To assess the role of the human kidney in leptin metabolism, we measured renal leptin net balance and urinary leptin excretion in 16 normal postabsorptive volunteers with varying degrees of obesity. Arterial leptin concentrations (11.6 ± 2.7 ng/ml) significantly exceeded renal vein concentrations (10.3 ± 2.5 ng/ml, P < 0.001). Renal leptin fractional extraction averaged 13.1 ± 1.1%, and renal leptin net balance (uptake) averaged 1,070 ± 253 ng/min. Lineweaver-Burk analysis indicated that renal leptin uptake followed saturation kinetics with an apparent Michaelis-Menten constant of 10.9 ng/ml and maximal velocity of 1,730 ng/min. Leptin was generally undetectable in urine. Using literature values for systemic leptin clearance, we calculated that renal leptin uptake could account for ∼80% of all leptin removal from plasma. These data indicate that the human kidney plays a substantial role in leptin removal from plasma by taking up and degrading the peptide.

People with type 1 diabetes (T1D) are at increased risk of developing low bone mineral density and fractures. Optimization of calcium intake is a key component of pediatric bone health care. Despite the known risk factors for impaired bone health in T1D and the known benefits of calcium on bone accrual, there are limited data describing calcium intake in youth with T1D. In this cross-sectional study, calcium intake was assessed in 238 youth with T1D. One third of study participants were found to have inadequate calcium intake. Female sex, especially during adolescence, and obesity were identified as specific risk factors for inadequate calcium intake. Given the known adverse effects of T1D on bone health, efforts to promote calcium intake in youth with T1D should be considered.

Introduction Zoledronic acid (ZA) is an intravenous bisphosphonate used to treat pediatric osteoporosis. Adverse events including hypocalcemia and acute phase reaction (APR) are common following first-infusion. The purpose of this report is to describe implementation of a ZA clinical practice guideline and the subsequent process changes to improve adherence to aspects of the protocol related to safety and efficacy. Methods Quality assurance was evaluated by chart review over a 5-year period to compare the prevalence of hypocalcemia and APR to published data. A quality improvement (QI) initiative consisting of process changes including the addition of an endocrine RN to coordinate infusions and a shift to patient/family self-scheduling of infusions was conducted. The effect of the interventions on safety (completion of pre- and post-infusion bloodwork) and efficacy (receipt of all prescribed infusions) outcomes was evaluated. Results Seventy-two patients received 244 infusions over the period. The frequency of hypocalcemia (22%) and APR (31%) was consistent with prior reports. 99% of patients received pre-infusion bloodwork, 78% received post-first-infusion bloodwork, and 47% received all prescribed infusions. QI initiatives increased the percentage of patients receiving post-first-infusion bloodwork from 67 to 79% and those receiving all infusions from 62 to 74%, but fell short of the goal of 90%. Conclusions The implementation of a standardized protocol for ZA use in children was successful in confirming patient eligibility with pre-infusion bloodwork but failed to ensure that patients obtained post-first-infusion bloodwork and received all prescribed infusions. Further efforts to systematize the management of children on ZA are needed. Supplementary Information The online version contains supplementary material available at 10.1007/s00774-021-01214-5.

1Corresponding author's email: Michael_Gough@urmc.rochester.edu RATIONALE: Animal studies indicate that estradiol (E2) protects against lethal sepsis through beneficial effects on immune and cardiovascular function. However, clinical studies indicate that total E2 levels are associated with mortality. The bioavailable fraction of E2 is the sum of free and albumin-bound hormone. It is unknown whether bioavailable E2 concentrations are also elevated in sepsis. METHODS: We measured plasma total E2, albumin, and sex-hormone binding globulin in 116 patients with severe sepsis or septic shock and 51 healthy age-and gender-matched control subjects. These measurements permitted calculation of free, albumin-bound, and bioavailable E2 concentrations. RESULTS: All E2 levels were higher in septic patients vs. controls and in sepsis non-survivors vs. survivors.Estradiol (E2) levels in control subjects, sepsis survivors, and sepsis non-survivors Controls (n=51) Survivors (n=80) Non-survivors (n=36) P value* Total E2 (pM) 114 (88-166) † 218 (94-799) ‡ 555 (281-1,980) § <0.001 Free E2 (pM) 3 (2-4) 7 (3-20) ‡ 29 (11-98) § <0.001 Albumin-bound E2 (pM) 97 (76-139) 142 (54-496) ‡ 343 (174-1,140) § <0.001 Bioavailable E2 (pM) 100 (78-142) 148 (58-530) ‡ 362 (186-1,249) § <0.001 *Kruskal-Wallis test assessing equality of concentrations among the 3 groups; †Median values and interquartile ranges (in parentheses) are shown; ‡p<0.05 for pairwise comparison between control subjects and sepsis survivors; §p<0.01 for pairwise comparison between sepsis survivors and sepsis non-survivors In addition, all E2 levels were correlated with number of organ failure free days (Spearman's rho = -0.33 --0.40, p<0.001) and Simplified Acute Physiology Score II (Spearman's rho = 0.34 -0.41, p<0.001). CONCLUSIONS: Total and bioavailable fractions of E2 are associated with sepsis, severity of illness, and sepsis mortality. Further studies are required to determine whether E2 concentrations simply index illness severity or, in addition, mediate some aspects of sepsis pathophysiology. This abstract is funded by: NIH, K23-HL080077, NCRR UL1RR024160 Am J Respir Crit Care Med