Plasma Neutrophil Gelatinase-Associated Lipocalin and Predicting Clinically Relevant Worsening Renal Function in Acute Heart Failure
Abstract
:1. Introduction
2. Results
2.1. Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Worsening Renal Function (WRF)
2.2. NGAL and Clinically Relevant WRF
2.3. NGAL, WRF, and Clinical Outcome
3. Discussion
3.1. Prediction of WRF
3.2. NGAL, Creatinine and Outcome
3.3. Clinical Perspectives
3.4. Limitations
4. Materials and Methods
4.1. Study Design and Population
4.2. Procedures and Definitions
4.3. Endpoints
4.4. Statistical Methods
5. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
Abbreviations
AHF | Acute Heart Failure |
AKI | Acute Kidney Injury |
LVEF | Left ventricular ejection fraction |
NGAL | Neutrophil Gelatinase-Associated Lipocalin |
WRF | Worsening Renal Function |
HR | Hazard Ratio |
SD | Standard Deviation |
References
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Categories | No WRF, Alive | No WRF, Dead | p * | No WRF, Total | WRF, Alive | WRF, Dead | p * | WRF, Total | p ** |
---|---|---|---|---|---|---|---|---|---|
(n = 936) | (n = 186) | (n = 1122) | (n = 247) | (n = 78) | (n = 325) | ||||
Demographics | |||||||||
Sex (% Male) | 64 (599) | 68.3 (127) | 0.302 | 64.7 (726) | 69.6 (172) | 71.8 (56) | 0.825 | 70.2 (228) | 0.079 |
Age (years) | 69.6 ± 11.6 | 72.4 ± 10.7 | 0.001 | 70 ± 11.5 | 71.1 ± 10.3 | 71.9 ± 10.7 | 0.578 | 71.3 ± 10.4 | 0.058 |
BMI (kg/m2) | 28.8 ± 6 | 27.8 ± 5.7 | 0.032 | 28.6 ± 6 | 29.1 ± 5.8 | 28.3 ± 6 | 0.311 | 28.9 ± 5.9 | 0.516 |
LVEF (% (n)) | 32.7 ± 12.8 | 28.6 ± 11 | 0.001 | 31.9 ± 12.5 | 36.5 ± 13.9 | 30.5 ± 13.4 | 0.021 | 34.9 ± 14 | 0.020 |
Systolic Blood Pressure (mmHg) | 125.7 ± 17.3 | 117.8 ± 17.2 | <0.001 | 124.4 ± 17.6 | 129.2 ± 16.6 | 120.1 ± 16.4 | <0.001 | 127 ± 17 | 0.015 |
Diastolic Blood Pressure (mmHg) | 74.8 ± 11.5 | 71 ± 10.7 | <0.001 | 74.1 ± 11.5 | 76.9 ± 12.1 | 71.2 ± 10.8 | <0.001 | 75.5 ± 12 | 0.060 |
Heart Rate (beats/min) | 81.6 ± 16.4 | 80.3 ± 15.1 | 0.286 | 81.4 ± 16.2 | 80.3 ± 14.9 | 78.8 ± 14.8 | 0.452 | 79.9 ± 14.9 | 0.124 |
Rolofylline administration (% (n)) | 65.2 (610) | 69.4 (129) | 0.310 | 65.9 (739) | 72.5 (179) | 65.4 (51) | 0.291 | 70.8 (230) | 0.112 |
Clinical Profile | |||||||||
Orthopnea (% (n)) | 96.6 (896) | 94.6 (175) | 0.287 | 96.2 (1071) | 95.1 (233) | 100 (78) | 0.099 | 96.3 (311) | 1.000 |
Rales (% (n)) | 63.5 (594) | 61.3 (114) | 0.621 | 63.2 (708) | 64.8 (160) | 65.4 (51) | 1.000 | 64.9 (211) | 0.605 |
