Creatinine, Blood Core Lab Study and Estimated Glomerular Filtration Rate

Creatinine, Blood Core Lab Study and Estimated Glomerular Filtration Rate (eGFR)

Synonym/Acronym

Cr, SCr

Rationale

To assess kidney function found in acute kidney injury and chronic kidney disease (CKD), related to drug reaction and disease such as diabetes.

A small group of studies in this manual have been identified as Core Lab Studies. The designation is meant to assist the reader in sorting the basic “always need to know” laboratory studies from the hundreds of other valuable studies found in the manual—a way to begin putting it all together.

Normal, abnormal, or various combinations of core lab study results can indicate that all is well, reveal a problem that requires further investigation with additional testing, signal a positive response to treatment, or suggest that the health status is as expected for the associated situation and time frame.

Creatinine (Cr) is included in the basic metabolic panel (BMP), comprehensive metabolic panel (CMP), general health panel, and renal function panel. Panels are used as general health and targeted screens to identify or monitor conditions such as bone disease, diabetes, hypertension, kidney disease, liver disease, or malnutrition. Serum creatinine (SCr) is also ordered with the urine creatinine clearance test.

Patient Preparation

There are no food, fluid, or medication restrictions unless by medical direction. Instruct the patient to refrain from excessive exercise for 8 hr before the test.

Normal Findings

Method: Spectrophotometry for Cr; immunoturbidometry for cystatin C.

Creatinine
Age	Conventional Units	SI Units (Conventional Units × 0.0884)
Newborn–11 mo	0.17–0.42 mg/dL	15–37 mmol/L
1–5 yr	0.19–0.51 mg/dL	17–45 mmol/L
6–10 yr	0.26–0.61 mg/dL	23–54 mmol/L
11–14 yr	0.35–0.86 mg/dL	31–76 mmol/L
15 yr–Adult male	0.61–1.21 mg/dL	54–107 mmol/L
15 yr–Adult female	0.59–1.04 mg/dL	52–92 mmol/L
Estimated Glomerular Filtration Rate (eGFR) Many laboratories now report blood Cr and cystatin C values with the corresponding eGFR.
Age	Conventional Units
Less than 18 yrs	Note: The eGFR equation generally recommended for individuals under 18 yrs of age is the Bedside Schwartz formula and is based on Cr levels and height in centimeters.
18–70 yrs	Greater than or equal to 60 mL/min/body surface area
Greater than 70 yr	Values in older adults remain relatively stable, after a period of decline related to loss of muscle mass during the transition from adult to older adult.
Cystatin C
Age	Conventional Units	SI Units (Conventional Units × 74.9)
Adult	0.56–1.2 mg/L	41.9–89.9 mmol/L
BUN/Cr Ratio	10:1 to 20:1

Values vary among laboratories due to differences in instrumentation.

Critical Findings and Potential Interventions ⬆ ⬇

Adults

Potential critical finding is greater than 7.4 mg/dL (SI: 654.2 micromol/L) (patient not on dialysis).

Children

Potential critical finding is greater than 3.8 mg/dL (SI: 336 micromol/L) (patient not on dialysis).

Timely notification to the requesting health-care provider (HCP) of any critical findings and related symptoms is a role expectation of the professional nurse. A listing of these findings varies among facilities.

Consideration may be given to verification of critical findings before action is taken. Policies vary among facilities and may include requesting immediate recollection and retesting by the laboratory or retesting using a rapid point-of-care testing instrument at the bedside, if available.

Chronic renal insufficiency is identified by Cr levels between 1.5 and 3 mg/dL (SI: 132.6 and 265.2 micromol/L); CKD is present at levels greater than 3 mg/dL (SI: 265.2 micromol/L).

Possible interventions may include renal or peritoneal dialysis and organ transplant, but early discovery of the cause of elevated Cr levels might avoid such drastic interventions.

Overview ⬆ ⬇

Study type: Blood collected in a red-, green-, or red/gray-top tube; related body system: Musculoskeletal and Urinary systems.

