Best use of cardiac biomarkers in patients with AL amyloidosis and renal failure

Abstract

In AL amyloidosis prognosis depends on the severity of heart dysfunction which is best assessed by natriuretic peptides (BNP and NT-proBNP). However, their clearance relies on glomerular filtration rate (GFR) and their concentration increases with renal failure. We evaluated the diagnostic and prognostic performance of NT-proBNP and BNP in 248 patients with AL amyloidosis with different degrees of renal failure. Patients were grouped according to GFR. Group 1 comprised 109 patients with GFR 60 mL/min/1.73 m 2 , Group 2, 77 subjects with GFR <60 and 15 mL/min/1.73 m 2 , and Group 3, 62 patients with GFR <15 mL/ min/1.73 m 2 . The ability of natriuretic peptides to detect heart involvement and to predict survival in the three groups was assessed. Decreasing eGFR required higher cutoffs of both NT-proBNP and BNP for detecting heart involvement and predicting survival. Both natriuretic peptides were independent prognostic markers in Groups 1 and 2, whereas in Group 3 only BNP independently predicted survival. Natriuretic peptides are powerful and useful markers of cardiac dysfunction and prognosis, provided that eGFR is considered in interpreting their clinical meaning. BNP should be preferred in patients with end-stage renal failure. Am. J. Hematol. 87:465-471, 2012. V

Biochemical markers in early diagnosis and management of systemic amyloidoses

“…In relation to this point, correct use of biomarkers and education of physicians to recognize early red flags (i.e., unexplained high NT-proBNP or/and albuminuria, Figure 1) have become the keystone for identifying pre-symptomatic patients with initial organ damage. The widely available biomarkers natriuretic peptide type-B (BNP), its N-terminal fragment (NT-proBNP) and troponins are routinely employed to evaluate, in particular, cardiac AL amyloidosis [5,7,19,[21][22][23][24][25][26]. In AL amyloidosis, NT-proBNP has 100% sensitivity in detecting cardiac involvement, anticipating echocardiographic abnormalities and preceding the onset of symptoms by several months [19,27].…”

“…Since renal function affects cardiac biomarkers, estimated glomerular filtration rate (eGFR) must be considered in interpreting their clinical meaning. Decreasing eGFR requires higher cut-offs of both NT-proBNP and BNP for detecting heart involvement and predicting survival [23], and BNP should be used instead of NT-proBNP in patients with eGFR < 30 mL/min. Nevertheless, natriuretic peptides remain powerful and useful markers also in patients with renal failure [23].…”

“…Decreasing eGFR requires higher cut-offs of both NT-proBNP and BNP for detecting heart involvement and predicting survival [23], and BNP should be used instead of NT-proBNP in patients with eGFR < 30 mL/min. Nevertheless, natriuretic peptides remain powerful and useful markers also in patients with renal failure [23]. Moreover, B-type natriuretic peptides should be used with great caution to evaluate amyloid heart dysfunction in patients with atrial fibrillation, since this condition is also associated with increased plasma concentration of these analytes [28][29][30].…”

“…Hematologic and cardiac response to therapy should be assessed frequently; cardiac response can be reliably evaluated using NT-proBNP, whose clinically significant decreases and increases demonstrate strong correlations with survival [21]. An NT-proBNP decrease of > 30% and > 300 ng/L (if baseline is ≥ 650 ng/L) [21] guides treatment adequacy, mindful of increases in renal failure [23].…”

Amyloid cardiomyopathy

“…circulating amyloidogenic precursors, and effective therapy is associated with decrease in absolute values. Change of NT-proBNP levels is currently used as a criterion for the evaluation of cardiac remission [31][32][33][34] . (Table 3., 4.…”