Test Id : CRCL

1. 24-Hour volume is required.

2. Patient's height in centimeters and weight in kilograms are required.

Both serum and urine are required. Serum must be collected no earlier than 72 hours before start of urine collection and no later than 72 hours after urine collection is completed.

Specimen Type: Serum

Collection Container/Tube:

Preferred: Serum gel

Acceptable: Red top

Submission Container/Tube: Plastic vial

Specimen Volume: 1 mL

Collection Instructions:

1. Centrifuge and aliquot serum into plastic vial.

2. Label specimen as serum.

Specimen Type: Urine

Supplies: Sarstedt Aliquot Tube, 5 mL (T914)

Specimen Volume: 5 mL

Collection Instructions:

1. Collect urine for 24 hours.

2. Refrigerate specimen within 4 hours of completion of 24-hour collection.

3. Label specimen as urine.

Additional Information: For multiple collections see Urine Preservatives-Collection and Transportation for 24-Hour Urine Specimens

• Urine Preservatives-Collection and Transportation for 24-Hour Urine Specimens

If not ordering electronically, complete, print, and send a Renal Diagnostics Test Request (T830) with the specimen.

Note: The addition of preservative or application of temperature controls must occur within 4 hours of completion of the collection.

Serum: 0.5 mL

Urine: 1 mL

Estimation of glomerular filtration rate

Estimated glomerular filtration rate (eGFR) using serum creatinine alone is calculated using the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation:

eGFR = 142 x min(standardized Scr/k,1)alpha x max(Scr/k, 1)-1.200 x (0.9938 x age) x 1.012 (if patient is female)

where:

-age is in years

-Scr is serum creatinine concentration

-k is 0.7 for females and 0.9 for males

-alpha is -0.241 for females and -0.302 for males

-min indicates the minimum of Scr/k or 1

-max indicates the maximum of Scr/k or 1

Use of an estimating or prediction equation to estimate GFR from serum creatinine should be employed for people with CKD and those with risk factors for CKD (diabetes, hypertension, cardiovascular disease, and family history of kidney disease). Reasons given for routine reporting of eGFR with every serum creatinine in adult (18 and over) patients include:

-GFR and creatinine clearance are poorly inferred from serum creatinine alone. GFR and creatinine clearance are inversely and nonlinearly related to serum creatinine. The effects of age and sex further cloud interpretation.

-Creatinine is commonly measured in routine clinical practice. Albuminuria (>30 mg/24 hour or urine albumin to creatinine ratio >30 mg/g) may be a more sensitive marker of early kidney disease, especially among patients with diabetic nephropathy. However, there is poor adherence to guidelines that suggest annual urinary albumin testing of patients with known diabetes. Therefore, if a depressed eGFR is calculated from a serum creatinine measurement, it may help providers recognize early CKD and pursue appropriate follow-up testing and therapeutic intervention.

-Monitoring kidney function (by GFR or creatinine clearance) is essential once albuminuria is discovered. Estimated GFR is a more practical means to closely follow changes in GFR over time, when compared to direct measurement using methods such as iothalamate clearance.

-The CKD-EPI equation does not require weight or height variables. From a serum creatinine measurement, it generates a GFR result normalized to a standard body surface area (1.73 m[2]) using sex and age. Unlike the Cockcroft-Gault equation, height and weight, which are often not available in the laboratory information system, are not required. The 2021 CKD-EPI Cr equation does not require race, so eGFR values for both African American and non-African American populations are no longer reported. The new 2021 CKD-EPI eGFR values cannot be directly compared to the previous 2009 CKD-EPI Cr eGFR values, which were separately reported for African American and non-African American populations.

The Kidney Disease: Improving Global Outcomes (KDIGO) CKD work group clinical practice guidelines,(1) as further defined by the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) commentary,(2) provided recommendations for reporting and interpretation of serum creatinine and eGFR, which were revised after development of a refit CKD-EPI Creatinine eGFR equation in 2021 that does not require a mathematical adjustment based on race:

1.4.3: Evaluation of GFR

-1.4.3.1: We recommend using serum creatinine and GFR estimating equation for initial assessment.

