J. S. McLeod1,4, J. T. Church1,2, M. A. Coughlin1,5, E. M. Perkins2, R. H. Bartlett2, R. Rabah3, G. B. Mychaliska1 1University Of Michigan,Department Of Pediatric Surgery,Ann Arbor, MI, USA 2University Of Michigan,Department Of General Surgery,Ann Arbor, MI, USA 3University Of Michigan,Department Of Pediatric And Perinatal Pathology,Ann Arbor, MI, USA 4Detroit Medical Center,Michael And Marian Ilitch Department Of Surgery,Detroit, MI, USA 5Henry Ford Health System,Department Of General Surgery,Detroid, MI, USA
Introduction:
Neonates born <28 weeks gestational age (GA) have exceptionally high morbidity and mortality. A novel approach would be to recreate the intrauterine environment with an artificial placenta (AP), utilizing venovenous extracorporeal life support (VV-ECLS) and avoiding ventilation. The effect of the AP on renal perfusion and development is unknown. The aim of this study was to evaluate renal injury following AP support, and to identify clinical and laboratory predictors of injury during AP support.
Methods:
Extremely premature lambs at 110-120 days GA (term=145; n=11) were delivered and placed on AP support, with jugular venous drainage and umbilical vein reinfusion. The lungs remained fluid-filled. The lambs received parenteral nutrition and voided spontaneously. Support was continued for a goal of 7 days. A subset of lambs (n=5) were transitioned to mechanical ventilation after 10-12 days of AP support. Creatinine (Cr) and blood urea nitrogen (BUN) were checked daily, normalized to birth weight, and the highest value over the last 3 days of life were used in statistical analysis. The renal injury score was based on evaluation of the following histologic findings: tubular dilation, tubular vacuolation, tubular nuclear apoptosis, epithelial necrosis, interstitial hemorrhage, edema and inflammation, tubular casts, and glomerular necrosis. Individual scores ranged from 0-4 based on % involvement of the field (0- No injury; 1- Injury to 25% of field; 2- Injury to 50% of the field; 3- Injury to 75% of the field; 4- Diffuse Injury). Means were compared using t-test. Correlation was evaluated using linear regression. P<0.05 was considered significant.
Results:
Survival was 6 – 14 days. Three of 11 lambs (27%) became anuric during AP support. Renal injury scores for all lambs ranged from 1-21 with a mean of 8.8. Anuric lambs demonstrated higher renal injury scores than non-anuric lambs, although this did not reach statistical significance (12.3±4.5 vs. 7.5±6.5; p=0.22). Anuric lambs also exhibited significantly higher BUN/kg in the last 3 days of life (22.1±5.4 vs. 9.2±6.6; p=0.03); this same significant difference was not seen with Cr/kg (0.76±0.6 vs. 0.27±0.29; p=0.29). BUN/kg correlated with renal injury score (p=0.02) while Cr/kg did not (p=0.20).
Conclusion:
Extremely premature lambs supported with the AP are vulnerable to renal failure. These data suggest BUN/kg may predict renal failure from both a clinical and histopathologic standpoint, while Cr/kg was not predictive. Future studies will aim to identify factors contributing to renal failure in AP supported premature lambs.
