# The Link Between Preterm Birth and Long-Term Renal Consequences: Current Knowledge and Emerging Therapeutic Targets

## TL;DR

Preterm birth increases the risk of long-term kidney problems, and understanding the mechanisms and biomarkers could help in early detection and treatment.

## Contribution

This review highlights the combined developmental and postnatal mechanisms linking preterm birth to chronic kidney disease and identifies emerging biomarkers for early risk stratification.

## Key findings

- Preterm birth leads to reduced nephron endowment and compensatory glomerular hypertrophy, increasing renal vulnerability.
- Postnatal factors like neonatal AKI and nephrotoxic medications accelerate renal injury in preterm individuals.
- Biomarkers such as cystatin C and imaging-based estimates may improve early detection of kidney risk in preterm individuals.

## Abstract

Background/Objectives: Preterm birth interrupts nephrogenesis during a critical developmental window, resulting in reduced nephron endowment and lifelong renal vulnerability. Evidence indicates that individuals born preterm are at increased risk for hypertension, albuminuria, and chronic kidney disease (CKD) across the life course. This review synthesizes current evidence linking prematurity with adverse renal outcomes, explores key pathophysiological mechanisms, and discusses emerging biomarkers together with therapeutic strategies. Methods: This comprehensive review integrates evidence from clinical cohort studies, population-based registries, meta-analyses and experimental models. Factors such as neonatal acute kidney injury (AKI), nephrotoxic exposures and cardiometabolic interactions were integrated to provide a life-course perspective. Results: Preterm birth leads to reduced nephron endowment, compensatory glomerular hypertrophy, and hyperfiltration, which predispose to progressive nephron loss. Postnatal factors, including neonatal AKI, inflammation, nephrotoxic medications, and later cardiometabolic stress, act as cumulative “hits”, accelerating renal injury trajectories. Clinical studies demonstrate a higher prevalence of reduced estimated glomerular filtration rate, albuminuria, elevated blood pressure, and smaller kidney volumes from childhood into adulthood. Emerging biomarkers such as cystatin C, alongside imaging-based estimates of nephron endowment, may enhance early risk stratification. Conclusions: Preterm birth represents an independent, lifelong risk factor for CKD through combined developmental and postnatal mechanisms. Structured long-term surveillance and early preventive strategies are essential to preserve renal reserve in this population. Advances in biomarker-guided monitoring and targeted interventions may enable earlier identification of high-risk individuals and support precision approaches to nephroprotection after prematurity.