|Year : 2017 | Volume
| Issue : 5 | Page : 1015-1020
|Outcome of childhood lupus nephritis in Saudi children
Sulaiman Mohammed Al-Mayouf1, Ali AlAmeer2, Areej Alfattani2, Abdullah Alsonbul2
1 Department of Pediatrics, Section of Rheumatology, King Faisal Specialist Hospital and Research Center; Department of Pediatrics, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
2 Department of Pediatrics, Section of Rheumatology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
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|Date of Web Publication||21-Sep-2017|
| Abstract|| |
Our aim in this study is to report the long-term renal outcome of a cohort of Saudi children with systemic lupus erythematosus (SLE). All patients with childhood lupus nephritis (cLN) proved by renal biopsy seen between January 2000 and June 2015 were reviewed. The renal outcome was assessed according to serum creatinine level, protein/creatinine ratio at the last follow-up visit, and/or evidence of renal impairment during follow-up period and end-stage renal disease (ESRD). Additional outcome measures include accrual damage measured by pediatric adaptation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (pSDI), and death related to SLE was determined. A total of 84 (72 females) cLN patients with follow-up duration of 9.3 years (±5.2) were included in this study. The mean current age was 19.4 years (±5.5) and mean age at onset was 9.2 years (±2.4). The most frequent histopathological class was proliferative glomerulonephritis (64.3%) followed by membranous nephritis (27.4%). The mean activity and chronicity indices were 5.9 (±3.9) and 2.9 (±2.2), respectively. Renal microthrombosis was found in 9 (10.7%) patients. All patients treated with immunosuppressive medications; cyclophosphamide used in 64 followed by mycophenolate mofetil in 42, then azathioprine in 19 patients, while rituximab used in 24 patients. At the last follow-up visit, the mean serum creatinine was 147 umol/L (±197) and the mean protein/ creatinine ratio was 0.8 (± 1.1) while the mean total pSDI was 1.9 (±1.9) and mean renal SDI was 0.7 (±1.1). Sixteen (19%) patients had ESRD and eight of them had class IV nephritis. However, there was no significant difference in ESRD by histological class. The overall survival rates were five years: 94% and 10 years: 87%. Infection was the leading cause of mortality. Our patients had severe cLN and required intensive treatment. Despite the survival rate is comparable to other studies, ESRD is more frequent and this may be attributed to genetic or ethnic factors.
|How to cite this article:|
Al-Mayouf SM, AlAmeer A, Alfattani A, Alsonbul A. Outcome of childhood lupus nephritis in Saudi children. Saudi J Kidney Dis Transpl 2017;28:1015-20
|How to cite this URL:|
Al-Mayouf SM, AlAmeer A, Alfattani A, Alsonbul A. Outcome of childhood lupus nephritis in Saudi children. Saudi J Kidney Dis Transpl [serial online] 2017 [cited 2019 May 23];28:1015-20. Available from: http://www.sjkdt.org/text.asp?2017/28/5/1015/215142
| Introduction|| |
Systemic lupus erythematosus (SLE) is a chronic, multisystem autoimmune disease, with a wide range of clinical and laboratory findings, depending on the severity and type of organ involvement. It predominantly affects young women in reproductive age. However, in 10%—20% of patients, the diagnosis is made for the first time in childhood.
Recent standardized disease indices suggest that children usually have more severe disease with higher rates of organ involvement at disease onset. Childhood lupus nephritis (cLN) occurs in almost 30%–60% of cases; it may present with proteinuria, hematuria, and hypertension and occasionally renal impairment. Furthermore, renal outcome has been reported in several studies that it is more frequent and aggressive compared to adult age group.,,,, Current reports showed remarkable improvement of the short-term survival and prognosis in childhood onset SLE, probably due to the implementation of new therapeutic strategies, including the early introduction of immunosuppressive drugs., Nevertheless, lupus nephritis continues to have poor outcome, especially diffuse proliferative glomerulo-nephritis, which is the most severe type and is most commonly associated with the development of end-stage renal disease (ESRD) or death.,,, Data on the renal outcome in Arab children with SLE are sparse, and to our knowledge, few cohort studies with an average follow-up periods of more than 10 years have been published.,, The aim of this study is to report the long-term renal outcome of a cohort of Saudi children with cLN.
| Materials and Methods|| |
The study cohort consisted of children with SLE who were undergoing treatment at the Lupus Clinic at King Faisal Specialist Hospital and Research Center (KFSHRC), Riyadh, Saudi Arabia, between January 2000 and June 2015. All included patients fulfilled the criteria of SLE using the Systemic Lupus International Collaborating Clinic classification criteria for SLE. In addition, they all had lupus nephritis proved by renal biopsy.
