In human urinary tract infections, host cells release the antimicrobial protein siderocalin (SCN; also known as lipocalin-2, neutrophil gelatinase-associated lipocalin, or 24p3) into the urinary tract. By binding to ferric catechol complexes, SCN can sequester iron, a growth-limiting nutrient for most bacterial pathogens. Recent evidence links the antibacterial activity of SCN in human urine to iron sequestration and metabolomic variation between individuals. To determine whether these metabolomic associations correspond to functional Fe(III)-binding SCN ligands, we devised a biophysical protein binding screen to identify SCN ligands through direct analysis of human urine. This screen revealed a series of physiologic unconjugated urinary catechols that were able to function as SCN ligands of which pyrogallol in particular was positively associated with high urinary SCN activity. In a purified, defined culture system, these physiologic SCN ligands were sufficient to activate SCN antibacterial activity against Escherichia coli. In the presence of multiple SCN ligands, native mass spectrometry demonstrated that SCN may preferentially combine different ligands to coordinate iron, suggesting that availability of specific ligand combinations affects in vivo SCN antibacterial activity. These results support a mechanistic link between the human urinary metabolome and innate immune function.

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Introduction Patients with lower urinary tract symptoms (LUTS) can be subcategorized into polyuria, normal or oliguria groups. Polyuria may be caused by pathologies including diabetes mellitus (DM), chronic kidney disease (CKD), diabetes insipidus (DI), or primary polydipsia (PPD). While fluid restriction is appropriate for some, doing so in all may result in serious complications. This study investigates the prevalence of these pathologies in LUTS patients with polyuria. Materials and Methods Two databases were retrospectively queried for men and women who filled out a lower urinary tract symptom score (LUTSS) questionnaire, 24‐h bladder diary (24HBD) and were polyuric (>2.5 L/day). Patients were divided into four groups: poorly controlled DM, DI, an CKD grade 3 and PPD. One‐way analysis of variance compared 24HBD and LUTSS questionnaires. Pearson correlation examined LUTSS and bother with 24‐h voided volume (24 HVV), maximum voided volume (MVV) and total voids. Results Among 814 patients who completed a 24HBD, 176 had polyuria (22%). Of the patients with complete data, 7.8% had poorly‐controlled DM, 3.1% had DI, 4.7% had CKD grade 3% and 84.4% had PPD. Amongst the four different sub‐groups, significant differences were seen in 24 HVV (p < 0.001), nocturnal urine volume (NUV) (p < 0.001), MVV (p = 0.003), daytime voids (p = 0.05), nocturnal polyuria index (NPi) (p < 0.001) and nocturia index (Ni) (p = 0.002). Significance was also seen between LUTSS and bother subscore (r = 0.68, p < 0.001), LUTSS and total voids (r = 0.29, p = 0.001) and bother sub‐score and total voids (r = 0.21, p = 0.019). Conclusions 22% of patients with LUTS were found to have polyuria based on a 24HBD. Within this cohort, four sub‐populations were identified as being demonstrating statistically significant differences in 24 HVV, NUV, MVV, daytime voids, NPi and Ni. Identifying the underlying etiology of polyuria should be carried out to safely treat patients with LUTS.

Aims: Nocturnal polyuria (NP) and global polyuria (GP) are not mutually exclusive. However, by rate, the common criteria for GP (40 mL/kg/24 hours [117 mL/kg/hour in a 70-kg individual] or 3000 mL/24 hours [125 mL/h]) are more stringent than those for NP (90 mL/hour during the sleep period or NP index [NPi; nocturnal volume/24-hour volume] > 0.33 [no minimum rate]). It remains unclear whether total nocturnal urine volume (NUV) may reliably delineate between NP patients with and without comorbid GP. Methods: A clinical database of men with lower urinary tract symptoms was searched for voiding diaries completed by patients reporting greater than or equal to 1 nocturnal void(s). Four separate analyses were performed using all combinations of the two NP and two GP criteria listed above. For each analysis, patients were included if they met the criteria for NP, and then stratified by presence or absence of GP (ie, NP + GP vs isolated NP). Results: Median NUV was greater among patients with NP + GP for all criteria combinations. Sensitivities greater than or equal to 80%/90%/100% for NP + GP were observed at 1275/1230/1085 mL for {NPi > 0.33 + 24-hour volume > 3000 mL}; 1075/1035/1035 mL for {NPi > 0.33 + 24-hour volume > 40 mL/kg}; 900/ 745/630 mL for {NUP > 90 mL/hour + 24-hour volume > 3000 mL}; and 1074/ 1035/990 mL for {NUP > 90 mL/hour + 24-hour volume > 40 mL/kg}. Conclusions: An inordinate NUV among men with NP is fairly sensitive for comorbid GP. In the appropriate clinical setting, nocturnal-only diaries may suffice in the evaluation and follow-up of patients with NP, so long as outlying nocturnal volumes prompt a 24-hour diary/urine collection. K E Y W O R D S adherence, global polyuria, nocturia, nocturnal polyuria, sensitivity, specificity