Increased Urinary Cystatin-C Levels Correlate with Reduced Renal Volumes in Neonates with Intrauterine Growth Restriction

Abstract

Background: Exposure to intrauterine growth retardation (IUGR) can have a negative impact on nephrogenesis resulting in limited fetal kidney development and supporting the hypothesis that IUGR represents a risk for renal function and long-term renal disease. Cystatin-C (Cys-C), a strong inhibitor of cysteine proteinases, is freely filtered by the kidney glomerulus and is reabsorbed by the tubules, where it is almost totally catabolized; what remains is subsequently eliminated in urine. In tubular diseases and in hyperfiltration conditions, it seems reasonable to postulate that Cys-C degradation would decrease, and consequently an increase in its urinary elimination would be observed. Objectives: The aim of this study was to investigate the urinary excretion of Cys-C simultaneously with the assessment of renal volumes in adequate for gestational age (AGA) and IUGR neonates in order to identify its clinical value in IUGR. Methods: Urinary Cys-C levels were measured using the enzyme immunoassay DetectX® Human Cystatin C kit in IUGR and AGA neonates. Whole renal and renal cortex volumeswere assessed with ultrasounds (Vocal II; Software, GE). Results: Urinary Cys-C levels in IUGR were significantly higher than those found in AGA and were negatively correlated to reduced whole renal and renal cortex volumes. Conclusions: The increased levels of Cys-C in the urine of neonates with IUGR were significantly associated with reduced renal/renal cortex volumes, suggesting that Cys-C could be taken as a surrogate of nephron mass. It also could be used as an early biochemical marker to identify IUGR neonates at high risk of developing long-term renal disease and to select patients for monitoring during childhood.

Neonatal Morbidities of Fetal Growth Restriction: Pathophysiology and Impact

“…FGR infants born preterm also have an increased risk of retinopathy of prematurity (57). FGR is linked to altered nephrogenesis, due to suboptimal tubular development caused by intrauterine hypoxia (58), and in turn, urinary Cystatin-C excretion is increased in FGR infants compared to appropriately-grown infants which is seen to reflect reduced renal volume (59). It is therefore suggested that increased secretion of Cystatin-C signifies nephron loss as a result of the negative impact of FGR on kidney development.…”

Long‐term renal tubular damage in intrauterine growth‐restricted rats

“…Barbati et al . reported that IUGR newborns had a statistically significant elevation of urinary Cys‐C, inversely correlated with whole renal/renal cortex volume . In proximal tubules, filtered Cys‐C is reabsorbed by megalin‐facilitated endocytosis, and its increased urinary elimination in IUGR children could be indicative of reduced degradation and reabsorption .…”

“…11,14 Barbati et al reported that IUGR newborns had a statistically significant elevation of urinary Cys-C, inversely correlated with whole renal/renal cortex volume. 19 In proximal tubules, filtered Cys-C is reabsorbed by megalinfacilitated endocytosis, and its increased urinary elimination in IUGR children could be indicative of reduced degradation and reabsorption. 15 In the present study, both b2-MG and Cys-C were elevated at 4 and 8 weeks of age, and, taking into account these previous reports, it can be said that due to the immature reabsorption function of the renal tubule, they flowed into urine.…”

Programmed Adult Kidney Disease: Importance of Fetal Environment

“…Another study has reported high levels of cystatin C, a marker of renal function, in LBW children (Franco et al, 2008b). Additionally, Barbati et al (2016) have shown high levels of cystatin C in urine of LBW neonates. These authors observed an inverse correlation between cystatin C levels and renal volume (Barbati et al, 2016).…”

“…Additionally, Barbati et al (2016) have shown high levels of cystatin C in urine of LBW neonates. These authors observed an inverse correlation between cystatin C levels and renal volume (Barbati et al, 2016).…”