title: High serum creatinine nonlinearity: a renal vital sign?
abstract: Patients with chronic kidney disease (CKD) may have nonlinear serum creatinine concentration (SC) trajectories, especially as CKD progresses. Variability in SC is associated with renal failure and death. However, present methods for measuring SC variability are unsatisfactory because they blend information about SC slope and variance. We propose an improved method for defining and calculating a patient's SC slope and variance so that they are mathematically distinct, and we test these methods in a large sample of US veterans, examining the correlation of SC slope and SC nonlinearity (SCNL) and the association of SCNL with time to stage 4 CKD (CKD4) and death. We found a strong correlation between SCNL and rate of CKD progression, time to CKD4, and time to death, even in patients with normal renal function. We therefore argue that SCNL may be a measure of renal autoregulatory dysfunction that provides an early warning sign for CKD progression.
authors.affiliation: Department of Medicine, Veterans Affairs Medical Center, Washington, District of Columbia; Division of Renal Diseases and Hypertension, Department of Medicine, George Washington University Medical Center, Washington, District of Columbia;
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Palant
authors.affiliation: Department of Medicine, Veterans Affairs Medical Center, Washington, District of Columbia; Division of Renal Diseases and Hypertension, Department of Medicine, George Washington University Medical Center, Washington, District of Columbia; Department of Anesthesiology and Critical Care Medicine, George Washington University Medical Center, Washington, District of Columbia;
authors.forename: Lakhmir S
authors.initials: LS
authors.lastname: Chawla
authors.affiliation: Department of Medicine, Veterans Affairs Medical Center, Washington, District of Columbia;
authors.forename: Charles
authors.initials: C
authors.lastname: Faselis
authors.affiliation: Department of Medicine, Veterans Affairs Medical Center, Washington, District of Columbia; Division of Renal Diseases and Hypertension, Department of Medicine, George Washington University Medical Center, Washington, District of Columbia;
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Medicine, University of Maryland at Baltimore, Baltimore, Maryland;
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Pallone
authors.affiliation: Division of Renal Diseases and Hypertension, Department of Medicine, George Washington University Medical Center, Washington, District of Columbia; National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland;
authors.forename: Paul L
authors.initials: PL
authors.lastname: Kimmel
authors.affiliation: Department of Medicine, Veterans Affairs Medical Center, Washington, District of Columbia; Biostatistics Core, Veterans Affairs Medical Center, Washington, District of Columbia; Department of Surgery, George Washington University School of Medicine and Health Sciences, Washington, District of Columbia amdur@gwu.edu.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Amdur
mesh_terms: D000818:Animals; D003404:Creatinine / Q000097:blood*; D006801:Humans; D007677:Kidney Function Tests; D017711:Nonlinear Dynamics; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000175:diagnosis
chemical_list: D003404:Creatinine
keywords: acute kidney injury; chronic kidney disease progression; serum creatinine concentration variability