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Creatinine, eGFR and ammonia

16 min

Skills you'll build4 skills
  • Recognize when a creatinine eGFR needs a cystatin C equation or a measured GFR
  • Calculate fractional sodium excretion using paired concentrations
  • Keep an ammonia specimen on ice and centrifuge it cold without delay
  • Check assay limits or use another method for a creatinine on an icteric specimen

At the bench: Assess specimen interference before reporting a chemistry result

Try first

Try first

A hospitalized man's creatinine was 1.0 mg/dL yesterday and is 1.9 mg/dL today. The report shows an eGFR calculated from today's creatinine. How well does that eGFR reflect his current kidney function?

Right. Keep going to follow the reasoning.

Keep going to see the reasoning.

Keep going to see the reasoning.

Keep going to see the reasoning.

Get the idea

Use the explanation to check your first decision.

Limits of eGFR

Creatinine comes from muscle at a fairly steady rate, and the kidney clears it mostly by filtration. In a steady state, plasma creatinine rises as filtration falls. A creatinine can stay within its reference interval while GFR drops, so each result is compared with the patient's baseline.1

The race-free CKD-EPI 2021 equation calculates an eGFR from a standardized creatinine, age and sex.2 It assumes typical creatinine production and a steady state. Low muscle mass, amputation, diet and a rapidly changing creatinine all make it less accurate. KDIGO 2024 advises a combined creatinine and cystatin C eGFR when creatinine is likely to be unreliable, and a measured GFR when the added accuracy could change a decision.3

Fractional excretion of sodium

FENa (%) = [urine sodium × plasma creatinine] ÷ [plasma sodium × urine creatinine] × 100, with matching units within the sodium pair and within the creatinine pair, and specimen identity and collection times checked before the four results are combined. The urine volume cancels, so no timed collection is needed. A creatinine in µmol/L is divided by 88.4 to give mg/dL.1 Diuretics raise urine sodium, and the result alone does not assign a cause to a kidney injury.4

Ammonia specimen handling

Amino acids continue to break down in collected blood, and ammonia rises while the tube waits. Handling determines whether the result is valid:1,5

  1. Draw without trauma.
  2. Put the tube on wet ice at once.
  3. Centrifuge it cold, at 0 to 4 °C, promptly.
  4. Analyze the plasma without delay, or freeze it.

Red cells contain 2 to 3 times the plasma ammonia, so a hemolyzed specimen is rejected. Tobacco smoke also contaminates the specimen.1,5

Creatinine on an icteric specimen

Bilirubin usually biases creatinine low. A rate-blanked Jaffe assay has shown a positive bias, so the direction cannot be assumed from the method family.6 Check the assay's stated bilirubin limit and the concentrations it was tested at, or measure by a validated alternate method. A result is never corrected from the icterus index. A new specimen has the same bilirubin, so a redraw does not help.1,6

Follow the bench demonstration

Sources for this step
References
  1. Bishop ML, Fody EP, Van Siclen C, Mistler JM, Moy M. Clinical Chemistry: Principles, Techniques, and Correlations. 9th ed. Jones & Bartlett Learning; 2023.
  2. 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
  3. Kidney Disease: Improving Global Outcomes CKD Work Group. KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. 2024;105(4S):S117-S314. doi:10.1016/j.kint.2023.10.018
  4. Abdelhafez M, Nayfeh T, Atieh A, et al. Diagnostic performance of fractional excretion of sodium for the differential diagnosis of acute kidney injury: a systematic review and meta-analysis. Clin J Am Soc Nephrol. 2022;17(6):785-797. doi:10.2215/CJN.14561121
  5. Mayo Clinic Laboratories. Ammonia, plasma. Accessed September 27, 2026. https://www.mayocliniclabs.com/test-catalog/overview/35130
  6. Cheung T, Tawfik A, Kampfrath T. Effects of bilirubin interference in the Roche kinetic alkaline picrate creatinine assay. J Appl Lab Med. 2018;3(1):152-154. doi:10.1373/jalm.2017.025528

Watch one

Read each decision and its explanation.

