In the NEWS: Too much salt intake doesn't lead to increased water drinking

Two published studies in JCI might change how we think the body handles “too much salt”

https://www.jci.org/articles/view/88532/version/3/pdf/render

https://dm5migu4zj3pb.cloudfront.net/manuscripts/88000/88530/JCI88530.v2.pdf

What we learnt in medical school:

If you eat a lot of salt — sodium chloride — you will become thirsty and drink water, diluting your blood enough to maintain the proper concentration of sodium. Ultimately you will excrete much of the excess salt and water in urine.

When salt intake was increased in Russian cosmonauts studied, the urine Na excretion did increase as expected. But, the urine volume was not associated with those changes. When salt intake was high, the folks drank less water in the long run and still excreted increased water amounts. Where was this extra water coming from? The crew members were increasing production of glucocorticoid hormones, which influence both metabolism and immune function and allowed fat breakdown leading to water production.

Taking these observations to the lab, the investigators began a study of mice in the laboratory. The more salt the investigators added to the animals’ diet, the less water the mice drank(counter to what we think science teaches us when we eat a high salt diet). The animals were getting water by not drinking it but via  increased levels of glucocorticoid hormones breaking  down fat and muscle in their own bodies. This freed up water for the body to use.

Now published, the authors report the unexpected observation that long-term high salt intake did not increase water consumption in humans but instead increased water retention. Moreover, salt and water balance was influenced by glucocorticoid and mineralocorticoid fluctuations. 

This leads to a even bigger question? – does high salt intake= potential weight loss as fat breakdown is happening? So in other words, a high salt intake body is behaving similar to a starving body.

 I am sure that there is more to it!  In the long run, this is probably not a good adaption of the body and high glucocorticoid state is likely a risk of diabetes.  But these studies show us that we really don’t understand salt homeostasis in humans as we thought we did.

Bravo to the scientists on publishing this alternate view on salt intake and water production.

Topic Discussion: Plain water intake and CKD

A recent article published in the Am J of Nephrology raises an interesting question- does drinking more plain water benefit CKD or renal disease? This was a study of analysis of the NHANES database.
Over 3000 patients reviewed and 13% had CKD and 18% had cardiovascular disease.
CKD turned out to be the highest amongst the lowest plain water drinkers( <2 liters/day) and lowest in the highest water drinkers( >4.5L/day).

The authors suggest a protective effect of plain water intake.  Unclear what the mechanism of this might be.  Two years ago, the Australians had shown a similar finding. In their study, they showed that increased fluid intake was protective for CKD. Increased urine volume might be protective for progression of CKD.  Even the lay press in NYTimes took notice of these findings and had a blog post on this very topic.

What is the mechanism for this? Any thoughts, could this be ADH related? or flow related?

Topic Discussion: Genetic Diabetes Insipidus

The arginine vasopressin gene (AVP gene), the arginine vasopressin receptor 2 gene (AVPR2), and the vasopressin-sensitive water channel gene (aquaporin 2 [AQP2])—provide the basis for understanding of three different hereditary forms of “pure” diabetes insipidus: Neurohypophyseal diabetes insipidus, X-linked nephrogenic diabetes insipidus (NDI), and non–X-linked NDI(AD and AR), respectively. Four main categories can be considered. 

Neurohypophyseal diabetes insipidus: Autosomal Dominant, they retain some limited capacity to secrete AVP during severe dehydration, and the polyuro-polydipsic symptoms usually appear after the first year of life, when the infant’s demand for water is more likely to be understood by adults. 

Delayed onset of disease and can get worse with age.  The gene mostly involved is AVP gene. 

X-linked NDI: Affected male patients do not concentrate their urine after administration of AVP. Because this form is a rare, recessive X-linked disease, female individuals are unlikely to be affected, but heterozygous female individuals can exhibit variable degrees of polyuria and polydipsia because of skewed X chromosome inactivation.  The gene mostly involved is AVP2 gene. V2 receptors have been tried as chaperone medications as a trial to help overcome the misfolding that happens as a result of the gene mutation and helps in NDI.

Autosomal recessive NDI: Some cases have been identified. They have defect in the AQP2 gene.

AQP2 mutations that are responsible for autosomal recessive NDI are characterized by misrouting of the misfolded mutant proteins and are trapped in the endoplasmic reticulum.
Autosomal Dominant linked NDI: Both males and females affected. A patient who presented shortly after birth and it is a defect in the AQP2 channel gene. 

A nice review can be found at JASN and NDT

TOPIC DISCUSSION: Clinical Pearls for electrolytes!

On a recent reading on Sodium and Water physiology, I realized again and again the following points

1. The best way to identify change in Na balance is to examine the extracellular volume status but there are no good ways to do that clinically( orthostatics, axillary sweat, skin turgor, physical exam??). Perhaps the hemotocrit might be the best marker we have.
2. There are no NORMAL values in electrolyte diseases, there are only what is EXPECTED of the kidney to do or the organ to do for the stimuli.
3. Classic one: " The acute discovery of a chronic condition does not make it an acute disorder"- By ML Halperin
4. Hypernatremia and "no thirst" leads to not a pleasant diagnosis to make requiring a MRI of the brain.

TOPIC DISCUSSION: Camels and their Kidney!

Ever wondered what the camel does differently than us to survive in the hot environment? The camel does have a special kidney and a special GI tract.The camel's kidney actually can concentrate the urine more than sea water but less than a dessert rat.  Since the camel can concentrate the urine more than sea water, salty water intake won't harm the animal. Investigators have studied the  structure of the camelian kidney to discover whether or not the anatomical features necessary for producing a highly concentrated urine were present or not. The relative thickness of the medulla was calculated in the camelian kidney as it has been demonstrated that this thickness has a direct relationship with the ability to produce a highly concentrated urine.  A relative thickness of the medulla is a good measure of the length of the loop of Henle which is an indicator of urine concentration. The thickness reported in camels was 7.89 in comparison to the value of 8.5 in kangaroo rats, much more than humans.
Also, what happens if you haven't drunk water in 5 days and all of a sudden you re hydrate. A dehydrated camel can replace water within minutes of drinking, and some of this water is quickly absorbed into the bloodstream. With water in the bloodstream, ADH declines and the kidney will return to normal renal function within 30 minutes of drinking. Not only does the camel adopt to scarce water but the kidney can also adopt to rapid dehydration and not lead to demylination of the brain.
What are some other features this animal has to store water for long periods of time?
Another interesting part of the camel physiology is that they have 3 stomachs, acting as storage( 1.5 gallons per stomach) for the water and hence when water is not available, they can slowly replenish the system. The camel stores water in its blood stream, an interesting physiological process. Capable of losing forty percent of its body's weight before becoming distressed, it is able to go five to seven days before having to drink. The amount it drinks when water is available would cause severe problems in most animals, up to 21 gallons in about 10 minutes.The camel's mouth, stomach, and teeth have all developed to allow it to eat plants that are not palatable to other desert animals.Contrary to popular myth, the camels don't store water in their humps, its full of fat for food storage.
Some of the rodents in the dessert can actually concentrate up to 7500mOsm.
Fun things you can learn from other animals who adopt better to water problems

http://www.ncbi.nlm.nih.gov/pubmed/511770
http://www.ncbi.nlm.nih.gov/pubmed/407772
http://www.ncbi.nlm.nih.gov/pubmed/475010