The Myth of Water and Salt: From Aquaretics to Tenapanor

Abstract

The impact of water intake has been studied in several renal diseases. For example, increasing water intake is useful to prevent primary and secondary nephrolithiasis. In autosomal dominant polycystic kidney disease, arginine vasopressin (AVP) is involved in the progression of the disease, and water intake could play a therapeutic role by inhibiting the synthesis of AVP, but its efficacy is still controversial. Conversely, the use of aquaretics, which are antagonists of AVP V2 receptors, results in the reduction of the increase rate of total kidney volume with a slower decline of glomerular filtration rate. In chronic kidney disease, AVP contributes to glomerular hyperfiltration, arterial hypertension, and synthesis of renin, resulting in renal sclerosis. Increased water intake could reduce AVP activation determining a potential protective effect on the kidney, but its efficacy has not yet been clearly demonstrated. On the other side, sodium and potassium play an important role in the control of arterial blood pressure and are involved in the development and progression of chronic kidney disease. Reduction of sodium intake and increase of potassium intake determine a decrease of arterial blood pressure with a beneficial effect on the kidney; however, adherence to sodium restriction is very poor. Regarding this, sodium-hydrogen exchanger isoform 3 inhibitors may reduce sodium absorption in the gut. The most recent sodium-hydrogen exchanger isoform 3 inhibitor, known as tenapanor, reduces extracellular fluid volume, left ventricular hypertrophy, albuminuria, and blood pressure in experimental studies and increases fecal loss of sodium in humans.

Higher Dietary Acid Load Is Associated With an Increased Risk of Calcium Oxalate Kidney Stones

“…It is also worth mentioning that FFQ cannot provide precise estimation of salt and water intake, and we did not measure sodium excretion in 24 h urinary sample or water consumption in a day, which might impact the risk of stone formation. Although sodium restriction has been frequently recommended in patients with kidney stones, adherence is generally poor (35), and therefore, it is unlikely that it would considerably change our findings. In support of this assertion, we made further adjustment for sodium intake, estimated through FFQ, across the tertiles of PRAL and NEAP, and observed no substantial change in our findings.…”

Dietary Aspects and Drug-Related Side Effects in Autosomal Dominant Polycystic Kidney Disease Progression

“…However, the level of water intake achieved by taking tolvaptan seems unachievable by means of a high water intake diet in the absence of increased thirst. In addition to a potential effect on ADPKD progression, high water intake can help prevent nephrolithiasis, a well-known complication of the disease [ 38 ].…”

Keeping the Diet Simple and Natural in Chronic Kidney Disease: A South African-Based Dietary Infographic

“…Current advice is based on the cornerstone that the CVD benefits of sodium restrictions outweigh the potential concerns (Table 3). 4,35…”