Prenatal famine exposure and estimated glomerular filtration rate across consecutive generations: association and epigenetic mediation in a population-based cohort study in Suihua China

Abstract

Prenatal malnutrition could promote renal dysfunction in adulthood, but it is unclear whether the detrimental effect could be transmitted to the next generation. We investigated whether famine exposure was associated with variation of estimated glomerular filtration rate(eGFR) in two generations and explored the mediation role of methylation alterations. The longitudinal analysis included 2909 participants from Suihua rural area. F1 and F2 generations were divided into non-famine and famine group based on their birth year and exposure status of their parents, respectively. The eGFR was calculated by using the chronic kidney disease epidemiology collaboration equation. We applied mixed-effect models to investigate the association between famine and ΔeGFR and tested blood DNA methylomes in 46 families across two generations. The mediation-analysis models were utilized to examine the mediation effect of methylation alterations on the famine-ΔeGFR association. In mixed-effect models, famine exposure was associated with declined ΔeGFR level in F1 (β:-8.32;95%CI:-11.51,-5.12) and in F2 (β:-6.11;95%CI:-11.88,-0.43). Methylation850K BeadChip data showed only 19 of 961 F1 differentially methylated sites showed concordant alterations in F2. The mediation-analysis results showed methylation alterations on AGTR1 and PRKCA might mediate the famine-ΔeGFR association. Overall, prenatal famine exposure may have long-term effects on eGFR decline across consecutive generations which might be partly mediated by methylation alterations on AGTR1 and PRKCA.

Consequences of exposure to prenatal famine on estimated glomerular filtration rate and risk of chronic kidney disease among survivors of the great Ethiopian famine (1983–85): a historical cohort study

“…However, only few longitudinal studies were conducted to investigate the long term consequence of perinatal famine on kidney function. Nonetheless, the available studies conducted among Chines and the Dutch famine survivors reported higher risk of CKD and or suboptimal kidney functional markers such as protein urea among prenatal famine exposed groups [11][12][13][14]21].…”

“…Atypically, common etiologies in low-income countries have been documented as diarrheal diseases, HIV infection, low birth weight, malaria and preterm birth [2,3]. Furthermore, data in recent decades also showed correlations between suboptimal kidney health among adults and their childhood adverse events such as prenatal famine exposure [11][12][13][14][15][16][17][18].…”

Consequences of exposure to prenatal famine on estimated glomerular filtration rate and risk of chronic kidney disease among survivors of the great Ethiopian famine (1983-85): a historical cohort study

“…However, only few longitudinal studies were conducted to investigate the long term consequence of perinatal famine on kidney function. Nonetheless, the available studies conducted among Chines and the Dutch famine survivors reported higher risk of CKD and or suboptimal kidney functional markers such as protein urea among prenatal famine exposed groups [11][12][13][14]22].…”

Consequences of Exposure to Prenatal Famine on Estimated Glomerular Filtration Rate and Risk of Chronic Kidney Disease Among Survivors of the Great Ethiopian Famine (1983-85): A Historical Cohort Study

“…Atypically, common etiologies in low income countries have been documented as diarrheal diseases, HIV infection, low birth weight, malaria and preterm birth [2][3]. Furthermore, data in recent decades also showed correlation between suboptimal kidney health and contextual risk factors such as prenatal unhealthy environment [11][12][13][14][15][16][17][18].…”

“…However, a limited number of longitudinal studies were done to investigate the long term consequence of perinatal famine on the kidney function. Yet, the available studies, conducted among Chines and the Dutch famine survivors reported an increased risk of CKD and or suboptimal kidney functional markers such as protein urea among prenatal famine exposed groups [11][12][13][14].…”