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Among 3655 participants of the Chronic Renal Insufficiency Cohort (CRIC) study who had nondialysis-dependent CKD, higher baseline plasma levels of C-terminal FGF23 were significantly and monotonically associated with time to first hospitalization with major infection, independent of biomarkers of inflammation or bone mineral metabolism. These findings suggest a possible role of FGF23 in the increased susceptibility to infection among individuals with CKD. The most frequent infections were of the urinary tract, followed by cellulitis\/osteomyelitis, pneumonia, and then bacteremia\/septicemia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Risk of infectious disease is increased among individuals with CKD. Fibroblast growth factor 23 (FGF23) is often elevated in CKD, and may impair immune function directly or indirectly through proinflammatory and vitamin D\u2013suppressing pathways. Whether FGF23 is associated with risk of infection has not been evaluated in a CKD population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In 3655 participants of the Chronic Renal Insufficiency Cohort study, we evaluated the association of baseline plasma levels of C-terminal FGF23 with time to first hospitalization with major infection, defined by hospital discharge with a diagnosis code for urinary tract infection, pneumonia, cellulitis\/osteomyelitis, or bacteremia\/septicemia. Multivariable Cox models were used to estimate hazard ratios (HRs) and adjust for confounding.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      During a median follow-up of 6.5 years, 1051 individuals (29%) were hospitalized with major infection. Multivariable Cox analysis indicated a graded increase in the risk of infection with higher levels of FGF23 (HR, 1.51; 95% CI, 1.23 to 1.85 with the highest quartile [\u2265235.9 RU\/ml] versus lowest quartile [&lt;95.3 RU\/ml]; HR, 1.26; 95% CI, 1.18 to 1.35 per SD increment in log FGF23). The association was consistent across infection subtypes and demographic and clinical subgroups, and remained significant after additional adjustment for biomarkers of inflammation (IL-6, TNF-\n                      <jats:italic toggle=\"yes\">\u03b1<\/jats:italic>\n                      , high-sensitivity C-reactive protein, fibrinogen, and albumin), and bone mineral metabolism (25-hydroxyvitamin D, phosphorus, calcium, and parathyroid hormone). The association was consistent across infection subtypes of urinary tract infection (482 cases), cellulitis\/osteomyelitis (422 cases), pneumonia (399 cases), and bacteremia\/septicemia (280 cases).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Among individuals with CKD, higher FGF23 levels were independently and monotonically associated with an increased risk of hospitalization with infection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.2019101106","type":"journal-article","created":{"date-parts":[[2020,6,23]],"date-time":"2020-06-23T16:35:13Z","timestamp":1592930113000},"page":"1836-1846","source":"Crossref","is-referenced-by-count":23,"title":["Fibroblast Growth Factor 23 and Risk of Hospitalization with Infection in Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort (CRIC) 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