Supplementary Online Content
Amino-terminal Pro B-Type Natriuretic Peptide for Diagnosis and Prognosis in Patients with
Renal Dysfunction: A Systematic Review and Meta-Analysis
Jennifer A. Schaub, MD; Steven G. Coca, MD, MS; Dennis G. Moledina, MBBS, Mark Gentry, MA,
MLS; Jeffrey M. Testani, MD, MS, Chirag R. Parikh, MD, PhD
List of Supplementary Tables and Figures
Table 1: Search Methods in Ovid (Medline for Prognosis)
Table 2A: Reported NT-proBNP Levels in Patients with eGFR>60 and eGFR<60
Table 2B: Reported NT-proBNP Levels by eGFR
Table 3: Meta-regression for Crude Estimates of NT-proBNP and Mortality
Figure 1: Flow Diagram of Studies Considered for Inclusion
Figure 2: Adjusted Estimates of Mortality in Patients with Preserved and Diminished Renal
Function (without Waldum)
Figure 3: Funnel Plots for Prognosis
References: References of Studies included in Systematic Review and Meta-analysis
Table 1: Search Methods in Ovid (Medline for Prognosis)
1. Natriuretic peptide, brain/
2. B type natriuretic peptide*.mp
3. Brain natriuretic peptide*.mp
4. Bnp*.mp
5. Probnp*.mp
6. pro bnp*.mp
7. Nt probnp*.mp
8. Ntprobnp*.mp
9. Natriuretic peptide type b.mp.
10. or/1-9
11. exp kidney disease/
12. (chronic kidney or chronic renal).tw.
13. (ckf or ckd or cki or crf or crd or cri or esrd or eskf or esrf).tw.
14. (pre-dialy$ or predialy$).tw.
15. ur$emi$.tw.
16. exp Renal Replacement Therapy/
17. (haemodialysis or hemodialysis).tw.
18. (hemofiltration or haemofiltration).tw.
19. (hemodiafiltration or haemodiafiltration).tw.
20. (CAPD or CCPD or APD).tw.
21. dialysis.tw.
22. (end stage kidney or end stage renal or endstage kidney or endstage renal).tw.
23. (acute renal failure or acute kidney failure or ARF or AKF).tw.
24. (acute kidney injury or AKI).tw.
25. (acute renal insufficienc* or acute kidney insufficienc*).tw.
26. acute tubular necrosis.tw.
27. acute kidney tubular necrosis.tw.
28. ATN.tw.
29. kidney fail*.tw.
30. renal fail*.tw.
31. (kidney insufficienc* or renal insufficienc*).tw.
32. (glomerular adj3 filtration adj3 rate).tw.
33. gfr.tw.
34. or/11-33
35. exp mortality/
36. prognosis/
37. follow up studies/
38. incidence/
39. mortality.tw.
40. prognos*.tw.
41. predict*.tw.
42. course*.tw.
43. or/35-42
44. 10 and 34 and 43
Table 2A: Reported NT-proBNP Levels in Patients with eGFR>60 and eGFR<60
NT-proBNP Level (pg/ml)
eGFR<60
Author, Year
Statistic
eGFR>60
Fu, 2013
Median
298.6
1027.5
Gorrison, 2007
Maximum
1800
4500
Palmer, 2009
Median (IQR)
888 (554-1501)
1370 (918-2593)
Van Kimmendade, 2006
Median (IQR)
3045 (1345-7620)
7214 (2757-16160)
IQR, interquartile range; eGFR, estimated GFR (ml/min/1.73m2)
Table 2B: Reported NT-proBNP Levels by eGFR
Study, Year
Statistic
Patient Pop
NT-proBNP Level (pg/ml)
eGFR 30-59
eGFR>90
eGFR 60-90
eGFR <30
All
175
280
412
524
HF only
2000
4000
6000
14000
Anwaruddin, 2006
Median
Chenevier-Gobeaux, 2005
Mean*
No HF
1000
1500
4000
4000
Horii, 2013
Median (IQR)
All
83.5(33.2-301)
160.5 (57.9-569.6)
499.8 (158-1387)
6220 (1317-23,246)
Masson, 2006
Median
All
500
600
1400
3000
Pimenta, 2007
Median (IQR)
All
4807 (2089-9847)
10578 (4538-20416)
10776 (5342-31264)
17789 (10639-43691)
IQR, interquartile range; eGFR, estimated GFR (ml/min/1.73m2)
*Estimated visually from figure
Table 3: Meta-regression for Crude Estimates of NT-proBNP and Mortality
Study Characteristic
Preserved Renal Function
2
Diminished Renal Function
Slope(SE)
I (%)
R (%)
Slope (SE)
I2 (%)
R2(%)
CAD
0.30 (0.15)
27.3
51.4
0.61* (0.17)
41.0
80.0
HF
-0.37* (0.11)
0.0
100
-0.67* (0.15)
30.3
87.4
Inpatient
0.14 (0.18)
46.3
0.0
0.07 (0.28)
74.6
12.7
Serum Cystatin C
0.24 (0.56)
51.0
0.0
-0.62 (0.41)
79.6
4.1
eGFR
-0.07 (0.20)
49.3
0.0
0.28 (0.28)
73.3
14.9
Assay
-0.06 (0.19)
50.9
0.0
0.18 (0.31)
81.9
0.0
Different Cut-point
0.23 (0.33)
81.3
0.0
-0.37 (0.11)
0.0
100.0
*Statistically significant with p-value <0.007
2
Figure 1:
Flow Diagram of Studies Considered for Inclusion
4669 articles located
657 duplicates removed
4012 titles reviewed
3433 rejected after
reviewing title
580 abstracts reviewed
325 rejected after
reviewing abstract
18 redundant abstracts
Question 1: 33 articles
Question 2: 203 articles
Question 1: 9 articles
Question 2: 30 articles
Reasons for article rejection:
-138 no sub-group analysis
-11 BNP only
-18 wrong outcome
-5 not symptomatic HF
-4 Unacceptable renal function
measure
-17 excluded GFR>60 or GFR<60
-2 Last author fabricated data
-1 Unacceptable NT-proBNP
measure
Figure 2:
Adjusted Estimates of Mortality in Patients with Preserved Renal Function (without Waldum)
Adjusted Estimates of Mortality in Patients with Diminished Renal Function (without
Waldum)
Figure 3: Funnel Plots for Prognosis
0.528
1.057
0.793
Standard Error
0.264
0.000
Funnel Plot for Crude Estimates of Prognosis in Patients with Normal Renal Function
-1.00
0.00
1.00
2.00
3.00
Log Relative Risk
0.704
1.055
1.407
Standard Error
0.352
0.000
Funnel Plot for Crude Estimates of Prognosis in Patients with Diminished Renal Function
-2.00
-1.00
0.00
1.00
Log Relative Risk
2.00
3.00
4.00
0.479
0.958
0.719
Standard Error
0.240
0.000
Funnel Plot for Adjusted Estimates of Prognosis in Patients with Normal Renal Function
-2.00
-1.00
0.00
1.00
2.00
Log Relative Risk
0.367
0.551
0.735
Standard Error
0.184
0.000
Funnel Plot for Adjusted Estimates of Prognosis in Patients with Diminished Renal Function
-1.00
-0.50
0.00
0.50
Log Relative Risk
1.00
1.50
2.00
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