1. TTKG Calculator
TTKG = (K+ urine / K+ serum) × (serum osmolality / urine osmolality)
Urine and serum samples should ideally be collected close together in time. Monovalent potassium: mEq/L ≡ mmol/L.
Transtubular Potassium Gradient
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Calculation steps
Validity status
Note: the interpretation above is educational and does not establish a diagnosis. Cutoff values vary between sources; clinical decisions require the full patient context assessed by a physician.
2. Interpretation tree
Choose the path based on serum potassium, then read the TTKG band. Your calculation result will automatically highlight the relevant path.
Hyperkalemia (serum K > 5.5 mEq/L)
TTKG > 4 → adequate renal excretion → look for non-renal causes: pseudohyperkalemia, potassium intake, K+ shift out of cells.
TTKG ≤ 4 → impaired renal excretion → consider hypoaldosteronism / drugs: ACE inhibitors, ARBs, K-sparing diuretics, trimethoprim, NSAIDs, heparin; type IV RTA.
Hypokalemia (serum K < 3.5 mEq/L)
TTKG < 3 → adequate renal conservation → non-renal losses: diarrhea, sweating, K+ shift into cells.
TTKG 3–4 → gray zone, indeterminate.
TTKG > 4 → renal losses: hyperaldosteronism, diuretics, vomiting, RTA.
TTKG > 7 → definite renal losses (Palmer & Clegg, AJKD 2019).
Normal serum potassium (3.5–5.5 mEq/L): TTKG 8–9 is typical on a normal diet; the bands above are only meaningful in hyper/hypokalemia.
3. Differential diagnosis table by band
| Condition | TTKG band | Interpretation | Main differential diagnoses |
|---|---|---|---|
| Hyperkalemia | ≤ 4 | Impaired renal excretion | Addison disease / primary hypoaldosteronism; type IV RTA (diabetes + CKD); drugs: ACE inhibitors, ARBs, spironolactone/eplerenone, trimethoprim, NSAIDs, heparin, cyclosporine; effective hypovolemia |
| Hyperkalemia | > 4 | Adequate renal excretion | Pseudohyperkalemia (hemolysis, thrombocytosis); excess potassium intake; transcellular shift outward: acidosis, insulin deficiency/hyperglycemia, hyperosmolality, rhabdomyolysis |
| Hypokalemia | > 4 (> 7 kuat) | Renal losses | Primary hyperaldosteronism (Conn syndrome); thiazide/loop diuretics; prolonged vomiting (metabolic alkalosis); type I/II RTA; hypomagnesemia; Bartter/Gitelman syndromes |
| Hypokalemia | < 3 | Non-renal losses | Diarrhea / laxatives (GI losses); heavy sweating; low potassium intake; intracellular shift: alkalosis, insulin, beta-agonists; periodic paralysis |
| Hypokalemia | 3–4 | Indeterminate | Repeat with a valid sample or use the urine K/creatinine ratio for comparison |
This table is educational; the list is not exhaustive and does not replace physician evaluation.
4. Step-by-step worked examples
Example A — normal serum potassium
UK = 40 mEq/L; SK = 5.0 mEq/L; Sosm = 285 mOsm/kg; Uosm = 600 mOsm/kg.
Potassium ratio = 40 / 5.0 = 8
Osmolality ratio = 285 / 600 = 0.475
TTKG = 8 × 0.475 = 3.80
Osmolality ratio = 285 / 600 = 0.475
TTKG = 8 × 0.475 = 3.80
Serum potassium 5.0 mEq/L is within the normal range → TTKG is read as reference context. Validity conditions are met (U_osm 600 > S_osm 285). The value 3.80 is below the typical 8–9 on a normal diet, which may reflect low potassium intake — definitive interpretation still requires clinical context.
Example B — hypokalemia with renal losses
UK = 60 mEq/L; SK = 3.0 mEq/L; Sosm = 280 mOsm/kg; Uosm = 500 mOsm/kg.
Potassium ratio = 60 / 3.0 = 20
Osmolality ratio = 280 / 500 = 0.56
TTKG = 20 × 0.56 = 11.20
Osmolality ratio = 280 / 500 = 0.56
TTKG = 20 × 0.56 = 11.20
Serum potassium 3.0 mEq/L = hypokalemia; TTKG 11.20 (> 7) indicates definite renal potassium loss. The example figures above were recomputed by the test suite (oracle) and match this page's calculation engine.
