Metabolic Acidosis Is an Independent Risk Factor of Renal Progression in Korean Chronic Kidney Disease Patients: The KNOW-CKD Study Results

Hyo Jin Kim; Hyunjin Ryu; Eunjeong Kang; Minjung Kang; Miyeun Han; Sang Heon Song; Joongyub Lee; Ji Yong Jung; Kyu-Beck Lee; Suah Sung; Eun Young Seong; Curie Ahn; Kook-Hwan Oh

doi:10.3389/fmed.2021.707588

Metabolic Acidosis Is an Independent Risk Factor of Renal Progression in Korean Chronic Kidney Disease Patients: The KNOW-CKD Study Results

Front Med (Lausanne). 2021 Jul 29:8:707588. doi: 10.3389/fmed.2021.707588. eCollection 2021.

Authors

Hyo Jin Kim^{1

2}, Hyunjin Ryu³, Eunjeong Kang⁴, Minjung Kang³, Miyeun Han⁵, Sang Heon Song^{1

2}, Joongyub Lee⁶, Ji Yong Jung⁷, Kyu-Beck Lee⁸, Suah Sung⁹, Eun Young Seong^{1

2}, Curie Ahn¹⁰, Kook-Hwan Oh^{3

11}

Affiliations

¹ Department of Internal Medicine, Pusan National University Hospital, Busan, South Korea.
² Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea.
³ Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.
⁴ Department of Internal Medicine, Ewha Womans University Seoul Hospital, Ewha Womans University College of Medicine, Seoul, South Korea.
⁵ Department of Internal Medicine, Hallym University Hangang Sacred Heart Hospital, Seoul, South Korea.
⁶ Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea.
⁷ Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, South Korea.
⁸ Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea.
⁹ Department of Internal Medicine, Eulji Medical Center, Eulji University, Seoul, South Korea.
¹⁰ Department of Internal Medicine, National Medical Center, Seoul, South Korea.
¹¹ Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.

Abstract

Background: We aimed to evaluate serum bicarbonate as a risk factor for renal progression, cardiovascular events, and mortality in Korean CKD patients. Methods: We analyzed 1,808 participants from a Korean CKD cohort whose serum bicarbonate levels were measured at enrollment. Serum bicarbonate levels were categorized as low, lower normal, higher normal, and high (total carbon dioxide <22, 22-26, 26.1-29.9, and ≥30 mmol/L, respectively) groups. Metabolic acidosis was defined as a serum bicarbonate level <22 mmol/L. The primary outcome was renal events defined as doubling of serum creatinine, 50% reduction of eGFR from the baseline values, or development of end-stage kidney disease. The secondary outcome consisted of cardiovascular events and death. In addition, patients whose eGFR values were measured more than three times during the follow-up period were analyzed for eGFR decline. The rapid decline in eGFR was defined as lower than the median value of the eGFR slope. Results: The mean serum bicarbonate level was 25.7 ± 3.7 mmol/L and 240 (13.2%) patients had metabolic acidosis. During the follow-up period of 55.2 ± 24.1 months, 545 (30.9%) patients developed renal events and 187 (10.6%) patients developed a composite of cardiovascular events and death. After adjustment, the low serum bicarbonate group experienced 1.27 times more renal events than the lower normal bicarbonate group [hazard ratio (HR): 1.27; 95% CI: 1.01-1.60, P = 0.043]. There was no significant association between the bicarbonate groups and the composite outcome of cardiovascular events and death. The low bicarbonate group showed a significantly rapid decline in eGFR [odds ratio (OR): 2.12; 95% CI: 1.39-3.22, P < 0.001] compared to the lower normal bicarbonate group. Conclusions: Metabolic acidosis was significantly associated with increased renal events and a rapid decline in renal function in Korean predialysis CKD patients.

Keywords: chronic kidney disease; metabolic acidosis; renal function decline; renal progression; serum bicarbonate.