Abstract
Background and Aims
Renal functional capacity is influenced by factors acting early in life, such as intrauterine environment, maturity, birth weight, length at birth, placental weight etc. Early life factors are responsible for the number of nephrons a person starts life with, and the consequence of a low nephron number is earlier kidney ageing and chronic kidney disease (CKD). Notably, most reports addressing early life factors in the context of adult kidney function use creatinine-based eGFR equations and/or albuminuria and lack longer follow-up (<30 years). Therefore, we aimed to identify early life factors associated with kidney function, determined by different creatinine and cystatin C equations and urinary albumin-to-creatinine ratio (UACR), more than 40 years later.
Method
94 women and 494 men, born 1923-50, who participated in The Malmo Diet and Cancer (MDC) study were analyzed. Perinatal data records including birth weight (BW), birth length, head circumference, gestational age, placenta weight (PW) and mother related risk factors were collected from hospital and regional state archives. After a follow-up of 46 to 67 years study subjects underwent physical examination, blood pressure measurements and estimation of glomerular filtration rate (eGFR) using 4 different equations: Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2012 creatinine and cystatin C formula (CKD-EPI_creatinine, CKD-EPI_cystatin C), cystatin C eGFR equation based on Caucasian, Asian, pediatric, and adult cohorts (CAPA), the Lund-Malmö revised creatinine based eGFR equation (LM_rev). Urinary albumin-to-creatinine ratio (UACR) was measured in morning urine samples, albuminuria was defined as UACR ⩾3 mg/mmol. Birth weight z-scores (gender specific BWz and combined BWz) acquired by using the equation as reported by Marsal et al.(1996). Four growth mismatch phenotypes defined by combining low or high BW z-score (lowBWz or hiBWz respectively) with lower or higher body mass index at 20 years of age (lowBMI20 ir hiBMI20 respectively).
Results
Linear regression analysis of early life factors indicated that in females birth weight was positively associated with kidney function measured by both CAPA and CKD-EPI_cystatin C. In the whole population, birth weight adjusted for gestational age and sex, together with prematurity were independently associated to CKD-EPI_cystatin C, while BW/PW ratio was related to LM_rev. Logistic regression analysis showed that only gender specific BWz and combined BWz shared the same odds ratios for age and pulse pressure adjusted albuminuria in males (OR 0,75 (95%CI [0,58; 0,96]). While analyzing postnatal growth mismatch we found that females with hiBWz/lowBMI20 phenotype had significantly worse kidney function acquired by both cystatin C equations compared to those with lowBWz/lowBMI20 phenotype (p=0.044 for CAPA, p=0.040 for CKD-EPI_cystatin C). The logistic regression analysis revealed that hiBWz/hiBMI20 phenotype was related to lower risk of age and pulse pressure adjusted albuminuria (OR 0,35 (95%CI[0,12;0,93])
Conclusion
Here we report that lower birth weight in females is associated with worse kidney function determined by cystatin C eGFR equations, while in males lower birth weight z-score is a risk factor for albuminuria in adulthood. Postnatal growth catch-up is not related to worse kidney function. We identified the protective phenotype (hiBWz/hiBMI20) for albuminuria in males and the unfavorable phenotype (hiBWz/lowBMI20) for kidney function in females. This suggests that lower birth weight and postnatal growth curve have a potential sex specific effect to kidney function and development of CKD in middle-aged Swedish subjects. Further studies are warranted to address early life factor prognostic accuracy in kidney function and outcomes prediction later in the lifetime.
Metabolic programming in early life in humans
