Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Aug 1;311(2):F305-9.
doi: 10.1152/ajprenal.00025.2016. Epub 2016 May 18.

High serum creatinine nonlinearity: a renal vital sign?

Carlos E Palant  1 , Lakhmir S Chawla  2 , Charles Faselis  3 , Ping Li  1 , Thomas L Pallone  4 , Paul L Kimmel  5 , Richard L Amdur  6
Affiliations
Review

High serum creatinine nonlinearity: a renal vital sign?

Carlos E Palant et al. Am J Physiol Renal Physiol. .

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.

Keywords: acute kidney injury; chronic kidney disease progression; serum creatinine concentration variability.

PubMed Disclaimer

Figures

Fig. 1.
Fig. 1.
Four hypothetical patterns of serum creatinine concentration (SC), measured monthly for 10 mo. Patterns A and B are nearly linear with equal mean SC (1.94), but the SD of B (0.61) is almost twice that of A (0.32) because B has a larger slope. The SD of A (0.32) and C (0.30) are similar, but their coefficients of variation (CVs) are different (0.16 for A, 0.21 for C) because their means are different. Pattern D has the lowest SD (0.21), and its CV (0.19) is lower than that of Patterns B and C although it is obviously the most nonlinear.
Fig. 2.
Fig. 2.
Kaplan-Meier survival estimates for time from admission to stage 4 chronic kidney disease (CKD4). MSE, mean square error.
Fig. A1.
Fig. A1.
Monthly peak SC values for computation.
See this image and copyright information in PMC

References

    1. Al-Aly Z, Balasubramanian S, McDonald JR, Scherrer JF, O'Hare AM. Greater variability in kidney function is associated with an increased risk of death. Kidney Int 82: 1208–1214, 2012. - PubMed
    1. Basile DP, Leonard EC, Beal AG, Schleuter D, Friedrich J. Persistent oxidative stress following renal ischemia-reperfusion injury increases ANG II hemodynamic and pro-fibrotic activity. Am J Physiol 11: F1494–F1502, 2012. - PMC - PubMed
    1. Bidani AK, Polichnowski AJ, Loutzenhiser R, Griffin KA. Renal microvascular dysfunction, hypertension and CKD progression. Curr Opin Nephrol Hypertens 22: 1–9, 2013. - PMC - PubMed
    1. Carlström M, Wilcox CS, Arendshorst WJ. Renal autoregulation in health and disease. Physiol Rev 95: 405–511, 2015. - PMC - PubMed
    1. Chen SC, Lin MY, Huang TH, Hung CC, Chiu YW, Chang JM, Tsai JC, Hwang SJ, Chen HC. Variability in estimated glomerular filtration rate by area under the curve predicts renal outcomes in chronic kidney disease. ScientificWorldJournal 2014: 802037, 2014. - PMC - PubMed

LinkOut - more resources