Life-course factors that predict chronic kidney disease in midlife
Creators: name: Liu, C
Publisher: name: University of Tasmania
Year: 2024

description: <b>Background:</b> Chronic kidney disease (CKD) is one of the major chronic diseases with high morbidity and mortality in general populations worldwide. Most individuals with CKD are asymptomatic until the disease becomes advanced (glomerular filtration rate [GFR] &lt;30 mL/min/1.73m<sup>2</sup>) or the development of clinical complications such as anaemia and mineral bone disease. There are known risk factors for CKD in adulthood including adiposity, smoking, hypertension, and diabetes but less is understood about risk factors in childhood and young adulthood. Identifying and avoiding exposures to risk factors early in life may help prevent the onset and progression of CKD.<b>Aims:</b> This thesis aimed (a) to perform a systematic review of the existing literature on associations of childhood modifiable risk factors with adulthood CKD or surrogate markers of CKD and (b) to investigate associations of lifestyle, clinical, and biochemical factors with surrogate markers of CKD including subclinical kidney damage (SKD), glomerular hyperfiltration, and albuminuria, in an Australian cohort followed from childhood to midlife.<b>Methods:</b> For the systematic review, three electronic databases (MEDLINE, EMBASE, and Web of Science) were searched on 4th March 2021, and updated on 6th May 2022. Articles were included if 1) they were population-based longitudinal studies, 2) exposures were potentially modifiable, for example through social or lifestyle modifications (socioeconomic position, adiposity, smoking, alcohol consumption, nutrition, physical activity, fitness, blood pressure, diabetes, and dyslipidaemia) and occurred during childhood (ages 2-19 years), and 3) the outcome was either CKD or surrogate markers of CKD in adulthood (ages 20 years or older).Original studies used data from the Childhood Determinants of Adult Health (CDAH) study. The CDAH study is a cohort study of 8,498 children aged 7-15 years who participated in the 1985 Australian Schools Health and Fitness Survey and were followed up when participants were aged 26-36 years (CDAH-1), 31-41 years (CDAH-2), and 36-49 years (CDAH-3) where lifestyle, clinical and biochemical data were collected from questionnaires (smoking, alcohol consumption, physical activity, diet), clinic measures (body mass index [BMI], cardiorespiratory fitness, systolic/diastolic blood pressure ), and laboratory tests (triglycerides, high-density lipoprotein cholesterol, glucose, C-reactive protein [CRP]). Kidney-related measurements, including serum and urine creatinine and urine albumin, were collected in CDAH-3. SKD was defined as either 1) an estimated GFR (eGFR) of 30 to 60 mL/min/1.73 m2 or 2) an eGFR &gt;60 mL/ min/1.73 m<sup>2</sup> with a urine albumin-creatinine ratio (UACR) ≥2.5 mg/mmol (males) or 3.5 mg/mmol (females). Glomerular hyperfiltration was defined by the upper 5th percentile value of eGFR, standardised for age and sex. Albuminuria was defined as UACR ≥2.5 mg/mmol in males or ≥3.5 mg/mmol in females.<b> Results</b>: In the systematic review, 15,232 articles were identified after deduplication, 17 met the inclusion criteria and investigated childhood blood pressure (n=8), adiposity (n=4), type 2 diabetes (n=1), socioeconomic position (n=1), famine (n=1), cardiorespiratory fitness (n=1), and a healthy lifestyle score (n=1). Positive associations were found between childhood adiposity, type 2 diabetes, low socioeconomic position and cardiorespiratory fitness in females, and the risk of CKD in adulthood; inconsistent associations were found with childhood blood pressure; no associations were found with childhood exposure to famine or the healthy lifestyle score.In analyses of data from the CDAH study, a healthy lifestyle score was generated from the sum scores (score range from 0 to 10) of five lifestyle factors (BMI, smoking, alcohol consumption, physical activity, and diet) and dichotomized as unhealthy (score range from 0 to 5), or healthy (score range from 6 to 10) categories in childhood and adulthood respectively. Childhood healthy lifestyle score was not associated with the risk of SKD in midlife. Compared with participants in the ‚"persistently healthy" group, being in "improving" "worsening" or "persistently unhealthy" groups did not increase the risk of SKD in midlife. Participants with BMI trajectories that reached or persisted at high levels from childhood to adulthood had a higher risk of SKD in midlife compared with those with persistently low BMI trajectory. Lower childhood cardiorespiratory fitness was associated with a higher risk of glomerular hyperfiltration in midlife in women. Participants who had metabolic syndrome (MetS) with high CRP in young adulthood, and persistent MetS from young to middle adulthood had a greater risk of having SKD in midlife compared with those without MetS or high CRP.<b>Conclusions: </b>The available published evidence suggests that the risk factors for CKD can appear as early as in childhood. High BMI trajectory, low cardiorespiratory fitness (in females), and having MetS with high CRP were associated with an increased risk of surrogate markers of CKD in midlife, though no significant association was found with a healthy lifestyle score in childhood or from childhood to adulthood. Taken together, this thesis deepens our understanding of the contribution of exposure to lifestyle, clinical, and biochemical factors in early life to the risk of CKD in later life and emphasises the importance of using a life-course perspective to CKD prevention and management.<br>