Creatinine

Creatinin

Enrico Canuto, Former Faculty, Politecnico di Torino, Torino, Italy

Draft

Introduction

Creatinine concentrations in blood serum and in urine [mg/dl] are intermediate indicators of kidney health. Creatinine is a by product of muscle metabolism that is excreted primarily and unchanged by kidneys [1]. Creatinine production reflects lean body mass, which changing little day by day, makes production rate fairly constant, but declining with the age in line with decreasing muscle mass.

Creatinine clearance q_{Cr} \: \textup{[ml/min]}  is the volume per unit time (volume flow) of blood plasma that is cleared of creatinine and is useful for deriving the standard clinically index of renal efficiency, the Glomerular Filtration Rate (GFR, see below). Given the urine concentration u_{Cr}, the serum concentration s_{Cr} and the urine volume flow q_{u}, we write

q_{Cr}=q_{u}\frac{u_{Cr}}{s_{Cr}}\; \textup{[ml/min]}\: \; \; (1)

Usually the clearance q_{Cr} is scaled to  a specific body by the body area ratio \alpha\left ( M \right ) =A\left ( M \right )/A_{0}, where A \: \left [ m^{2} \right ]  is the body surface area derived from the body mass M\: \left [ \textup{kg }\right ] and A_{0}=1.73\: \; m^{2}  is a reference body area (see the Appendix). Thus (1) is rewritten for a body of mass M as

q_{Cr}\left ( M \right )=\alpha \left ( M \right )q_{u}\frac{u_{Cr}}{s_{Cr}}\; \textup{[ml/min]}\: \; \; (2)For instance, given \alpha \left ( M \right )=1, q_{u}=1200/(24\cdot 60)=0.83\: \textup{ml/min}, u_{Cr}=90\;\textup{ mg/dl} and s_{Cr}=1\;\textup{ mg/dl}, we obtain q_{Cr}=75\: \textup{ml/min}.  The clinical lower limit is q_{Cr,min}=60\: \textup{ml/min}.

GFR experimental formulas

Glomerular filtration rate (GFR)  corresponds to renal clearance rate (like that of creatinine in (1)), when the serum solute is freely filtered from glomerular capillaries into the so called Bowman’s capsules without being re-absorbed and secreted by other kidney capillaries, which latter occurs to creatinine.

As a result, the measured creatinine clearance in (1) overestimates GFR by 10% and more [2]. Second, it does not account for body ageing. Third, it requires three measurements, two concentrations and urine flow. Several equations have been experimentally obtained from patient populations to account for age, gender, ethnicity and to just require the serum concentration s_{Cr}.  We just report the so called CKD-EPI formula (Chronic Kidney Disease Epidemiology Collaboration, 2009, [3]) :

\begin{matrix}q_{Cr}=\alpha \left ( M \right )141\left (\frac{s_{Cr}}{s\left ( \gamma \right )} \right )^{-\beta \left ( \eta \right )}\left ( 1-\epsilon \right )^\tau , \: \; s_{Cr}\geq s\left ( \gamma \right ) \\ \gamma =\left \{ male, female\right \} ,s\left ( \gamma \right )=\left \{ 0.9,0.7 \right \} \\\eta=\left \{ Caucasian,... \right \},\beta \left ( \eta \right )=\left \{ 1.21,... \right \} , \varepsilon =0.007\end{matrix} \: \; (3)

where \gamma denotes gender, \eta ethnicity and \tau the age in years [a]. For instance for a Caucasian male with \alpha \left ( M \right )=1s_{Cr}=1\: \; \textup{mg/dl} and \tau =75 \: \textup{a}, we obtain q_{Cr}=73 \: \textup{ml/min}.

The problem of formula (3) is the parameter uncertainty, which combines with the concentration measurement error.

Chemical structure

Naively, creatinine is a creatine molecule that losing a water molecule forces carbon and nitrogen to close as in Figure 1

Figure 1 -

TBC

References

[1] A.O. Hosten, Chapter 193: BUN and Creatinin, in A.O. Hosten et al. eds, Clinical Methods: The History, Physical, and Laboratory Examinations, 3rd edition (Butterworths, Boston, 1990), pp. 874-878.

[2] J.R. Delanghe and M.M. Speeckaert, creatinine determination according to Jaffe- what does it stands for?, NDT Plus, Vol. 4, 2011, pp. 83-86.

[3] Wikipedia, Globular filtration rate.

Appendix

Body surface area. A widely used formula is the Du Bois formula

\begin{matrix}A\left ( M \right )=A_{0}\frac{M}{M_{0}}^{0.425}\frac{H}{H_{0}}^{0.725}\: \left [ m^{2} \right ] \\ A_{0}=1.73\: \left [ m^{2} \right ], M_{0}=65\: \left [ kg \right ],H_{0}=1.7\: \left [ m\right ] \end{matrix}