DOI 10.1002/art.22362 Evaluation of renal improvement in juvenile systemic lupus erythematosus: Comment on the articles by Ruperto et al To the Editors: We read with great interest the 2 recent articles by The Pediatric Rheumatology International Trials Organization (PRINTO) and the American College of Rheumatology (ACR) on the provisional criteria for the evaluation of response to therapy in juvenile systemic lupus erythema- tosus (SLE) (1,2). These consensus statements with pro- spective evaluation of clinical progress are important in developing good models of care for affected children and in defining the prognosis of these children according to response to treatment. We were pleased to see that renal involvement was one of the 5 final domains included in this core set, due to its high incidence, increased severity, and major influence of prognosis in children (3,4). However, we are not in agree- ment with the definition of renal involvement of children and adolescents diagnosed with SLE. The suggested vari- able for evaluation of renal involvement was proteinuria as defined by a 24-hour urine specimen collection. Pediatric nephrology practices vary around the world, but 24-hour urine specimen collections are often techni- cally difficult to obtain and can be unreliable, especially in younger children. Therefore, instead we advocate moni- toring with early morning spot urine specimen albumin: creatinine ratios or protein:creatinine ratios (5). In addition, validating improvement in lupus nephritis by measuring proteinuria may be inaccurate because it may represent active or chronic disease. Significant pro- teinuria in active disease is largely alleviated by the use of immunosuppressive agents. We would also normally use an angiotensin-converting enzyme inhibitor and/or angio- tensin II type 1 receptor blocker to reduce proteinuria in children with SLE. Therefore, these therapeutic interven- tions render proteinuria a less reliable disease marker. Hypoalbuminemia may reflect inflammation and nutrition status as well as the degree of proteinuria. However, mon- itoring serum albumin levels may assist in determining improvements in children with nephrotic syndrome as part of their lupus nephritis. Proteinuria is only one of the important measurements of improvement of renal function; the others are blood pressure, and estimated or measured glomerular filtration rate (GFR). It has not been clearly shown which of these parameters or variables is the best measurement of im- provement of renal disease. Therefore, we feel that addi- tional information on improvement should include hyper- tension (defined by blood pressure above the 95th percentile for age, sex, and height percentile) (6). Many children with active lupus nephritis are hypertensive and will improve with treatment of their nephritis. However, blood pressure is similar to proteinuria, in that the variable is confounded by the treatment itself (i.e., antihyperten- sive medications). A normal serum creatinine level was defined as 0.6 –1.2 mg/dl (53–106 mol/liter) in the additional measures of the final core set. We believe that this is not acceptable because the serum creatinine value always needs to be related to the size of the child and his or her muscle mass. Serum creatinine levels in the higher range listed above are unlikely to be normal, even in an adolescent girl with SLE. Instead, a more accurate marker of renal function would be to estimate the GFR using creatinine clearance or Schwartz formula (7) or formally evaluate the GFR (e.g., using 51 Cr-labeled EDTA or iohexol) in those patients whose estimated GFR was 80 ml/minute/1.73m 2 . In summary, outcome studies of children with SLE and lupus nephritis should include core data on not only the degree of proteinuria, but also renal function and blood pressure. We believe the present criteria are insufficient to evaluate improvement of renal involvement of SLE. Stephen D. Marks, MBChB, MRCP, FRCPCH Kjell Tullus, MD, PhD, FRCPCH Great Ormond Street Hospital for Children NHS Trust London, UK 1. Ruperto N, Ravelli A, Oliveira S, Alessio M, Mihaylova D, Pasic S, et al, the Pediatric Rheumatology International Trials Organization (PRINTO), and the Pediatric Rheumatology Col- laborative Study Group (PRCSG). The Pediatric Rheumatology International Trials Organization/American College of Rheu- matology provisional criteria for the evaluation of response to therapy in juvenile systemic lupus erythematosus: prospective validation of the definition of improvement. Arthritis Rheum 2006;55:355– 63. 2. Ruperto N, Ravelli A, Cuttica R, Espada G, Ozen S, Porras O, et al, the Pediatric Rheumatology International Trials Organiza- tion (PRINTO), and the Pediatric Rheumatology Collaborative Study Group (PRCSG). The Pediatric Rheumatology Interna- tional Trials Organization criteria for the evaluation of re- sponse to therapy in juvenile systemic lupus erythematosus: prospective validation of the disease activity core set. Arthritis Rheum 2005;52:2854 – 64. 3. Font J, Cervera R, Espinosa G, Pallares L, Ramos-Casals M, Jimenez S, et al. Systemic lupus erythematosus (SLE) in childhood: analysis of clinical and immunological findings in 34 patients and comparison with SLE characteristics in adults. Ann Rheum Dis 1998;57:456 –9. 4. Tucker LB, Menon S, Schaller JG, Isenberg DA. Adult- and childhood-onset systemic lupus erythematosus: a comparison of onset, clinical features, serology, and outcome. Br J Rheu- matol 1995;34:866 –72. 5. Morales JV, Weber R, Wagner MB, Barros EJ. Is morning uri- nary protein/creatinine ratio a reliable estimator of 24-hour proteinuria in patients with glomerulonephritis and different levels of renal function? J Nephrol 2004;17:666 –72. 6. National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 2004;114(2 Suppl 4):555–76. Arthritis & Rheumatism (Arthritis Care & Research) Vol. 55, No. 6, December 15, 2006, pp 990 –993 © 2006, American College of Rheumatology LETTERS 990