Key result
In patients with primary focal segmental glomerulosclerosis, tubulointerstitial ACE2 mRNA expression was significantly lower in males compared to females (P = 0.0026).
Why the study?
The relationship between sex and renal ACE2 expression in humans with kidney disease represents an open clinical gap.
Does sex influence kidney ACE2 expression and its relationship with clinical and pathological variables in patients with primary focal segmental glomerulosclerosis?
Cross-Sectional (n=111)
Yes
Does sex influence kidney ACE2 expression and its relationship with clinical and pathological variables in patients with primary focal segmental glomerulosclerosis?
Sex is an important determinant of ACE2 expression in the tubulointerstitium of the kidney in FSGS, with males showing lower expression and stronger correlations with kidney fibrosis and inflammation genes.
BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) has been implicated in the pathogenesis of experimental kidney disease. ACE2 is on the X chromosome, and in mice, deletion of ACE2 leads to the development of focal segmental glomerulosclerosis (FSGS). The relationship between sex and renal ACE2 expression in humans with kidney disease is a gap in current knowledge. METHODS: We studied renal tubulointerstitial microarray data and clinical variables from subjects with FSGS enrolled in the Nephrotic Syndrome Study Network (NEPTUNE) study. We compared relationships between ACE2 expression and age, estimated glomerular filtration rate (eGFR), urinary albumin to creatinine ratio (UACR), interstitial fibrosis, tubular atrophy, and genes implicated in inflammation and fibrosis in male and female subjects. RESULTS: ACE2 mRNA expression was lower in the tubulointerstitium of males compared to females (P = 0.0026). Multiple linear regression analysis showed that ACE2 expression was related to sex and eGFR but not to age or treatment with renin angiotensin system blockade. ACE2 expression is also related to interstitial fibrosis, and tubular atrophy, in males but not in females. Genes involved in inflammation (CCL2 and TNF) correlated with ACE2 expression in males (TNF: r = -0.65, P < 0.0001; CCL2: r = -0.60, P < 0.0001) but not in females. TGFB1, a gene implicated in fibrosis correlated with ACE2 in both sexes. CONCLUSIONS: Sex is an important determinant of ACE2 expression in the tubulointerstitium of the kidney in FSGS. Sex also influences the relationships between ACE2, kidney fibrosis, and expression of genes involved in kidney inflammation.
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Maksimowski et al. (2021) conducted a cross-sectional in Primary focal segmental glomerulosclerosis (FSGS) (n=111). Male sex vs. Female sex was evaluated on Tubulointerstitial ACE2 mRNA expression (0.52 units lower in males, p=0.0026). In patients with primary focal segmental glomerulosclerosis, tubulointerstitial ACE2 mRNA expression was significantly lower in males compared to females (P = 0.0026).
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