Transtubular Potassium Gradient (TTKG) Calculator
Transtubular Potassium Gradient (TTKG) Calculator
Estimate distal nephron potassium handling from paired urine and serum values — and understand why nephrologists increasingly avoid it.
Transtubular Potassium Gradient (TTKG)
(Uk/Pk) ÷ (Uosm/Posm)Urine K 25, serum K 5.9 mmol/L, urine osm 600, serum osm 290 mOsm/kg
Formula
- urine K, serum K
- mmol/L
- urine osm, serum osm
- mOsm/kg
- validity
- requires urine osmolality > serum osmolality and urine sodium > 25 mmol/L
Worked example
Urine K 25, serum K 5.9 mmol/L, urine osm 600, serum osm 290 mOsm/kg
(25 ÷ 5.9) = 4.24
(600 ÷ 290) = 2.07
4.24 ÷ 2.07 = 2.0
Below 3 → low, consistent with hypoaldosteronism given the hyperkalaemia
Interpreting TTKG
| TTKG | Interpretation |
|---|---|
| < 3 | Low — in hyperkalaemia, suggests hypoaldosteronism or resistance |
| 3 – 7 | Intermediate |
| > 7 | High — in hypokalaemia, suggests renal potassium wasting (typically > 4) |
A widely taught index that has fallen out of favour
The transtubular potassium gradient was designed to estimate the potassium concentration at the end of the cortical collecting duct, correcting the raw urine potassium for how much water has been reabsorbed by that point, using osmolality as the marker of water reabsorption. In hyperkalaemia, a TTKG below 7 — some authors use below 5 — is taught as suggestive of hypoaldosteronism or aldosterone resistance, since aldosterone normally drives potassium secretion at that site. In hypokalaemia, a TTKG above 4 is taught as suggestive of renal potassium wasting rather than an extrarenal cause such as diarrhoea or poor intake.
It should be used only when urine osmolality exceeds serum osmolality and urine sodium exceeds 25 mmol/L, since the calculation assumes there is adequate distal sodium delivery and ongoing water reabsorption to interpret.
Be candid about its standing: the TTKG has fallen out of favour in nephrology. Its foundational assumption — that no significant osmole reabsorption occurs between the cortical and medullary collecting duct, so cortical osmolality can be inferred from the final urine osmolality — has been shown to be incorrect; urea reabsorption in the medullary collecting duct violates it. The index’s own original authors have publicly retracted their support for it. Many nephrologists now prefer the urine potassium-to-creatinine ratio, which needs no osmolality measurement and rests on a simpler assumption.
Frequently asked questions
What does a low TTKG mean in hyperkalaemia?
A TTKG below 7 (some use below 5) in hyperkalaemia suggests hypoaldosteronism or aldosterone resistance — the distal nephron is not secreting potassium as it should.
What does a high TTKG mean in hypokalaemia?
A TTKG above 4 in hypokalaemia suggests renal potassium wasting rather than an extrarenal cause such as poor intake or gastrointestinal loss.
Why has TTKG fallen out of favour?
Its core assumption — that no significant osmole reabsorption happens in the medullary collecting duct — is now known to be wrong, chiefly because of urea reabsorption there. The index’s original authors have retracted their support for it.
What is used instead of TTKG now?
Many nephrologists prefer the urine potassium-to-creatinine ratio, which avoids the osmolality assumption altogether and is simpler to obtain.
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References
- Ethier JH, Kamel KS, Magner PO, Lemann J, Halperin ML. The transtubular potassium concentration in patients with hypokalemia and hyperkalemia. Am J Kidney Dis. 1990;15(4):309–15.
- Kamel KS, Halperin ML. Use of urine electrolytes and urine osmolality in the clinical diagnosis of fluid, electrolytes, and acid-base disorders. Kidney Int Rep. 2021;6(5):1211–24.