Pornpen Srisawasdi

The effect of renal dysfunction on BNP, NT-proBNP, and their ratio.

We examined the effect of renal dysfunction on B-natriuretic peptide (BNP), N-terminal (NT)-proBNP, and their molar ratio at varying severities of cardiac function in 94 Thai patients with chest pain (52 men; 32 women), also measuring creatinine and left ventricular ejection fraction (LVEF). Renal function was classified into 5 stages by estimated glomerular filtration rate. The molar NT-proBNP/BNP ratio was calculated. Cardiac status was classified by LVEF (normal, >50%; moderate, 35%-50%; severe, <35%). BNP, NT-proBNP, and their ratio corresponded to renal disease stage exponential (0.51, 1.05, and 0.54, respectively; correlation coefficients, >or=0.95). BNP and the ratio are affected less than NT-proBNP by renal dysfunction, starting in stage III; NT-proBNP expresses effects starting in stage II. NT-proBNP is more sensitive than BNP to renal disease stage. For log of geometric means vs stage of renal disease, the BNP slopes and correlation coefficients vary considerably (slopes, 0.036-0.531; r(2), 0.017-0.99). The NT-proBNP slopes and regression coefficients vary considerably (slopes, 0.18-0.71; r(2), 0.33-0.99). For the ratio, the slopes show low variation (0.148-0.337), r(2) greater than 0.96, women differing from men (P = .012). The effect of renal disease differs by gender. BNP and NT-proBNP increase by stage III for women but not for men. One must consider renal function, gender, and LVEF when using BNP or NT-proBNP as cardiac biomarkers. The ratio of the 2 peptides is the most consistent marker across LVEFs.

Estimation of Plasma Small Dense LDL Cholesterol From Classic Lipid Measures

Calculated low-density lipoprotein cholesterol (cLDL-C) may differ from direct measurement (dLDL-C), and this difference may depend on presence of small, dense LDL (sdLDL) particles in addition to variation in triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C) concentrations. The presence of such dependence would offer a simple means to estimate sdLDL. We studied dependence of sdLDL on cLDL-C, dLDL-C, and other variables. We measured the levels of glucose, creatinine, total cholesterol, TG, HDL-C, and dLDL-C using standardized methods in 297 samples. For sdLDL cholesterol (sdLDL-C), a novel homogeneous assay was used. The cLDL-C was calculated using the Friedewald formula for 220 subjects after excluding for liver or renal disease. Using stepwise regression analysis identified non-HDL-C, cLDL-C, and dLDL-C as significant variables (P < .001; R(2) = 0.88). The regression equation was as follows: sdLDL-C (mg/dL) = 0.580 (non-HDL-C) + 0.407 (dLDL-C) - 0.719 (cLDL-C) - 12.05. The sdLDL-C concentration can be estimated from non-HDL-C, dLDL-C, and cLDL-C values. Identification of a simple, inexpensive marker for sdLDL particles provides a cost-effective method for screening cardiovascular disease risk.

The clearance of BNP modeled using the NT-proBNP-BNP relationship.

BACKGROUND The ventricular myocardium simultaneously secretes two natriuretic peptides useful in the evaluation of heart failure: BNP, hormonally active, and NT-proBNP, the N-terminal end, non-hormonally active, but ultimately their concentrations differ and their clearance patterns are poorly defined. METHODS We measured NT-proBNP and BNP in patients with and without heart failure and compared their concentrations using regression analysis. RESULTS The relationship between NT-proBNP with BNP is nonlinear. Between 45 and 70 pmol of BNP/L (class II heart failure) the slope is much higher than in other ranges and the NT-proBNP/BNP ratio reaches its maximum in patients with class II NYHA heart failure. CONCLUSIONS The difference in concentration for NT-proBNP and BNP can be related to the diffusion across the renal basement membrane. Their ratio is nonlinear because BNP is cleared faster than in patients with class II heart failure than other classes or normal, suggesting a change in a non-renal mode of clearance.

