| Abstract|| |
Systemic lupus erythematosus (SLE) is a multi-system disease of autoimmune origin. The relative incidences of the various manifestations in children with SLE are significantly different from adults and among different age-groups of children. To analyze the characteristics of childhood lupus nephritis (LN), we prospectively followed-up 23 cases of pediatric LN, diagnosed over a period of five years, in the pediatric rheumatology clinic at the Institute of Post Graduate Medical Education and Research, Kolkata, India. The resultant database was analyzed using standard statistical methods. Of all childhood lupus cases treated in our clinic over the last five years (n = 42), 54.7% (n = 23) had renal involvement. This study has tried to delineate the disease trends of childhood lupus from Eastern India. Certain important trends have emerged that are different from other contemporary Indian and International observations.
|How to cite this article:|
Nandi M, Mondal R. Renal involvement in childhood lupus: A study from Kolkata, India. Saudi J Kidney Dis Transpl 2012;23:871-5
|How to cite this URL:|
Nandi M, Mondal R. Renal involvement in childhood lupus: A study from Kolkata, India. Saudi J Kidney Dis Transpl [serial online] 2012 [cited 2020 May 29];23:871-5. Available from: http://www.sjkdt.org/text.asp?2012/23/4/871/98194
| Introduction|| |
Systemic lupus erythematosus (SLE) is a classic prototype of a multi-system disease of immunological origin with autoantibodies, polyclonal B-cell activation and T-cell dysfunction. The ensuing immune complexes are deposited or formed in situ in many organs and affect commonly the kidney as lupus nephritis (LN). Histological evidence of LN is present in most patients with SLE, even if they do not have clinical manifestations of renal disease.
The symptoms are generally related to hypertension, proteinuria and/or renal failure. In children, LN is often more severe than in adults. , Although there are a few reports on childhood SLE from a developing country like India, ,, none have exclusively studied the renal manifestations of childhood SLE. The aim of this study was to prospectively document the spectrum of LN in children, on presentation and, thereafter, on follow-up. This is the first such follow-up study from this part of the world where the health personnel may have to work under many constraints, and it may sometimes not be possible to provide optimum care.
| Aims and Objectives|| |
The study was conducted at the Pediatric Rheumatology Clinic, Department of Pediatrics, Institute of Post-Graduate Medical Education and Research, Kolkata, a tertiary care university hospital. It was a prospective observational study with plans for studying the spectrum of LN during acute presentation and thereafter, during follow-up of patients over a period of five years.
| Patients and Methods|| |
Patients We prospectively followed-up 23 patients of pediatric lupus with renal manifestations over a period of five years from August 2004 to July 2009 in the Pediatric Rheumatology Clinic. Children up to 12 years of age attend the pediatric rheumatology clinic as per the hospital protocol. Appropriate consent from the care-givers of the patients and the approval of the ethics committee were taken. The ACR case definition  was used for diagnosis of SLE. Clinical and laboratory features at the time of presentation were recorded.
LN was diagnosed in patients of SLE on the basis of presence of hypertension, nephritis/ nephrotic syndrome, abnormal urinalysis or raised serum creatinine for age. Baseline data on the age, sex, clinical features and investigation results were recorded at presentation and then at subsequent follow-up visits.
Hypertension was defined as systolic and/or diastolic blood pressure above the 95 th percentile for gender, age and height centile according to the recommendation of the fourth US Task Force on hypertension. 
Urinalysis was considered abnormal if it contained >5 red blood cells per high-power field of centrifuged specimen, urine protein >1+ and/or presence of red cell casts. Nephrotic range proteinuria was considered in patients showing excretion of >40 mg/m 2 /h protein or urine protein to creatinine ratio >3.0 or +++/++++ proteinuria in random sample. Early morning urine was tested by dipstick (Albustix®).
Serum creatinine more than twice the upper limit for age and gender was considered significant. Creatinine was measured by the Jaffe method-CREA (Roche 911) analyzer®.
Patients with LN were given treatment according to the standard protocol depending on the WHO histopathological class  or on the suggestive clinical manifestations when biopsy was not possible.
All patients were treated symptomatically in addition to specific immunosuppressives depending on the class of LN. Patients with class I disease were not given any specific treatment for LN. Their treatment regimen was dictated by extra-renal manifestations of the disease. Patients with class II LN who had proteinuria <1 g/day and normal renal function were also not given any specific treatment. Those with proteinuria >1 g/day were treated with oral prednisolone at an initial dose of 2 mg/kg/day (maximum 80 mg/day), which was tapered over the next three to four months to a maintenance dose of 0.5-0.75 mg/kg on alternate days for a minimum of three years or more. Patients with WHO class III or IV LN were treated with cyclophosphamide as infusion at a dose of 750-1000 mg/m 2 monthly for six months and every three months thereafter for the next 24 months. Patients with class V LN received prednisolone along with cyclosporine (3-6 mg/kg/day). Those with Class VI were not given immunosuppresives. They were given supportive care and renal replacement therapy as and when required. Wherever possible, various activity and chronicity indices were also taken into account while taking a decision regarding treatment options.