All patients were reviewed retrospectively for demographic characteristics, age at disease onset, disease duration, follow-up duration, and clinical and laboratory variables, including the renal biopsy that was reviewed by an experienced pathologist. The histopathology assessment included the class of nephritis according to the lupus nephritis classification in the International Society of Nephrology/Renal Pathology Society, activity, and chronicity indices of nephritis.
The patients were treated according to renal histopathological class and extra-renal manifestations. Patients with proliferative glome-rulonephritis received corticosteroids and hydroxychloroquine in addition to induction treatment with monthly cyclophosphamide for 6 doses, then switched to maintenance treatment either mycophenolate mofetil (MMF) or occasionally azathioprine. Patients with membranous glomerulonephritis, MMF used for induction and maintenance treatment. Rituximab was used as a second-line agent in patients who showed an inadequate response to cyclophosphamide or MMF.
Renal outcome assessed according to serum creatinine level, protein/creatinine ratio at the last follow-up visit, and/or evidence of renal impairment during follow-up period and ESRD regardless of dialysis or transplantation. These items are indicated in pediatric adaptation of Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index score (pSDI).
All collected data were analyzed under confidentiality practice, and no personal identity was revealed. All clinical and laboratory assessments were a result of routine medical care, and informed consent was taken at the time of the renal biopsy. The proposal approved by the Research Affairs Council at KFSHRC.
| Statistical Analysis|| |
SAS 9.2 (SAS Institute Inc., Cary, NC, USA) software was used for statistical analysis. The variables compared using 2-sample t-tests, Chi-square tests, and Fisher’s exact tests. The results expressed as a mean ± standard deviation for continuous variables and percentages for categorical variables. P <0.05 was considered significant.
| Results|| |
A total of 84 cLN patients with follow-up duration of 9.3 years (±5.2) were included in this study. Among 84 patients, 72 were females and the female: male ratio was 6:1. The mean current age was 19.4 years (±5.5) and mean age at onset was 9.2 years (±2.4). Seven patients were five years or younger at the onset of SLE.
Constitutional symptoms such as fever and fatigue observed frequently (80%). The most frequent clinical manifestations were mucocutaneous (78%), musculoskeletal (65%) and then neuropsychiatric features (30%). Most of the patients had hemolytic anemia, thrombocytopenia, and leukopenia appearing concurrently.
Proteinuria and hematuria (93% and 86%, respectively) were the most common findings at presentation. Nephrotic-range proteinuria was seen in 35 patients while hypertension observed in 40 patients and seven patients presented with renal impairment. The frequency of hypertension was more in the patients with proliferative glomerulonephritis while nephrotic-range proteinuria was seen in both diffuse proliferative glomerulonephritis and membranous glomerulonephritis.
The most frequent histopathological class was proliferative glomerulonephritis (64.3%) followed by membranous nephritis (27.4%). Thus, the majority of our patients presented with focal or diffuse proliferative glomerulo-nephritis.
All patients received corticosteroid for induction and maintenance treatment in addition to hydroxychloroquine. Furthermore, all patients were treated with immunosuppressive medications; cyclophosphamide used in 64 followed by MMF in 42 and then azathioprine in 19 patients while rituximab used in 24 patients. Rituximab was used as a second-line agent in patients who showed an inadequate response to cyclophosphamide or MMF [Table 1]. Treatment was guided by medical judgment of overall disease activity and severity.
At the last follow-up visit, the mean serum creatinine was 147 umol/L (±197) and the mean protein/creatinine ratio was 0.8 (±1.1) while the mean total pSDI was 1.9 (±1.9) and mean renal SDI was 0.7 (±1.1). The mean activity and chronicity were 6 (±3.9) and 4 (±2.2), respectively. Nine (10.7%) patients found to have renal microthrombosis as shown intraluminal aggregates and six of them had class IV nephritis with antiphospholipid antibody positivity [Table 1].
