Low serum hemoglobin (Hb) is associated with a higher risk for IgA nephropathy (IgAN) progression, a new study finds.
In a cohort of 1828 patients (mean age 34 years) with biopsy-proven IgAN, the mean estimated glomerular filtration rate (eGFR) was 99.70 mL/min/1.73 m2 and mean Hb was 123.47 g/L at baseline. During a median follow-up of about 7 years, 183 patients experienced the primary outcome: a 40% decline in eGFR, end-stage kidney disease (ESKD), or all-cause mortality.
Patients were grouped into quartiles of baseline Hb for analysis: less than 112 g/L (Q1), 112 to 123 g/L (Q2), 124 to 134 g/L (Q3), and 135 or higher g/L (Q4). In a fully adjusted model, quartiles 3, 2, and 1 had a significant 37%, 18%, and 91% higher risk for the primary outcome, respectively, compared with quartile 4 (P=0.02), Bin Zhu, MD, of Zhejiang Chinese Medical University in Hangzhou, China, and colleagues reported in the American Journal of Nephrology. Kidney failure risk increased by 39%, 20%, and 83%, respectively (P=0.04).
In a sex-based model, men and women with anemia (Hb less than 120 and 110 g/L, respectively) had a 64% and 68% higher risk for the primary outcome, respectively, and a 60% and 58% higher risk for kidney failure, respectively, compared with their counterparts without anemia.
“The present study suggested a nonlinear relationship between low hemoglobin levels and high risk of developing outcomes in IgAN,” Dr Zhu’s team reported. “This was consistent with previous reports that low hemoglobin/hematocrit levels in the general population may be associated with a higher risk of [ESKD], while hemoglobin-related improvements of outcomes were reduced in people with excessively higher hemoglobin levels.”
Anemia-associated hypoxia might promote proteinuria and renal function decline via HIF-1α signaling in IgAN, according to the investigators. Or, low levels of Hb may indicate worse tubular atrophy/interstitial fibrosis, they explained. Higher blood pressure may underlie the association between cases of excessively high Hb and IgAN progression.
In a discussion of study limitations, the authors noted that they did not assess smoking status, comorbid conditions, and use of erythropoiesis stimulating agents.
Zhu B, Liu WH, Yu DR, et al. The association of low hemoglobin levels with IgA nephropathy progression: a two-center cohort study of 1828 cases. Am J Nephrol. Published online July 21, 2020. doi:10.1159/000508770