Outcome was recorded as either complete remission (clinical and laboratory parameters), active disease, death or lost to follow-up.
| Statistical Analysis|| |
Data have been presented as mean for numerical variables and percentages for categorical variables. Key proportions have been expressed with 95% confidence interval (CI) values. Categorical variables have been compared between sub-groups by the Fisher-Exact test. Two-tailed P <0.05 has been considered statistically significant.
| Results|| |
Out of a total of 42 patients with SLE, 54.7% had clinical renal involvement (n = 23) [95% CI (37.28-67.48)]. Twenty-one had renal manifestations at initial presentation and two patients developed LN during follow-up in our clinic. There were 16 female and seven male patients (F:M = 2.3:1). Interestingly, clinical renal involvement was more frequent in boys (78%) than in girls (46%).
Regarding age, the youngest patient was a five-year old girl. Most of the patients were above eight years old. The mean age at diagnosis of LN was 9.6 years (range 5-11.2 years). The most frequent clinical presentations were hematuria (n = 17), proteinuria in nephrotic range (n = 8), oliguria (n = 12) and hypertension (n = 4) [Table 1].
|Table 1: Various clinical and laboratory evidences of renal involvement in patients with lupus.|
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Twenty-one out of the 23 patients tested positive for anti-nuclear antibody (ANA). Anti-dsDNA was positive in 82.6% of patients with lupus and renal manifestations. On the other hand, it was positive in only 57.1% of those who had lupus but no renal manifestation. (P = 0.081). Sixteen out of 23 (69%) had low C3 levels at presentation [95% CI (48.72-87.64%)].
Renal biopsy could be performed in 13 patients with LN. The most common histopathological diagnosis was class II (n = 8), followed by class III (n = 3), IV (n = 1) and V (n = 1). The break-up of clinical manifestations in those who underwent biopsy is shown in [Table 2]. Repeat biopsy was indicated in two patients. One of them showed change in class of LN from V to IV. The patient ultimately expired from complications of renal failure and uremia. The mean duration of follow-up of the study patients was 3.6 ± 1.6 years. Over this period, eight (34.7%) achieved complete remission, eight (34.7%) continued to have active disease and seven patients died (30.4%). The cause of death included renal failure (n = 3), disseminated intravascular coagulation (n = 1), infections (n = 2) and hypertensive congestive cardiac failure (n = 1).
|Table 2: Clinical renal manifestations according to histopathological class.|
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| Discussion|| |
In our study, renal involvement in SLE was found in 54.7% of the patients. Other Indian series have shown renal involvement in 56.2- 77.1% of their patients. ,, A study from Saudi Arabia showed renal involvement in 65% of their patients with SLE.  In Iran, this figure was 69%.  In a large Chinese series involving 137 children with SLE, LN was present in 56.2% of the cases  [Table 3].
|Table 3: Comparison of different series on patients with lupus with renal involvement.|
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Renal manifestations were more common and more severe in boys than in girls. This fact has also been reflected in other Indian and international series. ,, The mean age at diagnosis of LN (9.6 years) tallies with other Indian series. ,, The youngest patient was five years old. Other studies have also found that LN is rare in children less than five years of age. 
Hematuria and proteinuria were common clinical presentations of LN. Another Indian series from Vellore has also noted similar clinical involvement.  Because we could perform biopsy in only 13 of the 23 patients, it was not possible to arrive at a statistically significant correlation between the biopsy features and clinical manifestations. Renal biopsy could not be performed in the remaining ten patients because their guardians did not give consent or could not afford the expenses. Among the 13 patients who were biopsied, class II was the most common variety, a finding similar to previous reports. ,, However, a few other studies observed predominantly class III or IV LN. , One previous study on LN in Indian children found that class IV was the most common, followed by class II and class III.  Sorof et al  have shown that class II was the most common renal lesion in SLE, followed by class V. Hobbs et al  and Baqi et al  have shown class IV to be the most common lesion [Table 4]. Hypocomplementemia and positivity of anti-ds DNA, besides being helpful as diagnostic aids, were more frequently associated with presence of renal involvement, although the correlation was not statistically significant.
|Table 4: Comparison of different series of biopsy-proven lupus nephritis.|
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This is supported by international observations published before. 
