Improving clinical practice aimed at controlling hypertension is a pending issue in health systems. One of the methods currently used for this purpose is self blood pressure measurement (SBPM) whose use increases every day. The aims of this study are to establish the optimal cut-off point for the 3-day SMBP protocol and to identify factors that could affect the precision of the 3-day SMBP protocol using 24-h ambulatory blood pressure monitoring (ABPM) as a reference.This is a cross-sectional descriptive study to validate a diagnostic test performed by a primary care team in Murcia, Spain. A total of 153 hypertensive patients under 80 years of age who met the inclusion criteria were evaluated. ABPM was performed for 24 h. The SBPM protocol consisted of recording 2 measurements in the morning and 2 at night for 3 days.The cut-off point for SBP was set at 135 mmHg , and for DBP, it was set at 83 mmHg , which yielded the highest combined sensitivity and specificity. After carrying out the validation study with the new figures, we proceeded to establish which socio-demographic factors prevented a correct classification of patients. These errors were more common in male patients for the assessments of both DBP (OR = 2.4) and SBP (OR = 2.5); hypertensive patients with age < 67,5 years ; having no work activity  and with concomitant chronic kidney disease (CKD) (OR = 5.0).Being male, older than 67.5 years, with CKD or with no work activity increases the probability of being misclassified for hypertension during follow-up as assessed by SBPM over 3 days.This study was approved by the research ethics committee of the University of Murcia under registration number 1018/2015. A primary objective in any primary care consultation is to achieve good blood pressure (BP) control in hypertensive patients in order to reduce the likelihood of future cardiovascular events. Hypertension (HT) in Spain affects 36.7% of the total population, while approximately 40% of the general population in Europe is affected . In bothCurrently, SBPM is considered a useful tool both in the diagnosis and monitoring of hypertension , 4–6. AlThe main advantage of SBPM lies in its ability to obtain multiple BP records outside of the health care environment. Likewise, SBPM shows considerable agreement with ABPM in regard to detecting normotension and masked hypertension . The SBPThere is no doubt that SBPM is a useful clinical tool for hypertensive patients in Primary Care, where the good management of the short time available for the consultation and the reliability are essential for appropriate control of HT. Therefore, it is also necessary to have reliable cut-off values and an efficient daily SBPM decision-making scheme. Therefore, after demonstrating that the 3-day protocol is the most efficient option for the control of blood pressure in primary care, with a discriminative capacity and agreement with ABPM similar to other protocols , 11, theThis is a cross-sectional descriptive study for the validation of a diagnostic test.We worked with hypertensive patients registered in the computer system at the Vistalegre-La Flota Urban Health Centre in Murcia, Spain and those receiving routine care.December 2011 to December 2012.Inclusion criteria included the diagnosis of complicated and uncomplicated hypertension, an age of 18–80 years, sufficient vision and hearing to perform the self-measurement, and adequate intellectual capacity to obtain the measurements or the oversight of a responsible caregiver for doing so. The exclusion criteria that were considered are those considered valid in various international HT guidelines : ImmobilN = 2,245) were filtered from anonymized lists. The sample was calculated with an accuracy of 5%, a confidence level of 95%, and a sensitivity and specificity of 85.7 and 75%, respectively. An estimated prevalence of patients with uncontrolled BP of 35% (n = 141) was determined. From this figure, we calculated a percentage of expected losses of 15%, leading to a sample size of n = 153. The calculation of the sample size was performed using the online calculator by Fisterra [Duplicates, diagnostic errors, patients in the computerized clinical history, and those with their last visit to the health centre (to see a doctor or nurse) in the year prior to the start of the patient selection  [Microlife Watchbp Home) that were validated according to the standards of the Spanish Hypertension Society (SEH) and the British Hypertension Society (BHSOC) .The correct performance of the first 2 measurements on the first day was verified by the patient in front of the researcher. Then, the blood pressure monitor was given to the patient, who was instructed in writing to take 2 measurements in the morning (between 