Is Gender a Determinant for Evolution of Renal Failure? A Study in Autosomal Dominant Polycystic Kidney Disease

Gretz, Norbert; Zeier, Martin; Geberth, Steffen K.; Strauch, M; Ritz, Eberhard

doi:10.1016/s0272-6386(89)80068-x

Cited by 107 publications

(48 citation statements)

References 16 publications

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“…Also, males but not females develop the spontaneous glomerular lesion seen in the MWF/ ZTN substrain of Munich Wistar rats (18,24). This sex difference is clinically relevant since the rate of progression towards end stage renal failure in autosomal dominant polycystic kidney disease is significantly slower in women vs men (25). Men are at increased risk to develop end stage renal disease secondary to diabetes and hypertensive complications (26,27) and long It has been suggested that hypertrophy of the glomerular tuft provides a separate risk factor for development of glomerular injury by increased intramural tension (29)(30)(31).…”

Section: Resultsmentioning

confidence: 99%

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

Baylis¹

1994

J. Clin. Invest.

231

165

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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.

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Section: Resultsmentioning

confidence: 99%

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

Baylis¹

1994

J. Clin. Invest.

231

165

View full text Add to dashboard Cite

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“…Women with CKD show a slower decline in renal function over time compared with men with CKD. 17,[36][37][38][39] In addition, premenopausal women have a lower prevalence of CKD compared with age-matched men, but the incidence of the disease increases after menopause. 40 Experimental models of renal disease are widely established in male animals, which develop a more severe disease at a more rapid rate than female animals.…”

Section: Discussionmentioning

confidence: 99%

Antifibrotic Effect of Tamoxifen in a Model of Progressive Renal Disease

Dellê

Rocha

Cavaglieri

et al. 2012

Journal of the American Society of Nephrology

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Tamoxifen, a selective estrogen receptor modulator, has antifibrotic properties; however, whether it can attenuate renal fibrosis is unknown. In this study, we tested the effects of tamoxifen in a model of hypertensive nephrosclerosis (chronic inhibition of nitric oxide synthesis with L-NAME). After 30 days, treated rats had significantly lower levels of albuminuria as well as lower histologic scores for glomerulosclerosis and interstitial fibrosis than untreated controls. Tamoxifen was renoprotective despite having no effect on the sustained, severe hypertension induced by L-NAME. Tamoxifen prevented the accumulation of extracellular matrix by decreasing the expression of collagen I, collagen III, and fibronectin mRNA and protein. These renoprotective effects associated with inhibition of TGF-b1 and plasminogen activator inhibitor-1, and with a significant reduction in a-smooth muscle actin-positive cells in the renal interstitium. Furthermore, tamoxifen abrogated IL-1b-and angiotensin-II-induced proliferation of fibroblasts from both kidney explants and from the NRK-49F cell line. Tamoxifen also inhibited the expression of extracellular matrix components and the production and release of TGF-b1 into the supernatant of these cells. In summary, tamoxifen exhibits antifibrotic effects in the L-NAME model of hypertensive nephrosclerosis, likely through the inhibition of TGF-b1, suggesting that it may have therapeutic use in CKD treatment.

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“…Another study showed that mean patient age at the beginning of dialysis was 52.5 years among males and 58.1 years among females for German patients (12), suggesting a poorer outcome in male patients. However, another report showed that the mean age of patients reaching ESRD in Spain did not differ between genders (11), data similar to those reported in the present study.…”

Section: Discussionmentioning

confidence: 99%

Renal and extrarenal manifestations of autosomal dominant polycystic kidney disease

Romão

Neto

Teixeira

et al. 2006

Braz J Med Biol Res

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The objective of the present study was to determine the frequency of the most common clinical features in patients with autosomal dominant polycystic kidney disease in a sample of the Brazilian population. The medical records of 92 patients with autosomal dominant polycystic kidney disease attended during the period from 1985 to 2003 were reviewed. The following data were recorded: age at diagnosis, gender, associated clinical manifestations, occurrence of stroke, age at loss of renal function (beginning of dialysis), and presence of a family history. The involvement of abdominal viscera was investigated by ultrasonography. Intracranial alterations were prospectively investigated by magnetic resonance angiography in 42 asymptomatic patients, and complemented with digital subtraction arteriography when indicated. Mean age at diagnosis was 35.1 ± 14.9 years, and mean serum creatinine at referral was 2.4 ± 2.8 mg/dL. The most frequent clinical manifestations during the disease were arterial hypertension (63.3%), lumbar pain (55.4%), an abdominal mass (47.8%), and urinary infection (35.8%). Loss of renal function occurred in 27 patients (mean age: 45.4 ± 9.5 years). The liver was the second organ most frequently affected (39.1%). Stroke occurred in 7.6% of the patients. Asymptomatic intracranial aneurysm was detected in 3 patients and arachnoid cysts in 3 other patients. In conclusion, the most common clinical features were lumbar pain, arterial hypertension, abdominal mass, and urinary infection, and the most serious complications were chronic renal failure and stroke. Both intracranial aneurysms and arachnoid cysts occurred in asymptomatic patients at a frequency of 7.14%.

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Is Gender a Determinant for Evolution of Renal Failure? A Study in Autosomal Dominant Polycystic Kidney Disease

Cited by 107 publications

References 16 publications

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

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

Antifibrotic Effect of Tamoxifen in a Model of Progressive Renal Disease

Renal and extrarenal manifestations of autosomal dominant polycystic kidney disease

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