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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
ORIGINAL ARTICLE  
Year : 2018  |  Volume : 29  |  Issue : 4  |  Page : 816-821
Pediatric focal segmental glomerulosclerosis in Jordan: A tertiary hospital experience


1 Department of Pediatric Nephrology, Queen Rania Abdulla Children Hospital, Amman, Jordan
2 Department of Pediatric Nephrology, School of Medicine, University of Jordan, Amman, Jordan
3 Department of Nephrology, King Hussein Medical Center, Amman, Jordan

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Date of Submission04-Aug-2017
Date of Decision19-Sep-2017
Date of Acceptance19-Sep-2017
Date of Web Publication28-Aug-2018
 

   Abstract 

Our objective is to study the demographical data, clinical course and outcome of children with primary focal segmental glomerulosclerosis (FSGS) in Jordan. A retrospective chart review of patients with a diagnosis of FSGS at a tertiary care hospital from the period July 2010 to July 2016 was conducted. A total of 99 patients were analyzed. The mean age of presentation was 3.71 ± 2.59 years, 66% were male. At presentation, 66.6% of patients were steroid-resistant, 10% had a steroid dependant course and 20.2% had familial FSGS. Cyclosporine was used in 66.6% of children with a response rate of 46.9%. Long-term follow-up showed complete remission in 29.3%, partial remission in 31.3%, end-stage renal disease in 22.2%, and death in 11.1%. There is a high prevalence of familial FSGS in our Jordanian cohort with a high rate of progression to end-stage kidney disease.

How to cite this article:
Almardini RI, Albaramki JH, Al-Saliata GM, Farah MQ, AlRabadi KH, Albderat JT. Pediatric focal segmental glomerulosclerosis in Jordan: A tertiary hospital experience. Saudi J Kidney Dis Transpl 2018;29:816-21

How to cite this URL:
Almardini RI, Albaramki JH, Al-Saliata GM, Farah MQ, AlRabadi KH, Albderat JT. Pediatric focal segmental glomerulosclerosis in Jordan: A tertiary hospital experience. Saudi J Kidney Dis Transpl [serial online] 2018 [cited 2020 Jul 11];29:816-21. Available from: http://www.sjkdt.org/text.asp?2018/29/4/816/239655

   Introduction Top


Focal segmental glomerulosclerosis (FSGS) is a clinical-pathological entity characterized by steroid resistant nephrotic syndrome (SRNS) and segmental sclerosis involving some but not all the glomeruli.[1] It accounts for 7%-20% of cases of idiopathic nephrotic syndrome in the pediatric age group[2],[3] and is frequently associated with hematuria and hypertension, although in early stages it is indistinguishable from minimal change disease (MCD).

Primary FSGS can present at any age. Children over six year have a higher incidence than younger children.[3] The incidence of FSGS is rising worldwide.[4] In Canada, they reported an incidence of 0.37–0.94 new cases per 100,000 children per year.[5] Published data from our hospital showed that 23% of biopsied children and 41.1% of biopsied nephrotic children have FSGS.[6] A study from another hospital in Jordan showed a similar trend with 21% of biopsied children having FSGS.[7]

FSGS is usually steroid resistant, however 15%–20% of FSGS patients initially respond to steroids.[8] It is a clinical condition with a highly variable outcome; 50% reaching end stage kidney disease by the age of 15.[9],[10] In a multicenter study from Jordan; FSGS was the most common glomerulonephritis leading to end-stage renal disease (ESRD) in children as it was responsible for 10.2% of all cases of ESRD.[11]

There are no previous published reports describing the clinical features of FSGS in Jordan. This retrospective cohort was done to analyze the clinical characteristics, treatment and outcome of FSGS over a six-year period.


   Methods Top


This retrospective non-interventional descriptive study was conducted by reviewing medical charts of children with the diagnosis of FSGS at Queen Rania Hospital over a six year period extending from July 2010 to July 2016. Queen Rania Hospital is a tertiary referral center with 200-bed capacity. It receives children from all parts of Jordan and from nearby countries. Data collected included current age, gender, age of presentation, duration of follow-up, steroid responsiveness, the indication and the number of kidney biopsies, treatment modalities, family history, and the outcome. The results of kidney biopsies by light microscopy were reviewed. Secondary causes of FSGS were excluded from the study.