5. Osmolality unit converter
The conversion result will appear here.
Potassium: K+ is a monovalent ion, so 1 mEq/L is exactly equal to 1 mmol/L — no conversion needed. Osmolality is always expressed per kg of water (mOsm/kg H2O); do not confuse it with osmolarity (per liter of solution).
6. TTKG vs FEK vs urine K/creatinine ratio
| TTKG | FEK (fractional excretion of K+) | Rasio K/kreatinin urin spot | |
|---|---|---|---|
| Formula | (U_K / S_K) × (S_osm / U_osm) | (U_K × S_Cr) / (S_K × U_Cr) × 100% | U_K (mmol/L) / U_kreatinin (mmol/L) |
| What is needed | Urine K, serum K, urine osmolality, serum osmolality | Urine K, serum K, urine creatinine, serum creatinine | Urine K, urine creatinine |
| What it assesses | K+ concentration gradient in the cortical collecting duct | Fraction of filtered potassium that is excreted | Urine-concentration-corrected potassium excretion rate |
| Commonly used cutoffs | Hyperkalemia: >4 adequate; hypokalemia: >4 renal, <3 non-renal | > 10–15% indicates renal potassium wasting (cutoffs vary between sources) | < 1.5 mmol/mmol: appropriate response in non-renal hypokalemia; > 20 mmol/mmol: appropriate response in hyperkalemia (Halperin 2017) |
| Strengths | Directly assesses the distal secretion process | Creatinine-normalized — more stable against urine concentration variation | Simplest; no blood sample needed |
| Limitations | Requires strict validity conditions; disturbed by diuretics & osmotic diuresis; distal solute reabsorption assumption questioned (urea recycling) | Needs urine+serum creatinine; less reflective of the tubular gradient | Does not assess tubular mechanism; affected by muscle mass (creatinine) |
7. Methodology & primary sources
- Formula follows the West et al. formulation for the transtubular potassium gradient: TTKG = (U_K / S_K) ÷ (U_osm / S_osm).
- Interpretation cutoffs follow standard nephrology teaching: normal hyperkalemia response > 7 (ideal > 10); hypokalemia < 3 appropriate conservation, > 4 renal loss, > 7 definite renal wasting — per Palmer & Clegg, “Physiology and Pathophysiology of Potassium Homeostasis: Core Curriculum 2019”, Am J Kidney Dis.
- Validity conditions (U_osm > S_osm; U_Na > 25 mEq/L) per the formula’s derivation assumptions and standard literature.
- Critique & alternatives: Halperin, “Assessing the renal response in patients with potassium disorders: a shift in emphasis from the TTKG to the urine K+/creatinine ratio”, African Journal of Nephrology 2017 — medullary urea recycling violates the TTKG assumption; the urine K/creatinine ratio is recommended as an alternative.
- Calculations on this page run 100% in your browser (no server); an independent decimal-precision oracle test suite accompanies this tool.
Medical disclaimer: this page is for education. Do not change medication doses or therapy based on calculator results without consulting a physician. If you experience electrolyte disturbance symptoms (severe weakness, palpitations, tingling), seek medical help.
8. Frequently asked questions (FAQ)
What is the TTKG (transtubular potassium gradient)?
TTKG is a semi-quantitative index that estimates the ratio of potassium concentration in the cortical collecting duct lumen to plasma potassium, corrected for water reabsorption in the medulla. It is used to assess whether the kidneys contribute to hyperkalemia or hypokalemia, and was formulated by West et al.: TTKG = (urine K / serum K) × (serum osmolality / urine osmolality).
How is the TTKG formula calculated?
TTKG = (U_K / S_K) × (S_osm / U_osm), where U_K is urine potassium (mEq/L), S_K serum potassium (mEq/L), S_osm serum osmolality (mOsm/kg), and U_osm urine osmolality (mOsm/kg). Example: U_K 40, S_K 5.0, S_osm 285, U_osm 600 → (40/5) × (285/600) = 8 × 0.475 = 3.80.
What is a normal TTKG value?
In people on a normal diet with normal serum potassium, TTKG is generally 8–9. In hyperkalemia, a normal renal response is expected to produce a TTKG above 7 (ideally above 10). In hypokalemia, appropriately responding kidneys should suppress TTKG below 3. A “normal” value is always read together with the serum potassium context.
When is a TTKG result considered valid?
