Haptoglobin phenotype among patients with IgA nephropathy: Impact on disease progression and response to treatment

Abstract

IgA nephropathy (IgAN) is characterized by proteinuria, hypertension, and decreased glomerular filtration rate at the time of diagnosis. However, the underlying mechanism is still obscure. The impact of haptoglobin (Hp) phenotype, as a genetic risk factor, on the progression of IgAN has not been studied yet. The current study examines whether Hp phenotype influences IgAN progression and response to treatment. The study included 40patients with IgAN, 26 non-IgAN chronic kidney disease (CKD), 114 patients on hemodialysis, and 150healthy subjects. Blood and urine samples were collected at baseline and 6months after initiation therapy. Serum creatinine, total proteinuria, and Hp phenotype were determined in all patients and healthy controls. Approximately 17% of IgAN patients were Hp 1-1, 40% Hp 2-1, and 42.5% Hp 2-2. In contrast, in non-IgAN CKD patients, the prevalence of Hp 1-1, Hp 2-1, and Hp 2-2 was 8%, 19%, and 73%, respectively. In hemodialytic patients, prevalence of Hp 1-1, Hp 2-1, and Hp 2-2 was 10.5, 49.1, and 40.4%, respectively. In healthy subjects, the distribution of Hp 1-1, Hp 2-1, and Hp 2-2 was 7, 39, and 54%, respectively. Interestingly, IgAN Hp 2-2 and Hp 2-1 patients were more stable and responded better to treatment with routine therapy than other patients with Hp phenotype. The prevalence of Hp 1-1 phenotype is higher in IgAN patients than in the general population in Israel, and even more than in patients with CKD or subjects on hemodialysis. Patients with Hp 2-2 exhibited a better renal response to the routine therapies.