TTKG Calculator: Transtubular Potassium Gradient
Enter serum potassium, urine potassium, serum osmolality, and urine osmolality to calculate the transtubular potassium gradient (TTKG). This index estimates the potassium concentration gradient across the cortical collecting duct and helps distinguish between renal and non-renal causes of potassium disorders. Results update instantly with a full interpretation and step-by-step breakdown.
Formula
Worked example
A patient with hypokalemia (serum K = 3.2 mmol/L) has urine K = 15 mmol/L, serum Osm = 290 mOsm/kg, and urine Osm = 450 mOsm/kg. K+ ratio = 15/3.2 = 4.69. Osmolality ratio = 450/290 = 1.552. TTKG = 4.69/1.552 = 3.02. Because TTKG >= 3 in the setting of hypokalemia, this indicates inappropriate renal potassium wasting rather than extra-renal loss.
What is the transtubular potassium gradient?
The transtubular potassium gradient (TTKG) is a calculated index that estimates the concentration gradient of potassium across the cortical collecting duct of the kidney. The collecting duct is the primary site where aldosterone controls potassium secretion, so the TTKG acts as a functional readout of mineralocorticoid activity. A high TTKG means the kidney is actively excreting potassium; a low TTKG means potassium is being retained. Because the collecting duct is permeable to water, the raw urine-to-serum potassium ratio is divided by the urine-to-serum osmolality ratio to correct for water reabsorption that occurs in the medullary portion of the duct, giving an index that more closely reflects actual tubular secretion. The concept was introduced in 1990 by West and colleagues and remains a practical bedside tool for narrowing the differential diagnosis of potassium disorders.
TTKG formula and prerequisites
The formula is: TTKG = (Urine K / Serum K) / (Urine Osm / Serum Osm), which simplifies to (Urine K x Serum Osm) / (Serum K x Urine Osm). Two prerequisites must be satisfied for the result to be valid. First, urine osmolality must be at least 300 mOsm/kg, because at lower concentrations the tubular fluid has been diluted before reaching the collecting duct and the correction factor is distorted. Second, urine sodium should be at least 25 mmol/L; very low luminal sodium blunts the electrochemical driving force for potassium secretion and can falsely lower the TTKG even when aldosterone is high. Always confirm both values before acting on a TTKG result. If prerequisites are not met, a 24-hour urine potassium collection or a spot urine potassium-to-creatinine ratio offers a more reliable assessment.
Interpreting TTKG in hypokalemia
When serum potassium is below 3.5 mmol/L, a healthy kidney should conserve potassium and drive the TTKG below 3. A TTKG below 3 in this setting confirms appropriate renal conservation and shifts attention to extra-renal causes: gastrointestinal losses (diarrhea, vomiting, laxative abuse), transcellular redistribution (insulin excess, beta-agonists, alkalosis), or inadequate dietary intake. A TTKG of 3 or above in a hypokalemic patient is inappropriate because the kidney is still excreting potassium despite depletion. This pattern points to renal wasting conditions such as primary hyperaldosteronism (Conn syndrome), secondary hyperaldosteronism (renovascular hypertension, heart failure, cirrhosis), Bartter syndrome, Gitelman syndrome, Liddle syndrome, or diuretic use targeting the loop or distal tubule.
Interpreting TTKG in hyperkalemia
When serum potassium exceeds 5.0 mmol/L, the kidneys should be excreting potassium vigorously. An optimal TTKG is above 7, and values above 10 are common with robust mineralocorticoid activity. A TTKG below 7 in a hyperkalemic patient indicates impaired tubular potassium secretion. The most common causes are hypoaldosteronism (Addison disease, bilateral adrenal destruction), type IV renal tubular acidosis (seen in diabetic nephropathy and chronic kidney disease), and medication effects from ACE inhibitors, angiotensin receptor blockers, potassium-sparing diuretics (spironolactone, eplerenone, amiloride), NSAIDs, or heparin, all of which reduce aldosterone synthesis or effect. Pseudohypoaldosteronism is a rarer cause of a low TTKG despite normal or high aldosterone levels. When TTKG is above 7 and hyperkalemia is still present, the cause is likely excessive potassium load (dietary, IV supplementation, blood transfusion), tissue breakdown (rhabdomyolysis, tumor lysis), or transcellular shift (acidosis, insulin deficiency, hyperosmolality).
