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

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.

To explore the relationship between Hp polymorphisms and polyuria (>40 mL/kg/24 hours).

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.

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).

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.