Age-dependent glomerular damage in the rat. Dissociation between glomerular injury and both glomerular hypertension and hypertrophy. Male gender as a primary risk factor.

Abstract

The glomerulus develops progressive injury with advancing age which is particularly pronounced in males and is not the result of any specific disease process. In the present studies conducted in rats, glomerular function and structure were examined in adult (8 mo), elderly (12 mo), and old (19 mo) Munich Wistar rats. Intact males and females and castrated rats of both sexes were studied to determine the role of the sex hormones in mediating age-dependent glomerular damage. Intact males developed glomerular injury and proteinuria whereas females, both intact and ovariectomized, and castrated males were protected from injury. Glomerular blood pressure did not increase with advancing age in any group and did not correlate with glomerular damage. Glomerular volume did increase with advancing age in all groups but did not correlate with glomerular damage. We found that the presence of the androgens rather than the absence of the estrogens provide the risk factor for development of age-dependent glomerular damage. Neither glomerular hypertension nor glomerular hypertrophy provide the primary mechanism by which age-dependent glomerular injury occurs in the intact male. (J. Clin. Invest. 1994.

Decreased alpha-adrenergic constriction of renal preglomerular arteries occurs with age and is gender-specific in the rat

“…Weight gain among gender groups grew somewhat exponentially as is consistent with that already reported in the literature (Roth et al 1993;Anderson et al 1994;Galbusera et al 1988;Properzi et al 1992;Scolnick et al 1992;Sawaki et al 1995;Baylis 1994). In addition, male weights were significantly greater at all age groups compared to the female.…”

Morphometric Study of Gender Differences with Regard to Age-Related Changes in the C57BL/6 Mouse Kidney

“…Specifically, from 12 to 24 months of age, a markedly greater relative increase in renal corpuscle diameter was observed in females, compared to males, suggesting that glomerular hypertrophy is more severe in females than males during this period. Several studies have described close relationships between glomerular hypertrophy and glomerulopathy in aging mice and rats [4,13,19,22], however, no direct relationship between the two events has been reported [2,14,17]. In the present study, similar age-related increases in both renal corpuscle diameter and glomerular damage scores were observed, particularly in males.…”

Invited Review: A Contemporary Overview of Chronic Progressive Nephropathy in the Laboratory Rat, and Its Significance for Human Risk Assessment

“…Also, long-term administration of androgen has been shown to enhance CPN lesions and accelerate renal dysfunction in female rats (Tanaka et al, 1995). Thus, it is the presence of the male sex steroids, androgens, that are associated with the risk for developing CPN, rather than an absence of estrogens (Baylis, 1994).…”