HMG–CoA reductase activation and urinary pellet cholesterol elevations in acute kidney injury
ACM Johnson, LB Ware, J Himmelfarb… - Clinical Journal of the …, 2011 - journals.lww.com
ACM Johnson, LB Ware, J Himmelfarb, RA Zager
Clinical Journal of the American Society of Nephrology, 2011•journals.lww.comResults AKI+ patients had an approximate doubling of urinary pellet cholesterol content
compared with control urine samples (versus normal; P< 0.001). The values significantly
correlated (r, 0.5; P< 0.01) with serum, but not urine, creatinine concentrations. Conversely,
neither critical illness without AKI nor chronic kidney disease raised pellet cholesterol levels.
Increased HMGCR activity in the AKI+ patients was supported by three-to fourfold increased
levels of Pol II, and of H3K4m3, at the HMGCR gene (versus controls or AKI− patients) …
compared with control urine samples (versus normal; P< 0.001). The values significantly
correlated (r, 0.5; P< 0.01) with serum, but not urine, creatinine concentrations. Conversely,
neither critical illness without AKI nor chronic kidney disease raised pellet cholesterol levels.
Increased HMGCR activity in the AKI+ patients was supported by three-to fourfold increased
levels of Pol II, and of H3K4m3, at the HMGCR gene (versus controls or AKI− patients) …
Results
AKI+ patients had an approximate doubling of urinary pellet cholesterol content compared with control urine samples (versus normal; P< 0.001). The values significantly correlated (r, 0.5; P< 0.01) with serum, but not urine, creatinine concentrations. Conversely, neither critical illness without AKI nor chronic kidney disease raised pellet cholesterol levels. Increased HMGCR activity in the AKI+ patients was supported by three-to fourfold increased levels of Pol II, and of H3K4m3, at the HMGCR gene (versus controls or AKI− patients).
Conclusions
(1) Clinical AKI, like experimental AKI, induces HMGCR gene activation;(2) increased urinary pellet cholesterol levels result; and (3) urine pellet cholesterol levels may have potential AKI biomarker utility. The latter will require future testing in a large prospective trial.
Lippincott Williams & Wilkins