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.
© 2019 John Wiley & Sons Ltd.