Calculate the transtubular potassium gradient (TTKG) to assess renal potassium handling in hyperkalemia and hypokalemia. Includes interpretation, validity checks, and differential diagnosis tables.
The Transtubular Potassium Gradient (TTKG) estimates the potassium concentration in the cortical collecting duct lumen relative to the peritubular capillary, providing insight into whether the distal nephron is appropriately secreting or conserving potassium. It helps distinguish renal from extrarenal causes of both hyperkalemia and hypokalemia — a fundamental step in potassium disorder workup.
The TTKG is calculated as (Urine K / Serum K) divided by (Urine Osm / Serum Osm), effectively "correcting" the urine potassium for water reabsorption in the medullary collecting duct. In hyperkalemia, a TTKG less than 5 suggests impaired renal potassium excretion (hypoaldosteronism, K-sparing diuretics, tubular defects), while a TTKG greater than 7 indicates appropriate renal response (suggesting the hyperkalemia is from K+ loading or transcellular shift). In hypokalemia, a TTKG greater than 3 indicates renal potassium wasting.
This calculator computes the TTKG, validates the urine concentration prerequisite (Urine Osm must exceed Serum Osm), provides scenario-specific interpretation with color-coded results, and includes comprehensive differential diagnosis tables for both hyperkalemia and hypokalemia organized by TTKG range.
The TTKG provides an immediate bedside estimate of distal nephron potassium secretion using routine lab values, without waiting for a 24-hour urine collection. In the emergency setting — particularly with severe hyperkalemia requiring urgent treatment decisions — the TTKG can rapidly distinguish renal from extrarenal causes and guide therapy selection (e.g., fludrocortisone for hypoaldosteronism vs. insulin/glucose for transcellular shift).
TTKG = (U_K / S_K) / (U_Osm / S_Osm) = (U_K × S_Osm) / (S_K × U_Osm) Validity: requires U_Osm > S_Osm and U_Na > 25 mEq/L Hyperkalemia: TTKG < 5 = impaired excretion; > 7 = appropriate Hypokalemia: TTKG < 2 = appropriate conservation; > 3 = renal wasting
Result: TTKG = 2.3 — Impaired renal K⁺ excretion
TTKG = (25 × 290) / (6.2 × 500) = 7250 / 3100 = 2.3. In the setting of hyperkalemia (K⁺ 6.2), a TTKG of 2.3 is inappropriately low (expected > 7). This indicates the kidneys are not adequately secreting potassium, suggesting hypoaldosteronism, K⁺-sparing diuretic effect, or tubular defect.
Use consistent units, verify assumptions, and document conversion standards for repeatable outcomes.
Most mistakes come from mixed standards, rounding too early, or misread labels. Recheck final values before use. ## Practical Notes
Use this for repeatability, keep assumptions explicit. ## Practical Notes
Track units and conversion paths before applying the result. ## Practical Notes
Use this note as a quick practical validation checkpoint. ## Practical Notes
Keep this guidance aligned to expected inputs. ## Practical Notes
Use as a sanity check against edge-case outputs. ## Practical Notes
Capture likely mistakes before publishing this value. ## Practical Notes
Document expected ranges when sharing results.
The TTKG requires concentrated urine (U_Osm > S_Osm) and adequate sodium delivery to the distal nephron (U_Na > 25 mEq/L). In the setting of water diuresis (dilute urine) or very low sodium intake, the TTKG is unreliable. Some nephrologists argue the TTKG has fundamental limitations and prefer 24-hour urine K⁺ or urine K/creatinine ratio.
Type 4 renal tubular acidosis (hypoaldosteronism, very common in diabetic nephropathy), ACE inhibitors, ARBs, K⁺-sparing diuretics (spironolactone, amiloride, triamterene), TMP-SMX, heparin, calcineurin inhibitors, and adrenal insufficiency. Use this as a practical reminder before finalizing the result.
Indirectly. In hypokalemia with a TTKG > 3, the kidney is wasting potassium, which can be from excess aldosterone. However, the aldosterone-to-renin ratio (ARR) is the specific screening test. TTKG distinguishes renal from GI causes but does not specify the renal mechanism.
Borderline values are common in chronic kidney disease where nephron mass reduction impairs K⁺ excretion even with adequate aldosterone. Consider checking an aldosterone level and evaluating GFR. A fludrocortisone trial may help differentiate aldosterone deficiency from tubular resistance.
Some researchers (including the original authors) have questioned whether the TTKG accurately reflects collecting duct K⁺ secretion because urea recycling in the medulla can alter the osmolality correction. Despite this, TTKG remains widely used in clinical practice because no simple alternative exists for bedside assessment of renal K⁺ handling.
A 24-hour urine potassium collection is more robust: > 30 mEq/day in hypokalemia indicates renal wasting. A spot urine K⁺/creatinine ratio > 15 mEq/g also suggests renal loss. These avoid the osmolality assumptions inherent in the TTKG calculation.