Short-Term Gestation, Long-Term Risk: Prematurity and Chronic Kidney Disease

Abstract

Thanks to remarkable advances in neonatal intensive care, infants who once had little chance for survival can now enter adulthood. Yet the consequences of premature birth or low birth weight (LBW) on nephrogenesis, final nephron number, and long-term kidney function are unclear. This review focuses on the theory, experimental evidence, and observational data that suggest an increased risk of chronic kidney disease (CKD) for infants born prematurely. Many premature and LBW infants begin life with an incomplete complement of immature nephrons. They are then exposed to a variety of external stressors that can hinder ongoing kidney development or cause additional nephron loss such as hemodynamic alterations, nephrotoxic medications, infections, and suboptimal nutrition. Acute kidney injury, in particular, may be a significant risk factor for the development of CKD. According to Brenner' s hypothesis, patients with decreased nephron number develop hyperfiltration that results in sodium retention, hypertension, nephron loss, and CKD due to secondary focal segmental glomerulosclerosis. Because the risk of CKD in premature and LBW infants has not been accurately determined, there are no evidence-based recommendations for screening or management. Yet with the first generation of infants from the surfactant era only now reaching adulthood, it is possible that there is already an unrecognized epidemic of CKD. We suggest individualized, risk-based assessments of premature and LBW infants due to the increased risk of CKD and call for additional research into the long-term risk for CKD these infants face.

Neonatal Acute Kidney Injury

“…14,15 The impact of prematurity, intrauterine growth restriction, and AKI on nephrogenesis has not been fully delineated, but small studies suggest that the extrauterine environment and AKI are detrimental to optimal nephrogenesis. [16][17][18][19] There are significant changes in neonatal renal blood flow after birth that are relevant to the study of AKI in neonates. In comparison with the 20% to 25% of cardiac output received by the adult kidney, at birth the kidneys receive 2.5% to 4.0% of the cardiac output.…”

Preterm birth: risk factor for early-onset chronic diseases

“…9 Structural and functional changes that mediate programing of hypertension and cardiovascular disorders following preterm birth are still unclear but likely involve multiple organ systems including the vasculature and heart, kidneys and sympathetic nervous system. 13,14 Recent comprehensive vascular phenotyping in people born preterm showed structural macrovascular changes -particularly a narrowing of the aorta -and microvascular dysfunction evident by early adulthood. 15 These long-term changes may, in part, be driven by coassociated perinatal factors such as maternal hypertension and post-…”

Drug-induced impairment of renal function

“…9 Several factors may explain this, including increased susceptibility of the neonatal immature kidney to nephrotoxic insults as well as the use of multiple nephrotoxic agents in critically ill newborns. 10,11 Some drugs induce renal injury in the context of a systemic syndrome. For example, a particular drug may possess inherent nephrotoxic potential, which is increased in the setting of sepsis and decreased effective circulating volume.…”