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American Society for Clinical Pathology (ASCP) 2007 Annual Meeting

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Kidney Impairment Independently Affects NT-ProBNP Levels

Carole Bullock, MA October 22, 2007 Editors' Recommendations

Specialist Clinics for Reducing Emergency Admissions in Patients With Heart Failure Statin Therapy and Clinical Outcomes in Myocardial Infarction Patients Complicated by Acute Heart Failure End-stage Renal Disease and Dialysis in HIV-positive Patients

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Perioperative Management of the Patient With Chronic Renal Failure Chronic Kidney Disease Uremia

October 22, 2007 (New Orleans) Kidney impairment raises levels of N-terminal proBtype natriuretic peptide (NT-proBNP), a finding that may mean that the tests for this neurohormone lose their specificity for congestive heart failure (CHF), which is common in elderly patients, according to a multicenter study. However, a new formula presented here at the American Society for Clinical Pathology (ASCP) 2007 Annual Meeting may provide a way to "fine tune" the test, improving its accuracy in the future. NT-proBNP, as measured by tests made by Roche Diagnostics and Response Biomedical are commonly evaluated through blood tests given in hospital emergency departments to predict the risk for myocardial infarction in patients with coronary heart disease; they also have served more recently as a diagnostic tool for CHF risk stratification. "Older individuals develop a [reduction in the] number of nephron units that progresses until there is no functional reserve, which means that the test may not be as predictive for patients over 50, due to a failing renal condition," Larry Bernstein, MD, chief of clinical pathology, New York Methodist Hospital, Brooklyn, said during his poster presentation.

In the Renal Insufficiency in Predicting NT-ProBNP Level Elevation (RIPPLE) study, Dr. Bernstein and colleagues examined the effects of risk factors, such as renal insufficiency, on the predictive value of NT-proBNP in a large group of patients from 3 major metropolitan areas. "Impaired renal function elevates NT-proBNP independently of congestive heart failure or anemia. Our study found that the effect of renal disease was substantial, and it may have an even greater effect than [CHF] on NT-proBNP test results," Dr. Bernstein told Medscape Pathology. In the study, 1184 patients from 3 sites who presented to the emergency departments with shortness of breath or symptoms suggestive of CHF. The patients underwent testing for NTproBNP levels and were examined for the size of the effect of renal insufficiency on NTproBNP concentration. All patients were evaluated for end-stage renal disease or chronic renal insufficiency. Patients with elevated troponin T exceeding 0.07 ng/mL and atrial fibrillation were excluded, leaving 834 patients in the study. The diagnostic studies evaluated included an electrocardiogram, a hemoglobin concentration, a white blood cell count, troponin T, creatinine, and a transthoracic echocardiogram for left ventricular and valvular dysfunction. These are either tests that had to be applied or comorbidities that had to be accounted for to isolate the effects of kidney function. To isolate the effect of the patients' renal function, the NT-proBNP levels were normalized to remove the effect of the estimated glomerular filtration rate (eGFR) by dividing 1000*log(NT-proBNP) by eGFR. Data were further normalized to age younger than 50 years by means ratios. Thirty-nine patients with renal impairment had a mean NT-proBNP level of 8753 pg/mL compared with 2558 pg/mL in 320 patients without renal impairment ( P = .0001), after removing confounders. The receiver operating characteristic curve of the NormKLog(NT-proBNP/eGFR) by eGFR gives an area under the curve of 0.865; sensitivity and specificity were invariant. "The report provides an opportunity to eliminate the multiple reference ranges and have one basic reference range that removes the large effect of the kidney. This algorithm that was used to study the effects of the kidney...will have potential for clinicians' use as well and eventually could be incorporated into a simple laboratory report," Dr. Bernstein said. ASCP President Lee Hilborne, MD, professor of pathology and laboratory medicine at the David Geffen School of Medicine at the University of California, Los Angeles, told Medscape Pathology, "It's important to understand the overall condition of the patient, and the test may not provide the whole picture." The study was did not receive commercial support. Dr. Bernstein and Dr. Hilborne have disclosed no relevant financial relationships.

American Society for Clinical Pathology 2007 Annual Meeting: Abstract 6. Presented October 18, 2007.
J Intern Med. 2006 Dec;260(6):568-76.

Circulating levels of pro-atrial natriuretic peptide in lower respiratory tract infections.

Mller B, Sess E, Schuetz P, Mller C, Bingisser R, Bergmann A, Stolz D, Tamm M, Morgenthaler NG, Christ-Crain M. Author information Abstract

OBJECTIVE: To analyse the mid region of plasma N-terminal pro-atrial natriuretic peptide (MR-proANP) levels in patients with lower respiratory tract infections to evaluate its prognostic use for the severity of disease and outcome. DESIGN: Prospective observational study. Setting. Emergency department of a university hospital. SUBJECTS: A total of 545 consecutive patients with lower respiratory tract infections and 50 healthy controls. Interventions. MR-proANP was measured in serum from all patients using a new sandwich immunoassay. RESULTS: MR-proANP levels (median [IQR], in pmol L(-1)) were significantly higher in patients with lower respiratory tract infections when compared with controls (138.0 [74.1-279.0] vs. 72.7 [62.5-89.5], P < 0.001), with highest levels in patients with community-acquired pneumonia (CAP). MR-proANP, but not C-reactive protein (CRP) levels, gradually increased with increasing severity of CAP, classified according to the pneumonia severity index (PSI) score (P < 0.001). On admission, MR-proANP levels were significantly higher in nonsurvivors when compared with survivors (293.0 [154.0-633.0] vs. 129.0 [71.4-255.0], P < 0.001). In a receiver operating characteristic (ROC) analysis for the prediction of survival of patients with CAP the area under the ROC curve (AUC) for MR-proANP was 0.69, similar when compared with the PSI (AUC 0.74, P = 0.31), and better when compared with other biomarkers, i.e. procalcitonin (AUC 0.57, P = 0.08), CRP (AUC 0.52, P = 0.02), and leucocyte count (AUC 0.56, P = 0.07).

CONCLUSIONS: MR-proANP levels are increased in lower respiratory tract infections, especially in CAP. Together with other clinical, radiographic and laboratory findings, MR-proANP levels might be helpful for the risk stratification in CAP.

Koch and Singer [13] found a sex-related difference in the second decade of life, with higher BNP concentrations in girls. In another study, NT-proBNP levels showed no gender- or age-related differences The findings of this study support higher NT-proBNP levels in pubertal girls. This was reported by Schwachtgen et al. [28], but not by Albers et al. [1], Nir et al. [23], or Rauh and Koch [26].
However, abnormal LFTs were also associated with elevated NT proBNP a marker of fluid overload, which shows that pathophysiology of the phenomenon is more complex and needs to be further studied
Hogenhuis J, Voors AA, Jaarsma T, Hoes AW, Hillege HL, Kragten JA, et al. Anaemia and renal dysfunction are independently associated with BNP and NT-proBNP levels in patients with heart failure. Eur J Heart Fail. 2007; 9: 787-794. Wold Knudsen C, Vik-Mo H, Omland T. Blood haemoglobin is an independent predictor of B-type natriuretic peptide (BNP). Clin Sci (Lond). 2005; 109: 69-74.

Obese patients had lower BNP and NT-proBNP compared with overweight or normal-weight individuals (P _ 0.001) and decreased mortality compared with normal-weight individuals (P _ 0.001). In this study population, obese patients had significantly lower BNP and NT-proBNP that reflected lower mortality.