Edema (% (n)) | 71.2 (666) | 71 (132) | 1.000 | 71.1 (798) | 63.6 (157) | 60.3 (47) | 0.695 | 62.8 (204) | 0.005 |
Jugular venous pressure (% (n)) | 41.2 (344) | 49.4 (81) | 0.064 | 42.5 (425) | 40.3 (87) | 43.7 (31) | 0.716 | 41.1 (118) | 0.716 |
Medical History | |||||||||
Hypertension (% (n)) | 80.1 (750) | 79 (147) | 0.810 | 79.9 (897) | 79.8 (197) | 74.4 (58) | 0.394 | 78.5 (255) | 0.612 |
Diabetes Mellitus (% (n)) | 44.9 (420) | 45.7 (85) | 0.899 | 45 (505) | 44.5 (110) | 41.6 (32) | 0.743 | 43.8 (142) | 0.754 |
Hypercholesterolemia (% (n)) | 45.7 (427) | 42.5 (79) | 0.472 | 45.1 (506) | 51.4 (127) | 48.7 (38) | 0.775 | 50.8 (165) | 0.084 |
Smoking (% (n)) | 18.6 (174) | 19.5 (36) | 0.867 | 18.8 (210) | 14.2 (35) | 20.5 (16) | 0.250 | 15.7 (51) | 0.247 |
Ischemic Heart Disease (% (n)) | 69.3 (648) | 74.6 (138) | 0.177 | 70.2 (786) | 69.2 (171) | 73.1 (57) | 0.613 | 70.2 (228) | 1.000 |
Myocardial Infarction (% (n)) | 49 (458) | 54.3 (100) | 0.216 | 49.9 (558) | 48.2 (119) | 52.6 (41) | 0.585 | 49.2 (160) | 0.879 |
PCI (% (n)) | 21.9 (203) | 26.8 (49) | 0.182 | 22.7 (252) | 22.3 (55) | 23.4 (18) | 0.962 | 22.5 (73) | 1.000 |
CABG (% (n)) | 18.6 (172) | 21.9 (40) | 0.349 | 19.1 (212) | 21.9 (54) | 25.6 (20) | 0.590 | 22.8 (74) | 0.168 |
Peripheral Vascular Disease (% (n)) | 10.2 (95) | 15.1 (28) | 0.069 | 11 (123) | 11 (27) | 14.3 (11) | 0.559 | 11.8 (38) | 0.769 |
Atrial Fibrillation (% (n)) | 55.6 (518) | 57 (106) | 0.797 | 55.9 (624) | 55.1 (136) | 50 (39) | 0.515 | 53.8 (175) | 0.561 |
NYHA Class | 0.426 | 0.059 | 0.578 | ||||||
I–II | 16.6 (155) | 13.4 (25) | 16 (180) | 19.8 (49) | 10.3 (8) | 17.5 (57) | |||
III | 44.9 (420) | 49.5 (92) | 45.6 (512) | 45.7 (113) | 59 (46) | 48.9 (159) | |||
IV | 32.8 (307) | 31.7 (59) | 32.6 (366) | 31.6 (78) | 26.9 (21) | 30.5 (99) | |||
ICD therapy (% (n)) | 12.6 (118) | 17.2 (32) | 0.119 | 13.4 (150) | 12.6 (31) | 19.2 (15) | 0.197 | 14.2 (46) | 0.790 |
CRT therapy (% (n)) | 7.2 (67) | 14 (26) | 0.003 | 8.3 (93) | 11.3 (28) | 9 (7) | 0.706 | 10.8 (35) | 0.205 |
Stroke (% (n)) | 8.3 (78) | 9.1 (17) | 0.828 | 8.5 (95) | 12.6 (31) | 19.2 (15) | 0.197 | 14.2 (46) | 0.003 |
COPD (% (n)) | 19.4 (181) | 21.6 (40) | 0.545 | 19.7 (221) | 18.6 (46) | 21.8 (17) | 0.650 | 19.4 (63) | 0.953 |
Prior Medication Use | |||||||||
ACE inhibitors or ARB (% (n)) | 76.4 (715) | 69.9 (130) | 0.074 | 75.3 (845) | 76.5 (189) | 71.8 (56) | 0.488 | 75.4 (245) | 1.000 |
