Normal BNP and NT-proBNP are more helpful to rule out heart failure rather than ruling it in. 20 This was demonstrated in CKD patients as well in a study of 142 euvolemic patients. Median NT-proBNP and BNP levels were found to be 59 and 311 pg/ml, respectively. 21
To rule out ADHF, the values of these markers were determined in 142 euvolemic patients with GFR 38 SD14 ml/min per 1.73 m2. In another study of 151 patients a NT-proBNP cutoff value of <1000 pg/mL was used to ascertain that patients were no longer volume overloaded and to decrease the diuretic dose in patients with acute kidney injury. These patients had lower cardiovascular event rates. 22
There are many variables that influence the levels of BNP and NT-proBNP.
In one study NT- proBNP levels were studied in different age groups. The suggested cutoff of NT-proBNP 450 pg/mL for <50 years of age, 900 pg/mL for 50–75 years and 1,800 pg/mL for >75 years gave 90% sensitivity and 84% specificity for acute HF. 17
We also found that the older patients >75 years had higher NT BNP values. However in the >75 years CKD population with ADHF, there was no statistically significant difference, although the mean values were much higher.
There have been many studies that have looked at the relationship of BNP and NT-proBNP in the setting of CKD for the diagnosis of ADHF. Although it has been suggested that a higher cut-off value of BNP and NT-proBNP for diagnosis of HF be used, the absolute values remain debatable.
In the Breathing Not Properly study, in patients with an eGFI of less than 60 mL/min, a BNP cutoff of less than 200 pg/mL was suggested to rule-out HF. 23
Using a cut point of 1,200 pg/ml of NT pro-BNP for subjects with GFR<60 ml/min/1.73 m2, a study evaluating 599 patients found sensitivity to be 89% and specificity to be 72%.24
In a meta- analysis of 9 studies with 4,287 patients, NT-proBNP was higher in CKD patients with ADHF as compared to non CKD individuals. The median cut off point was 1,980 pg/ml.25
In another study on patients with a mean GFR of 27.7 ± 14ml/min/1.73m2, NT-proBNP cutoff for the diagnosis of ADHF in patients with an EF of 42.9 ± 6.8% was 4502 pg/ml.. 26
We showed that the cutoff for CKD patients for NT-proBNP was 1750 pg/ml.
Plasma BNP and NT-proBNP concentrations were shown to be increased with declining renal function. This was demonstrated in a study of 213 patients with CKD. Since NT-proBNP clearance may be predominantly renal, it was shown that a declining GFR had a greater effect on plasma NT-proBNP than on BNP.
Mean BNP concentration increased by 20.6% for every 10-mL/min/1.73 m2 (0.17-mL/s) decline in eGFR. Whereas there was a 37.7% increase in NT-proBNP. NT-proBNP/BNP ratio was also shown to increase with CKD stage.27
In another study of 381 patients, presenting with dyspnea to the emergency room, NT BNP and BNP values were determined. NT-proBNP and BNP cut-off points rose with deteriorating GFR: from 1360 and 290pg/ml in patients with eGFR 60-89 ml/min/1.73 m2, to 6550 and 515pg/ml in patients CKD Stage 4.28
We also had similar findings of progressive increase in NT-proBNP with worsening GFR.
We had ascertained our patients to be in ADHF on clinical grounds, however the use of 2D Echo and elevated left ventricular filling pressure (LVFP) may be used to make a definitive diagnosis of ADHF and improve diagnostic accuracy when used in addition to clinical parameters.
Echocardiography non-invasively identifies the presence of increased LV filling pressures.29
Use of both natriuretic peptides and echocardiography can be used to confirm
heart failure and provide risk stratification across all stages of heart failure and in particular diagnose heart failure when BNP or NT-proBNP levels fall in the intermediate or “grey” zone.30
In a study of 116 patients hospitalized with ADHF, simultaneous BNP and 2D echo using E/Ea (reflecting LVFP) had an incremental predictive power for the outcome of cardiac death or readmission for ADHF had an incremental predictive power for the outcome of cardiac death or readmission for ADHF.31
It has been shown that an elevated BNP level along with an E/e' ratio >15 (part of the assessment of LVFP) has the greatest risk of mortality in the setting of an acute myocardial infarction.32
Better HF clinical outcomes have been shown when BNP-guided management and ultrasound (lung US and LV filling pressure) are used.33
Another retrospective research found that combining BNP and LVFP resulted in improved survival and a lower incidence of acute kidney injury.34
Thus, a position paper has recommended the use of BNP and LVFP in the management of HF patients in the ambulatory setting.35
NT-proBNP also correlated strongly with indices of LVFP in a study of sixty-eight symptomatic patients with isolated diastolic dysfunction.36
We also had a similar finding of positive correlation.
The NT-proBNP cutoff for patients with a high LVFP was 2760 pg/ml.
The range of NT Pro BNP values to rule in volume overload has been put forth and is between 1000-6550 pg/ml.
The cutoff value for NT-proBNP in our study for CKD patients was 1750 pg/ml and the cutoff in patients with high LVFP was 2760 pg/ml. We showed that when ROC was generated for patients with CKD, clinical volume overload and with a high LVFP, a cut off value of 3737 pg/ml was obtained. Sensitivity and specificity were 69% and 70% respectively with AUC of 0.77.
Thus, ADHF can be ruled in by using a cutoff of 3787pg/ml of NT-proBNP and a high LVFP.
The cut off of 3787 pg/ml may be more reliable as a cutoff for the diagnosis of ADHF as the clinical scenario of volume overload has been verified with a high LVFP. This cutoff value of NT-proBNP in patients with a high LVFP could help in confirmation of ADHF and help in patient management.
Our cutoff was higher than many papers. This could be explained by the fact that the mean GFR in our patient population was lower (32.06ml/min/1.73m2) than in previous studies and that half the patients had an EF of <55%. Using a high LVFP also leads to a higher cutoff.
The mean NT-proBNP values were also higher than in previous studies. Our mean value of NT BNP was higher than the cutoff value as our data was skewed.
NT-proBNP has also been strongly associated with severity of diastolic dysfunction, with diastolic dysfunction being identified in one out of every four patients with elevated NT pro BNP.37
Although it did not function well as a screening test for diastolic dysfunction in a cross-sectional analysis from the Chronic Renal Insufficiency Cohort (CRIC) Study, the highest quartile of NT-proBNP was associated with two-fold odds of diastolic dysfunction in the CKD population compared with the lowest quartile in a cross-sectional analysis from the Chronic Renal Insufficiency Cohort (CRIC) Study.38
We have also found a positive correlation of diastolic dysfunction with NT BNP.
NT BNP value has been shown to be higher in patients with lower ejection fraction.39
We found a negative correlation of NT BNP with EF. This has been shown in CKD 3-4 patients in whom there was a higher BNP cutoff value for the diagnosis of ADHF in HFrEF as compared to the patients with HFpEF with CKD stages 3–4.17
In another study of stable ischemic heart disease patients BNP and NT BNP showed a negative correlation to LVEF (r = -0.50 and -0.46).40