A random urine and a plasma specimen are collected together at 10:15 from a patient with a rising creatinine. The medication record shows no diuretic.

What is the fractional excretion of sodium?

TestResultPreviousReference intervalFlag
Plasma sodium136 mmol/L136–145 mmol/L136–145
Plasma creatinine2.4 mg/dL High2 days ago: 1.1 mg/dL1.1 mg/dL2 days ago0.7–1.3 mg/dL0.7–1.3High
Urine sodium18 mmol/L
Urine creatinine120 mg/dL

Specimen: H 4, L 8, I 2. Plasma and random urine, collected together

  1. Check the pairing: both specimens have the same identifiers and the 10:15 collection time.

    The four results can be combined only when they come from the same patient at the same time.

  2. Check the units: both sodiums in mmol/L, both creatinines in mg/dL.

    Each pair must share units so that the units cancel.

  3. Numerator: 18 mmol/L × 2.4 mg/dL = 43.2.

    Urine sodium goes with plasma creatinine in the numerator.

  4. Denominator: 136 mmol/L × 120 mg/dL = 16,320.

    Plasma sodium goes with urine creatinine in the denominator.

  5. Divide and scale: 43.2 ÷ 16,320 × 100 = 0.26%.

    The quotient is a fraction, and multiplying by 100 makes it a percentage.

  6. Check the medication record before the result is interpreted. No diuretic was given.

    A diuretic raises urine sodium and would limit the interpretation.

FENa = (18 × 2.4) ÷ (136 × 120) × 100 = 0.26%.

Practice this skill

Your turn

Problem 1 of 3 · Hints available

A person with very low muscle mass has a creatinine-based estimated GFR (eGFR) of 95 mL/min/1.73 m². How does this estimate likely compare with the true GFR?

Correct. Low muscle mass generates little creatinine, so serum creatinine is low and the equation overestimates GFR. Standardized cystatin C, which depends less on muscle mass, usually improves the estimate.

Incorrect. Indexing to 1.73 m2 standardizes body size. It does not correct for how little creatinine a small muscle mass produces.

Incorrect. Retention would raise serum creatinine. Here low muscle mass lowers creatinine generation, so the estimate is falsely high.

Hint
  1. Ask where creatinine comes from.
  2. Low muscle mass produces less creatinine. Consider what a low creatinine does to the calculated eGFR.

Review Filtration markers and eGFR

Problem 2 of 3 · Hints available

Plasma ammonia is ordered. Which handling supports a reliable result?

Correct. Ammonia rises quickly in collected blood as amino acids deaminate, so put the tube on wet ice at once, centrifuge it cold at 0 to 4 °C, and analyze the plasma without delay or freeze it.

Incorrect. Whole blood left for a batch run stays unseparated until analysis. Separate the plasma cold and promptly, then analyze it at once or freeze it.

Incorrect. Amino acids deaminate quickly in blood left at room temperature, so ammonia rises during the delay. Put the tube on wet ice at once and centrifuge it cold.

Hint
  1. Ammonia continues to form in blood after the draw.
  2. Ask which handling slows that reaction from the moment of collection.

Review Specimen handling

Problem 3 of 3 · On your own

Paired results are urine sodium 64 mmol/L, plasma sodium 140 mmol/L, urine creatinine 40 mg/dL and plasma creatinine 265.2 µmol/L. What is the fractional excretion of sodium, to one decimal place?

Show the answer

3.4 %

Plasma creatinine = 265.2 ÷ 88.4 = 3.0 mg/dL. FENa = (64 × 3.0) ÷ (140 × 40) × 100 = 192 ÷ 5,600 × 100 = 3.4%. Leaving the plasma creatinine in µmol/L gives 303%, because the creatinine units no longer cancel.

Review Fractional excretion of sodium

For reference

Sources checked