Our aim was to evaluate published methods that use serum cystatin C (s-CysC) for measuring glomerular filtration rate (GFR) in children and to discuss advantages and limitations of s-CysC and of established GFR methods. A comprehensive literature review of clinical studies in children evaluating s-CysC or CysC-based formulas and plasma creatinine or creatinine-based formulas against an exogenous reference method using receiver operating characteristics (ROC) curves or Bland-Altman plots is presented. The comparison of s-CysC with plasma creatinine indicated that s-CysC was superior to plasma creatinine in five of 13 studies; four studies showed no difference, and, in four studies, no statistical comparison was made. Comparison of s-CysC and the Schwartz formula showed that s-CysC was superior to the Schwartz formula in two of seven studies; two studies demonstrated no difference, and, in one study, the Schwartz formula was superior to s-CysC. In two studies no statistical comparison was made. The CysC-based prediction equations all had high accuracy but low agreement when compared with a reference GFR, in the range of 30-40% at best. S-CysC is most likely superior to plasma creatinine and at least equal to creatinine-based formulas. CysC-based prediction equations are at least as good as creatinine-based formulas but cannot replace exogenous methods.
Patients on antiretroviral therapy are reported to have an increased risk of cardiovascular disease. We aimed to investigate the effect of n-3 polyunsaturated fatty acids (n-3 PUFAs) on plasma lipids, lipoproteins and inflammatory markers in HIV-infected patients treated with antiretroviral therapy. We randomized 51 patients in a placebo-controlled, double-blind trial to receive either 2 capsules of Omacor twice daily or 2 capsules of placebo. Compliance was measured by determining levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in neutrophils. Plasma triglycerides were reduced in the n-3 PUFA group by 0.14 mmol/l after 12 weeks of treatment (n=26), while plasma triglycerides increased by 0.36 mmol/l in the control group (n=25). The difference between groups was significant, p=0.03. No significant effect of treatment was found for total cholesterol, high-density lipoprotein (HDL) or low-density lipoprotein (LDL) cholesterol or apolipoproteins. There was a significant increase in leukotriene B5 (LTB5) and LTB5/LTB4 ratio in the n-3 PUFA group compared to the control group. Baseline values for intercellular adhesion molecule-1 (ICAM), vascular cell adhesion molecule-1 (VCAM) and highly sensitive C-reactive protein (hsCRP) were comparable at baseline, and the intervention did not change these parameters significantly. The present study showed that treatment with n-3 PUFA slightly decreased plasma triglycerides and induced anti-inflammatory effects by increasing formation of anti-inflammatory LTB5.
INTRODUCTION:
The diagnosis of bile acid diarrhea is often missed because the availability of the 75seleno-taurohomocholic acid (SeHCAT) test is limited. We aimed to compare the biomarkers 7α-hydroxy-4-cholesten-3-one (C4) and fibroblast growth factor 19 (FGF19) with the SeHCAT test.
METHODS:
Patients with chronic diarrhea without intestinal resection referred for SeHCAT were prospectively recruited for this diagnostic accuracy study. Blood was sampled at fasting and after a stimulation meal with chenodeoxycholic acid. SeHCAT retention ≤10% defined bile acid diarrhea and >10% defined miscellaneous diarrhea. Receiver operating characteristics (ROC) were analyzed with SeHCAT as the gold standard. www.clinicaltrials.gov (NCT03059537).
RESULTS:
Patients with bile acid diarrhea (n = 26) had mean C4 of 30 ng/mL (95% confidence interval: 19–46) vs 8 (7–11; P < 0.001) in the miscellaneous diarrhea group (n = 45). Area under the ROC curve (ROCAUC) for C4 was 0.83 (0.72–0.93). C4 < 15 ng/mL had 85% (74%–96%) negative predictive value; C4 > 48 ng/mL had 82% (59%–100%) positive predictive value. Twenty patients had C4 values 15–48 ng/mL, of whom 11/20 had SeHCAT ≤10%. Median fasting FGF19 was 72 pg/mL (interquartile range: 53–146) vs 119 (84–240) (P = 0.004); ROCAUC was 0.71 (0.58–0.83). Stimulated FGF19 responses did not differ (P = 0.54).
DISCUSSION:
We identified C4 thresholds with clinically useful predictive values for the diagnosis of and screening for bile acid diarrhea in patients with chronic watery diarrhea. Further validation of the cutoff values with the placebo-controlled effect of sequestrant therapy is warranted (see Visual Abstract, Supplementary Digital Content 2, http://links.lww.com/AJG/B603).
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