Supplementary Material for: Serum Potassium Levels and Mortality in Hemodialysis Patients: A Retrospective Cohort Study

<i>Background:</i> Hyperkalemia is common in patients receiving maintenance hemodialysis. However, few studies have examined the association between serum potassium level and mortality. <i>Methods:</i> This study used annual cohorts of hemodialysis patients during 2007-2010. To determine hyperkalemia prevalence, monthly hyperkalemia was defined as serum potassium level ≥5.5 mEq/l; prevalence was calculated as a ratio of hyperkalemia episodes to follow-up time, reported separately by long and short interdialytic interval. To determine the impact of hyperkalemia on mortality, patients in the 2010 cohort were followed from first potassium measurement until death or a censoring event; hyperkalemia was defined, sequentially, by potassium levels 5.5-6.0 mEq/l at 0.1 mEq/l intervals. Time-dependent Cox proportional hazards modeling was used to estimate the association between hyperkalemia and mortality. <i>Results:</i> The 4 annual cohorts ranged from 28,774 to 36,888 patients. Mean age was approximately 63 years, about 56% were men, 51% were white and 44% had end-stage renal disease caused by diabetes. Hyperkalemia prevalence was consistently estimated at 16.3-16.8 events per 100 patient-months. Prevalence on the day after the long interdialytic interval was 2.0-2.4 times as high as on the day after the short interval. Hyperkalemia, when defined as serum potassium ≥5.7 mEq/l, was associated with all-cause mortality (adjusted hazards ratio (AHR) 1.13, 95% CI 1.01-1.28, p = 0.037, vs. <5.7 mEq/l) after adjustment. AHRs increased progressively as the hyperkalemia threshold increased, reaching 1.37 (95% CI 1.16-1.62, p < 0.0001) for ≥6.0 mEq/l. <i>Conclusions:</i> The long interdialytic interval was associated with increased likelihood of hyperkalemia. Hyperkalemia was associated with all-cause mortality beginning at serum potassium ≥5.7 mEq/l; mortality risk estimates increased ordinally through ≥6.0 mEq/l, suggesting a threshold at which serum potassium becomes substantially more dangerous

Supplementary Material for: Vitronectin Binds to a Specific Stretch within the Head Region of Yersinia Adhesin A and Thereby Modulates Yersinia enterocolitica Host Interaction

Complement resistance is an important virulence trait of <i>Yersinia enterocolitica (Ye)</i>. The predominant virulence factor expressed by <i>Ye</i> is <i>Yersinia</i> adhesin A (YadA), which enables bacterial attachment to host cells and extracellular matrix and additionally allows the acquisition of soluble serum factors. The serum glycoprotein vitronectin (Vn) acts as an inhibitory regulator of the terminal complement complex by inhibiting the lytic pore formation. Here, we show YadA-mediated direct interaction of <i>Ye</i> with Vn and investigated the role of this Vn binding during mouse infection in vivo. Using different <i>Yersinia</i> strains, we identified a short stretch in the YadA head domain of <i>Ye</i>O:9 E40, similar to the ‘uptake region' of <i>Y. pseudotuberculosis</i> YPIII YadA, as crucial for efficient Vn binding. Using recombinant fragments of Vn, we found the C-terminal part of Vn, including heparin-binding domain 3, to be responsible for binding to YadA. Moreover, we found that Vn bound to the bacterial surface is still functionally active and thus inhibits C5b-9 formation. In a mouse infection model, we demonstrate that Vn reduces complement-mediated killing of <i>Ye</i> O:9 E40 and, thus, improved bacterial survival. Taken together, these findings show that YadA-mediated Vn binding influences <i>Ye</i> pathogenesis