Chronic kidney disease (CKD) is a significant health concern worldwide. International research has been undertaken to evaluate the risk factors common to cardiovascular disease, diabetes, and hypertension; these three diseases are all associated with CKD. Albuminuria, which can result from increased glomerular permeability to proteins, is considered an independent risk factor predictive of kidney or cardiovascular disease. The National Kidney Foundation and American Society for Clinical Pathology recommend using timed or random urine albumin (formerly microalbumin) and eGFR together to screen for CKD. The tests are sometimes ordered together in a bundle called the Kidney Profile:

The urine albumin assesses for kidney damage. Urine creatinine is also measured in order to report the albumin/creatinine ratio (ACR). For additional information regarding urine albumin and the albumin creatinine ratio (ACR) refer to the study titled “Albumin, Urine and Albumin to Creatinine Ratio (ACR).”
The eGFR assesses for kidney function. Either serum creatinine and/or cystatin C levels are required for the estimation formulas.

Creatinine

Creatinine is the end product of creatine metabolism. Creatine resides almost exclusively in skeletal muscle, where it participates in energy-requiring metabolic reactions. In these processes, creatine is irreversibly converted to Cr, which then circulates to the kidneys and is excreted into the urine at a relatively consistent rate. The amount of Cr generated in an individual is proportional to the mass of skeletal muscle present and remains fairly constant, unless there is massive muscle damage resulting from crushing injury or degenerative muscle disease. Cr values normally decrease with age owing to diminishing muscle mass. Conditions involving degenerative muscle wasting or massive muscle trauma from a crushing injury will also result in decreased Cr levels.

Creatinine, a longstanding marker for kidney function, is now routinely evaluated in combination with other markers of kidney health in order to identify kidney disease and provide clinical interventions sooner. Kidney function, as with other bodily functions, normally diminishes with age; estimated loss of filtration occurs at the rate of 1% per year beginning at age 40 yr. Many kidney related diseases (e.g. diabetic nephropathy, hypertension) progress without signs or symptoms until a significant amount of kidney function is lost (30%–40%).

When one kidney becomes damaged, diseased, or removed (by nephrectomy) the remaining healthy kidney can compensate; no change in kidney function is expected. Diseases such as diabetes affect both kidneys over time. Kidney transplantation of a single healthy kidney can restore a normal level of renal function; the second non-functioning kidney is usually left in place.

Screening for CKD is recommended for high-risk individuals with:

cardiovascular disease
diabetes
family history of kidney failure
hypertension
older adults

BUN and BUN/Cr ratio

BUN and BUN/Cr ratio BUN is another marker for kidney function often ordered with blood Cr for comparison and mentioned here because it is required to calculate the BUN/Cr ratio. While Cr levels remain fairly constant over time, BUN levels can vary due to normal circumstances including fluctuations in protein intake, protein catabolism, and fluid levels (second and third trimester pregnancy), making it a less valuable marker than Cr, in some ways. BUN can also vary due to pathologic conditions other than kidney disease (e.g., liver disease). For additional information regarding BUN, refer to the study titled “Urea Nitrogen, Blood, Core Lab Study.” The BUN/Cr ratio is a useful indicator of kidney disease. The normal BUN/creatinine ratio is 10:1 to 20:1 (e.g., if a patient has a BUN of 10 mg/dL and a Cr of 0.91 mg/dL the ratio is calculated:10/0.91 or BUN/Cr ratio = 11 or 11:1).

Cystatin C

Cystatin C, also known as cystatin 3 and CST3, is now recognized as a useful biomarker for kidney damage. It is also used to monitor function of transplanted kidneys. It is a low-molecular-weight molecule belonging in the family of proteinase inhibitors. Cystatin C is produced by all nucleated cells in the body and is freely filtered by the glomerular membrane in the kidney. It is broken down in the tubules; it does not reenter circulation, small amounts may be excreted in the urine. Cystatin is believed to be a better marker of kidney function than Cr in some ways because levels are independent of variations in age, gender, or muscle mass.

eGFR

GFR is a measure of kidney function. The kidney’s primary function is to filter waste products and excess water from the blood. Other important functions include maintaining pH and electrolyte balance and production of hormones that regulate critical feedback loops over functions involving acid-base balance, blood pressure, bone health, electrolyte balance, hydration, and production of red blood cells. Each kidney contains more than a million glomeruli; GFR refers to the amount of blood that is filtered by the glomeruli per minute.

