Urinary Beta 2-Microglobulin as a Prognostic marker in children with pyelonephritis Running title: Beta 2-Microglobulin a Prognostic marker

Urinary tract infection (UTI) is common in children. UTI with or without vesico-ureteral reflux (VUR) may result in renal scarring. Severe renal scarring impairs renal function and may result in hypertension, renal insufficiency, and end stage renal disease requiring dialyses or transplantation. Beta 2 micro-globulin (ß2MG) is a low molecular weight protein freely filtered by the glomeruli and then actively reabsorbed normally up to 99.9% in the proximal tubules; its urinary excretion is an indication of proximal tubular cell dysfunction. The current study aimed to determine whether urinary ß2MG excretion would be elevated in patients with various grades of renal scar, and also its relationship with renal outcome in long term follow-up. Urinary ß2MG and Creatinine (Cr) were measured in 83 spot urine samples of patients that 53 of them did DMSA renal scan both at the time of admission to confirm pyelonephritis, and 6 month later to detect scars. ß2MG was measured by radioimmunoassay method using ß2MG 96-test kit (RADIM Company; Germany), and the creatinine was measurd by spectrophotometry and was recorded as microgram per mg creatinine. Twenty children had various grades of renal scars.Results were compared with the ratios of 19 children with low uptake scanning, 14 children with normal scanning after recovery from pyelonephritis, and 30 normal children served as controls. EXCEL and SPSS softwares were employed to compare the mean urinary ß2MG in groups by student t-test, ANOVA, and Unpaired t-test at P,0.05 significance level. Subsequently patients were followed up for 6 years.\\r\\n The mean urinary ß2MG/Cr ratio was significantly higher in the scarring group (5.23 ± 10.6) than in the normal group (0.19 ± 0.2), and in low uptake group (0.49 ± 0.86) (P < 0.05). When mean ß2MG/Cr ratios were compared for each grade of scarring; patients with sever scar (grade III) had higher values (14.69 ± 15.82) than grades I (0.36 ± 0.35) and II (3.37 ± 5.20) (P < 0.05). Patients without renal scar had a ß2MG/Cr ratio below 0.46 microgram/mg Cr. The mean ß2MG was also higher in the refluxing group (3.45 ± 7.97) than nonrefluxing group (0.23 ± 0.24) ug/mgCr (P = 0.01). Three patients who had the highest ß2MG/Cr ratio values (33.3, 27, and 26.6 microgram/mg Cr) had sever scar that rapidly progressed to ESRD. They were transplanted 2 years later; after transplantation they still had recurrent UTIs. 2nd patient underwent native nephrectomy for renal abscess.\\r\\n Results of the current study revealed that mean ß2MG/Cr ratio was higher in patients with renal scar and poor outcome. Measurement of Urinary ß2MG may be useful in the early detection of tubular damage in refluxing patients and patients with renal scars and has prognostic significance.