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Creatinine, eGFR and ammonia

16 min

  • 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

Read the full reference

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 describe his kidney function right now?

Right. The next section explains why.

The next section explains it.

The next section explains it.

The next section explains it.

Get the idea

An eGFR is an estimate

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 turns a standardized creatinine, age and sex into an eGFR.2 It assumes typical creatinine production and a steady state. Low muscle mass, amputation, diet and a rapidly changing creatinine all push it away from the true GFR. KDIGO 2024 advises a combined creatinine and cystatin C eGFR when creatinine is likely to mislead, 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 starts rising in the tube

Amino acids keep breaking down in collected blood, and ammonia climbs while the tube waits. The handling decides whether the result means anything: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 hold 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 carries the same bilirubin, so a redraw does not help.1,6

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

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/L
Plasma creatinine2.4 mg/dL1.1 mg/dL2 days ago0.7–1.3 mg/dLHigh
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 carry the same identity and the 10:15 collection time.

    The four results only make one ratio when they belong to 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 what the number can say.

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

Your turn

Problem 1 of 3

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 sits low and the equation returns a GFR above the true value. 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 errs upward.

Hint
  1. Ask where creatinine comes from.
  2. Little muscle makes little creatinine. Follow what a low creatinine does to the equation's answer.

Review Filtration markers and eGFR

Problem 2 of 3

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 waiting for a batch stays on its cells 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 climbs during the wait. Put the tube on wet ice at once and centrifuge it cold.

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

Review Specimen handling

Problem 3 of 3

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

Keep

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