The indications for kidney biopsy were: SRNS, steroid dependent nephrotic syndrome prior to cytotoxic therapy, late steroid resistance and as follow-up after two years of calcineurins inhibitor treatment for patients with previous diagnosis of MCD. The standard definitions of the disease and the response to treatment were used as per the KDIGO 2012 guidelines.[12] The definition used to assess clinical course were as follows:

  1. SRNS was defined as failure of achieving remission after eight weeks of steroid therapy. Steroid dependence was defined as relapses during steroid tapering or within two weeks of stopping steroid. Remission was defined by achieving clinical response and urinary protein/creatinine ratio (uPCR) <0.2 mg/dL or nil protein on urine dipstick for three consecutive days.
  2. Partial remission was defined by clinical improvement with proteinuria reduction of 50% or greater of the presenting value and an absolute uPCR between 0.20 and 2.00 mg/mg.
  3. Non-responders were those who failed to reduce urine protein excretion by 50% from baseline or had persistent PCR >2 mg/mg.


The estimated glomerular filtration rate (eGFR) was calculated using the Schwartz formula.[13] The definition of chronic kidney disease was a persistent GFR <60 mL/min/1.73 m2. ESRD was defined as eGFR <10 mL/ min/1/73 m2.

The standard protocol for treatment was prednisolone at a dosage of 60 mg/m2/day for four to six weeks. In case of remission the dose was reduced to 40 mg/m2/day every other day for another four weeks and then gradually tapered over three to six months.

In the steroid resistant group, kidney biopsies were taken after six to eight weeks of predni-solone to establish the histological diagnosis and as a baseline before starting a second line of therapy.

Cyclosporine was the most common second line of therapy used at a dosage of 3-5 mg/kg/day in two divided doses to keep a target trough level between (100–150 ng/dL) for a period of two years in those who responded. Cyclosporine therapy was continued for six months and stopped in those who failed to show partial or complete response.

Patients who failed to respond to both steroid and cyclosporine were maintained on conservative treatment as diuretics and angiotensin converting enzyme inhibitors. Other second lines of therapy were used in a few cases as; pulse methylprednisolone at a dosage of 30 mg/kg/day for three doses; tacrolimus at a dosage of 0.1 mg/kg/day in two divided doses, mycophenloate mofetil at a dosage of 1200 mg/m2/day in two divided doses.

The study was approved by the research and ethical committee of the hospital.


   Results Top


A total of 99 patients were included in the study, 60 % (n = 60) were males, 39% (n = 39) were females, with a male to female ratio of 1.8:1. Mean current age was 8.11 ± 4.26 years with the age range between one and 18 year. Mean age at presentation was 3.71 ± 2.59 years with a range of two months and 14 years. Thirteen patients presented under the age of one year. The youngest age was two months. 61.6% presented between two and five years.

At presentation, 66.6% (n = 66) of patients were steroid resistant and were started on a second line of therapy [Table 1]. Twenty patients (20.2%) were not started on steroid due to the presence of a positive family history in siblings or cousins and were labeled as familial FSGS and were placed on supportive measures as diuretics and angiotensin converting enzyme inhibitors. Ten percent (n = 10) had a steroid dependent clinical course, two were initially steroid dependent but changed to late steroid resistance, one presented as rapidly progressive glomerulonephritis that received kidney transplantation but unfortunately had recurrence of FSGS after transplant.
Table 1: The initial response to steroid.

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Response and type of second line treatment are shown in [Table 2]. Cyclosporine was the most commonly used second line therapy in 66 (66.6%) of children. 31 (46.9%) responded and achieved complete remission, Seven (10.6%) had a partial response. Twenty-eight (42.4%) were resistant.
Table 2: Patients treated with second line treatment.

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Four patients received pulse methylpredni-solone after eight weeks of prednisolone; all of them failed to show a response, so cyclos-porine was started as a third line of therapy and they responded to it.