7:00 and 10:00 a.m.) and 2 before going to bed (between 21:00 and 23:00 p.m.) with 1–2 min between measurements for 3 consecutive days. A total of 12 measurements were obtained for each patient (the first day measurements were later discarded), establishing the 3-day SBPM pattern. The instruments used in this study included 2 ABPM devices zerland)  and 10 aRegarding the definitions of the variables applied in this study, we defined poor HT control as when the mean BP measured by ABPM over 24 h was greater than 130/80 mmHg. For the 3-day SMBP, we considered uncontrolled average blood pressure as greater than 135/85 mmHg.This descriptive study was carried out with the demographic variables of age, sex and work status, taking into account the records of spanish administrative document (TSI) that accredits access to citizens to health care benefits. If the patient was not active: TSI < 002  or active: TSI 003 ; TSI > 4 . Clinical variables included associated comorbidities such as a diagnoses of dyslipidaemia, diabetes mellitus, chronic kidney disease, atrial fibrillation, and stroke.The statistical programs SPSS version 22 and Epidat version 3.1 were used to analyse the data.p < 0.05 were considered statistically significant, and 95% confidence intervals (95%CI) were calculated. The sources of the data were the BP records collected by SBPM and ABPM as well as the electronic health records of the patients in the OMI-AP program.Categorical variables are presented as absolute frequencies (%) and quantitative variables as the means and standard deviations. Values of A comparison of the data collected using the 3-day SBPM (discarding measurements from the first day) was performed using the figures obtained by the 24-h ABPM as the reference standard. Given the results obtained by De León-Robert et al. , the 3-dA total of 419 patients were selected for inclusion in the analysis, of whom 153 completed SBPM and ABPM with the required quality  than for systolic pressure .According to the results of the ROC curve, the cut-off point where sensitivity and specificity were optimized was 135.5/83 mmHg for the diagnosis of uncontrolled HT. The mean differences between the two methods (ABPM and SBPM) are 10 and 5 mmHg for systolic and diastolic pressure respectively Fig. . The conBased on this cut-off point, the sensitivity of the SBPM-DAYS-2&3 test for identifying cases with control problems in some BP measurements was 87.7%, while its specificity was notably lower (62.5%) (Table < 3 (low income level) (OR = 3.6) and in hypertensive patients with concomitant chronic kidney disease (OR = 5.0) ; this figure dropped to 1 out of every 6 for the assessment of diastolic HT. The variables associated with obtaining an erroneous result with the SBPM-DAYS-2&3 test were sex, age, work status and chronic kidney disease. These errors were approximately 2.5 times more common in male patients for the assessments of both DBP (OR = 2.4) and SBP (OR = 2.5). Regarding the latter, in subjects of more advanced ages (> 67.5 years), the validity of the test was lower (OR = 1.5). The same pattern occurred in patients with TSI The diagnostic capacity of SBPM, using ABPM as a reference, for the assessment of HT has been widely investigated by several studies . The posThe current guidelines on hypertension by various societies do not provide clear recommendations in their protocols about all of the factors that can diminish the accuracy of SBPM as a follow-up method in HT. The Japanese and Brazilian guidelines refer to the need for bladder emptying before taking BP measurements, something not mentioned in the European or American guidelines . For AlmAmong the clinical factors evaluated by our study, it is worth mentioning the significant influence of the diagnosis of chronic kidney disease in the sample as a factor involved in limiting the accuracy of the SBPM-DAYS-2&3 protocol. Studies in kidney patients indicate greater arterial rigidity in these patients, which could be the cause. Although arteriosclerosis is also common among diabetic patients, no significant difference was found between diabetic and non-diabetic patients.This study was performed with a small sample size in a single health centre in Spain, wich is not necessarily representative of the general population. However, as a strength, the study was conducted in the field of usual clinical practice.The cut-off point with the highest joint sensitivity and specificity for the SMBP-DAYS-2&3 protocol is 135.5/83 mmHg. Being male, over 67.5 years of age, having low income level, and having a diagnosis of chronic kidney disease can all reduce the validity of the SMBP-DAYS-2&3 protocol for classifying hypertensive patients as poorly controlled during follow-up.