TTKG interpretation by clinical context
| Clinical context | TTKG value | Interpretation | Likely cause |
|---|---|---|---|
| Hypokalemia | < 3 | Appropriate K+ conservation | Extra-renal loss (GI, redistribution) |
| Hypokalemia | >= 3 | Renal K+ wasting | Hyperaldosteronism, Bartter/Gitelman, diuretics |
| Normal serum K | 8-9 | Normal (typical diet) | Intact renal K+ handling |
| Normal serum K | < 8 | Below normal | Low dietary K+ or mild aldosterone deficiency |
| Normal serum K | > 9 | Above normal | High K+ intake, hyperaldosteronism |
| Hyperkalemia | < 5 | Inadequate K+ excretion | Hypoaldosteronism, type IV RTA |
| Hyperkalemia | 5-7 | Borderline excretion | Partial mineralocorticoid deficiency |
| Hyperkalemia | > 7 | Adequate excretion | Non-renal hyperkalemia, K+ shift, excess intake |
Threshold values vary by serum potassium status. These are consensus values; individual laboratory and dietary factors may shift expected ranges.
Frequently asked questions
What is a normal TTKG value?
For a person eating a typical Western diet with a normal serum potassium, the TTKG normally falls between 8 and 9. Values can rise above 10 with a high-potassium diet and fall below 8 with very low potassium intake, so diet context matters. In hypokalemia, a TTKG below 3 is expected (appropriate conservation); in hyperkalemia, a TTKG above 7 (ideally above 10) is expected (active excretion). The "normal" range shifts depending on the clinical question being asked.
When is the TTKG not valid?
The TTKG becomes unreliable in two main situations. First, when urine osmolality is below 300 mOsm/kg: this means the kidney is diluting urine before it reaches the collecting duct, invalidating the osmolality correction. Second, when urine sodium is below 25 mmol/L: very low luminal sodium reduces the electrical gradient for potassium secretion so the TTKG underestimates true mineralocorticoid activity. In both cases, consider a 24-hour urine potassium excretion measurement or a spot urine potassium-to-creatinine ratio as alternatives.
What does a low TTKG mean in hyperkalemia?
A TTKG below 5-7 in a patient with hyperkalemia means the kidney cannot adequately excrete potassium, pointing to a problem with mineralocorticoid production or action. Common causes include Addison disease, type IV renal tubular acidosis (especially in diabetics with chronic kidney disease), and medications such as ACE inhibitors, ARBs, potassium-sparing diuretics, NSAIDs, or heparin. Measuring plasma aldosterone and renin helps distinguish primary aldosterone deficiency from resistance at the tubule.
What does a high TTKG mean in hypokalemia?
A TTKG of 3 or above in a hypokalemic patient means the kidneys are inappropriately losing potassium despite the deficiency. This points to mineralocorticoid excess or tubular dysfunction. Primary hyperaldosteronism (Conn syndrome) is the most common cause and is associated with hypertension. Bartter and Gitelman syndromes cause renal wasting with normal to low blood pressure and are typically diagnosed in childhood or young adulthood. Active diuretic use is another common culprit that must be excluded.
How is the TTKG different from the urine potassium-to-creatinine ratio?
Both indices assess renal potassium handling from a spot urine sample, but they differ in their correction method. The TTKG corrects for water reabsorption using the osmolality ratio, making it a physiological estimate of collecting duct secretion. The urine potassium-to-creatinine ratio (UK/Cr) corrects for urine concentration using creatinine as a surrogate for glomerular filtration, analogous to fractional excretion. UK/Cr above 15-20 mmol/mmol generally suggests renal wasting. Neither test requires a 24-hour collection, but the UK/Cr is often preferred when the urine osmolality prerequisite for TTKG cannot be met. The two tests complement each other in practice.