GFR can be measured by calculating the rate at which an injected marker (e.g., inulin) is excreted into the urine by the kidneys. Measured GFR is still the gold standard and most accurate way to determine GFR. Measured GFR should be used in situations where improved accuracy would influence treatment decisions, but it is more complicated to perform and impractical for routine use given the near instantaneous availability of mathematically derived algorithms.

There are multiple formulas in use for calculation of the eGFR. Either Cr or cystatin may be used. The most common formulas use SCr value, age, and correction factors for gender and race. Studies have shown that people of specific descent are at increased risk of developing CKD (African, Native American, and Pacific Islander); Hispanics are 1.5 times more likely than non-Hispanics to develop CKD. Continuing to use race in estimating eGFR is being reevaluated; incorporating race doesn’t consider the (genetic) diversity found in communities of color or take into account the issue of requiring multiracial individuals to choose a single category for race. In September 2021, the National Kidney Foundation and American Society of Nephrology joint task force released its final report which outlines a race-free approach for the diagnosis of kidney disease and recommends the use of the CKD-EPI Cr calculation (2021) for eGFR. The recommendation was endorsed by the United States Pathology and Laboratory Society Leadership in February 2022. Laboratories have begun to transition to race-free eGFR calculations.

The eGFR calculation based on blood cystatin C level is recommended for confirmatory testing in circumstances when eGFR based on serum creatinine is less accurate, such as:

acute kidney injury
medications affecting kidney function
variations in muscle mass (e.g., amputees, body builders, males vs. females)
variations in muscle metabolism (e.g., extremes in age, i.e., pediatric and geriatric; extremes in body weight, vegetarians)

Recommendations for measuring and reporting creatinine values and eGFR (formulas are available that use Cr and/or cystatin to calculate eGFR):

At this time, all laboratories should be using Cr methods calibrated to be isotope dilution mass spectrometry (IDMS) traceable. IDMS is the international reference method used to standardize measurement of Cr.
Serum/plasma Cr levels should be reported to the nearest hundredth (two decimal places) in conventional units (mg/dL).
Serum/plasma Cr levels should be reported to the nearest whole number in standard international units (mmol/L).
Lab reports that include SCr for adults should also include the corresponding eGFR.
The National Kidney Foundation recommends the use of the CKD-EPI (2021) race-free calculation for Cr to arrive at the eGFR.
The National Kidney Foundation kidney disease outcome quality initiative (KDOQI) and kidney disease improving global outcome (KDIGO) guidelines recommend confirming Cr based eGFR values that are between 45 and 59 mL/min/body surface, with an ACR less than 30 mg/g, using an eGFR calculation based on both creatinine and cystatin C.
Lab reports that include eGFR should specify the equation used (e.g., CKD-EPI creatinine equation [2021], CKD-EPI creatinine and cystatin C equation [2012], CKD-EPI creatinine and cystatin C equation [2021], CKD-EPI cystatin C equation [2012], CKD-EPI creatinine equation [2009], etc.).
The eGFR (adult) should be reported to the nearest whole number in mL/min/1.73m² (based on a body surface area of 1.73 m²).
The CKD-EPI (2009) equation for adults is valid only for patients between the ages of 18 and 70.

eGFR for Pregnant Females and Children Under 18 Years of Age

The 2009 Bedside Schwartz formula, is recommended for estimating GFR for children under 18 yr of age. It is an IDMS-traceable equation using serum Cr results from a method that has a calibration traceable to the IDMS. eGFR = 0.413 × (height/Scr) if height is expressed in centimeters OR 41.3 × (height/Scr) if height is expressed in meters. The formula uses the patient’s height in centimeters and the serum Cr value where the GFR (mL/min/1.73 m2) = (0.41 × height cm)/serum Cr mg/dL (SI Units: GFR (mL/min/1.73 m2) = (36.2 × height cm)/serum Cr micromol/L. For consistency in the interpretation of test results, it is important to know whether the Cr has been measured using IDMS-traceable test methods and equations.

