Table 3.
Summary of human studies on NGAL and cardiac disease.
| Reference | Population | Renal function | Specimen(s) | NGAL levels: Diseased vs. control subjects | Other major findings |
|---|---|---|---|---|---|
| Chronic heart failure | |||||
| Damman (10) | Clinically stable CHF outpatients (LVEF <45%) (n=90) | Mean eGFR 64 mL/min/1.73 m2 | Urine | Diseased > controls | sCr, eGFR, urinary albumin excretion and NT-pro-BNP were significantly correlated with urinary NGAL levels, combining CHF patients and controls. |
| Damman (16) | Clinically stable CHF outpatients (LVEF <45%) (n=90) | Mean measured GFR 78 mL/min/1.73 m2 | Urine | Diseased > controls | sCr, measured GFR, urinary albumin excretion and NT-pro-BNP did not correlate with urinary NGAL levels among CHF patients. NGAL levels did not differ between patients with CHF with or without CKD. |
| Poniatowski (17) | CHF due to CAD (n=150) | Mean eGFR 74.6–85.8 mL/min/1.73 m2 | Serum and urine | No controls | In multiple regression analysis, predictors of serum NGAL were NYHA class, cystatin C, and eGFR. |
| Bolignano (18) | CHF (elderly, age >65 years) (n=46) | Mean eGFR 71.5–73.6 mL/min/1.73 m2 | Serum | Diseased > controls | NGAL correlated with NYHA class. CHF patients with a serum NGAL value >783 ng/mL had a significantly higher mortality (HR 4.08, 95% CI 1.29–12.96) over a 2-year follow-up. |
| Yndestad (9) | CHF (n=150) | Mean eGFR not stated but 120/150 pts had sCr <1.4 mg/dL | Serum | Diseased > controls | Highest NGAL levels observed in NYHA class III and IV NGAL correlated with Nt-pro-BNP, but not with LVEF, cardiac index, and LV dimensions. NGAL also correlated with leukocyte count and CRP. |
| Shrestha (19) | CHF (LVEF ≤35%) (n=130) | Mean eGFR 72 mL/min/1.73 m2 | Plasma | No controls | Patients with ischemic etiology for CHF demonstrated higher NGAL levels compared with non-ischemic etiology [84 (IQR 64,129) vs. 72 (IQR 52, 102) ng/mL, respectively; p=0.024]. |
| Acute heart failure | |||||
| Yndestad (9) | Acute post-MI HF (n=236) | Mean eGFR not stated | Serum | No controls | Elevated NGAL levels were found in patients with NYHA class III (vs. NYHA I/II), both at baseline and on follow-up. NGAL correlated weakly with Nt-pro-BNP and leukocyte count. Patients with higher baseline serum NGAL levels (above the median) tended to have more adverse CV events. |
| Shrestha (19) | AHF admitted to ICU (LVEF ≤35%) (n=69) | Mean eGFR 71 mL/min/1.73 m2 | Plasma | No controls | NGAL levels were modestly associated with indices of diastolic dysfunction, but not after adjustment for renal function. There was no association between plasma NGAL and hemodynamic indices of intracardiac pressures. |
| Alvelos (20) | AHF admitted to hospital (n =121) | Mean eGFR 40 mL/min/1.73 m2 | Serum | No controls | NGAL and BNP were independent predictors of death and rehospitalization at 3 months. |
| Maisel (21) | AHF admitted to hospital (n=186) | Median eGFR 55–57 mL/min/1.73 m2 at discharge | Plasma | No controls | NGAL and BNP at time of hospital discharge were independent predictors of death and AHF rehospitalization at 30 days. |
| Coronary heart disease | |||||
| Haapio (22) | Suspected CHD who underwent nuclear stress perfusion testing (n=34) | Mean sCr 0.9–1.0 mg/dL | Plasma | No controls | NGAL levels were below limits of detection in 11/34 subjects. Patients with detectable plasma NGAL had more segmental perfusion defects at rest, and lower LVEF at rest and with stress, and lower end systolic volume with stress. |
| Choi (23) | Angiographically confirmed CHD (n=49) | NS | Serum | Diseased > controls | On multivariable analysis, NGAL level, systolic blood pressure and insulin resistance were independently associated with the presence of CHD. NGAL correlated positively with body weight, fasting insulin levels and insulin resistance, and negatively with HDL levels. |
| Zografos (11) | Suspected CHD who underwent angiography (n=73) | All pts had “normal sCr” | Serum | No controls | NGAL levels were higher in patients with angiographically confirmed CHD compared to those with normal coronary arteries. NGAL levels correlated with the number of diseased vessels and the severity of the CHD. |
| Astrom Olsson (24) | Patients with first AMI (n=49) | NS | Serum | No controls | There was no change in NGAL levels following reperfusion of AMI by percutaneous coronary intervention. |
NS, not stated.