What it is
The transtubular potassium gradient estimates the driving force for potassium secretion in the cortical collecting duct — a surrogate for aldosterone activity. It asks whether the kidney is responding appropriately to a given plasma potassium, helping separate renal from non-renal causes of dyskalemia.
Formula
$$ TTKG = \frac{U_K / P_K}{U_{osm} / P_{osm}} $$
where U and P are urine and plasma potassium (mEq/L) and osmolality (mOsm/kg). The urine osmolality term corrects for water reabsorbed distally, back-estimating the potassium concentration at the end of the cortical collecting duct.
When to use
Workup of hyperkalemia or unexplained hypokalemia, to gauge whether renal potassium handling is appropriate. Validity preconditions matter: the result is only interpretable when urine osmolality > plasma osmolality AND urine Na > 25 mEq/L (adequate distal sodium delivery). This tool flags the calculation as invalid when urine is not concentrated relative to plasma.
Interpretation
- Hyperkalemia: an appropriate kidney drives TTKG >7–8. A value <5–7 suggests hypoaldosteronism (or aldosterone resistance) — the kidney is failing to excrete potassium.
- Hypokalemia: an appropriate kidney conserves potassium, giving TTKG <3. A value >3 implies inappropriate renal potassium wasting.
Worked example
Hyperkalemic child: urine K 40, plasma K 6.0, urine osm 600, plasma osm 300.
$$ TTKG = \frac{40/6.0}{600/300} = \frac{6.67}{2.0} = 3.3 $$
Urine osm (600) > plasma osm (300), so the gradient is interpretable. A TTKG of 3.3 during hyperkalemia is inappropriately low (expected >7) — pointing toward hypoaldosteronism; confirm with urine Na >25 and aldosterone/renin studies.
Pitfalls
- The model is contested. It assumes no significant potassium or osmole handling in the medullary collecting duct; medullary urea recycling undermines that assumption, and many nephrologists now prefer the urine K/creatinine ratio. Treat TTKG as one data point, not a verdict.
- Preconditions are non-negotiable. If urine osm ≤ plasma osm or urine Na <25, the number is meaningless — low distal sodium delivery alone can suppress secretion.
- Acid-base and drugs confound it (e.g. RTA, ACE inhibitors, potassium-sparing diuretics, trimethoprim).
- Always interpret alongside plasma potassium, volume status, urine sodium, and acid-base data.
Run it: Transtubular Potassium Gradient (TTKG)
Decision support for qualified clinicians only — verify against current primary guidelines and your clinical judgement.