Two classic conditions: (1) urine osmolality greater than serum osmolality (some sources require U_osm ≥ 300 mOsm/kg) for the water-reabsorption correction to be valid; and (2) urine sodium above 25 mEq/L so that distal sodium delivery suffices for potassium secretion. If the conditions are not met, this calculator shows a warning and the result should not be interpreted.
Why is TTKG invalid when urine osmolality is lower than serum?
The TTKG formula uses the osmolality ratio to estimate how much water is reabsorbed after the cortical collecting duct. When urine is more dilute than serum, that assumption collapses — the kidneys are diluting urine — so the resulting number does not reflect the true potassium gradient.
What does a low TTKG mean in hyperkalemia?
TTKG ≤ 4 in hyperkalemia indicates inadequate renal potassium excretion, pointing to impaired mineralocorticoid production or action: hypoaldosteronism (e.g. Addison disease), type IV renal tubular acidosis (often in diabetes with chronic kidney disease), or drugs such as ACE inhibitors, ARBs, potassium-sparing diuretics, trimethoprim, NSAIDs, and heparin. Conversely, TTKG > 4 points to non-renal causes such as pseudohyperkalemia or potassium shift out of cells.
What does a high TTKG mean in hypokalemia?
TTKG > 4 in hypokalemia indicates potassium loss through the kidneys: primary hyperaldosteronism, thiazide/loop diuretic effect, prolonged vomiting, or renal tubular acidosis. Values above 7 indicate definite renal potassium wasting (Palmer & Clegg, AJKD 2019). TTKG < 3 instead shows the kidneys responding appropriately, so the loss comes from outside the kidneys, e.g. diarrhea.
What does the TTKG 3–4 gray zone mean in hypokalemia?
The 3–4 range in hypokalemia is indeterminate: it can occur with either an appropriate renal response or mild renal potassium loss. Do not draw conclusions in this range; repeat the test with a sample meeting validity conditions or compare with the urine potassium/creatinine ratio.
Why is TTKG unreliable with diuretic use or osmotic diuresis?
Loop and thiazide diuretics increase tubular flow rate, pushing urine potassium out and making TTKG look high without reflecting mineralocorticoid activity. In osmotic diuresis (e.g. heavy glucosuria, mannitol administration), the assumption that little solute is reabsorbed in the medullary collecting duct — the foundation of the TTKG formula — does not hold. In both conditions use alternatives such as 24-hour potassium excretion or the urine K/creatinine ratio.
How does TTKG differ from FEK (fractional excretion of potassium)?
Both assess renal potassium handling but from different angles. TTKG estimates the potassium concentration gradient in the cortical collecting duct and needs urine–serum osmolality. FEK = (U_K × S_Cr) / (S_K × U_Cr) × 100% measures the fraction of filtered potassium excreted and needs urine–serum creatinine; values above 10–15% generally indicate renal potassium wasting. TTKG is more sensitive to hydration status (via the osmolality correction), while FEK is more stable against urine concentration variation because it is creatinine-normalized.
Are there alternatives when TTKG is invalid?
Yes. Halperin (African Journal of Nephrology, 2017) recommends the potassium/creatinine ratio on a spot urine sample: a ratio below 1.5 mmol/mmol indicates an appropriate renal response in non-renal hypokalemia, while above 20 mmol/mmol indicates an appropriate response in hyperkalemia. The reason: medullary urea recycling violates the TTKG assumption that little solute is reabsorbed distal to the cortical collecting duct, so the ratio to creatinine — whose excretion rate is relatively constant — is considered more robust.
Are mEq/L and mmol/L interchangeable for potassium?
Yes. Potassium is a monovalent ion (K+), so 1 mEq/L is exactly equal to 1 mmol/L. For osmolality, the standard unit is mOsm/kg H2O; 1 Osm/kg = 1,000 mOsm/kg. This calculator provides its unit converter.
What is the difference between serum and plasma potassium for TTKG?
Serum potassium is slightly higher than plasma (a difference of 0.1–0.4 mEq/L) because platelets release potassium during clotting. For TTKG either can be used as long as it is consistent, but beware of pseudohyperkalemia: sample hemolysis, severe thrombocytosis, or leukocytosis can raise serum potassium artificially and produce a misleading interpretation.
Can TTKG be used in children?
It can, with caution. Pediatric TTKG reference values are reported as 4.1–10.5 (infants 4.9–15.5), slightly different from adults. The interpretation principle — compare against potassium status and meet validity conditions — remains the same, but adult cutoffs cannot be pasted as-is onto pediatric patients.