-1.4.3.2: We suggest using additional tests (such as cystatin C or a clearance measurement) for confirmatory testing in specific circumstances when eGFR based on serum creatinine is less accurate.

-1.4.3.3: We recommend that clinicians:

Use a GFR estimating equation to derive GFR from serum creatinine (eGFRcreat) rather than relying on the serum creatinine concentration alone.

Understand clinical settings in which eGFR creat is less accurate.

-1.4.3.4: We recommend that clinical laboratories should:

Measure serum creatinine using a specific assay with calibration traceable to the international standard reference materials and minimal bias compared to isotope-dilution mass spectrometry (IDMS) reference methodology.

Report eGFRcreat in addition to the serum creatinine concentration in adults and specify the equation used whenever reporting eGFRcreat.

Report eGFRcreat in adults using the 2021 CKD-EPI creatinine equation.

When reporting serum creatinine:

We recommend that serum creatinine concentration be reported and rounded to the nearest whole number when expressed as standard international units (mmol/L) and rounded to the nearest 100th of a whole number when expressed as conventional units (mg/dL).

When reporting eGFRcreat:

-We recommend that eGFRcreat should be reported and rounded to the nearest whole number and relative to a body surface area of 1.73 m(2) in adults using the units mL/min/1.73 m(2).

-We recommend eGFRcreat levels less than 60 mL/min/1.73 m(2) should be reported as "decreased".

1.4.3.8: We suggest measuring GFR using an exogenous filtration marker under circumstances where more accurate ascertainment of GFR will impact treatment decisions.

Creatinine Clearance:

Creatinine is derived from the metabolism of creatine from skeletal muscle and dietary meat intake and is released into the circulation at a relatively constant rate. Thus, the serum creatinine concentration is usually stable. Creatinine is freely filtered by glomeruli and not reabsorbed or metabolized by kidney tubules. Therefore, creatinine clearance can be used to assess GFR. However, approximately 15% of excreted urine creatinine is derived from proximal tubular secretion. Because of the tubular secretion of creatinine, creatinine clearance typically overestimates true GFR by 10% to 15%.

Creatinine clearance is usually determined from measurement of creatinine in a 24-hour urine specimen and from a serum specimen obtained during the same collection period. However, shorter time periods can be used. A key consideration is accurate timing and collection of the urine sample. Creatinine clearance normalized to body surface area is calculated by the equation:

2.54 cm=1 inch

1 kg=2.2 pounds (lbs)

Patient surface area (SA)=wt (kg)(0.425) X ht (cm)(0.725) X 0.007184

CREATININE CLEARANCE

Males:

0-18 years: Not established

19-75 years: 77-160 mL/min/body surface area (BSA)

> or =76 years: Not established

Females:

0-17 years: Not established

18-29 years: 78-161 mL/min/BSA

30-39 years: 72-154 mL/min/BSA

40-49 years: 67-146 mL/min/BSA

50-59 years: 62-139 mL/min/BSA

60-72 years: 56-131 mL/min/BSA

> or =73 years: Not established

CREATININE, URINE:

Reported in units of mg/dL

CREATININE, SERUM

Males:

0-11 months: 0.17-0.42 mg/dL

1-5 years: 0.19-0.49 mg/dL

6-10 years: 0.26-0.61 mg/dL

11-14 years: 0.35-0.86 mg/dL

> or =15 years: 0.74-1.35 mg/dL

Females:

0-11 months: 0.17-0.42 mg/dL

1-5 years: 0.19-0.49 mg/dL

6-10 years: 0.26-0.61 mg/dL

11-15 years: 0.35-0.86 mg/dL

> or =16 years: 0.59-1.04 mg/dL

Estimated glomerular filtration rate (eGFR)

> or =18 years old: > or =60 mL/min/BSA

eGFR calculated using the 2021 CKD-EPI creatinine equation

Note: eGFR results will not be calculated for patients younger than 18 years old.