Treatment of hypertension improves cardiovascular, renal, and cerebrovascular outcomes. However, the benefit of treatment may be different according to the patients’ characteristics. Additionally, the target blood pressure or initial drug choice should be customized according to the special conditions of the hypertensive patients. In this part III, we reviewed previous data and presented recommendations for some special populations such as diabetes mellitus, chronic kidney disease, elderly people, and cardio-cerebrovascular disease. It is important to detect white coat HTN [high office blood pressure (BP) but normal out-of-office BP] and masked HTN  using out-of-office BP measurement. White coat effect is more frequently observed in women and older adults. If the diagnosis is not made correctly, it may result in side effects associated with unnecessary medication. Therefore, it is recommended to exclude white coat HTN as much as possible before initiating antihypertensive medication. In patients who are already on medication, it is important to check the effectiveness before adding medication for more aggressive treatment.For the patients with white coat HTN, lifestyle modifications and regular BP monitoring are recommended. Although there is little evidence, pharmacological treatment as well as lifestyle modifications could be considered when metabolic disturbances and/or subclinical organ damage occurs with white coat HTN . PharmacMany hypertensive patients have obesity and metabolic abnormalities with alterations of lipid and glucose metabolism. Furthermore, subclinical organ damage is common in these patients. Metabolic syndrome consists of abdominal obesity, dyslipidemia, dysglycemia, and raised BP. The criteria for clinical diagnosis of metabolic syndrome are: 1) abdominal obesity; 2) fasting glucose ≥100 mg/dL (diabetes included); 3) triglycerides ≥150 mg/dL; 4) high-density lipoprotein (HDL)-cholesterol < 40 mg/dL in men and < 50 mg/dL in women; and 5) BP ≥130/85 mmHg .The prevalence of metabolic syndrome has been increased over the last 10 years, as reported in the Korean National Health and Nutritional Survey. The prevalence of metabolic syndrome in Korean aged over 30 years is 30.5% . HoweverIn Western countries, people with metabolic syndrome have at 1.5–2-fold higher risk of CV events and death than those without metabolic syndrome and incident diabetes is 5-fold higher in people with metabolic syndrome , 20.In Asian countries, metabolic syndrome had a relative risk of incident diabetes of 3–4, which is a little lower compared to that in Western countries , 22. TheIn hypertensive patients with metabolic syndrome, antihypertensive treatment is used to prevent CV morbidity and mortality, while lowering or preventing incident diabetes. Antihypertensive treatment in non-diabetic patients with metabolic syndrome is discussed below, while that treatment for diabetic/CVD patients with metabolic syndrome is discussed in other respective sections of the special situations chapter. Lifestyle modifications, especially weight reduction and regular exercise, are strongly recommended in all hypertensive patients, as they decrease BP, improve metabolic abnormalities, and delay incident diabetes , 11.Hypertensive patients should be treated with antihypertensive medication as well as lifestyle modification, but there is no evidence available for the drug treatment in prehypertensive patients –14.Antihypertensive drugs should lower BP effectively as well as have favorable or neutral effects on insulin sensitivity and metabolic abnormalities. Thus, ACE inhibitors, ARBs, and calcium channel blockers are preferred. Among beta-blockers, vasodilating beta-blockers such as carvedilol and nebivolol can be used as combination therapy with ACE inhibitors/ARBs.Thiazides and thiazide-like diuretics are avoided as monotherapy or at high doses, but are used as combination therapy or at low doses. High dose diuretics can induce hypokalemia and new onset diabetes, and have unfavorable effects on lipid metabolism. The preferred approach is combination of ACE inhibitors/ARBs with diuretics to minimize their unfavorable effects on glucose and lipid metabolism.The prevalence of HTN is two-fold in diabetic patients compared to that in the general population, and the occurrence of diabetes is 2.5-fold higher in hypertensive patients , 38. TheThe recommended target for BP in diabetic patients is < 140/85 mmHg. In previous guidelines, the recommended BP was < 130/80 mmHg or < 140/80 mmHg in diabetic patients , 40–43. According to a recent meta-analysis, all classes of antihypertensive agents, such as ACE inhibitors, ARBs, calcium channel blockers, beta-blockers and diuretics can be used in diabetic patients . HoweverThe treatment of HTN in older adults reduces the risk of CVD and mortality. The benefit of treatment is also observed with regard to isolated systolic HTN. Accordingly, HTN needs to be actively diagnosed and treated in older adults.However, the benefit of pharmacological treatment for grade I hypertensive