Beta blockers (% (n)) | 74.7 (699) | 75.3 (140) | 0.939 | 74.8 (839) | 74.5 (184) | 67.9 (53) | 0.323 | 72.9 (237) | 0.547 |
MRA (% (n)) | 45.8 (429) | 48.4 (90) | 0.577 | 46.3 (519) | 47.4 (117) | 59 (46) | 0.097 | 50.2 (163) | 0.239 |
Calcium Antagonists (% (n)) | 12.7 (119) | 8.6 (16) | 0.147 | 12 (135) | 21.9 (54) | 7.7 (6) | 0.008 | 18.5 (60) | 0.004 |
Nitrates (% (n)) | 26.9 (252) | 26.9 (50) | 1.000 | 26.9 (302) | 27.5 (68) | 29.5 (23) | 0.849 | 28 (91) | 0.752 |
Digoxin (% (n)) | 31 (290) | 31.2 (58) | 1.000 | 31 (348) | 32.4 (80) | 20.5 (16) | 0.063 | 29.5 (96) | 0.660 |
Laboratory Values | |||||||||
Creatinine (mg/dL) | 1.3 (1.1–1.7) | 1.5 (1.2–2.1) | <0.001 | 1.3 (1.1–1.7) | 1.4 (1.2–1.8) | 1.7 (1.3–2) | 0.002 | 1.5 (1.2–1.8) | <0.001 |
eGFR (mL/min/1.73 m2) | 52 (39–66) | 45 (33–60) | <0.001 | 51 (38–65) | 48 (38–62) | 40 (32–51) | <0.001 | 46 (37–59) | <0.001 |
NGAL (ng/mL) | 78 (50–123) | 96 (58–137) | 0.008 | 81 (52–127) | 90 (56–142) | 131 (72–187) | 0.002 | 93 (58–151) | <0.001 |
Blood Urea Nitrogen (mg/dL) | 28 (21–38) | 37 (26–51) | <0.001 | 29 (22–40) | 28 (23–38) | 41 (30–55) | <0.001 | 31 (24–43) | 0.029 |
Sodium (mmol/L) | 140 (137–143) | 138 (135–141) | <0.001 | 140 (137–142) | 141 (138–143) | 139 (136–142) | 0.010 | 140 (138–143) | 0.063 |
Potassium (mmol/L) | 4.2 (3.9–4.6) | 4.3 (3.9–4.8) | 0.175 | 4.2 (3.9–4.6) | 4.3 (4–4.7) | 4.3 (3.9–4.7) | 0.815 | 4.3 (3.9–4.7) | 0.090 |
Hemoglobin (g/dL) | 12.9 ± 2 | 12.7 ± 1.9 | 0.216 | 12.8 ± 2 | 12.5 ± 1.9 | 12.3 ± 1.8 | 0.399 | 12.5 ± 1.9 | 0.007 |
Anemia (% (n)) | 38.3 (314) | 44.4 (75) | 0.169 | 39.4 (389) | 46.6 (102) | 49.3 (34) | 0.800 | 47 (136) | 0.021 |
BNP (mg/dL) | 1195 (815–2228) | 1895 (1172–3300) | <0.001 | 1351 (852–2433) | 1073 (718–1616) | 1749 (1153–2829) | 0.006 | 1190 (779–2078) | 0.227 |
Baseline Values | |||
WRF definition | Creatinine AUC | NGAL AUC | p * |
≥0.3 mg/dL increase | 0.571 | 0.569 | 0.930 |
Day 2 Values | |||
WRF definition | Creatinine AUC | NGAL AUC | p * |
≥0.3 mg/dL increase | 0.617 | 0.570 | 0.097 |
Change on Day 2 | |||
WRF definition | Creatinine AUC | NGAL AUC | p * |
≥0.3 mg/dL increase | 0.718 | 0.491 | <0.001 |
Variables | OR (95% CI) | χ2 | p |
---|---|---|---|
Cholesterol (per SD) | 1.33 (1.16–1.52) | 16.26 | <0.001 |
Hemoglobin (per SD) | 0.77 (0.67–0.90) | 11.45 | 0.001 |
NGAL (per SD) | 1.23 (1.08–1.40) | 9.79 | 0.002 |
History of Stroke | 1.89 (1.25–2.83) | 9.52 | 0.002 |
Male Sex | 1.48 (1.10–2.01) | 6.55 | 0.010 |
Albumin (per SD) | 1.19 (1.03–1.38) | 5.77 | 0.016 |
