Cavalier, Etienne

ABSTRACT Background Differences in the performance of estimated glomerular filtration rate (eGFR) equations have been attributed to the mathematical form of the equations and to differences between patient demographics and measurement methods. We evaluated differences in serum creatinine (SCr) and eGFR in cohorts matched for age, sex, body mass index (BMI) and measured GFR (mGFR). Methods White North Americans from Minnesota (n = 1093) and the Chronic Renal Insufficiency Cohort (CRIC) (n = 1548) and White subjects from the European Kidney Function Consortium (EKFC) cohort (n = 7727) were matched for demographic patient characteristics (sex, age ± 3 years, BMI ± 2.5 kg/m2) and renal function (mGFR ± 3 ml/min/1.73 m2). SCr was measured with isotope dilution mass spectrometry (IDMS)-traceable assays in the Minnesota and EKFC cohorts and with non-standardized SCr assays recalculated to IDMS in the CRIC. The Minnesota cohort and CRIC shared a common method to measure GFR (renal clearance of iothalamate), while the EKFC cohort used a variety of exogenous markers and methods, all with recognized sufficient accuracy. We compared the SCr levels and eGFR predictions [for Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and EKFC equations] of patients fulfilling these matching criteria. Results For 305 matched individuals, mean SCr (mg/dL) was not different between the Minnesota and EKFC cohorts (females 0.83 ± 0.20 versus 0.86 ± 0.23, males 1.06 ± 0.23 versus 1.12 ± 0.37; P > .05) but significantly different from the CRIC [females 1.13 ± 0.23 (P < .0001), males 1.42 ± 0.31 (P < .0001)]. The CKD-EPI equations performed better than the EKFC equation in the CRIC, while the opposite was true in the Minnesota and EKFC cohorts. Conclusion Significant differences in SCr concentrations between the Minnesota and EKFC cohorts versus CRIC were observed in subjects with the same level of mGFR and equal demographic characteristics and can be explained by the difference in SCr calibration.

Objective Long-term androgen deprivation therapy (ADT) negatively influences bone. The short-term effects on bone and mineral homeostasis are less known. Therefore, we aimed to investigate the early effects of ADT on calcium/phosphate homeostasis and bone turnover. Design Prospective cohort study. Methods Eugonadal adult, male sex offenders, who were referred for ADT to the endocrine outpatient clinic, received cyproterone acetate. Changes in blood markers of calcium/phosphate homeostasis and bone turnover between baseline and first follow-up visit were studied. Results Of 26 screened patients, 17 were included. The median age was 44 (range 20–75) years. The median time interval between baseline and first follow-up was 13 (6–27) weeks. Compared to baseline, an 81% decrease was observed for median total testosterone (to 3.4 nmol/L (0.4–12.2); P < 0.0001) and free testosterone (to 0.06 nmol/L (0.01–0.18); P < 0.0001). Median total estradiol decreased by 71% (to 17.6 pmol/L (4.7–35.6); P < 0.0001). Increased serum calcium (P < 0.0001) and phosphate (P = 0.0016) was observed, paralleled by decreased PTH (P = 0.0156) and 1,25-dihydroxyvitamin D3 (P = 0.0134). The stable calcium isotope ratio (δ44/42Ca) decreased (P = 0.0458), indicating net calcium loss from bone. Bone-specific alkaline phosphatase and osteocalcin decreased (P < 0.0001 and P = 0.0056, respectively), periostin tended to decrease (P = 0.0500), whereas sclerostin increased (P < 0.0001), indicating suppressed bone formation. Serum bone resorption markers (TRAP, CTX) were unaltered. Conclusions In adult men, calcium release from the skeleton occurs early following sex steroid deprivation, reflecting early bone resorption. The increase of sclerostin and reduction of bone formation markers, without changes in resorption markers, suggests a dominant negative effect on bone formation in the acute phase.