Soluble concentrations of the terminal complement complex C5b-9 correlate with end-organ injury in preeclampsia.

OBJECTIVE: We sought to determine if soluble levels of C5b-9, the terminal complement complex, correlate with end-organ injury in preeclampsia. STUDY DESIGN: Project COPA (Complement and Preeclampsia in the Americas), a multi-center observational study in Colombia from 2015 to 2016, enrolled hypertensive pregnant women into four groups: chronic hypertension, gestational hypertension, preeclampsia, and preeclampsia with severe features. Trained coordinators collected clinical data, blood and urine. End-organ injury was defined by serum creatinine ≥ 1.0 mg/dl, aspartate transaminase ≥ 70U/L, platelet count < 150,000/µl, or lactate dehydrogenase ≥ 500 U/L. Data were analyzed by χ2 or Fisher's exact test with significance at P < 0.05. MAIN OUTCOME MEASURE: C5b-9 concentrations in plasma and urine, using enzyme linked immunosorbent assays. RESULTS: In total, 298 hypertensive participants were enrolled. Plasma and urine C5b-9 levels were measured in all participants and stratified by quartile (Q1-4), from lowest to highest C5b-9 concentration. Participants with low plasma C5b-9 levels (Q1) were more likely to have end-organ injury compared to those with higher levels (Q2-Q4) [platelet count < 150,000/µl (20.8% vs. 8.4%, P = 0.01); elevated serum creatinine ≥ 1.0 mg/dl (14.9% vs. 4.5%, P = 0.009)]. In contrast, participants with high urinary C5b-9 levels (Q4) were more likely to have end-organ injury compared to those with lower levels (Q1-Q3) [platelet count < 150,000/µl (19.7% vs. 7.4%, P = 0.003); elevated serum creatinine ≥ 1.0 mg/dl (12.3% vs. 4.4%, P = 0.025)]. CONCLUSION: We identified a pattern of increased urine and low plasma C5b-9 levels in patients with preeclampsia and end-organ injury. Soluble C5b-9 levels may be used to identify complement-mediated end-organ injury in preeclampsia.

Recomendaciones para el uso racional de la prueba 25-hidroxivitamina D Resumen de política

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The exponential increase in the request for laboratory tests of 25-Hydroxyvitamin D or [25 (OH) D has ignited the alarms and generated a strong call for attention, since it may reflect deficiencies in the standardization of clinical practice and in the use non-systematic scientific evidence for decision-making in real life, which allows to analyze the indications of the test, its frequency, interpretation and even to assess the impact for health systems, especially when contrasted with the minimum or almost. No effects of the strategy of screening or supplying indiscriminately to the general population, without considering a comprehensive clinical assessment of risks and needs of people. From a purely public health impact point of view, the consequence of massive and unspecified requests is affecting most of the health systems and institutions at the global level. The primary studies that determined average population intake values have been widely used in the formulation of recommendations in Clinical Practice Guidelines, but unfortunately misinterpreted as cut points to diagnose disease and allow the exaggerated prescription of nutritional substitution. The coefficient of variation in routine tests to measure blood levels of 25 (OH) D is high (28%), decreasing the overall accuracy of the test and simultaneously, increasing both the falsely high and falsely low values. The most recent scientific evidence analyzes and seriously questions the usefulness and the real effect of the massive and indiscriminate practice of prescribing vitamin D without an exhaustive risk analysis. The available evidence is insufficient to recommend a general substitution of vitamin D to prevent fractures, falls, changes in bone mineral density, incidence of cardiovascular diseases, cerebrovascular disease, neoplasms and also to modify the growth curve of mothers' children. They received vitamin D as a substitute during pregnancy. The recommendations presented in the document are based on the critical analysis of current evidence and the principles of good clinical practice and invite to consider a rational use of 25 (OH) D tests in the context of a clinical practice focused on people and a comprehensive assessment of needs and risks. The principles of good practice suggest that clinicians may be able to justify that the results of the 25 (OH) D test strongly influence and define clinical practice and modify the outcomes that interest people and impact their health and wellness. Currently there is no clarity on how to interpret the results, and the relationship between symptoms and 25 (OH) D levels, which may not be consistent with the high prevalence of vitamin D deficiency reported. For this reason, it is suggested to review the rationale of the request for tests for systematic monitoring of levels of 25 (OH) D or in all cases where substitution is performed. Consider the use of 25 (OH) D tests within the comprehensive evaluation of people with suspicion or confirmation of the following conditions: rickets, osteomalacia, osteoporosis, hyper or hypoparathyroidism, malabsorption syndromes, sarcopenia, metabolic bone disease.

Terminal Complement Activation in Preeclampsia.

OBJECTIVE: To evaluate whether C5b-9 concentrations in blood and urine are increased in preeclampsia with severe features. METHODS: The Complement and Preeclampsia in the Americas study is a prospective, multicenter case-control study performed at six centers in Colombia from November 2015 to July 2016. The case group included women with preeclampsia with severe features, and the control group included women who were healthy or had chronic hypertension, gestational hypertension, or preeclampsia without severe features. We enrolled two women in the control group for every woman in the case group. Soluble C5b-9 concentrations were measured by enzyme-linked immunosorbent assays in blood and urine. The primary outcome was C5b-9 concentrations in women in the case group compared with all women in the control group, and the secondary outcome was C5b-9 levels in women in the case group compared with individual control subgroups. Differences were assessed by test of medians, and associations were further evaluated by receiver operating characteristic curve analysis and logistic regression with α=0.05. RESULTS: Three hundred fifty-two patients were enrolled. Plasma C5b-9 concentrations did not differ significantly between women in the case group and those in the control group, but urine C5b-9 concentrations were higher in women in the case group (median [interquartile range] 9.9 [1.6-43.7] vs 1.8 [0.54-4.1] ng/mL, P<.001). In subgroup analysis, plasma C5b-9 concentrations were increased in women in the case group compared with healthy women in the control group (median [interquartile range] 2,778 [1,633-4,230] vs 1,374 [1,064-2,332] ng/mL, P<.001), and urine C5b-9 concentrations were increased in women in the case group compared with all control subgroups (P<.001). Using receiver operating characteristic analysis, urine C5b-9 concentrations differentiated preeclampsia with severe features from hypertensive women in the control group (area under the receiver operating characteristic curve 0.74, 95% CI 0.68-0.80). Urine C5b-9 22 ng/mL or greater (range 0-158.4 ng/mL) was the optimal cut point for diagnosis of preeclampsia with severe features with adjusted odds ratio of 10.0 (95% CI 3.5-28.8, P<.001). CONCLUSION: Urinary excretion of terminal complement effector C5b-9 is higher in women with preeclampsia with severe features compared with women with other hypertensive disorders of pregnancy and women without hypertension.