Decreased creatinine clearance indicates decreased glomerular filtration rate (GFR). This can be due to conditions such as progressive kidney disease or result from adverse effect on renal hemodynamics that are often reversible, including drug effects or decreases in effective renal perfusion (eg, volume depletion, heart failure).

Increased creatinine clearance is often referred to as hyperfiltration and is most commonly seen during pregnancy or in patients with early diabetes mellitus, before diabetic nephropathy has occurred. It may also occur with large dietary protein intake.

A major limitation of creatinine clearance is that its accuracy worsens in relation to the amount of tubular creatinine secretion. Often as GFR declines, the contribution of urine creatinine from tubular secretion increases, further increasing the discrepancy between true GFR and measured creatinine clearance.

Estimated GFR:

According to the Kidney Disease: Improving Global Outcomes (KDIGO) CKD work group, chronic kidney disease (CKD) is defined as the abnormalities of kidney structure of function, present for more than 3 months, with implications for health.(1,2) CKD should be classified by cause, GFR category, and albuminuria category.(1,2)

KDIGO guidelines provide the following GFR categories(1,2):

*In the absence of evidence of kidney damage, neither G1 nor G2 fulfill criteria for CKD.

Urinary albumin excretion can also be used to further subdivide CKD stages.

One of the major limitations of creatinine clearance is erroneous results due to incomplete urine collections. Accurate results depend upon a complete and accurately timed collection.

Result can be falsely decreased in patients with elevated levels of N-acetyl-p-benzoquinone imine (metabolite of acetaminophen), N-acetylcysteine, and metamizole.

1. Inker LA, Astor BC, Fox CH, et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for the evaluation and management of CKD. Am J Kidney Dis. 2014;63(5):713-735. doi:10.1053/j.ajkd.2014.01.416

2. National Kidney Foundation. KDOQI Clinical Practice Guideline for Diabetes and CKD: 2012 Update. Am J Kidney Dis. 2012;60(5):850-886. doi:10.1053/j.ajkd.2012.07.005. Erratum in: Am J Kidney Dis. 2013 Jun;61(6):1049

3. Inker LA, Perrone RD. Assessment of kidney function. In: Sterns RH, Forman JP, eds. UpToDate; 2021. Updated February 2024. Accessed April 1, 2024. Available at www.uptodate.com/contents/assessment-of-kidney-function

4. Kasiske BL, Keane WF. Laboratory assessment of renal disease: clearance, urinalysis, and renal biopsy. In: Brenner BM, ed. The Kidney. 6th ed. WB Saunders Company; 2000:1129-1170

5. Delaney MP, Lamb EJ. Kidney disease. In: Rifai N, Horvath AR, Wittwer CT, eds. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 6th ed. Elsevier; 2018:1256-1323

6. Miller WG, Kaufman HW, Levey AS, et al. National Kidney Foundation Laboratory Engagement Working Group recommendations for implementing the CKD-EPI 2021 race-free equations for estimated glomerular filtration rate: Practical guidance for clinical laboratories. Clin Chem. 2022;68(4):511-520. doi:10.1093/clinchem/hvab278

7. Inker LA, Eneanya ND, Coresh J, et al. New creatinine- and cystatin C-based equations to estimate GFR without race. N Engl J Med. 2021;385(19):1737-1749. doi:10.1056/NEJMoa2102953

The enzymatic method is based on the determination of sarcosine from creatinine with the aid of creatininase, creatinase, and sarcosine oxidase. The liberated hydrogen peroxide is measured via a modified Trinder reaction using a colorimetric indicator. Optimization of the buffer system and the colorimetric indicator enables the creatinine concentration to be quantified both precisely and specifically.(Package insert: Creatinine plus ver 2. Roche Diagnostics; V15.0, 03/2019)

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This test has been cleared, approved, or is exempt by the US Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.

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