Severe paediatric systemic lupus erythematosus nephritis—a single-centre experience

David J. Hobbs 2 3 Gina-Marie Barletta 2 3 Jurat S. Rajpal 1 3 Miriam N. Rajpal 1 3 David P. Weismantel 0 3 James D. Birmingham 3 4 Timothy E. Bunchman 2 3 0 Department of Family Medicine, Michigan State University College of Human Medicine , East Lansing, MI 1 Pediatric Resident Physicians, University of Minnesota , Minneapolis, MN 2 Pediatric Nephrology, Helen DeVos Children's Hospital and Michigan State University College of Human Medicine , Grand Rapids, MI 3 Severe paediatric SLE nephritis 4 Pediatric Rheumatology, Helen DeVos Children's Hospital , Grand Rapids, MI, USA Background. Paediatric patients with systemic lupus erythematosus (SLE) often have severe presentations including lupus nephritis (LN). Few paediatric studies have evaluated the anticardiolipin antibody (aCL) and renal histology. The purpose of this study was to evaluate clinicopathologic features, including aCL, short-term clinical and renal histologic outcomes of paediatric patients with new-onset SLE nephritis. Methods. We conducted a single centre, retrospective inception cohort study. Charts were reviewed at presentation (initial renal biopsy), 6-month (follow-up biopsy) and 12month follow-up. Results. The population consisted of 21 patients (median age, 14.5 years): 19/21 were female, 6/21 African American, 3/21 Asian, 9/21 Caucasian and 3/21 Hispanic. At presentation, 19/21 had elevated aCL, 15/21 hypertensive, 12/21 nephrotic and 7/21 required haemodialysis (HD)2/7 HD patients had thrombotic microangiopathy, - Received for publication: 3.3.09; Accepted in revised form: 1.9.09 1/7 crescentic glomerulonephritis. Two patients had thromboembolism: both had aCL, were taking oral contraceptives and required HD, one was nephrotic and the other had elevated lupus anticoagulant. Initial biopsies revealed 6/21 ISN/RPS class II nephritis, 3/21 class III, 7/21 class IV and 5/21 class V. Treatment consisted of methylprednisolone, corticosteroids, cyclophosphamide or mycophenolate mofetil. Follow-up biopsies revealed 12/13 to have improved histology. Indication for a follow-up biopsy was severe illness at presentation. At 12-month follow-up, no patients were nephrotic (P < 0.001) or required HD (P < 0.001), and 3/14 had elevated aCL (P < 0.001). Conclusion. Elevated aCL, hypertension, nephrotic syndrome and need for HD were common presentations among our paediatric SLE nephritis population. Renal histology and aCL were helpful in the therapeutic management. Introduction Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease with multiorgan involvement. Paediatric patients with SLE often have severe disease presentations including renal involvement, which ranges from asymptomatic urinary findings to acute renal failure [14]. Lupus nephritis (LN) remains one of the most important factors influencing therapeutic management and long-term prognosis [58]. An early renal biopsy and, perhaps, follow-up renal biopsy are therefore essential to aid in the management of this difficult to treat the paediatric population [9]. SLE is characterized by the appearance of autoantibodies well before the clinical onset of symptoms [10,11]. The presence of anticardiolipin (aCL) antibodies at disease presentation negatively impacts renal outcomes and is predictive of a more severe disease course [1113]. Paediatric patients with SLE and antiphospholipid antibodies, primarily lupus anticoagulants (LAC) and elevated aCL antibody, are also at risk of developing thromboembolic events [1418]. This is of particular concern in paediatrics since children with SLE exhibit a higher prevalence of aCL antibody than adults [3]. Screening of aCL antibody in paediatric patients may therefore serve to identify paediatric patients at risk for poor renal outcomes, severe disease course and thromboembolism. Since the inception of our paediatric nephrology program, we have routinely performed renal biopsies on paediatric patients presenting with SLE and evidence of LN. A follow-up renal biopsy is commonly performed on patients after 6 months of treatment to assess for therapeutic management. We routinely obtain laboratory studies, including aCL antibody, initial and follow-up renal biopsies, which has been reported in few paediatric studies. The purpose of this study was to evaluate the clinicopathologic features, including aCL antibody, as well as short-term clinical and renal histologic outcomes of paediatric patients with newonset SLE nephritis. Subjects and methods We conducted a single centre, retrospective inception cohort study of paediatric patients diagnosed with SLE and biopsy-proven LN at Helen DeVos Childrens Hospital from September 2003 to September 2008. This study was approved by the Spectrum Health Institutional Review Board. For inclusion into the study, subjects were required to meet four or more of the American College of Rheumatology (ACR) classification criteria for SLE [19,20], and have histological evidence of LN by a renal biopsy at disease presentation. Hypertension was defined as three or more diastolic or systolic blood pressures greater than or equal to the 95th percentile for age, gender, and height or the use of antihypertensive therapy [21]. Nephrotic Syndrome was defined as (1) 40 mg/m2/h of urinary protein or protein-to-creatinine ratio >3.0 on a random urine sample, (2) hypoalbuminaemia with serum albumin <2.5 g/dl, and (3) peripheral oedema. We did not include (4) hypercholesterolaemia in the definition of nephrotic syndrome due to lack of data. Charts were reviewed at disease presentationat the time of the initial renal biopsy and prior to treatment with cyclophosphamide (CYP) or mycophenolate mofetil (MMF), at the time of the repeat renal biopsyduring 6-month follow-up, and at 12-month follow-up. The following data were obtained: demographic data [age, gender, race/ethnicity], clinical data [nephrotic syndrome, hypertension, need for haemodialysis, thromboembolism, use of oral contraceptive pills (OCPs)], laboratory data [aCL antibody, double stranded DNA (dsDNA) antibody, lupus anticoagulant, C3, C4, serum creatinine, haemoglobin, platelet count, and white blood count], and renal histology evaluated according to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification [22]. C3 and C4 were measured by rate nephelometry in a Beckman Immage rate nephelometer (Beckman Coulter, Inc.; normal >80 mg/dl and >15 mg/dl, respectively). Anti-dsDNA antibodies were detected by ELISA (Varelisa, Pharmacia Diagnostics; normal <34 IU/ml). The presence of lupus anticoagulant was measured using a modified dilute Russell viper venom test (dRVVT) (Siemens, formerly Dade Behringer; normal value <45 s, normal ratio <1.2). Anticardiolipin antibodies were detected using the commercially available Varelisa Cardiolipin Antibody Screen test (Pharmacia Diagnostics, Freiburg, Germany). The assay is adjusted to internationally recognized standard sera established by Harris et al. and det (...truncated)