From prematurity and low birth weight to CKD: opportunities for intervention

Preterm birth (<37 completed gestational weeks), low birth weight (<2500g) and small for gestational age (SGA, birth weight <10th percentile for gestational age) are interrelated neonatal phenotypes that adversely affect lifelong kidney health. They have been grouped under the term small vulnerable newborn (SVN). Being born as SVN ranks fifth among risk factors for early mortality and imposes a lifelong susceptibility for chronic kidney disease (CKD). The combination of extreme prematurity and SGA triples CKD-risk in early adulthood. Globally, around 35 million SVN are born annually and will contribute to rising CKD morbidity and mortality. In SVN, nephron mass is reduced because prematurity interrupts and an adverse intrauterine environment impairs nephron endowment. Maladaptive responses to low nephron mass include glomerular hyperfiltration, glomerular hypertension and glomerular sclerosis. In addition, complications of prematurity cause renal hypoperfusion and pharmacological treatment on the neonatal intensive care unit (NICU) can be nephrotoxic, both contributing to neonatal acute kidney injury (AKI). Neonatal AKI is common, has a high acute mortality and is a potentially modifiable second hit towards CKD. Preventive strategies include optimizing maternal health to prevent SVN, improved detection and avoidance of neonatal AKI by reduction of nephrotoxicity and kidney hypoperfusion during NICU-treatment and systematic documentation of AKI at discharge. Physicians and families should be educated about the child's lifelong CKD risk. Follow-up should be stratified by completed gestational weeks, birth weight, occurrence of AKI and comorbidities. Follow-up aims are early identification and treatment of CKD progression factors and complications.