Tubular dysfunction in extremely low birth weight survivors

Background: Extremely low birth weight (ELBW) survivors may develop glomerulosclerosis due to low nephron number, whereas their tubular function remains unknown except for hypercalciuria and phosphaturia. Methods: Fifty-three subjects (30 boys and 23 girls, aged 7 months-19 years, median 36 months) were studied retrospectively. The median gestational age and birth weight were 26 weeks (range 22–32) and 745 g (range 316–999), respectively. Urine calcium-to-creatinine ratio (Ca/Cr), N-acetyl-β-d-glucosaminidase-to-creatinine ratio (NAG/Cr), β2 microglobulin-to-creatinine ratio (β2m/Cr), uric acid-to-creatinine ratio (UA/Cr), glucose-to-creatinine ratio (glu/Cr), and microalbumin-to-creatinine ratio (malb/Cr) were examined. We also assessed the association between urine parameters and current age, gestational age, birth weight, and predictors of renal injury. Follow-up data were analyzed in 43 subjects 4–6 years later. Results: Ninety percent of subjects had at least one tubular dysfunction. Frequency of elevated values was NAG/Cr 77.5%, UA/Cr 54.1%, β2m/Cr 38.2%, malb/Cr 30.4%, Ca/Cr 21.5%, and glu/Cr 20.5%. There were significant negative correlations between the current age and Ca/Cr, NAG/Cr, glu/Cr, and UA/Cr, suggesting tubular function maturation. Urine β2M/Cr and glu/Cr were negatively correlated with the gestational age. There were significant associations between elevated glu/Cr and asphyxia or neonatal acute kidney injury, and elevated NAG/Cr and indomethacin use, although these were not confirmed by multivariate analysis. At follow-up, the frequency of elevated NAG/Cr, glu/Cr, UA/Cr, and malb/Cr was reduced but that of elevated Ca/Cr, IgG/Cr, and β2m/Cr remained similar or increased. Conclusion: Tubular dysfunction is common in ELBW survivors. Some abnormalities resolved with age while some remained persistent or even increased.