Nephrology Question 8 Instructor

What does the term ‘TTKG’ mean and how do you calculate it? What assumptions are necessary for the formula to be valid?

Consider this case:

A 42 year old male with HIV is admitted with PCP pneumonia. They are treated with high dose Septra. On day 5 of admission, the following results are noted:

Serum K = 6 mmol/L
Serum osmolality = 300 mosmol/L
Urine osmolality = 480 mosmol/L
Urine K = 20 mmol/L.

In the preceding patient with hyperkalemia, calculate the TTKG. What does this tell you about their ability to excrete potassium? Can you explain why this is happening?

The etiology of hyperkalemia is often due to impaired excretion of potassium in the distal nephron. Aldosterone function in the cortical collecting duct can be estimated by measuring the potassium concentration in tubular fluid at the end of the cortical collecting duct. Since this cannot be measured directly, it can be estimated by the transtubular potassium (K) gradient (TTKG). The TTKG is defined by formula:

TTKG = [Urine K ÷ (Urine osmolality / Plasma osmolality)] ÷ Plasma K

This formula effectively determines the ratio of urine to plasma potassium, but uses a correction factor (urine osmolality/plasma osmolality) to take into account the fact that water is reabsorbed along the medullary collecting duct.

To use the TTKG, the following assumptions must be valid:

  • There is no potassium reabsorption or secretion in the medullary collecting tubule.
  • Urine osmolality at the end of the cortical collecting tubule is similar to that of the plasma.

In the case provided:

TTKG = [Urine K ÷ (Urine osmolality / Plasma osmolality)] ÷ Plasma K
= [20 ÷ (480/300)] ÷ 6
= 2.1

In the setting of hyperkalemia, one would expect a TTKG of >10. The suppressed TTKG suggests inadequate aldosterone or an impaired response of the distal nephron to aldosterone. In this patient, the trimethoprim blocks the epithelial sodium channel in the cortical collecting duct and effectively acts like a potassium-sparing diuretic and inhibits the effect of aldosterone.


Ethier JH; Kamel KS; Magner PO; Lemann J Jr; Halperin ML. The transtubular potassium concentration in patients with hypokalemia and hyperkalemia. Am J Kidney Dis 1990 Apr;15(4):309-15.

H. Velazquez, M. A. Perazella, F. S. Wright and D. H. Ellison. Renal Mechanism of Trimethoprim-induced Hyperkalemia. Ann Intern Med 1993; 296-301.

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