Risk of Chronic Kidney Disease Higher When Born Premature

Abstract

Source: Crump C, Sundquist J, Winkleby MA, et al. Preterm birth and risk of chronic kidney disease from childhood into mid-adulthood: national cohort study. BMJ. 2019; 365: l1346; doi: 10.1136/bmj.l1346Investigators from multiple institutions conducted a national cohort study to assess the association of preterm birth and chronic kidney disease (CKD). Investigators used the Swedish birth registry to identify singleton live births from 1973 to 2014. The primary exposure variable was gestational age at birth, which was recorded in the registry by using maternal report of last menstrual period in the 1970s and ultrasonography thereafter. Gestational age was categorized as extremely preterm (22–27 weeks), very preterm (28–33 weeks), late preterm (34–36 weeks), early term (37–38 weeks), full term (39–41 weeks), and post-term (≥42 weeks).The primary outcome was a diagnosis of CKD from birth to December 31, 2015, determined using ICD codes from Swedish hospital and national registries. Data on covariates were abstracted from the Swedish birth registry and national census data, including birth year; sex; birth order; and maternal characteristics such as maternal smoking, preeclampsia, and diabetes. Investigators calculated incidence rates of CKD in person-years overall. Cox proportional regression was used to assess the hazard ratio for associations between gestational age at birth and risk of CKD, including hazard ratios for CKD diagnosis across age ranges (0–9, 10–19, and 20–43 years old), after adjusting for potential confounders.There were 4,186,615 participants included in the analysis, most of whom were born full term (N=2,895,746; 69%). Overall, 4,305 (0.1%) participants had CKD over 87 million person-years of follow-up, for an incidence rate of 4.95 per 100,000 person-years. Compared to those born full term, participants born at a younger gestational age had a significantly increased risk of CKD, with an adjusted hazard ratio (aHR) for CKD among extremely preterm infants of 3.01 (95% CI, 1.67–5.45); very preterm, 2.22 (95% CI, 1.79–2.75); late preterm, 1.84 (95% CI, 1.62–2.08); and early term, 1.30 (95% CI, 1.20–1.40). Among those born prematurely (<37 weeks), the risk of CKD diagnosis was highest at 0–9 years of age (aHR, 5.09; 95% CI, 4.11–6.31).The investigators conclude that preterm birth is strongly associated with development of CKD.Dr Sanchez-Kazi has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Most nephron units develop during the third trimester of pregnancy, so interruption of nephrogenesis with premature birth leads to less nephron endowment. Kidney volume or kidney size is used commonly as a surrogate marker for kidney development; however, imaging cannot measure glomerular hypertrophy and hyperfiltration. Hypertrophy of the glomerulus can lead to glomerulosclerosis, increasing the risk of CKD, hypertension, and proteinuria.1,2The strength of the current study is the high number of participants included in the analysis and long follow-up, until 43 years of age. The surprising finding in this study is the slight increased risk of CKD in early term birth, given that nephrogenesis should be finished by 36 weeks. No other risk factors in early term infants were mentioned in the study to explain this finding. The weakness of the study is the absence of kidney volume measurements and lack of birth weight as variables for calculating risk for CKD.Multiple studies have demonstrated that the risk factors for CKD in childhood and adulthood are low birth weight, prematurity, and intrauterine growth restriction. Low birth weight, <10th percentile for age, and infants who were small for gestational age are at greater risk of developing CKD and end-stage renal disease during childhood and early adolescence.3–5Low birth weight, prematurity, and intrauterine growth restriction also were associated with smaller kidney volume measured with renal ultrasonography in childhood. Although no differences in renal function were demonstrated by Paquette et al,6 hypertension, higher renin level, and 10% less kidney volume were found in adults 18–29 years old who were born at ≤29-weeks’ gestational age. Hyperfiltration likely accounts for the normal kidney function. In contrast, higher fetal weight during the second and third trimesters and 6 months postnatally correlated with larger kidney volume at 6 years of age.7 Post-term infants had higher renal function during childhood.7Histological findings in premature kidneys include a greater percentage of abnormal glomeruli and evidence of hyperfiltration in the remaining glomeruli.8Prematurity is a significant risk factor for CKD during childhood and middle adulthood.