patients older than 80 years remains controversial. Thus, the characteristics of the patient should be considered. The characteristic findings of elderly hypertensive patients are increased SBP and widened pulse pressure due to increased central arterial stiffness. Moreover, atherosclerotic renovascular HTN is commonly observed. Non-dipper, increased daytime BP variability, and orthostatic or postprandial hypotension are also characteristic findings in elderly patients with HTN.The non-pharmacological treatment in elderly HTN patients is effective; however, the impact on the patient’s quality of life should be considered . Target HTN is a major risk factor of CAD and is associated with the occurrence of myocardial infarction. The incidence of ischemic heart disease increases when SBP is > 140 mmHg and mortality increases when SBP is > 120 mmHg , 62. ConHTN is the most important risk factor in heart failure –69. StriHypertension is one of the risk factor for atrial fibrillation and atrial fibrillation is frequently observed in hypertensive patients, but it can be prevented with BP control , 73. PatThe progression of carotid atherosclerosis can be prevented by lowering BP. For this purpose, calcium channel blockers and ACE inhibitors are superior to beta-blockers and diuretics , 80.Most antihypertensive drugs decrease vascular stiffness because BP reduction can decrease vascular wall stress and pulse wave velocity. However, it is not clear whether there is any difference in the reduction of arterial stiffness according to drug class –83. ReniIt is important to control the CVD risk factors because patients with peripheral arterial disease (PAD) have a higher risk of CV mortality  . LowerinLifestyle modifications such as salt restriction, weight control, moderation of alcohol intake, and regular aerobic exercise are very important. Pharmacological treatment consists of ACE inhibitors, ARBs, and aspirin , 93. ACEIn patients with aortic aneurysm, it is strongly recommended to lower the BP to the lowest levels tolerated by the patient . Beta-bl2), urinary abnormalities including albuminuria , hematuria and pyuria, electrolyte disturbances caused by tubular dysfunction, renal structural abnormalities detected by imaging or biopsy procedures, and renal transplants. CKD patients frequently suffer from HTN; hence, the rate of decline in renal function and the incidence of CV complications can be reduced with HTN control [CKD is defined as the presence of kidney injury for > 3 months, with markers of kidney injury being a decrease in estimated glomerular filtration rate (eGFR)  must routinely precede drug therapy. According to an epidemiologic study, with each increase of 20/10 mmHg from BP level of 115/75 mmHg or higher, deaths from stroke increased at least two-fold. Conversely, a 10/5 mmHg decrease in BP resulted in a 40% decrease in deaths from stroke . In addiIn general, the BP rises in acute ischemic stroke . It is aWhen thrombolytic therapy is used in the hyperacute period of an ischemic stroke, the incidence of bleeding is closely related to the BP before and after thrombolysis; hence, the target BP should be < 185/110 mmHg. For thrombolytic therapy using tissue-plasminogen activator (t-PA), the drug could only be administered after the BP was < 185/110 mmHg. The antihypertensive regimens consisting of intravenous drugs such as labetalol, nicardipine, diltiazem, nitroglycerin, and nitroprusside are recommended –143. In From a theoretical viewpoint, the optimal BP treatment in the acute phase of a parenchymal hemorrhage could prevent re-bleeding and subsequent expansion of a hematoma and edema; hence, it is recommended to lower the BP during the acute phase of the hemorrhage. If the SBP is ≥200 mmHg or if the mean BP is ≥150 mmHg, the BP should be lowered by monitoring BP every 5 min. In patients with increased intracranial pressure, BP should be lowered by maintaining the cerebral perfusion pressure between 60 and 80 mmHg using an intracranial pressure monitoring device only when the SBP is > 180 mmHg or the mean BP is > 30 mmHg. Because a sudden drop of BP during the acute phase is associated with higher mortality rates, it is recommended to maintain a cerebral perfusion pressure of ≥60 mmHg. When the SBP is 180 mmHg or the mean BP is 130 mmHg—as long as there is no evidence of increased intracranial pressure, with the assessment of BP every 15 min—the BP should be lowered below the level of 80% of baseline BP, < 160/90 mmHg, or mean BP < 110 mmHg. Antihypertensive regimens including intravenous drugs such as labetalol, nicardipine, diltiazem, nitroglycerin, and nitroprusside are recommended , 151.HTN treatment as a measure of secondary prevention after stroke significantly reduces mortality and the recurrence of stroke or vascular diseases , 160. ReErectile dysfunction is considered to be one of the a CV risk factors associated with poor prognosis . TherefoIn general, the prevalence of erectile dysfunction associated with antihypertensive medication is reported to be 0–25%, but the