Exogenous interferences with Jaffe creatinine assays: addition of sodium dodecyl sulfate to reagent eliminates bilirubin and total protein interference with Jaffe methods

Background: The study evaluated the impact of interferences on the analytical specificity of three commercial and commonly used creatinine methods (two Jaffe and one enzymatic).

Hyperprolactinemia in Thai children and adolescents with autism spectrum disorder treated with risperidone.

Hyperprolactinemia is a common adverse effect observed in children with autism spectrum disorder (ASD) during pharmacotherapy with risperidone. The main aim of this study was to investigate important clinical factors influencing the prolactin response in risperidone-treated Thai ASD. A total of 147 children and adolescents (127 males and 20 females) aged 3–19 years with ASD received risperidone treatment (0.10–6.00 mg/day) for up to 158 weeks. Prolactin levels were measured by chemiluminescence immunoassay. The clinical data of patients collected from medical records – age, weight, height, body mass index, dose of risperidone, duration of treatment, and drug-use pattern – were recorded. Hyperprolactinemia was observed in 66 of 147 (44.90%) subjects. Median prolactin level at the high doses (24.00, interquartile range [IQR] 14.30–29.20) of risperidone was significantly found to be higher than at the recommended (16.20, IQR 10.65–22.30) and low (11.70, IQR 7.51–16.50) doses of risperidone. There was no relationship between prolactin levels and duration of risperidone treatment. Dose-dependence is identified as a main factor associated with hyperprolactinemia in Thai children and adolescents with ASD treated with risperidone. This study suggests that risperidone treatment causes prolactin elevations and the effects of risperidone on prolactin are probably dose-related in pediatric patients.

Renal Dysfunction, Hemodialysis, and the NT-proBNP/BNP Ratio

With great interest we read the article by Srisawasdi et al.1 They found that the ratio between N-terminal (NT)-pro-B-natriuretic peptide (BNP) and BNP increases exponentially with the stage of renal disease. van Kimmenade et al,2 however, suggested the NT-proBNP/BNP ratio increases only slightly and shows a linear trend. Their findings are used to support the hypothesis that BNP and NT-proBNP concentrations rely equally on the glomerular filtration rate and predominantly on cardiac diseases, rather than on renal clearance.2,3 The findings by Srisawasdi et al1 suggest otherwise, and they rightly advocate that renal dysfunction should be taken into account when interpreting the diagnostic and prognostic potential of NT-proBNP and BNP. Missing in the data from Srisawasdi et al1 are the ratios in the patients with end-stage renal disease who were treated with hemodialysis. On reading the article by Srisawasdi et al,1 we decided to take a look at the NT-proBNP/BNP ratios in a population of patients receiving long-term hemodialysis for whom we recently described cardiac biomarker concentrations4 and their relationship …

Polymorphisms of the ApoE (Apolipoprotein E) Gene and Their Influence on Dyslipidemia in HIV-1-Infected Individuals

The purpose of this retrospective case-control study was to investigate the frequency of Apolipoprotein E (ApoE) polymorphisms and their influence on antiretroviral therapy (ART)-induced lipodystrophy or dyslipidemia in HIV-infected Thai patients. The clinical characteristics and frequencies of ApoE genotypes were compared between the case (moderate to severe lipodystrophy, n = 67) and control (absent to mild lipodystrophy, n = 18) groups. The ApoE genotype frequencies among the 85 participants were 2.35% (n = 2) for E2/E2, 20% (n = 17) for E2/E3, 9.41% (n = 8) for E2/E4, 36.47% (n = 31) for E3/E3, 30.59% (n = 26) for E3/E4, and 1.18% (n = 1) for E4/E4. None of the ApoE genotypes showed association with ART-induced lipodystrophy. However, the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-cholesterol), and ApoB were lower in patients carrying the E2 allele but higher in E4 carriers. Interestingly, the ratios between TC and high-density lipoprotein (TC/HDL cholesterol ratio) and ApoB/ApoA-I ratio were significantly higher in the case group. Patients carrying the E2 allele displayed protective lipid profile, while those carrying E4 appeared to be at higher risk of dyslipidemia. In conclusion, ApoE polymorphisms were not associated with lipodystrophy in patients undergoing antiretroviral therapy but influenced lipid alteration.

