Water (H2O) is the most abundant and important molecule of life. Natural water contains small amount of heavy isotopes. Previously, few animal model studies have shown that the isotopic composition of body water could play important roles in physiology and pathophysiology. Here we study the stable isotopic ratios of hydrogen (δ2H) and oxygen (δ18O) in human blood plasma. The stable isotopic ratio is defined and determined by δsample = [(Rsample/RSTD)−1] * 1000, where R is the molar ratio of rare to abundant, for example, 18O/16O. We observe that the δ2H and the δ18O in human blood plasma are associated with the human renal functions. The water isotope ratios of the δ2H and δ18O in human blood plasma of the control subjects are comparable to those of the diabetes subjects (with healthy kidney), but are statistically higher than those of the end stage renal disease subjects (p<0.001 for both ANOVA and Student's t-test). In addition, our data indicate the existence of the biological homeostasis of water isotopes in all subjects, except the end stage renal disease subjects under the haemodialysis treatment. Furthermore, the unexpected water contents (δ2H and δ18O) in blood plasma of body water may shed light on a novel assessment of renal functions.

Life does not sustain without water. For water, there is a natural abundance of stable isotope hydrogen and oxygen. Water molecules get across cell membranes through a plasma membrane protein, named aquaporin. Moreover, the kidney is the main organ to maintain water homeostasis. Here, we study the stable isotopic ratios of hydrogen and oxygen in human blood plasma and erythrocyte corresponding to kidney functions. We extract waters from human plasma and erythrocyte, collected from 110 participants, including 51 clinically stable outpatients with end‐stage renal disease (ESRD) and 59 subjects with normal renal function (NRF). We observed that (i) both extracellular (blood plasma) and intracellular (erythrocyte) biology waters are isotopic differences between the ESRD and NRF participants, (ii) the natural abundance of isotopic waters of ESRD is hypo‐isotopic, and (iii) the isotopic enrichment of water between erythrocyte and blood plasma are distinct. In addition, we introduce an empirical formula using entropy transformation to describe isotopic water enrichment for biology. Accordingly, the natural abundance of stable isotope water of blood plasma and erythrocyte may be possibly put in practice a new sign for assessments of kidney dysfunctions.