PLOS ONE | DOI:10.1371/journal.pone.0153429

 

Association of Kidney Disease Measures with Cause-

Specific Mortality: The Korean Heart Study

Yejin Mok, Kunihiro Matsushita, Yingying Sang, Shoshana H. Ballew, Morgan Grams, Sang Yop Shin,
Sun Ha Jee, Josef Coresh

 

Abstract

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 themost 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/1.73m2 and 54.3%for proteinuria ≥1+). Lower eGFR (<60 vs. ≥60 ml/min/1.73m2) was significantly associated withmortality 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/1.73m2 when eGFR 45–59 ml/min/1.73m2 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.

Conclusion: 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.