Dysregulated mineral metabolism in patients with acute kidney injury and risk of adverse outcomes

Leaf, David E.; Waikar, Sushrut S.; Wolf, Myles; Cremers, Serge; Bhan, Ishir; Stern, Leonard

doi:10.1111/cen.12172

Cited by 63 publications

(53 citation statements)

References 33 publications

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“…Only 0.03% of 25OHD is free [24], with close to 88% bound to vitamin D binding protein (DBP) and the remainder to albumin [38]. Although free 25OHD is most readily available for conversion into 1,25OH2D [37], the albumin-bound component of total 25OHD can be easily mobilized in times of need and provides a larger pool of 25OHD to maintain optimal vitamin D-mediated autocrine and paracrine activity [39]. By contrast, the 25OHD-DBP complex is very stable, with an affinity of binding several orders of magnitude greater than that of 25(OH)D to albumin [37].…”

Section: Discussionmentioning

confidence: 99%

Effect of Cholecalciferol Supplementation on Vitamin D Status and Cathelicidin Levels in Sepsis

Quraishi

Pascale

Needleman

et al. 2015

Critical Care Medicine

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152

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Objectives To compare changes in vitamin D status and cathelicidin (LL-37) levels in septic ICU patients treated with placebo versus cholecalciferol. Design Randomized, placebo-controlled, trial. Setting Medical and surgical ICUs of a single teaching hospital in Boston, MA. Patients 30 adult ICU patients. Interventions Placebo (n=10) versus 200,000 IU cholecalciferol (n=10) versus 400,000 IU cholecalciferol (n=10), within 24 hours of new-onset severe sepsis or septic shock. Measurements and Main Results Blood samples were obtained at baseline (day 1) and on days 3, 5, and 7, to assess total 25-hydroxyvitamin D (25OHD), as well as vitamin D binding protein and albumin to calculate bioavailable 25OHD. Plasma LL-37 and high sensitivity C-reactive protein (hsCRP) levels were also measured. At baseline, median (IQR) plasma 25OHD was 17 (13 to 22) ng/mL and peaked by day 5 in both intervention groups. Groups were compared using Kruskal-Wallis tests. Relative to baseline, on day 5, median change in biomarkers for placebo, 200,000 IU cholecalciferol, and 400,000 IU cholecalciferol groups, respectively, were: 1) total 25OHD: 3 (-3 to 8)%, 49 (30 to 82)%, and 69 (55 to 106)%, (P<0.001); 2) bioavailable 25OHD: 4 (-8 to 7)%, 45 (40 to 70)%, and 96 (58 to 136)%, (P<0.01); and 3) LL-37: -17 (-9 to -23)%, 4 (-10 to 14)%, and 30 (23 to 48)%, (P=0.04). Change in hsCRP levels did not differ between groups. A positive correlation was observed between bioavailable 25OHD and LL-37 (Spearman's rho=0.44, P=0.03), but not for total 25OHD and LL-37. Conclusions High-dose cholecalciferol supplementation rapidly and safely improves 25OHD and bioavailable 25OHD levels in patients with severe sepsis or septic shock. Changes in bioavailable 25OHD are associated with concomitant increases in circulating LL-37 levels. Larger trials are needed to verify these findings and to assess whether optimizing vitamin D status improves sepsis-related clinical outcomes.

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Section: Discussionmentioning

confidence: 99%

Effect of Cholecalciferol Supplementation on Vitamin D Status and Cathelicidin Levels in Sepsis

Quraishi

Pascale

Needleman

et al. 2015

Critical Care Medicine

Self Cite

152

160

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“…[26-28] Interestingly, while both 25OH D and 1,25OH D levels decreased in a sample of 30 patients with AKI, only the bioavailable fraction of 25OH D, calculated as the sum of the albumin-bound and free fractions, correlated with severity of sepsis and risk of death in the cohort. [29] Parathyroid hormone (PTH) is elevated, presumably as a consequence of hypocalcemia.…”

Section: Mineral Metabolism In Akimentioning

confidence: 99%

Fibroblast growth factor 23 in acute kidney injury

Christov

2014

Current Opinion in Nephrology and Hypertension

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Purpose of review to review emerging literature on changes in fibroblast growth factor 23 (FGF23) levels in the setting of acute kidney injury. Recent findings studies suggest that FGF23 levels are elevated in patients with acute kidney injury, and correlate with increased risk of death or need for dialysis (in adults) or prolonged ventilation time and higher fluid gain (in children). Animal work shows that the etiology behind this FGF23 increase is multi-factorial and includes increased production in bone and decreased clearance, but not vitamin D or PTH-activated pathways. Interestingly, FGF23 levels were found to be mildly elevated even in hospitalized patients without kidney injury, although this observation may be limited to only c-terminal FGF23 fragments. The prognostic implications of an elevated FGF23 value in patients with acute kidney injury need to be confirmed in larger cohorts and evaluated for long-term outcomes such as development of new CKD or CKD progression, as well as cardiovascular disease, similar to studies of FGF23 in the prevalent CKD population. Summary FGF23 levels are elevated in patients with AKI and are associated with morbidity and mortality is small human studies. Mechanistic work in animals suggests that the elevation is independent of PTH or vitamin D-signaling pathways. Much work remains to understand the physiology behind FGF23 elevation and the long-term effects of FGF23 in AKI.

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“…There are limited data (mostly from children 2 ) that AKI survivors have higher levels of BP, consistent with animal models showing that postischemic rats develop salt-sensitive hypertension. 3 As discussed by Wu et al, there is a growing literature linking AKI to abnormalities in mineral metabolism, especially elevations in levels of fibroblast growth factor-23, 4,5 a novel biomarker that has garnered great interest recently as likely being directly cardiotoxic. 6 Finally, AKI is associated with acute increases in inflammatory cytokine levels.…”

mentioning

confidence: 99%