The equations have not been validated for pregnant women (GFR is significantly increased in pregnancy); patients older than 70; patients with serious comorbidities; or patients with extremes in body size, muscle mass, or nutritional status. eGFR calculators can be found at the NKDEP Web site (www.niddk.nih.gov/health-information /communication-programs /nkdep); links are provided for various calculators (e.g., adult and pediatric patients), select the appropriate link to access the desired calculator.

Creatinine clearance

The creatinine clearance test measures a blood sample and a urine sample to determine the rate at which the kidneys are clearing creatinine from the blood; this reflects the glomerular filtration rate (GFR) and is based on an estimate of body surface. eGFR formulas are now routinely used to evaluate kidney function; their use has become more common than use of other tests that reflect GFR, such as the urine creatinine or inulin clearance tests. For additional information regarding the creatinine clearance and marker injection tests, refer to the study titled “Creatinine, Urine, and Creatinine Clearance, Urine.”

Indications ⬆ ⬇

Assess a known or suspected disorder involving muscles in the absence of kidney disease.
Evaluate known or suspected impairment of kidney function.

Interfering Factors ⬆ ⬇

Factors That May Alter the Results of the Study

Drugs and other substances that may increase Cr levels include amiodarone, aminoglycosides, amphotericin B, captopril, carbutamide, carvedilol, cephalosporins, chlorthalidone, cimetidine, cisplatin, cyclosporine, doxycycline, ethylene glycol, fibrates, lisinopril, methicillin, NSAIDs, paromomycin, penicillins, pentamidine, plicamycin, radiographic medium, ramitidine, tetracycline, thiazides, triamterene, trimethoprim, vancomycin, and vasopressin.
Drugs and other substances that may decrease Cr levels include captopril, citrates, dopamine, ibuprofen, and lisinopril.
High blood levels of bilirubin and glucose can cause false decreases in Cr.
A diet high in meat can cause increased Cr levels.
Ketosis can cause a significant increase in Cr.

Other Considerations

Hemolyzed specimens are unsuitable for analysis.

Potential Medical Diagnosis: Clinical Significance of Results ⬆ ⬇

Increased In

Acromegaly(related to increased muscle mass)
Dehydration(related to hemoconcentration)
Gigantism(related to increased muscle mass)
Heart failure (related to decreased renal blood flow)
HELLP syndrome of pregnancy; variant of preeclampsia (hemolysis, elevated liver enzymes, low platelet count)
Kidney disease, acute kidney injury, and CKD (related to decreased urinary excretion)
Poliomyelitis(related to increased release from damaged muscle)
Pregnancy-induced hypertension (related to reduced GFR and decreased urinary excretion)
Renal calculi(related to decreased kidney excretion due to obstruction)
Rhabdomyolysis(related to increased release from damaged muscle)
Shock(related to increased release from damaged muscle)

Decreased In

Decreased muscle mass(related to debilitating disease or increasing age)
Hyperthyroidism (related to increased GFR)
Inadequate protein intake(related to decreased muscle mass)
Liver disease (severe) (related to fluid retention)
Muscular dystrophy(related to decreased muscle mass)
Pregnancy (related to increased GFR and renal clearance)
Small stature(related to decreased muscle mass)

eGFR

eGFR is used to classify the five stages of CKD

Degree of impairment:
- Stage 1 (normal or increased GFR with or without early kidney disease): GFR greater than 90 mL/min/1.73 m²
- Stage 2 (damage with mild reduction in GFR): GFR between 60 and 89 mL/min/1.73 m²
- Stage 3 (moderate reduction in GFR): GFR between 30 and 59 mL/min/1.73 m²
- Stage 4 (severe reduction in GFR): GFR between 15 and 29 mL/min/1.73 m²
- Stage 5 (kidney failure/end stage renal disease): GFR less than 15 mL/min/1.73 m²

BUN/Cr Ratio

The ratio can provide a general indication of an underlying cause; it should not be evaluated in isolation because it doesn’t always point to a clear or accurate finding. For example, the individual BUN and Cr levels are both elevated in chronic kidney disease but the ratio is often normal.

