Beyond Drinking: Disorders of Water Homeostasis in Patients with CKD

Dr. Tomas Berl

Dr. Tomas Berl

In a recent article published in AJKD, Combs and Berl reviewed the epidemiology, pathophysiology, and management of disorders of water homeostasis that occur in patients with chronic kidney diseases including long-term dialytic support. Dr. Tomas Berl (TBE), corresponding author from the University of Colorado, discusses this review with Dr. Helbert Rondon (eAJKD), eAJKD Contributor.

eAJKD: Can you briefly summarize the main points of your review?

TBE: We sought to bring attention to recent studies on the epidemiology of dysnatremias in patients with kidney disease. Hyponatremia is not uncommon in such patients, and is more common that hypernatremia. As is the case with other conditions associated with abnormal serum sodium concentrations, patients with kidney disease and hyper- or hyponatremia have a higher mortality when compared to those with normonatremia. The article also reviews the pathogenesis of both the concentrating and diluting defects in kidney disease as learned from animal and human studies. Finally, the article summarizes how dysnatremias in kidney disease patients should be approached therapeutically, with a special emphasis on the treatment of patients on dialytic support.

eAKJD: Why is it that hypernatremia has a low prevalence in patients with chronic kidney disease despite the fact that urine concentrating defects appear earlier in the course of the disease?

TBE: There is a second line of defense mediated by thirst against the development of hypernatremia. Thirst responses, to the best of my knowledge, have not been very well studied in patients with kidney disease, but I believe it is not known to be impaired. So we have a better defense against hypernatremia than hyponatremia. This is true not only for people with chronic kidney disease, but for the general population as well. Water intake is in large measure habitual, especially in this society. People probably drink more water than they really need, and this makes them more prone to hyponatremia. Furthermore it must be recognized that the concentrating defect is not severe until kidney failure is fairly advanced.

eAJKD: There are a few cases in the literature of long-term dialysis patients who develop refractory hyponatremia that resolved only after bilateral nephrectomy. Is post-dialysis hypovolemic thirst partly responsible for the hyponatremia seen in these patients?

TBE: Hypovolemia is in fact a potent dipsogen. This is probably mediated by angiotensin II, a potent stimulant of thirst. In fact, excessive water intake in dialysis patients is fairly common. We have all seen patients who return for their dialysis treatment with inordinate weight gains. There have been cases that you allude to in which patients have had nephrectomies to try to ablate their renin-angiotensin system. However, that procedure is not as common anymore because the results have been inconsistent. The above mechanism is one of the hypotheses that have been put forth for the dipsogenic response to hypovolemic dialysis.

eAJKD: There is a difference between sodium concentration and what is called “sodium activity,” which implies sodium is measured in plasma water. Based solely on activity measurements, a standard of 140 mEq/L sodium bath is hypotonic compared to the patient’s plasma water sodium, which is actually closer to 150 mEq/L. Sodium ions should diffuse from the patient into the dialysate by chemical gradient, but you don’t see that in clinical practice. The Donnan effect has been implicated as one of the protective mechanism for this: negatively charged proteins in plasma do not allow for positively charged sodium ions to diffuse. Can hyponatremia in long-term dialysis patients or patients on CRRT be ascribed to the dialysis procedure per se?

TBE: We rarely measure post-dialysis or post-CRRT sodium concentrations, but it has not been my impression that we’ve seen clinically significant decrements in serum sodiums despite the small differences that you very nicely suggest between activity and concentration.

eAKJD: Osmotic demyelination syndrome is an infrequent occurrence in long-term dialysis patients. You mentioned in your review that one of the mechanisms that might be protective is the high urea levels present in these patients. Can you comment on the potential mechanisms that have been implicated in this protective effect of urea?

TBE: Osmotic demyelination appears to be initiated by excessive decrements in water in brains previously adapted to hyponatremia by loss of organic osmolytes. The accumulation of urea in such brains presumably prevents this excessive water loss, thereby protecting it from the downstream events that culminate in demyelination. There are studies that have looked at this in experimental animals. When urea was not allowed to accumulate, brain lesions did develop pointing to the vital role of urea in the protective process.

eAJKD: It has been recently shown in animal studies that hyponatremia may play a causative role in the development of osteoporosis. Is there a pathogenetic role of hyponatremia in the development of renal osteodystrophy in patients with chronic kidney disease?

TBE: That’s an interesting question that I don’t think has been explored. It may be of some interest to see whether patients with chronic kidney disease who are also hyponatremic have more severe bone loss, but it would take quite a large population of patients to answer this question. As you are aware, there are multiple factors involved in the pathogenesis of metabolic bone disease in renal patients, that to dissect the role of hyponatremia may become challenging.

To view the article abstract or full-text (subscription required), please visit

1 Comment on Beyond Drinking: Disorders of Water Homeostasis in Patients with CKD

  1. Cristina Gluhovschi // January 12, 2014 at 9:39 am // Reply

    Because salt and water are like “Love and Marriage” i will add a famous quotation by John Milton: “In Physic(s), things of melancholic hue and quality are used against melancholy, sour against sour, salt to remove salt humours”
    cristina a. gluhovschi

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