The mortality rate in our series was 30.4% after a mean follow-up of 3.6 years, which is higher than other series reported from India.  Most of the patients who died were referred late with advanced disease in a critical state, either having established renal failure or overwhelming infections. However, during the past 20 years, new therapeutic approaches, including the use of cytotoxic agents and better management of infections, have improved renal survival rates, which have reached 80% at ten years in the best of centers. ,
Our study does have some limitations, and the results should be interpreted in light of these. The diagnostic and therapeutic modalities offered to these children may not have been optimum due to various constraints. Renal biopsy could not be carried out in all the patients.
We intend to keep these patients on follow-up for longer duration, up to adulthood if possible, which might help us in addressing the issues of possibilities peculiar to children, such as drug side-effects of growth inhibition, fertility issues and the impact of the disease and treatment on intellectual and emotional development.
Our study attempts to delineate the spectrum of LN for the first time from Eastern India where the diagnostic and therapeutic options may not always be optimum due to various constraints. Early diagnosis and aggressive treatment may improve the outcome significantly. We need more well-designed prospective studies with adequate numbers of patients with LN to come to more statistically significant conclusions regarding diagnostic and treatment options from this part of the world.
| References|| |
|1.||Al Salloum AA. Lupus nephritis in childhood. Saudi J Kidney Dis Transpl 2003;14:43-56. |
|2.||Cassidy JT, Petty RE. Systemic Lupus Erythematosus. In Textbook of Pediatric Rheumatology, 4 th ed. Philadelphia: W.B Saunders Company; 2001. p.396-449. |
|3.||Singh S, Kumar L, Khetarpal R, et al .Clinical and immunological profile of SLE: Some unusual features. Indian Pediatr 1997;34:979-86. |
|4.||Ali US, Dalvi RB, Merchant RH, et al. Sytemic lupus Erythematosus in Indian children. Indian Pediatr 1989;26:868-73. |
|5.||Agarwal I, Kumar TS, Rajini K, Kirubakaran C, Danda D. Clinical Features and outcome of Systemic Lupus Erythematosus. Indian Pediatr 2009;46:711-5. |
|6.||National High Blood Pressure Education Programme. The fourth report on the diagnosis, evaluation and treatment of high blood pressure in children and adolescents. Pediatrics (2004)114(Suppl):555-76. |
|7.||Weening JJ, D'Agati VD, Schwartz MM, et al. The classification of glomerulonephritis in systemic lupus erythematosis revisited. Am Soc Nephrol 2004;15:241-50. |
|8.||Bahabri S, Sabban EA, Al Rashed A, et al. Juvenile systemic lupus erythematosus in 60 Saudi children; Ann Saudi Med 1997;17:612-5. |
|9.||Ataei N, Haydarpour M, Madani A, et al Outcome of lupus nephritis in Iranian children: Prognostic significance of certain features. Pediatr Nephrol 2008;23:749-55. |
|10.||Chen JH, Lin CY, Chen WP, Tang RB, Hwang B. Systemic lupus erythematosus in children. Zhonghua Min Guo Wei Sheng Wu Ji Mian Yi Xue Za Zhi. Chinese journal of microbiology an immunology 1987;20:23-8. |
|11.||McCurdy DK, Lehman TJ, Bernstein B, et al. Lupus nephritis: prognostic factors in children. Pediatrics 1992;89:240-6. |
|12.||Emre S, Bilge I, Sirin A, et al. Lupus nephritis in children: prognostic significance of clinico-pathological findings. Nephron 2001;87:118-26. |
|13.||Hari P, Bagga A, Mahajan P, Dinda A. Outcome of lupus nephritis in Indian children Lupus 2009; 18:348-54. |
|14.||Sorof JM, Perez MD, Brewer ED, Hawkins EP, Warren RW. Increasing incidence of childhood class V lupus nephritis. J Rheumatol 1998;25:1413-8. |
|15.||Hobbs DJ, Barletta GM, Rajpal JS, Rajpal MN, Weismantel DP, Birminggham JD, Bunchman TE. Severe paediatric systemic lupus erythematosus nephritis-a single-centre experience. Nephrol Dial Transplant 2010;25:457-63. |
|16.||Baqi N, Moazami S, Singh A, Ahmad H, Balachandra S, Tejani A. Lupus nephritis in children: A longitudinal study of prognostic factors and therapy. J Am Soc Nephrol 1996;7:924-9. |
Pediatric Rheumatology Clinic, Department of Pediatrics, Institute of Post Graduate Medical Education and Research, Kolkata
[Table 1], [Table 2], [Table 3], [Table 4]