Increased In

Decreased blood flow to kidneys (e.g., related to heart failure, dehydration, or urinary tract obstruction of recent onset, conditions that increase reabsorption of urea)
Decreased muscle mass (related to a disproportionate increase in BUN relative to Cr)
Hyperthyroidism (where BUN levels may increase and Cr levels decrease)
Increased production of urea (related to advanced liver disease; increased protein from GI bleeding)
Increased dietary intake of protein (related to a disproportionate increase in BUN relative to Cr)

Decreased In

Liver disease (related to decreased urea production by damaged liver)
Liver trauma (related to decreased urea production by damaged liver)
Fluid overload(related to a dilutional effect on blood levels)
Hypothyroidism (related to an associated reduction in kidney function)
Malnutrition (dependent on degree of malnutrition: related to decreased protein intake and relatively stable Cr level; in severe cases where significant muscle wasting also occurs the Cr may be disproportionately increased)
Pregnancy (related to the dilutional effect on blood levels)
Starvation(dependent on degree of muscle wasting: related to decreased protein intake and relatively stable Cr level; in severe cases where significant muscle wasting also occurs the Cr may be disproportionately increased)
Rhabdomyolysis (related to significant muscle breakdown and significantly increased Cr levels)

Nursing Implications, Nursing Process, Clinical Judgement ⬆

Potential Nursing Problems: Assessment & Nursing Diagnosis

Problems		Signs and Symptoms
Cardiac output (decreased—related to excess fluid volume, pericarditis, electrolyte imbalance, toxin accumulation)		Weak peripheral pulses, slow capillary refill, decreased urinary output, cool clammy skin, tachypnea, dyspnea, altered level of consciousness, abnormal heart sounds, fatigue, hypoxia, loud holosystolic murmur, ECG changes, increased jugular venous distention (JVD)
Fluid volume (excess—related to excess fluid and sodium intake, compromised renal function)		Edema, shortness of breath, increased weight, ascites, rales, rhonchi, diluted laboratory values, jugular venous distention (JVD), tachycardia, restlessness

Before the Study: Planning and Implementation

Teaching the Patient What to Expect

Discuss how this test can assist in assessing kidney function.
Explain that a blood sample is needed for the test.

After the Study: Implementation & Evaluation Potential Nursing Actions

Treatment Considerations

Cardiac Output

Facilitate management of decreased cardiac output.
Assess peripheral pulses and capillary refill.
Monitor blood pressure and check for orthostatic changes.
Assess respiratory rate, breath sounds, skin color and temperature, and level of consciousness.
Monitor and trend urinary output.
Administer ordered oxygen and assess effectiveness with pulse oximetry.
Facilitate ordered ECG.
Administer ordered inotropic and peripheral vasodilator medications, nitrates, sodium bicarbonate, glucose, and insulin drip.

Fluid Volume

Facilitate management of fluid volume excess.
Record and trend daily weight.
Record, trend, and ensure accurate intake and output.
Monitor laboratory values that reflect alterations in fluid status and kidney function: potassium, BUN, Cr, calcium, Hgb, Hct, and sodium.
Manage underlying cause of fluid excess (limit fluids).
Monitor urine characteristics and call attention to urine volumes less than the minimal amount (30 mL/hr).
Establish baseline assessment data: heart rate, blood pressure, JVD, shortness of breath, dyspnea, or crackles.
Ensure adherence to a low-sodium diet; administer prescribed diuretic and antihypertensive.
Elevate feet when sitting and head of the bed when resting.
Monitor oxygenation with pulse oximetry and ordered oxygen.

Nutritional Considerations

Increased Cr levels may be associated with kidney disease.
The nutritional needs of patients with kidney disease vary widely and are in constant flux.
Anorexia, nausea, and vomiting commonly occur, prompting the need for continuous monitoring for malnutrition, especially among patients receiving long-term hemodialysis therapy.

Clinical Judgement

Consider which educational formats will best achieve the outcome of dietary adherence in those with renal compromise.

Follow-Up and Desired Outcomes

Acknowledges contact information provided for the American Diabetes Association (www.diabetes.org), NKF (www.kidney.org), or NKDEP (www.nkdep.nih.gov).
Acknowledges the importance of adhering to scheduled laboratory blood draws to better manage trends in disease process and adapt therapeutic interventions to meet identified changes.