prevalence may be affected by underlying conditions such as endothelial dysfunction, and oxidative stress . ErectilHigh BP occurring during pregnancy can be divided into four categories: 1) chronic HTN in pregnancy: existing HTN or taking antihypertensive medication before the 20th week of pregnancy; 2) gestational HTN: newly diagnosed HTN after the 20th week of pregnancy in the absence of proteinuria; 3) pre-eclampsia: HTN diagnosed after 20 weeks of pregnancy accompanied by proteinuria ; and 4) pre-eclampsia superimposed on chronic HTN: pre-eclampsia diagnosed in the chronic HTN pregnant women. Based on the BP level, it is classified as mild: 140–149/90–99 mmHg, moderate: 150–159/100–109 mmHg, and severe: 160/110 mmHg or higher.Generally, there are few controversies regarding drug treatment for BP of > 160/110 mmHg or higher. Previous studies have reported that patients with BP > 150/95 mmHg are more likely to be hospitalized due to incident stroke during the peripartum period , 168. InAntihypertensive drugs used during pregnancy are methyldopa, labetalol, and nifedipine. Specific drugs are selected in consideration of the drug class previously used, their side effects, and the risk of teratogenicity. Beta-blockers can cause fetal growth retardation, thus they can be used later in the pregnancy. Diuretics should be prescribed cautiously because they can induce volume depletion. ACE inhibitors or ARBs may increase the risk of congenital malformations in pregnancy, it is recommended to replace these drugs before pregnancy or when planning a pregnancy. If a pregnancy is detected during the administration of ACE inhibitors or ARBs, they should be discontinued and replaced promptly. In emergency situations, such as pre-eclampsia, intravenous labetalol is recommended but intravenous nitroprusside or nitroglycerin could be alternatives. After delivery, BP should be controlled below 140/90 mmHg.Gestational HTN and preeclampsia are associated with an increased risk of developing HTN after delivery and pre-eclampsia is a risk factor for CVD. Patients with a history of pre-eclampsia have about a two-fold risk of ischemic heart disease, stroke, and venous thrombosis and a four-fold risk of developing sustained HTN. Especially in cases of preeclampsia within 32 weeks of gestation, stillbirth, and fetal growth retardation, the risk of HTN increases much more. Thus, active BP control and lifestyle modification even after delivery is strongly recommended for patients with HTN during pregnancy.In younger populations, women have lower prevalence of HTN than men. But after menopause, the prevalence of HTN in women increases rapidly as reaches the prevalence in men in their 60s and prevalence becomes even higher than that in men in their 70s or 80s. As for age, the increase in pulse pressure is the same between men and women, however, the systolic and diastolic BPs are higher in women after menopause. Care should be taken in the diagnosis of HTN in menopausal women, because white coat HTN occurs more frequently in these women.After menopause, weight gain, hormonal changes, and psychological changes occur . In partThere is no difference in HTN treatment between women and men. Additionally, there is no difference in BP reduction and drug effects between women and men . Oral coContinuous positive airway pressure (CPAP) therapy is effective in improving sleep apnea. However, in studies concerning sleep apnea, CPAP was reported cause a 2–3 mmHg decrease of BP, and the effects differed according to adherence, disease severity, and daytime sleepiness –177, 179Vascular disease and its related factors are the major risk factors of dementia, including Alzheimer’s disease , 186. HT


Dehydration is a risk factor for early neurological deterioration (END) after ischemic stroke, yet the underlying mechanism is unclear. Outbalanced coagulation activation may contribute to ischemia progression, concurrently with dehydration‐induced blood viscosity change. We aimed to investigate whether the contribution of dehydration to END was mediated by blood coagulation activation.We retrospectively evaluated consecutive patients presenting with mild or moderate stroke  within 24 hr of onset between Jan 2016 and Dec 2017. Dehydration was defined by a serum nitrogen to creatinine ratio (BUN/Cr) of ≥15 and blood coagulation activity was assessed with thromboelastography (TEG). The correlations between BUN/Cr and TEG parameters were assessed and their relationship in the development of END was analyzed.p = 0.008), shorter R and K on TEG test . Comparison between patients with and without dehydration revealed no significant differences in TEG parameters. Multivariate regression suggested that dehydration status  and shorter R tercile on TEG  were independently associated with END; however, the odds ratio of R for END remained unchanged after adjustment for dehydration status.Of 244 patients, 64 (26.2%) developed END within 3 days after admission. Patients with END had significantly higher BUN/Cr (19.2 ± 5.7 vs. 15.3 ± 2.9, Our findings