The Relationship between Circulating Kidney Injury Molecule-1 and Cardiovascular Morbidity and Mortality in Hemodialysis Patients
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Alexandru Florin Sircuța1,2,3, Iulia Dana Grosu1,2,3, Adalbert Schiller1,2
1Department of Internal Medicine II-Nephrology University Clinic, "Victor Babeș" University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timișoara, Romania.
Insights
Low plasma kidney injury molecule-1 (KIM-1) levels in hemodialysis patients indicate increased cardiovascular risk and mortality. Higher KIM-1 levels were observed in hemodialysis patients compared to non-dialysis CKD patients.
Area of Science:
- Nephrology
- Cardiology
- Biomarker Discovery
Background:
- Chronic kidney disease (CKD) patients on hemodialysis (HD) face high mortality risks.
- Plasma kidney injury molecule-1 (KIM-1) is a potential biomarker for tubulointerstitial injury, cardiovascular mortality, and coronary artery calcification in HD patients.
Purpose of the Study:
- To evaluate plasma KIM-1 as a marker for cardiovascular disease (CVD) and mortality in CKD stage 5 HD patients.
Main Methods:
- Prospective case-control study of 63 CKD5-HD patients and 52 non-dialysis CKD patients.
- Assessed plasma KIM-1 using enzyme-linked immunosorbent assay.
- Collected data on CVD, inflammation, anemia, and followed patients for 48 months for mortality.
Main Results:
- Plasma KIM-1 correlated with inflammation (CRP, IL-6) and anemia markers (hematocrit, hemoglobin).
- Patients with left ventricular hypertrophy had lower KIM-1 levels.
- Mortality rates were 22.23% at 24 months and 50.73% at 48 months.
- KIM-1 levels < 82.98 pg/mL were linked to decreased survival (p < 0.001).
Conclusions:
- Low plasma KIM-1 levels in HD patients are associated with cardiovascular changes and higher mortality risk.
- Plasma KIM-1 levels are significantly elevated in HD patients compared to non-dialysis CKD patients.
Background:
The importance of identifying mortality biomarkers in chronic kidney disease (CKD), and especially in patients treated with hemodialysis (HD), has become evident. In addition to being a marker of tubulointerstitial injury, plasma kidney injury molecule-1 (KIM-1) has been mentioned in regard to HD patients as a risk marker for cardiovascular (CV) mortality and coronary artery calcification. The aim of this study was to assess the level of plasma KIM-1 as a marker of cardiovascular disease (CVD) and mortality in CKD5-HD patients (patients with CKD stage G5D treated with hemodialysis).
Methods:
We conducted a prospective case-control study that included 63 CKD5-HD patients (HD for 1-5 years) followed up for 48 months and a control group consisting of 52 non-dialysis patients diagnosed with CKD stages G1-G5 (ND-CKD). All patients had a CVD baseline assessment including medical history, echocardiography, and electrocardiography (ECG). Circulating plasma KIM-1 levels were determined with single-molecule counting immunoassay technology using an enzyme-linked immunosorbent assay. We obtained the following parameters: serum creatinine and urea; the inflammation markers CRP (C-reactive protein) and IL-6 (interleukin-6); and the anemia markers complete blood count, serum ferritin, and transferrin saturation (TSAT).
Results:
The mean plasma KIM-1 level was 403.8 ± 546.8 pg/mL, showing a statistically significant correlation with inflammation (CRP, R = 0.28, p = 0.02; IL-6, R = 0.36, p = 0.005) and with anemia (hematocrit, R = -0.5, p = -0.0316; hemoglobin (Hb), R = -0.5, p = 0.02). We found that patients with left ventricular hypertrophy (LVH) on echocardiography (59.7%) had significantly lower mean levels of plasma KIM-1 than patients from the control group (155.51 vs. 432.12 pg/mL; p = 0.026). Regarding the patients' follow-up, we assessed all-cause mortality as an endpoint. After 24 months of follow-up, we found a mortality rate of 22.23%, while after 48 months, the mortality rate was 50.73%. A plasma KIM-1 level < 82.98 pg/mL was significantly associated with decreased survival in hemodialysis patients (p < 0.001).
Conclusions:
In patients treated with hemodialysis, low levels of plasma KIM-1 were associated with cardiovascular changes and an increased risk of mortality. Plasma KIM-1 levels were significantly higher in HD patients compared to ND-CKD patients.
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