I have been thinking a lot about the June 6th #NephJC discussion on
Increased salt consumption induces body water conservation and decreases fluid intake.
https://www.ncbi.nlm.nih.gov/pubmed/28414302
Thanks to all for a stimulating interlude, but it left me confused and a bit overwhelmed.
I pride myself on salt and water and this feeling was disconcerting. So I thought more about it and here is my take on this paper and the “controversy” it seemed to create:
NY Times: “Why everything we know about salt may be wrong”
Let’s assume I am in a steady state on 6 grams salt a day. For the sake of this part, to simplify my point and the math, and for now only, let’s pretend potassium and protein (urea) intake and excretion don’t exist and look at Na excretion only and how it is excreted as the intake increases.
If I double my salt intake to 12 grams, to excrete it and be in steady state, I would have to either 1) double my urine osmolality (urine Na) with the same urine volume (and same water intake), or 2) keep the same urine osmolality but double my water intake and double my urine output. In fact, other urine osms were present (urea and K) so since Na wasn’t the only osm responsible, doubling is hardly necessary, but the point is: to excrete the increased osmotic load from increased Na intake you could either drink more and keep the same Uosm or not drink more and concentrate your urine more.
This study showed that, if fluid intake amounts were reliable, doubling the intake of Na did not increase the intake of water (they actually claim it went down (Fig 1 B), I look at the data and am not convinced of that at all, but I am convinced that water intake did not at least go up). And while Na excretion is not day to day Na in = Na out, it does achieve steady state eventually. So again, since water intake did not seem to increase with an increase in Na intake, the subjects had to increase their urine osmolality to excrete the increased osms (Na), and you do that by reabsorbing more water from the urine, ADH etc.
The title of the article was “Increased Salt Consumption induces body water conservation (Urine concentration) and decreases fluid intake”, so that isn’t that hard to understand, nor should it be so surprising based on the above.
But why didn’t they drink more? Maybe they didn’t need to drink more:
I know if I eat something very salty I get thirsty, and that makes sense as my serum osmolality acutely goes up and that stimulates thirst (very sensitive mechanism). I think this is the “surprise” of this study that water intake did NOT go up. However, this study I suspect is different than me pigging out on pizza, as the increased Na intake is spread out during the day and you don’t have an acute Na load that may drive thirst.
Also, 12 grams of salt (this is 4.8 grams of sodium, NOT 12 grams of sodium) isn’t really that much (from a kidney excretion aspect), the average (average) sodium intake /day in America is 3.4 grams or almost 9 grams of salt!
One Original recipe Kentucky fried Chicken breast has 1.2 grams of sodium which is 3 grams of salt!
Still, does it make sense that the 12 gram Na intake group did not drink more? Lets play with some numbers.
6 grams of salt is 102 meq (verified in Figure 1 F) = 204 mosm/day of solute to excrete.
12 grams of salt is 204 meq (verified in Figure 1 F) = 408 mosm/d.
Now let’s say I eat 1 mg/kg/d of protein, that is 70 gr protein, protein is 16% nitrogen, = 11.2 grams Nitrogen. One mole of nitrogen (N2) is 28 grams, so that 11.2 grams = .4 moles or 400 mmoles = 400 mosm of protein based solute/day to excrete.
Lets add 50 meq K a day = 100 more mosm/d of solute/day to excrete.
Total Daily mosm 6 gm salt diet = 204+400+100= 704 mosm.
Total Daily mosm 12 gm salt diet = 408+400+100 = 908 mosm.
They drank (Figure 1A top panel) ~ 2500 ml/day and you can subtract 500 ml/day for insensible loss, and you have 2000 ml/d of urine (Figure 1A middle panel and 1D) to excrete 704 and 908 mosm, which is 352/l and 454 mosm/l urine osmolarity respectively (actually, totally in the range seen in Table 2).
The higher Na intake group can easily excrete the increased solute load from that increase in salt intake by simply concentrating their urine a bit more. They really don’t need to drink more water. What if they went to 24 grams of salt a day, at some point you can only concentrate your urine so much and you would have to drink more to excrete the extra salt.
No surprises here.
What about the rest of the paper? They found “infradian-rhythmical” “circasemiseptan”,”circaseptan” (huh?) rhythms of aldo and cortisol release. The later (cortisol) bursts seemed to be there for protein breakdown to supply more urea for the concentration mechanism, I guess that makes physiologic sense, although the Uosm aren’t really that high even at the highest to think you would have to actively do something like break down protein to supply urea to increase concentrating ability. Along the same line they found that increased salt excretion (higher intake group) was associated with decreased urea excretion. OK, maybe at first to generate a higher medullary tonicity, but you cannot decrease urea excretion forever, or you would become azotemic, you retain enough to build up the medullary osmotic gradient then you must have: urea created = urea excreted, steady state…
Still it is remarkable that while Na in = Na out eventually, it does not follow a daily pattern. I usually try to understand things teleologically, but I can’t make any sense of this. This to me is the only real interesting finding of the paper.
Commentary by Roger Rodby aka @NephRodby
PS: Finally, the term negative free water clearance is used a lot in this paper. If we are talking about negative electrolyte free water clearance then that would mean the urine Na + K would have to be higher than the plasma Na (Urine desalination), which I strongly doubt. I suspect they are using the old definition of osmolar free water clearance (takes into account urea, which is an ineffective osm and thus has limited clinical utility). Saying that they (higher Na intake group) had greater negative (osmolar) free water clearance only means they concentrated their urine more, which we see.