This study investigated the contribution of high SCr levels (reflecting abnormal renal function) in VLBW infants to the development of ROP requiring treatment during the first month of life. The incidence of ROP requiring treatment was higher in the high SCr group than in the normal SCr group.
Previous studies have reported the possibility of shared genetic, physiologic, and pathologic pathways between the kidney and eye.11,12 It is known that retinal vascularization and nephrogenesis are most active at the end of the second trimester and the beginning of the third trimester, and maturity end at term GA.13,14 Further, several studies have reported a local renin-angiotensin-aldosterone system in the retina, which affected the development of retinal diseases such as ROP.12 However, the relationship between abnormal renal function and ROP has not been elucidated due to the difficulty in diagnosing abnormal renal function in premature infants.
SCr, but not renal injury, is commonly used as a surrogate marker of renal function. The current definition of acute kidney injury (AKI) is based on the changes in SCr and/or urine volume. However, in clinical practice, it is difficult to accurately measure urine output and non-oliguric AKI has been reported in newborns.15 In addition, this definition of AKI was not based on changes in physiological SCr during the early life of a newborn, especially preterm infants.6,16,17 The change in SCr in early life is likely to include a combination of physiological and pathological components. Therefore, the normal range of Cr over time in stable VLBW infants without the risk factors affecting renal function was important to determine early SCr changes and their clinical utility to establish a diagnostic threshold for AKI. A recent study reported relative physiological changes in Cr levels of VLBW infants.7
In our study, the high SCr group was classified based on the 95th percentile value of SCr after 5 days of age for each GA. The SCr level of the neonate for at least 72 h after birth was known to reflect the maternal SCr level.18 Auron and Mhanna 19 reported that SCr reached a plateau on day 5 after birth in VLBW infants. Bateman et al.7 reported that preterm infants of 25–27 weeks’ GA also presented a transient peak of SCr on days 2 to 3 after birth. Thereafter, the SCr levels in all groups of infants decreased gradually for 6 to 8 weeks.
The high SCr group showed significantly lower GA, BW, and SCr at birth than the normal SCr group. In the present study, we demonstrated that the lower SCr level at birth in the high SCr group is associated with lower GA and BW, these findings were similar to those of a previous study by Go et al.20. A majority of infants in the high SCr group showed high values within the first two weeks of life. Thirty-one (49.2%, not shown in this article) infants had higher SCr levels in the second week than in the first week. In addition, as the use of inotropes within the first week of birth, the use of nephrotoxic drugs, and RDS incidence were reported in the high SCr group, it can be inferred that VLBW infants with high levels of SCr are affected by hemodynamic instability during the postnatal transition.
In Soonchunhyang Cheonan University Hospital, transfusion was performed according to the guidelines regulating pediatric transfusion.21 The high SCr group received the first blood transfusion earlier, and fewer blood samplings were performed before the first transfusion than the normal SCr group. Recently, Lust et al reported an association between early red cell transfusion and the development of severe ROP, independent of GA.3 These results might suggest that anemia is attributed to other etiologies in addition to blood loss, such as damage to RBC synthesis via Epo production and required transfusion in the high SCr group
The results of our present study showed that lower GA and high SCr group were independent risk factors for ROP requiring treatment. Low GA is known as one of the strongest risk factors for the development of ROP.1,22 To the best of our knowledge, this is the first study establishing the association between high SCr levels and ROP requiring treatment.
Further validation of the SCr reference ranges requires additional studies to determine the precise mechanism underlying the SCr elevation and its contribution to short-term and long-term complications.
Our present study had limitations; a large difference in the number of VLBW infants was observed among GA categories: 51 infants in GA 25–27 weeks, 94 in GA 28–29 weeks, and 97 in GA 30–32 weeks. In addition, this retrospective study was based on the medical records of infants admitted to the hospital. Therefore, we were unable to investigate the factors determining the glomerular filtration rate or tubular function, such as creatinine clearance or fractional excretion of sodium.