suggested that the contribution of dehydration to END after ischemic stroke was mediated by blood coagulation activation. This fluid depletion reduces total plasma volume, undermines cerebral perfusion, and changes blood viscosity, potentially exacerbating the degree of hypoxia and scope of the penumbra. A few observational studies reported a two–fourfold increase in the risk for clinical deterioration in dehydrated patients during the early stage of stroke  first‐ever acute ischemic stroke within 24 hr after symptom onset; (b) 18–80 years of age; (c) mild or moderate stroke on admission assessed by a National Institutes of Health Stroke Scale (NIHSS) score ≤14 , kinetic time , angle , maximum amplitude , clot strength , estimated percentage lysis , and LY30 (clot lysis since the decay of MA over 30 min).Clinical data were collected from the electronic records of the initial assessment when patients arrived at the emergency department, including demographic characteristics, vascular risk factors, and NIHSS score. Laboratory tests, including blood cell counts, lipid profile, BUN, creatinine and C‐reactive protein measurement and other biochemical variables, were performed within 12 hr after admission. The degree of dehydration status was assessed using the blood urea nitrogen/creatinine ratio (BUN/Cr) because of its ready availability in clinical practice and reliability tested in previous studies . Continuous variables were presented as the mean ± standard deviation if normally distributed or median  if skewed; categorical variables were presented as a percentage. Comparison of variables between END and non‐END patients was performed using Student's 33.1p = 0.001), higher median baseline NIHSS scores , and higher hs‐CRP levels . Dehydration was more frequently observed in patients experiencing END ; specifically, patients with END had a significantly higher mean BUN/Cr ratio  and urine specific gravity  (Table p = 0.001) and K , indicating faster clotting activation. No significant differences were detected in any TEG parameters, including indicators from clotting formation , platelet function , or lysis processes  at the group level  male participants. Dehydration was identified in 134 (55.2%) patients with BUN/Cr ≧15 at admission. The median interval from symptom onset to admission was 8.2 hr, and 64 (26.2%) patients developed END within 3 days afterward. Follow‐up MRI was carried out in 56 END patients, among whom 35 showed diffusion‐weighted image (DWI) hyperintensity enlargement or new lesions outside the initial region, 19 showed no changes, and three showed hemorrhagic transformation on susceptibility‐weighted imaging. Demographic and clinical data are shown in Table R time: beta −0.027, p = 0.721; K time: beta‐0.012, p = 0.877; angle: beta 0.091, p = 0.216; MA: beta 0.122, p = 0.100; G: beta −0.096, p = 0.192; EPL%: beta 0.055, p = 0.471; LY30%: beta 0.084, p = 0.263; A: beta −0.139, p = 0.066; CI: beta −0.065, p = 0.372).In the comparison of TEG values between the dehydration group and the nondehydration group, no significant differences were detected at the group level. To further explore the correlation between dehydration status and blood coagulation activity, we performed a multivariate linear regression analysis. After adjusting for age, sex, baseline NIHSS score, and DM history, a linear regression model indicated no significant correlations between the BUN/Cr ratio and each result of the TEG test (p = 0.003). Other significant risk factors included dehydration status, female sex, higher baseline NIHSS score, history of DM, and higher serum hs‐CRP level.  and each TEG parameter. Despite extensive evidence supporting the clinical relevance, the mechanism of how dehydration contributes to ischemia progression immediately after stroke onset remains unclear. Some studies have indicated that hemoconcentration following dehydration contributes to an increase in pivotal factors involved in blood clotting cascades, such as platelets and fibrinogen (Dmitrieva & Burg, Second, our results suggested that blood hypercoagulability was also significantly associated with END, independent of the detrimental effect of dehydration. Thrombotic tendency has been proposed as another important risk factor for ischemia progression, predisposing the slowed blood flow in microvascular circulation distal to the occluded artery to thrombosis. In fact, some studies reported that dehydration status was negatively associated with the development of collaterality, especially secondary collateral flow through leptomeningeal anastomoses. Although our study did not support the hypothesis that dehydration per se leads to blood hypercoagulability in the early phase of stroke, blood hypercoagulability could also increase the risk of collateral failure by forming small thrombi in oligemic brain tissue. Thus, it may play an independent role in the development of END immediately after stroke onset.Our study had some limitations. First, this was a retrospective single‐center study, and we enrolled only patients