The transtubular potassium gradient (TTKG) is an index reflecting the conservation of potassium in the cortical collecting ducts of the kidneys. TTKG is considered to reflect mainly aldosterone bioactivity with regard to its kaliuretic response.

TTKG is clinically useful in diagnosis for patients suffering from hyper or hypokalemia in determining renal or non-renal cause of the condition. Expected responses are for hyperkalemia or potassium ingestion to result in excretion of potassium and a TTKG to increase (e.g. >10) and for conditions of hypokalemia, for potassium to be retained and the TTKG to decrease (e.g. <2).

In this tool, we assume that the urine and plasma osmolality are similar at the end of the cortical collecting tubule and that potassium is neither excreted nor reabsorbed in the medullary collecting tubule.

The formula used is:

• TTKG = (Urine K * Plasmaosm) / (Plasma K * Urineosm)
• TTKG = Trans-Tubular Potassium Gradient
• Urine K = Urine potassium (in mEq/L or mmol/L)
• Plasma K = Plasma potassium (in mEq/L or mmol/L)
• Plasmaosm = Plasma osmolality (in mOsm/kg or mmol/kg)
• Urineosm = Urine osmolality (in mOsm/kg or mmol/kg)

^* Note: For this formula to be valid the following items must be presents:

• Urineosm >300 mOsm/kg
• UrineNa >25 mEq/L (Na=sodium)

Interpretation:

• Normal responses
• Normal subjects on normal diets usually have TTKG of ~8-9
• Hypokalemia should result in a TTKG <2
• Hyperkalemia should result in a TTKG >10
• A potassium load (50 mmol oral potassium) results in normal subjects to have TTKG of 13.1±3.8
• Abnormal responses
• In a hypokalemic patient, a TTKG of >7 should raise suspicion of hyperaldosteronism as the cause
• Hypokalemia not resulting in a TTKG <2 (suggests renal loss as cause)
• Hyperkalemia not resulting in a TTKG >10 (may suggest a type IV renal tubular acidosis)

In one study (Joo, et al), had the following findings in hypokalemic patients with differing etiologies:

• Mineralocorticoid excess [TTKG=13.3±4.4]
• Diuretic use [TTKG=8.6±1.3]
• Diarrhea [TTKG=1.6±0.3]
• Normal controls with normal potassium level [TTKG=5.0±0.7]

References:

1. Choi MJ, Ziyadeh FN. The Utility of the Transtubular Potassium Gradient in the Evaluation of Hyperkalemia. J Am Soc Nephrol. 2008;19:424-6.
2. Ethier JH, Kamel KS, Magner PO, et al. The transtubular potassium concentration in patients with hypokalemia and hyperkalemia. Am J Kidney Dis. 1990 Apr;15(4):309-15.
3. Joo KW, Chang SH, Lee JG, et al. Transtubular potassium concentration gradient (TTKG) and urine ammonium in differential diagnosis of hypokalemia. J Nephrol. 2000 Mar-Apr;13(2):120-5.
4. Mayan H, Kantor R, Farfel Z, et al. Trans-tubular potassium gradient in patients with drug-induced hyperkalemia. Nephron. 2001 Sep;89(1):56-61.
5. West ML, Marsden PA, Richardson RM, et al. New clinical approach to the evaluate disorders of potassium excretion. Miner Electrolye Metab . 1986;12(4):234-8.