Associations of Nephron Number, Birth Weight, and Causes of Death in a Community at High Risk of Hypertension and Cardiovascular Disease.

RATIONALE &

OBJECTIVE

Low birth weight (LBW) and low nephron number may increase the risk of hypertension and cardiovascular disease (CVD).

STUDY

DESIGN

Total glomerular number was determined by stereological analysis of autopsy kidneys from 336 participants. Health Department-recorded birth weights were obtained for 204 participants who were ≤55 years old.

OUTCOMES: Birth weight, nephron number.

PREDICTORS: Hypertension, CVD, age, biological sex, body mass index, poverty index, and APOL1 genotype.

ANALYTICAL APPROACH: Relationships were investigated using group comparisons and regression models.

SETTINGS &

PARTICIPANTS

Performance sites: Autopsies, University Medical Center, Jackson, MS; Stereology, Department of Anatomy and Developmental Biology, Monash University, Melbourne; APOL1 genotyping, Basic Research Laboratory, Center for Cancer Research, National Institutes of Health, Frederick, Maryland.

RESULTS

In total, 170 participants having birth weights were adults, 29% of adults were hypertensive, and 40% died of CVD. Genotyping identified 22 Black participants with 2 APOL1 risk alleles. A median of 718,409 glomeruli per kidney was found for participants with LBW (< 2.5 kg), which was significantly less than the median of 936,937 glomeruli found with birth weights from 3.0 to 4.0 kg (P < 0.001). Among adults ≤ 55 years old, hypertension correlated with age (P < 0.001) and the severity of glomerulosclerosis (P < 0.001), and CVD death correlated with hypertension (P = 0.01). However, neither LBW nor nephron number was associated with hypertension or CVD death or with an APLO1 high-risk genotype. Among participants aged 65-89 years, increased glomerulosclerosis was associated with a lower median glomerular number (759,623; P = 0.02) and with hypertension (P < 0.01).

LIMITATIONS: Relationships of predictors to outcomes are abridged by death at recruitment.

CONCLUSIONS

LBW and low nephron number were not related to hypertension or CVD in adults ≤ 55 years of age, but a glomerulosclerosis-related reduction in glomerular number may contribute to hypertension and CVD in later life.