Haptoglobin 1‐1 phenotype: A risk factor for 24‐hours polyuria

Abstract

Background Haptoglobin (Hp) displays three major phenotypes (Hp 1‐1, Hp 2‐2 and Hp 2‐1). Hp 1‐1 has been implicated in high blood pressure and salt sensitivity, and thus may mediate excess urine production. Aim To explore the relationship between Hp polymorphisms and polyuria (>40 mL/kg/24 hours). Methodology Post hoc analysis of a prospective observational study of subjects who completed a renal function profile between October 2011 and February 2015 (n = 170). Hp phenotypes were determined by starch gel electrophoresis using haemoglobin‐supplemented serum. The distribution of Hp phenotypes in subjects with and without polyuria was compared to a reference group of the same geography and ethnic composition. Diuresis rate, sodium clearance and free water clearance were compared within and between phenotypes. Results The Hp1 allele frequency was significantly overexpressed in subjects with polyuria compared to the reference group (0.500 vs 0.400, P < .05). Consistently, the Hp 1‐1 phenotype was more prevalent in subjects with polyuria compared to the reference group (28% vs 16%, P < .05). In contrast to Hp 2‐1/2‐2, Hp 1‐1 demonstrated no circadian variation in diuresis rate, sodium clearance or free water clearance. A significant association between plasma Hp concentration and 24‐hours sodium clearance was observed in Hp 1‐1 subjects without polyuria (β = 0.222; 95% CI 0.003‐0.441; P = .047). Conclusion The Hp1 allele was more frequent in subjects with polyuria, and participants with the Hp 1‐1 phenotype were at greater risk for polyuria. Hp 1‐1 subjects demonstrated an altered ability to concentrate urine with a slower continuous excretion of sodium throughout the day. Plasma Hp concentration of Hp 1‐1 was positively correlated with 24‐hours sodium clearance in subjects without polyuria.

The Influence of Salt Sensitivity Phenotype on Sodium Excretion and Diuresis: A Chrononutrition Pilot Study

“…In our previously published study, we demonstrated that Hp polymorphism-related salt sensitivity in Hp1-1 phenotype lacked circadian rhythm in diuresis, renal clearance of free water, and sodium, in contrast to Hp2-2/2-1 phenotypes [ 18 ]. Hp is a haemoglobin clearing plasma protein that displays three major phenotypes in humans as Hp 1-1, Hp 2-2, and Hp 2–1 [ 33 ], and Hp1‐1 has been associated in high BP and salt sensitivity [ 34 ].…”

“…In our previously published study, haptoglobin (Hp) polymorphism-related salt sensitivity in sodium and water handling were reported [ 18 ]. In this study, we hypothesized that healthy individuals who display a low rate of sodium excretion after an acute high salt load react inappropriately with salt and water retention and are therefore called “salt-sensitive”.…”