There were no significant differences in gender, age of onset, and duration of follow-up period among patients with different nephritis classes. Furthermore, there was no significant difference in the age, gender, and disease duration between the histopathological classes. There was a predisposition that diffuse proliferative glomerulonephritis was associated with more severe renal features. However, there was no statistical correlation. Furthermore, the age, gender, disease duration, and histopathological findings did not statistically affect the total pSDI and renal SDI. Sixteen (19%) patients progressed to ESRD and required regular dialysis. [Table 2] outlines the demographic and characteristic features and comparison of patients with and without ESRD. Although the occurrence of ESRD was more frequent in females. Yet, there was no significant difference. Patients who progressed to ESRD were followed for longer period. However, the age of onset and age at diagnosis were comparable. The spectrum of histopatho-logical findings showed class IV nephritis in eight patients, six patients had class V nephritis, and two patients had crescent sclerosis; no significant difference existed in ESRD by histopathological class. The indices of activity and chronicity were higher in patients with ESRD. Patients with ESRD received more intense treatment. However, there was no significant difference between both groups.
|Table 2: Demographic and clinical characteristic features of Saudi children with lupus nephritis.|
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Seven patients (all females) died during the follow-up period; infection was the leading cause of mortality. The overall survival rates were 94% and 87% at 5 and 10 years, respectively.
| Discussion|| |
Our study is a retrospective analysis of 84 patients with cLN proved by renal biopsy with reasonably long follow-up duration. We believe that this study is representative for cLN outcome in Saudi Arabia since our center is the main tertiary care pediatric rheumatic disease. Most of our patients were younger than 10 years of age at the disease onset, and majority of the patients were female, similar to other studies., The interval duration between the disease onset and diagnosis is not that long. The spectrum of histopathological findings was similar to previously reported cohorts; proliferative glomerulonephritis was the most common histopathological class.,, Furthermore, on renal biopsy, the activity and chronicity indices were mild to moderate. However, 10% patients found to have renal microthrombosis without significant association with anti-phospholipid antibody positivity.
We used the traditional treatment protocol for cLN; patients with proliferative glomerulo-nephritis usually treated with monthly cyclo-phosphamide as an induction treatment, then switched to MMF or occasionally azathioprine for maintenance, while for membranous glomerulonephritis, MMF is commonly used. Moreover, rituximab considered a second-line agent. We believed that our patients received intensive immunosuppressive treatment; nevertheless, 16 patients progressed to ESRD. They had longer duration follow-up and higher indices of activity and chronicity than patients without ESRD. Treatment regimens did not appear to be related to disease progression. In this study, we could not find predictive factors for renal outcome; there were no differences in age of onset and duration of follow-up period among patients with different histopatho-logical classes.
Several reports considered an early-onset disease and male gender and longer disease duration at presentation, as poor factors for severe renal disease and poor renal outcome.,, ESRD-free survival rates are variable among different cohorts. This could be attributed to more severe disease in different ethnicities.,, Although the rate of ESRD in our cohort was more frequent in females. However, the occurrence was statistically not different in both genders, and this result is inconsistent with previous findings and other studies. We did not have enough explanation for this finding. However, patients in this cohort had proved nephritis by renal biopsy while other studies might include patients without histo-pathological prove. Moreover, gender, disease duration, and therapy did not affect the proposed renal outcome parameters.
All deceased patients were females and died due to infection. In general, infection remains the most common cause of death in children with SLE. Unfortunately, in this study, we did not look for the predictive factors of mortality; nonetheless, it could be related to intensive treatment, cumulative disease activity, and damage.
Our work had limitations, including the retrospective nature of the study. Furthermore, this study did not comprise potential prognostic factors such as the initial renal function parameters, the efficacy of treatment, and calculation of renal survival.
We believe that our study is important because it is the first report of long-term outcome of cLN from Saudi Arabia. It showed that cLN is severe and required intensive immunosuppressive treatment. Despite the survival rate is comparable to other studies, ESRD is more frequent and this may be attributed to genetic or ethnic factors. Further investigations needed to clarify these issues.
Conflict of interest: None declared.
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Sulaiman Mohammed Al-Mayouf
Department of Pediatrics, Section of Rheumatology, King Faisal Specialist Hospital and Research Center, P. O. Box 3354, Riyadh 11211
[Table 1], [Table 2]
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