I was never a big fan of the trans-tubular potassium gradient. I taught it because it was expected core knowledge for medicine residents. While I thought it was a poor test to assist in clinical management I delighted in using it to teach physiology. Understanding how the TTKG works, why it works and the thinking behind the exclusion criteria required sophisticated understanding of potassium and solute handling in the distal nephron.
My primary complaint of the TTKG was how useless it was in the assessment of hyperkalemia. In persistent hyperkalemia the TTKG is always inappropriately low (except in cases of rhabdomyolysis or tumor lysis syndrome where it is possible to get persistent hyperkalemia despite normal renal potassium handling, woe to the patient, whose doctor is relying on the TTKG to diagnose rhabdo). The TTKG was not useful for differentiating the various elements of renal potassium handling that can go off the rails to cause hyperkalemia.
The TTKG could do a neat job of differentiating renal from extra-renal potassium losses in hypokalemia.
Then in 2011 this article came out which showed urea cycling to occur in the late cortical collecting duct. The authors believed that urea delivery to the cortical collecting duct was an important driver of potassium secretion. This broke one of the central assumptions of the TTKG: that no appreciable solute resorption occurs in the medullary collecting duct, the only reason the osmolality increases is the absorption of water.
It looks like the editors of UpToDate have voted the TTKG off the island, here is what UpToDate has to say about the TTKG. In Evaluation of the patient with hypokalemia:
Trans-tubular potassium concentration gradient — The transtubular potassium concentration gradient (TTKG) has been primarily used in the evaluation of patients with hyperkalemia. However, we do not recommend using the TTKG. Details pertaining to the TTKG and the reasons for our recommendation not to use it in hyperkalemia are discussed in detail elsewhere. (See “Causes and evaluation of hyperkalemia in adults”, section on ‘Transtubular potassium gradient’.)
In Causes and evaluation of hyperkalemia in adults
Trans-tubular potassium gradient — It would be desirable to assess the degree of aldosterone activity in patients with hyperkalemia by estimating the tubular fluid potassium concentration at the most distal site of potassium secretion in the cortical collecting tubule. Although this measurement cannot be made in humans, it was proposed that the potassium concentration at this site could be estimated clinically from calculation of the transtubular potassium gradient (TTKG) [91-93].
However, in a later publication, the authors of the original studies found that the assumptions underlying the TTKG were not valid [94]. It was concluded that the TTKG was not a reliable test for the diagnosis of hyperkalemia. We recommend not using the TTKG to evaluate patients with hyperkalemia.
RIP TTKG