Outcome of lupus nephritis in childhood onset SLE in North and Central India: single-centre experience over 25 years.

INTRODUCTION: Childhood SLE (cSLE) has a higher prevalence of lupus nephritis (LN), and there are ethnic variations in response to treatment as well as outcome of LN. There are limited data on long-term outcome of LN in cSLE from the Indian subcontinent. METHODS: Retrospective analysis of case records of patients with cSLE (satisfying revised American College of Rheumatology (ACR) 1997 criteria for diagnosis) and age of onset <18 years was conducted from 1989 to 2013. Data on clinical features, renal involvement and biopsy findings, treatment, renal outcome, damage accrual and mortality were collected. End-stage renal disease (ESRD) was defined as the need for renal replacement therapy. Actuarial ESRD-free survival was studied as the primary outcome measure using Kaplan-Meier analysis. RESULTS: Among 205 children with cSLE, 134 (121 girls) had evidence of LN. The mean age at disease onset was 13.7 ± 3.5 years and the mean disease duration at presentation was 1.9 ± 2.5 years. Kidney biopsy was available for 92 patients, and histology included: 13 (14.2%) Class II, 24 (26%) Class III, 43 (46.7%) Class IV and 12 (13.1%) Class V LN. The mean follow-up period was 6.75 ± 5.7 years. At last visit, 81 (60.4%) children were in complete remission, 28 (20.9%) were in partial remission, 15 (11.2%) still had active nephritis and 10 (7.4%) had progressed to ESRD. Almost two-thirds (62.9%) of patients experienced lupus flares, and mean flare rate was 0.09 flares/patient follow-up year. Fifty-six (43.8%) children accrued damage and the mean Systemic Lupus International Collaborating Clinics (SLICC)/ACR damage score was 0.79 ± 1.13. Actuarial ESRD-free survival at five, 10 and 15 years was 91.1%, 79% and 76.2%, and five-, 10- and 15-year renal survival was 93.8%, 87.1% and 84%, respectively. Although multiple factors individually predicted poor outcome (death/ESRD), only raised serum creatinine at onset (R square = 0.65, p ≤ 0.0001) and damage accrual (R square = 0.62, p ≤ 0.0001) remained significant on multivariate analysis. Eleven (8.2%) children died during the follow-up period, and infections were the leading cause of mortality. CONCLUSIONS: Long-term outcome of LN in cSLE in our cohort was better than previous reports from India. However, a high rate of major infection still remains the leading cause of mortality.

Optic nerve involvement in childhood onset systemic lupus erythematosus: Three cases and a review of the literature.

The ocular system can be affected in systemic lupus erythematosus (SLE) in one third of patients. However, optic nerve involvement is relatively uncommon, but is more so in pediatric SLE patients, where it can occur in 1% of cases. We report three children with SLE who presented with optic nerve involvement. Two children had optic neuritis, with optic neuritis being the first manifestation in one child. The third child had ischaemic optic neuropathy secondary to antiphospholipid syndrome. A careful work up for SLE should be performed in every child with optic nerve disease. Prompt diagnosis and early treatment results in a better prognosis.

Childhood lupus nephritis in a developing country-24 years' single-center experience from North India.

OBJECTIVE: Data on outcome of childhood lupus nephritis from developing countries are sparse. This study looks at outcome in children with lupus nephritis from a federal government-funded teaching hospital in North India. METHODS: This study included children less than 14 years of age with lupus nephritis who presented to a single center during a period of 24 years (1991 to 2013). Data on clinical characteristics and outcome were extracted from medical records. The primary outcome was actuarial survival (time-to-death) and secondary outcome was actuarial renal survival using Kaplan-Meier analysis. A worst-case scenario that assumed children who were lost to follow-up as having either died or gone into end-stage renal disease was also calculated. Log-rank test and Cox-regression were used to assess difference in survival by histological class and predictors of poor outcome, respectively. RESULTS: This study included 72 children, with a female:male ratio of 3:1, mean (±SD) age at onset of lupus 9.3 (±2.4) years and mean (±SD) time from onset-to-nephritis being 9.4 (±12.6) months. Renal biopsy was conducted in 53 children. The most common histological class was class IV (35 children). Mortality occurred in 22 children (30%), with half of these occurring at presentation. The two important causes of death were infection and end-stage renal disease. Actuarial survival was 81%, 67% and 59% at one, five and 10 years, respectively. In the worst-case scenario, actuarial survival was 72%, 53% and 38%, respectively. Renal survival was 96%, 89% and 78% (worst-case scenario 86%, 73% and 52%) at one, five and 10 years, respectively. There was no difference in survival by histological class. On univariate analysis, serum creatinine at presentation (hazard ratio = 2.2 (95% CI 1.3-3.9)) and serious infection (hazard ratio 7.9 (95% CI 2.6-23.5)) were statistically significant predictors of time-to-death. CONCLUSION: Outcome of children with lupus nephritis from India is worse than developed countries. Nearly one-third of the children died, half at presentation, with common causes being infection and end-stage renal disease.

Urinary CXCL-10/IP-10 and MCP-1 as markers to assess activity of lupus nephritis.

OBJECTIVE: IP-10 and MCP-1 are pro-inflammatory chemokines which are involved in the immunopathogenesis of lupus nephritis and may thus be useful biomarkers. METHODS: SLE patients fulfilling ACR 1997 criteria were included. SLEDAI was calculated and blood and urine samples collected. Active lupus was defined as SLEDAI ≥4. Active patients were divided into active renal (proteinuria ≥ 500 mg/day or active sediment in urine) and active non-renal lupus. Patients with active renal lupus were followed until the nephritis became inactive, when a second sample was collected. Serum and urinary levels of MCP-1 and IP-10 (pg/ml) were measured by ELISA. Urinary values were normalized for urinary spot creatinine (in mg/dL. Thus the values were expressed as pg/mg creatinine × 100 creatinine). RESULTS: A total of 136 patients with SLE including 78 active (46 active renal and 32 active non-renal) were included. Median age was 25 (10-55) years and SLE duration was 23 (six to 48) months. Both serum (data not shown) and urinary levels of MCP-1 (35.2 (12.7-71.7), 9.4 (4.4-17), p < 0.001) and IP-10 (9.5 (4.4-17.9), 3.9 (1.9-9.3), p < 0.001) were higher in active compared to inactive SLE. However, in active renal compared to active non-renal SLE, there was no difference in serum levels; only urinary levels of MCP-1 (46.2 (19.9-125), 12.7 (5.8-43.9), p < 0.001) and IP-10 (12.5 (5.6-22.7), 5.2 (2.3-12.2), p < 0.05) were higher. On longitudinal follow-up of active renal patients (n = 24), there was a decrease in urinary levels of MCP-1 and IP-10 (p = 0.005). On ROC analysis, urinary MCP-1 outperformed C4 and urinary IP-10, but was similar to dsDNA and C3 in differentiating active renal from non-renal SLE. CONCLUSIONS: Urinary and serum IP-10 and MCP-1 are potentially useful markers of lupus activity; however, only the urinary levels are indicative of renal activity. However, on ROC analysis, they are not better than conventional markers.