Association of Kidney Disease Measures with Cause-Specific Mortality: The Korean Heart Study.
BACKGROUND
The link of low estimated glomerular filtration rate (eGFR) and high proteinuria to cardiovascular disease (CVD) mortality is well known. However, its link to mortality due to other causes is less clear.


METHODS
We studied 367,932 adults (20-93 years old) in the Korean Heart Study (baseline between 1996-2004 and follow-up until 2011) and assessed the associations of creatinine-based eGFR and dipstick proteinuria with mortality due to CVD (1,608 cases), cancer (4,035 cases), and other (non-CVD/non-cancer) causes (3,152 cases) after adjusting for potential confounders.


RESULTS
Although cancer was overall the most common cause of mortality, in participants with chronic kidney disease (CKD), non-CVD/non-cancer mortality accounted for approximately half of cause of death (47.0%for eGFR <60 ml/min/1.73 m2 and 54.3% for proteinuria ≥1+). Lower eGFR (<60 vs. ≥60 ml/min/1.73 m2) was significantly associated with mortality due to CVD (adjusted hazard ratio 1.49 [95% CI, 1.24-1.78]) and non-CVD/non-cancer causes (1.78 [1.54-2.05]). The risk of cancer mortality only reached significance at eGFR <45 ml/min/1.73 m2 when eGFR 45-59 ml/min/1.73 m2 was set as a reference (1.62 [1.10-2.39]). High proteinuria (dipstick ≥1+ vs. negative/trace) was consistently associated with mortality due to CVD (1.93 [1.66-2.25]), cancer (1.49 [1.32-1.68]), and other causes (2.19 [1.96-2.45]). Examining finer mortality causes, low eGFR and high proteinuria were commonly associated with mortality due to coronary heart disease, any infectious disease, diabetes, and renal failure. In addition, proteinuria was also related to death from stroke, cancers of stomach, liver, pancreas, and lung, myeloma, pneumonia, and viral hepatitis.


CONCLUSIONS
Low eGFR was associated with CVD and non-CVD/non-cancer mortality, whereas higher proteinuria was consistently related to mortality due to CVD, cancer, and other causes. These findings suggest the need for multidisciplinary prevention and management strategies in individuals with CKD, particularly when proteinuria is present.
Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United States of America.|Department of Epidemiology and Health Promotion, and Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, Korea.
Yejin
Y
Mok
Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United States of America.
Kunihiro
K
Matsushita
Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United States of America.
Yingying
Y
Sang
Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United States of America.
Shoshana H
SH
Ballew
Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United States of America.
Morgan
M
Grams
Department of Internal medicine, Korea Medical Institute, Seoul, Korea.
Sang Yop
SY
Shin
Department of Epidemiology and Health Promotion, and Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, Korea.
Sun Ha
SH
Jee
Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United States of America.
Josef
J
Coresh
D000328:Adult; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000401:mortality; D002423:Cause of Death; D003404:Creatinine / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism / Q000401:mortality; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000401:mortality; D007723:Korea; D009369:Neoplasms / Q000378:metabolism / Q000401:mortality; D011507:Proteinuria / Q000378:metabolism / Q000401:mortality; D051436:Renal Insufficiency, Chronic / Q000378:metabolism / Q000401:mortality*; D012307:Risk Factors; D055815:Young Adult
D003404:Creatinine