Four patients who were referred from other hospitals were already started on tacrolimus as a second line; two of them were resistant for they turned to have familial FSGS since they had another sibling with the same condition, one responded and the other had a partial response.

Myocphenloate mofetil was used as a second line of therapy in six patients whose initial biopsy showed MCD and when repeated it showed FSGS. All failed to respond to mycophenolate while they responded well to cyclosporine.

One of the patients developed mild cyclospo-rine toxicity in the form of mild arteriolar hyalinosis, so cyclosporine was stopped and he was maintained on prednisolone. He developed a relapse with severe generalized edema, pericardial effusion and intravascular volume depletion leading to acute renal failure. He was treated conservatively by extensive hemodialysis (HD) and albumin infusions, his acute renal failure resolved and then he was recommenced on cyclosporine again and after six weeks went into remission taking the benefit of cyclosporine in inducing remission over the risk of having severe nephrotic syndrome and renal failure.

Mean duration of follow-up was 4.35 ± 2.80 years, range (6 months–12 years), 37.4% were followed for more than five years.

30.3% of our cohort (n = 30) progressed to ESRD of whom eight died, 11 were on HD, three were on peritoneal dialysis and eight had a living related donor transplant. Recurrence after transplant occurred in one patient [Table 3].
Table 3: The outcome at the end of the cohort.

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Long-term follow-up of our cohort of patients showed death in 11.1% (n = 11); complete remission in 29.3% (n = 29); partial remission with normal kidney function test in 31.3% (n = 31); ESRD in 22.2% (n = 22); chronic kidney disease in 3% (n = 4) and two lost follow-up [Table 3].

Regarding kidney function status at death: six died while on dialysis due to dialysis related complications, one died one year after transplant with a lymphoproliferative disease with normal kidney function test, one had chronic kidney disease, one had ESRD and two died with normal kidney function.

After reviewing kidney biopsies, 67.6% (n = 67) had FSGS on initial biopsy, six patients had MCD on initial biopsy, and because of their clinical course a second biopsy was done and showed FSGS. Fourteen patients had a history of similar cases in the family and for that reason they did not have a biopsy.


   Discussion Top


This is the first retrospective cohort of children with FSGS in Jordan over a six-year period with 37.4% of this cohort being followed for more than five years. Previous studies of FSGS in children have been performed worldwide and most of them had excluded children who were less than one year and those with a family history of glomerulo-nephritis[14] but in this cohort those were included as 13% of our children presented below the age of one year. In our cohort, we had a high prevalence of familial FSGS (20.2%) which is attributed to the high rate of consanguinity among the Jordanian population. Our hospital data showed that 41% of biopsied nephrotic and 53.3% of SRNS children had FSGS which is higher than that found in other Arabic countries. Bakr et al showed that 16.2% of 741 biopsied nephrotic Egyptian children had FSGS.[15] Surveys from North America and the United Kingdom have reported biopsy proven FSGS in 15%–20% of nephrotic syndrome.[16] This difference in prevalence can be explained by difference of indications for renal biopsy in some studies, small sample size and the variation in the prevalence of familial FSGS in some Arabic countries.

The mean age of presentation in our children was 3.71 years which is younger than other studies from Egypt and Turkey that reported a mean age of 6–7 years at baseline.[14],[17] This younger age of presentation can be explained by the high prevalence of familial cases of FSGS. In our study, there was a predominance of male patients (60%) as observed in other studies.[14],[17],[18]

In our cohort, SRNS was the most common clinical presentation of FSGS as in the Egyptian study done by El-Refaey et al,[14] while SDNS was the common clinical presentation in a cohort from Pakistan.[19]

In our current study, 29.3% achieved complete remission at last follow-up and partial remission was achieved in 31.3%. El-Refaey et al[14] reported in his 72 cohort of Egyptian children that only 16.7% achieved complete remission while 47.2% had partial remission, whereas a study from the Turkish pediatric nephrology FSGS study group of 148 patients reported complete remission in 33.8%.[20]

Data from previous cohort studies of FSGS in children have shown that the outcome is variable and the frequency of end-stage renal[17],[20],[21] disease ranges widely from 25% to 50%[17],[20],[21] after 15 years of follow-up. In our study, 30% of the patients progressed to end stage renal disease which is comparable to the study from Turkish pediatric nephrology group.[20]

The study had several limitations, as being a retrospective study and the lack of genetic testing in children with familial FSGS. However, most of our patients were managed with the same medical protocol and by the same medical team. Future multicenter studies with a larger number of patients and a longer duration of follow-up are needed.


