With uncertainty as to how intensive blood pressure (BP) lowering impacts kidney outcomes, novel approaches are needed to assess kidney disease risk during hypertension treatment.  In a study recently published in AJKD, Simon B. Ascher and colleagues determined whether longitudinal N-terminal pro–B-type natriuretic peptide (NT–proBNP) measurements during hypertension treatment are associated with kidney function decline.

AJKDBlog Interviews Editor Timothy Yau (@Maximal_Change) caught up with Dr Ascher to discuss whether, beyond serving as a cardiac marker, NT–proBNP levels impact the progression of chronic kidney disease (CKD).

Dr. Ascher is a hospitalist researcher at the University of California Davis. His research focuses on personalizing clinical decision-making for kidney and cardiovascular disease prevention and on using kidney and cardiac biomarkers to understand chronic kidney disease.

AJKDBlog:  Can we start with just a basic physiologic understanding of N-terminal pro-B-type natriuretic peptide (NT-proBNP)? Many of our readers will be familiar with this test in patients with congestive heart failure, but tell us what it is, how it is measured, what elevated levels suggest, and how it may impact kidney health?

Dr Ascher: NT-proBNP is released by the heart in response to ventricular wall stress caused by pressure or volume overload, and plasma concentrations can be measured using point-of-care or central lab immunoassays. In patients with chronic kidney disease (CKD), providers may dismiss elevated NT-proBNP concentrations because it is known that NT-proBNP is excretion by the kidneys, so many patients with kidney disease can have elevated blood NT-proBNP levels without symptoms or signs of heart failure. However, several studies show that higher levels of NT-proBNP in patients without heart failure are strongly prognostic of adverse cardiovascular and kidney outcomes. Elevated NT-proBNP concentrations may instead reflect chronic neurohormonal activation and venous congestion that can contribute to the development and progression of CKD.

AJKDBlog:  For your study, you utilized the SPRINT cohort, which we are quite familiar with. Tell us when you measured NT-proBNP in these patients and what outcomes you were looking at?

Dr Ascher: We measured NT-proBNP levels at the baseline and year 1 study visits to determine whether baseline and 1-year changes in NT-proBNP were associated with subsequent changes in kidney function. We evaluated two outcomes: annualized change in estimated glomerular filtration rate (eGFR), and a ≥30% decrease in eGFR during follow-up. We evaluated these outcomes in the overall SPRINT cohort as well as separately among those with and without CKD at baseline.

AJKDBlog:  The great thing about utilizing populations like SPRINT are the robust numbers. Over 8,000 participants were included in your analysis. How did you stratify NT-proBNP changes and what did you observe between these groups?

Dr Ascher: 1-year change in NT–proBNP was categorized as a ≥25% decrease, ≥25% increase, or <25% change (i.e., stable) relative to the baseline NT–proBNP level. Compared with participants with stable 1-year NT–proBNP levels, those with increases in NT–proBNP had similar baseline characteristics, and those with decreases in NT–proBNP were younger, less likely to report White race, and had higher blood pressure and eGFR at baseline.

AJKDBlog:  Was there a correlation between increases or decreases in NT-proBNP and either annualized GFR slope (primary outcome) or 30% decrease in GFR (secondary outcome)?

Dr Ascher: Among SPRINT participants with CKD at baseline, we observed that longitudinal decreases in NT-proBNP concentrations compared with stable NT-proBNP were associated with a significantly slower decline in eGFR, whereas longitudinal increases in NT-proBNP were associated with significantly faster decline in eGFR as well as increased risk of experiencing a ≥30% decrease in eGFR. Among those without CKD at baseline, decreases in NT-proBNP similarly associated with slower decline in eGFR, while increases in NT-proBNP had no association with subsequent change in eGFR. These associations were independent of baseline NT-proBNP, eGFR, and albuminuria, and were similar irrespective of randomization to a target systolic blood pressure of <120 mm Hg or <140 mm Hg in SPRINT. We also conducted several additional analyses that make it unlikely that these findings were explained by chance, regression to the mean, or confounding by reduced NT–proBNP clearance from CKD.

AJKDBlog:  Has NT-proBNP been associated with kidney function decline in other studies? How does your study expand on findings from prior studies looking at this biomarker?

Dr Ascher: Prior studies show that higher NT-proBNP concentrations at baseline are associated with increased risk of incident CKD among individuals with preserved kidney function and increased risk of CKD progression and kidney failure among individuals with CKD. This study expands upon these findings by demonstrating that longitudinal increases in NT-proBNP over time are also independently associated kidney function decline, particularly among individuals with CKD.

AJKDBlog: Lastly, and most importantly, how do you see the findings from this paper translating into clinical practice?  Is NT-proBNP something that should be assessed as part of CKD risk assessment?  Do you see NT-proBNP being something that can be incorporated into current risk calculators such as KFRE?

Dr Ascher: Our findings suggest a plausible role for routine NT-proBNP measurements among individuals with hypertension to provide ongoing cardiac and kidney disease risk assessment. Because NT-proBNP levels can be elevated due to lower eGFR, it may be difficult to utilize a single NT-proBNP measurement. Using serial outpatient NT-proBNP measures in asymptomatic patients could be a useful benchmark for comparison for diagnosing heart failure or informing kidney disease risk. In fact, some of the co-authors have already incorporated routine NT-proBNP measurements for new patients in their CKD clinics. Additional experience with this approach may guide us about the utility of both improved heart failure diagnosis and CKD prognosis above and beyond existing tools. Importantly, the KFRE cannot be used for persons with preserved GFR (> 60 ml/min) and is most useful for persons with very advanced CKD. NT-proBNP might be particularly useful for cardio-renal prognosis among hypertensive persons without CKD or at early CKD stages.

To view Ascher et al (Open Access), please visit AJKD.org.

Title: Changes in Natriuretic Peptide Levels and Subsequent Kidney Function Decline in SPRINT
Authors:  Simon B. Ascher, Jarett D. Berry, Ronit Katz, James A. de Lemos, Nisha Bansal, Pranav S. Garimella, Stein I. Hallan, Nicholas Wettersten, Vasantha K. Jotwani, Anthony A. Killeen, Joachim H. Ix, Michael G. Shlipak
DOI: 10.1053/j.ajkd.2023.09.018