Early growth and kidney function and size at 10 years in Ethiopian children

Abstract

Background: Globally, non-communicable diseases (NCDs) are the primary causes of morbidity, mortality, and diminished quality of life in the 21st century. Among NCDs, chronic kidney disease (CKD) has emerged as a global public health priority, yet its true burden in Low- and Middle-Income Countries (LMICs) remains poorly understood. Adverse exposures during prenatal, infancy and childhood has detrimental effect on determining individual susceptibility for later life chronic diseases, including CKD. Therefore, having a clear understanding of early life modifiable risk factors is crucial to design and implement appropriate interventions that aimed to safeguard later life kidney health. However, there is paucity of evidence on the possible role of linear growth and body composition in early childhood on later life kidney function and size, particularly in LMICs. Objective: This PhD aimed to examine the associations of linear growth and birth body composition and their accretion during early childhood with kidney function and size at 10 years. Method: This thesis is based on the Ethiopian infant anthropometry and body composition (iABC) birth cohort. At birth, 571 participants included in the follow-up, of these 355 were enrolled in the latest follow-up at a mean age of 10 years. Markers of kidney function (Serum cystatin C and creatinine) was determined and kidney dimensions measured in the latest follow-up. Linear spline mixed effect modeling (LSMEM) was used to estimate linear growth velocities 0-3, 3-6, 6-24, 24-48 and 48-76 months (Paper1). Conditional growth modeling was used to compute FM and FFM accretions 0-3, 3-6, 6-48 and 48-60 months (Paper 2). Glomerular filtration rate (GFR) was estimated using both cystatin C and creatinine-based estimation formulas (Paper 3). In the first two papers, associations of the estimated linear growth velocities, birth FM, birth FFM and their accretion with kidney outcomes at 10-years were analyzed using multiple linear regression analyses. In the third paper, Bland–Altman plot was used to determine the agreement between estimated glomerular filtration rate (eGFR) estimated using cystatin-C (eGFRcyst) and creatinine-based (eGFRcr) formulas. While multinomial logistic regression analysis was used to identify factors associated with higher eGFRcys and eGFRcr. Results: A higher linear growth velocity and FFM accretion after 2 years of age were positively associated with serum cystatin C level at the 10-year follow-up. However, higher FFM accretion 3-6 months was negatively associated with serum cystatin C level at the 10-year follow-up. Higher birth FFM, linear growth velocities and FFM accretion in all distinct growth periods during early childhood 12 was associated with greater kidney volume at the 10-year follow-up, although this relationship was not significant in the period 0-3 months. Higher FM accretion 6-48 and 48-60 months were positively associated with kidney volume at the 10-year follow-up. A poor agreement was found between eGFRcys and eGFRcr, with only 94 (27.6%) children having concordant results. Conclusion: In general, the finding reviled that greater linear growth and FFM accretions during all distinct growth periods in early childhood favors kidney size. Nevertheless, higher FM accretion after 6 months of age was associated with larger kidney volume at the 10-year follow-up. Higher FFM accretion 3-6 months associated with better kidney function at the 10-year follow-up. In contrary, both higher linear growth velocities and FFM accretion after 2 years of age was associated with lower kidney function at the 10-year follow-up.