Introduction:
Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterised by the involvement of multiple organ systems. 50-80% of the children affected with SLE may be at risk for developing renal complications. There is a dearth of prospective medical literature on childhood SLE nephritis, particularly from low-middle income countries (LMIC). The Indian Childhood Lupus Nephritis Registry aims to ascertain the epidemiology, clinico-pathological spectrum and treatment outcomes of the same
Methods:
This ongoing prospective multicentre registry, endorsed by the Indian Society of Pediatric Nephrology, involves 10 centres across India and was initiated in August 2020. Children aged ≤ 18 years, diagnosed with SLE as per the SLICC 2019 criteria and diagnosed with lupus nephritis (LN) by kidney biopsy, are enrolled after taking detailed informed consent. If kidney biopsy is contraindicated, subjects with suspected lupus nephritis (24-hour urinary protein ≥ 0.5 gm or UPCR ≥ 0.5 and/or active urinary sediment and/or with impairment of eGFR) are enrolled, with subsequent biopsy confirmation when feasible. Children with drug induced lupus, mixed connective tissue disorder or with parents not willing to give consent are excluded. At enrolment, basic demographic information, clinical parameters, laboratory parameters and histopathological characteristics are noted. Treating physicians are at liberty to choose treatment regime in line with standard protocol. Patients are followed up at least 1 monthly during the initiation phase and then at least 3 monthly during the maintenance phase. Renal response is assessed in terms of core renal parameters i.e. proteinuria, urinary RBC / WBC / casts and serum creatinine at defined end points of 1 month, 3 months, 6 months, 12 months, 18 months and 24 months, and categorised as complete response (CR), partial response (PR), or no response. Any adverse event like end stage renal disease, death or switch of therapy is recorded. Lupus outcome is assessed in terms of immunological parameters C3, C4 and anti-dsDNA. We are hereby presenting the renal outcome data of children who have completed 1 year of follow up.
Results:
42 children enrolled in the registry have completed 1 year follow up till now. Age - median 12 (IQR: 10-14) years. 32 females (76%) and 10 males (24%) with male: female ratio – 1: 3.2. LN was present at onset in 22 (52%) whereas 17 (40%) developed LN within the first 3 years of diagnosis. Mucocutaneous manifestations were the most common extra-renal manifestations noted. Edema (n=30, 71%) and hypertension (n=28, 67%) were the most common renal manifestations seen. Significant proteinuria was present in all, with 74% (n=31) having nephrotic range proteinuria. Median eGFR – 81(IQR:60-107) ml/m2/min. Acute Kidney Injury (AKI) noted in 24 (57%) at onset (stage 1 in 15 i.e. 62%, stage 2 in 5 i.e. 21% and stage 3 in 4 i.e. 17%; all stage 3 AKI required intermittent hemodialysis). ANA positive in 39 (93%), anti-dsDNA in 33 (79%), hypocomplementemia in 40 (95%), APLA in 7 (17%) and DCT in 20 (48%). Pure Class 4 LN was the commonest histopathological category (n=18, 43%) followed by combined class 3/ 4 and class 5 in 10 (25%). All children with proliferative LN received 3-6 pulses of methylprednisolone. Mycophenolate mofetil (MMF) was used as the first line agent in majority (n=23, 55%) and Cyclophosphamide (CYC) in 17 (40%) whereas 2 children (5%, class 2 lupus nephritis) did not receive any. Second line agent had to be used in 12 (30%) of these children (MMF in 6 i.e. 50%, Tacrolimus in 3 i.e. 25% and rituximab in 3 i.e. 25%). Disease proved refractory to first and second line agents in 3 (7%) who received MMF (n=1, 33%) or Tacrolimus (n=2, 67%). At the end of 1 year, 31 (74%) achieved complete renal response, 8 (19%) achieved partial response and 3 (7%) achieved non response. None had developed CKD stage 2 or worse at 1 year. Total of 9 children had one flare each in the first year. 2 (5%) children developed serious infections requiring hospitalisation.
Conclusions:
Our registry represents one of the very few pediatic LN cohorts from Southern Asia followed up prospectively. It reiterates the fact that timely and aggressive management helps to achieve good response rates in pediatric LN. As we continue further enrolments in the registry, we hope to come up with a larger cohort that enables better mapping of kidney and overall outcomes, and comparison of treatment modalities in children with LN in LMIC.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.