Small-Dense LDL Cholesterol/Large-Buoyant LDL Cholesterol Ratio as an Excellent Marker for Indicating Lipodystrophy in HIV-Infected Patients

OBJECTIVES To examine whether the lipid parameters are predicting factors for human immunodeficiency virus (HIV)-associated lipodystrophy. METHODS Whole-body fat compositions of HIV-positive patients receiving stavudine-containing antiretroviral regimens (n = 79) were determined. Lipodystrophy was defined as a ratio of trunk fat mass/lower limb fat mass greater than 2.28. Blood samples were analyzed for total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), small-dense LDL-C (sdLDL-C), apoAI, apoB, lipoprotein(a), and CD4 cell counts. Large-buoyant LDL-C (lbLDL-C) was calculated (LDL-C minus sdLDL-C). RESULTS Twenty-six patients were classified as having lipodystrophy. The mean values of triglycerides, HDL-C, sdLDL-C, apoB, TC/HDL-C, apolipoprotein (apo) B/apoAI, and sdLDL-C/lbLDL-C showed significant differences between patients with and without lipodystrophy (P < .02). Using logistic regression analysis, sdLDL-C/lbLDL-C was identified as a significant predictor of lipodystrophy (P < .001). At a ratio of 0.554, the odds ratio was 17.8 with a likelihood ratio of 5.5. CONCLUSIONS The sdLDL-C/lbLDL-C ratio is an excellent marker for indicating lipodystrophy in HIV-infected patients.

Implementation of cellulomonas cholesterol oxidase for total serum cholesterol determination by the endpoint method.

Cellulomonas has been shown to be a good source of cholesterol oxidase in addition to Streptomyces for serum cholesterol determination by the endpoint method, inexpensive in cost, and showing excellent performance. For clinical use, we have assessed the reliability of Cellulomonas reagent for cholesterol determination. We constructed the user‐defined endpoint methods on three automated analyzers. The analytical performances (linearity, precision, recovery, interference, stability, and comparison with the standardized method) of Cellulomonas cholesterol reagents were evaluated and compared to those of Streptomyces reagents. Linearity (18.1–23.3 mmol/L) and stability of reagents (6–11 weeks) depended on the analyzers being used. The average within‐run and between‐day % coefficients of variation (CVs) ranged from 1.44 to 2.45 and 1.98 to 2.99, respectively, and were within National Cholesterol Education Program analytical criteria (≤3%). All assays using both reagents compared favorably with the commercial method and appeared accurate near the clinical decision cut‐points. Hemoglobin concentration at 7.5 g/L only affected the assay using single wavelength measurement. Bilirubin decreased in serum cholesterol recovery while lipemia generated a positive interference with all methods. Cellulomonas enzyme is analytically reliable when used for serum cholesterol determination by the endpoint method. Its analytical performance is equivalent to Streptomyces enzymes and meets the analytical goals. It has an advantage over the other enzymes in that it does not ship in the frozen state. J. Clin. Lab. Anal. 22:50–58, 2008.© 2008 Wiley‐Liss, Inc.

Advantages and disadvantages of serum cholesterol determination by the kinetic vs the end point method.

Enzymatic assays for cholesterol determination can use an end point or a kinetic method. We evaluated and compared the performance of these methods. We constructed user-defined methods on 3 automated analyzers using Streptomyces cholesterol reagents to evaluate the analytic performance of both methods. Linearity (700-900 mg/dL) and stability of reagents (5-11 weeks) depended on the analyzers. The coefficients of variation for imprecision were 2.41% to 2.99% and 3.78% to 5.52% for the end point and kinetic methods, respectively. The end point method showed less bias at decision cut points (-0.8% to 1.3%) than did the kinetic method (-1.1% to 3.6%) but was more affected by interfering substances.The advantages of the end point over the kinetic method are better precision and lower reagent cost. The end point imprecision fell within National Cholesterol Education Program guidelines (<or=3%), but the kinetic did not. The kinetic method showed less interference and required shorter analysis time.