Rolofylline treatment | 1.39 (1.04–1.87) | 4.78 | 0.029 |
WRF definition | MV Model * OR (95% CI) | χ2 | p-value ** | AUC | p-value *** |
---|---|---|---|---|---|
WRF and 180-day mortality **** | |||||
≥0.3 mg/dL increase | |||||
Creatinine | 1.26 (1.02–1.55) | 4.81 | 0.028 | 0.670 | 0.021 |
NGAL | 1.25 (1.04–1.48) | 6.52 | 0.011 | ||
≥25% & ≥0.3mg/dL increase | |||||
Creatinine | 1.03 (0.78–1.33) | 0.04 | 0.833 | 0.637 | 0.017 |
NGAL | 1.31 (1.06–1.56) | 7.53 | 0.006 | ||
WRF and 60-day endpoint **** | |||||
≥0.3 mg/dL increase | |||||
Creatinine | 1.25 (1.03–1.5) | 5.36 | 0.021 | 0.656 | 0.001 |
NGAL | 1.32 (1.12–1.55) | 11.69 | 0.001 | ||
≥25% & ≥0.3mg/dL increase | |||||
Creatinine | 1.03 (0.81–1.29) | 0.05 | 0.821 | 0.633 | 0.005 |
NGAL | 1.31 (1.09–1.55) | 9.57 | 0.002 |
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Damman, K.; Valente, M.A.E.; Van Veldhuisen, D.J.; Cleland, J.G.F.; O’Connor, C.M.; Metra, M.; Ponikowski, P.; Cotter, G.; Davison, B.; Givertz, M.M.; et al. Plasma Neutrophil Gelatinase-Associated Lipocalin and Predicting Clinically Relevant Worsening Renal Function in Acute Heart Failure. Int. J. Mol. Sci. 2017, 18, 1470. https://doi.org/10.3390/ijms18071470
Damman K, Valente MAE, Van Veldhuisen DJ, Cleland JGF, O’Connor CM, Metra M, Ponikowski P, Cotter G, Davison B, Givertz MM, et al. Plasma Neutrophil Gelatinase-Associated Lipocalin and Predicting Clinically Relevant Worsening Renal Function in Acute Heart Failure. International Journal of Molecular Sciences. 2017; 18(7):1470. https://doi.org/10.3390/ijms18071470
Chicago/Turabian StyleDamman, Kevin, Mattia A. E. Valente, Dirk J. Van Veldhuisen, John G. F. Cleland, Christopher M. O’Connor, Marco Metra, Piotr Ponikowski, Gad Cotter, Beth Davison, Michael M. Givertz, and et al. 2017. "Plasma Neutrophil Gelatinase-Associated Lipocalin and Predicting Clinically Relevant Worsening Renal Function in Acute Heart Failure" International Journal of Molecular Sciences 18, no. 7: 1470. https://doi.org/10.3390/ijms18071470
APA StyleDamman, K., Valente, M. A. E., Van Veldhuisen, D. J., Cleland, J. G. F., O’Connor, C. M., Metra, M., Ponikowski, P., Cotter, G., Davison, B., Givertz, M. M., Bloomfield, D. M., Hillege, H. L., & Voors, A. A. (2017). Plasma Neutrophil Gelatinase-Associated Lipocalin and Predicting Clinically Relevant Worsening Renal Function in Acute Heart Failure. International Journal of Molecular Sciences, 18(7), 1470. https://doi.org/10.3390/ijms18071470