Natremia after fasting 12 h, kidney disease and aging

Dmitrieva et al. report that middle-age high-normal natremia after 12-h fasting is a risk factor for accelerated biological aging and premature mortality.¹ The manuscript was widely publicized in the lay press and, like others,² interpreted as supporting a need for the general population to increase water intake (“The results suggest that proper hydration may slow down aging and prolong a disease-free life”, ”Researchers Find Super Simple Key to Healthy Aging:Good Hydration!”).³ However, excessive water intake may be lethal.⁴ A recent Science manuscript has emphasized the obvious:fluid needs are multifactorial, food (e.g., fruits) may contribute to fluid ingestion.⁵ Given the high prevalence of high fasting natremia, a likely explanation is that participants complied with what they believed were the fasting instructions and refrained from eating or drinking fluid before blood sampling, as opposed to them having a thirst defect.¹ In the absence of overnight water ingestion, the key determinant of morning natremia is the urine concentration capacity of the kidneys. A urine concentration defect (i.e., partial nephrogenic diabetes insipidus) is an early feature of chronic kidney disease (CKD). Interestingly, 6 of the 15 biomarkers of biological aging used (i.e., GFR, creatinine, urea, uric acid, cystatin-C, β-2-microglobulin) directly reflect kidney function, while others (e.g., SBP, CRP) are indirectly related to kidney function. Thus, the data are consistent with high fasting natremia reflecting kidney dysfunction, a known risk factor for biological aging and premature mortality. Outcomes may thus not improve by drinking more fluid, but by early detection and treatment of CKD.

Declaration of interests

AO has received grants from Sanofi and consultancy or speaker fees or travel support from Adviccene, Alexion, Astellas, Astrazeneca, Amicus, Amgen, Boehringer Ingelheim, Fresenius Medical Care, GSK, Bayer, Sanofi-Genzyme, Menarini, Mundipharma, Kyowa Kirin, Lilly, Freeline, Idorsia, Chiesi, Otsuka, Novo-Nordisk, Sysmex and Vifor Fresenius Medical Care Renal Pharma and is Director of the Catedra Mundipharma-UAM of diabetic kidney disease and the Catedra Astrazeneca-UAM of chronic kidney disease and electrolytes. He has stock in Telara Farma.