   Conclusion Top


This is the first report of pediatric FSGS in Jordan. FSGS in our population presents at an early age with most of our children being steroid resistant. Cyclosporine was the most commonly used therapy with a favorable response of 46.9%. There was a high rate of progression to end stage renal disease and a high rate of familial FSGS due to the high rate of consanguinity in the Jordanian population.

Conflict of interest: None declared.

 
   References Top

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Hadidi R, Hadidi M, alDabbas M. Spectrum of biopsy-proven kidney disease in children at a Jordanian hospital. Saudi J Kidney Dis Transpl 2014;25:680-3.  Back to cited text no. 7
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Zagury A, Oliveira AL, Montalvão JA, et al. Steroid-resistant idiopathic nephrotic syndrome in children: Long-term follow-up and risk factors for end-stage renal disease. J Bras Nefrol 2013;35:191-9.  Back to cited text no. 9
    
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Akl KF, Albaramki JH, Hazza I, et al. Aetiology of paediatric end-stage renal failure in Jordan: A multicentre study. West Indian Med J 2015;65:263-6.  Back to cited text no. 11
    
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Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. KDIGO clinical practice guideline for glome-rulonephritis. Kidney Int Suppl 2012;2:139-274.  Back to cited text no. 12
    
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Schwartz GJ, Haycock GB, Edelmann CM Jr., Spitzer A. A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 1976; 58:259-63.  Back to cited text no. 13
    
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El-Refaey AM, Bakr A, Hammad A, et al. Primary focal segmental glomerulosclerosis in Egyptian children: A 10-year single-centre experience. Pediatr Nephrol 2010;25:1369-73.  Back to cited text no. 14
    
15.
Bakr A, Eid R, Sarhan A, et al. Pathological profile of biopsied Egyptian children with primary nephrotic syndrome: 15-year single center experience. J Nephrol 2014;27:419-23.  Back to cited text no. 15
    
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Hogg R, Middleton J, Vehaskari VM. Focal segmental glomerulosclerosis – Epidemiology aspects in children and adults. Pediatr Nephrol 2007;22:183-6.  Back to cited text no. 16
    
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Sozeri B, Mir S, Mutlubas F, Sen S. The long-term results of pediatric patients with primary focal and segmental glomerulosclerosis. Saudi J Kidney Dis Transpl 2010;21:87-92.  Back to cited text no. 17
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Abrantes MM, Cardoso LS, Lima EM, et al. Clinical course of 110 children and adolescents with primary focal segmental glomerulosclerosis. Pediatr Nephrol 2006;21:482-9.  Back to cited text no. 18
    
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Lanewala A, Mubarak M, Kazi JI, et al. A clinicopathologic study of primary focal segmental glomerulosclerosis in children. Saudi J Kidney Dis Transpl 2012;23:513-20.  Back to cited text no. 19
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20.
Beşbaş N, Ozaltin F, Emre S, et al. Clinical course of primary focal segmental glomerulo-sclerosis (FSGS) in Turkish children: A report from the Turkish pediatric nephrology FSGS study group. Turk J Pediatr 2010;52:255-61.  Back to cited text no. 20
    
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Paik KH, Lee BH, Cho HY, et al. Primary focal segmental glomerular sclerosis in children: Clinical course and prognosis. Pediatr Nephrol 2007;22:389-95.  Back to cited text no. 21
    

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Correspondence Address:
Dr. Jumana H Albaramki
Department of Pediatric Nephrology, School of Medicine, Jordan University, P. O. Box 1459, Amman 11821
Jordan
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DOI: 10.4103/1319-2442.239655

PMID: 30152417

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