.||Nash MA. The nephrotic syndrome. In: Edelmann CM, ed. Pediatric kidney disease, Boston, Little, Brown, and Company; 1992. |
|25.||Kumar J, Culati S, Sharma P, Sharma RK. Histopathologial spectrum of childhood nephrotic syndrome in Indian children. Pediatr Nephrol 2003;18:660-75. |
|26.||Simpson AK, Wong W, Morris MC. Pediatric nephrotic syndrome in Auckland, New Zealand. J Pediatr 1998;16:360-2. |
|27.||ISKDC: Nephrotic syndrome in children: Prediction of histopathology from clinical and laboratory characteristics at time of diagnosis. Kidney Int 1978;13:159-65. |
|28.||McIntyre P, Craig JC. Prevention of serious bacterial infection in children with nephrotic syndrome, J Paediatr Child Health 1998;34: 314-7. |
|29.||Citak A, Emre S, Sâirin A, Bilge I, Nayir A. Hemostatic problems and thromboembolic complications in nephrotic children. Pediatr Nephrol 2000;14:138-42. |
|30.||The Southwest Pediatric Nephrology Study Group. Focal segmental glomerulosclerosis in children with idiopathic nephrotic syndrome: A report of the Southwest Pediatric Nephrology Study Group. Kidney Int 1985;27:442-9. |
|31.||Asinobi AO, Gbadegesin RA, Ogunkunle OO. Increased steroid responsiveness of young children with nephrotic syndrome in Nigeria. Ann Trop Pediatr 2005;25:199-203. |
|32.||Ahmadzzadeh A, Derakhshan A. Idiopathic nephrotic syndrome in Iran. Indian Pediatr 2007;45:52-3. |
Waleed Z Mohamed
Department of Nephrology, Dawmat Aljandal General Hospital, Dawmat Aljandal
[Table 1], [Table 2]