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Gang Wang, Fernand Mac-Moune Lai, Ka-Bik Lai, Kai-Ming Chow, Bonnie Ching-Ha Kwan, Philip Kam-Tao Li, and Cheuk-Chun Szeto

Background

Podocyte injury and its subsequent loss in urine play an important role in the pathogenesis of diabetic nephropathy; blockade of the renin–angiotensin system may ameliorate the damage.

Methods

In a non-randomized setting, we studied 71 patients with diabetic nephropathy on a stable dose of angiotensin-converting enzyme inhibitor (ACEI). In 37 patients, angiotensin receptor blocker (ARB) was added (the combination group); ACEI alone was continued in the other 34 (the control group). The mRNA expressions of nephrin, podocin, and synaptopodin in urinary sediment were measured at 0 and 12 weeks.

Results

Baseline glomerular filtration rate (GFR) correlated with the urinary expression of nephrin (r=0.320, P=0.007), podocin (r=0.336, P=0.004), and synaptopodin (r=0.350, P=0.003). After adjusting for the baseline expression, the combination group had a significantly lower urinary synaptopodin expression (7.49 (95% confidence interval CI, 0.62–115.29) vs 14.83 (95% CI, 1.03–241.43), P=0.026) than the control group after 12 weeks of treatment. The percentage change in urinary podocin expression over 12 weeks of treatment had a modest correlation with the rate of GFR decline in 1 year (r=−0.243, P=0.041).

Conclusion

In patients with diabetic nephropathy, urinary mRNA expression of podocyte markers correlated with baseline renal function. Urinary expression of synaptopodin was lower after 12 weeks of ACEI and ARB combination therapy. Our result suggests that serial measurement of urinary podocyte markers may have a value for the monitoring of therapeutic response.

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Jiayu Wang, Xikang Fan, Mingjia Yang, Mingyang Song, Kai Wang, Edward Giovannucci, Hongxia Ma, Guangfu Jin, Zhibin Hu, Hongbing Shen, and Dong Hang

Objective

Testosterone is a critical determinant of health in both genders. However, the relationship between circulating levels of testosterone and mortality remains undetermined.

Methods

We examined the associations of serum total testosterone (TT) and free testosterone (FT) with all-cause and cause-specific mortality in 154 965 men and 93 314 postmenopausal women from UK Biobank. Cox regression models were used to calculate the hazard ratios (HR) and 95% CIs. Given multiple testing, P < 0.005 was considered statistically significant.

Results

Over a median follow-up of 8.9 (inter-quartile range: 8.3–9.5) years, we documented 5754 deaths in men, including 1243 (21.6%) from CVD and 2987 (51.9%) from cancer. In postmenopausal women, 2435 deaths occurred, including 346 (14.2%) from CVD and 1583 (65.0%) from cancer. TT and FT concentrations were inversely associated with all-cause mortality in men, with the multivariable HR of 0.82 (95% CI: 0.75–0.91) and 0.80 (95% CI: 0.73–0.87) for the highest (Q5) vs the lowest quintile (Q1), respectively. In postmenopausal women, TT concentrations showed a positive association with all-cause mortality (HR for Q5 vs Q1 = 1.20, 95% CI: 1.06–1.37). Furthermore, higher TT and FT concentrations were associated with a lower risk of cancer mortality in men (both P for trend = 0.001), whereas TT concentrations were suggestively associated with a higher risk of cancer mortality in postmenopausal women (P for trend = 0.03).

Conclusions

Our findings suggest that high levels of circulating testosterone may be beneficial for all-cause and cancer mortality in men but detrimental in postmenopausal women.