with mild or moderate stroke; selection bias should be taken into consideration while generalizing the results. Second, no gold standard exists for dehydration evaluation. Although BUN/Cr is commonly used to assess dehydration status, it may be influenced by other factors such as acute kidney injury, gastrointestinal bleeding and others that we did not consider in our study. Third, TEG was a coagulation test in vitro, and we used a blood sample from peripheral venous blood; some discrepancy may exist with the cerebral circulation. Finally, our study focused on the early phase immediately after stroke onset, and the correlation between dehydration status and blood coagulability in later stages still needs to be elucidated in further studies.5Our findings suggest that dehydration status and blood hypercoagulability are more prominent in patients with END after ischemic stroke and are significantly associated with the development of END. However, our results do not support the hypothesis that the contribution of dehydration to END could be mediated by activating the coagulation cascade. Further studies are warranted to better understand END pathophysiology and will facilitate early awareness of END and improve stroke care.The authors declare no conflict of interest with this publication.


Echocardiographic characteristics across the spectrum of chronic kidney disease (CKD) have not been well described. We assessed the echocardiographic characteristics of patients with preserved renal function and mild or moderate CKD referred for echocardiography and determined whether echocardiographic parameters of left ventricular (LV) and right ventricular (RV) structure and function were associated with changes in renal function and mortality.This retrospective cohort study enrolled all adult patients who had at least one trans-thoracic echocardiography between 2004 and 2014 in our institution. The composite outcome of doubling of serum creatinine or initiation of maintenance dialysis or kidney transplantation was the primary outcome. Mortality was the secondary outcome.29,219 patients were included. Patients with worse renal function had higher prevalence of structural and functional LV and RV abnormalities. Higher estimated glomerular filtration rate (eGFR) was independently associated with preserved LV ejection fraction, preserved RV systolic function, and lower LV mass, left atrial diameter, pulmonary artery pressure, and right atrial pressure, as well as normal RV structure. 1041 composite renal events were observed. 8780 patients died during the follow-up. Pulmonary artery pressure and the RV, but not the LV, echocardiographic parameters were independently associated with the composite renal outcome. In contrast, RV systolic function, RV dilation or hypertrophy, LV ejection fraction group, LV diameter quartile, and pulmonary artery pressure quartile were independently associated with all-cause mortality.Echocardiographic abnormalities are frequent even in early CKD. Echocardiographic assessment particularly of the RV may provide useful information for the care of patients with CKD.The online version of this article (10.1186/s12882-018-0975-5) contains supplementary material, which is available to authorized users. In the Echocardiography can identify abnormalities in heart function or structure that are associated with kidney dysfunction . AbnormaAlthough these data are intriguing, the echocardiographic characteristics of patients across the spectrum of cardiac function – with both preserved or reduced LV ejection fraction and with or without CHF – have not been adequately described across different eGFR stages, especially in patients with mildly decreased eGFR. It is also uncertain whether echocardiographic parameters predict CKD progression. The objective of this study was to describe the echocardiographic characteristics of patients with preserved renal function and mild or moderate CKD referred for echocardiography, and to assess associations of echocardiographic parameters with changes in renal function.2 during this time period. For patients who had more than one echocardiogram, the first one was used.Patients were included if they had at least one trans-thoracic echocardiography with tissue Doppler imaging at a Partners affiliated healthcare facility between January 1st 2004 and January 6th 2014, were ≥ 18 years old at the time of echocardiography, and had at least one eGFR between 30 and 120 ml/min/1.73mPatients on maintenance dialysis or a history of kidney or heart transplant were excluded, as were those without creatinine values from 365 days before to 90 days after echocardiography.2).The study was designed to capture patients with preserved renal function and mild or moderate CKD , a registry of all patients followed at a Partners healthcare facility, was used to retrieve all encounters, medication prescriptions, laboratory tests, and echocardiography results conducted during this time period.To avoid misdiagnosis of acute kidney injury at the time of baseline echocardiography as CKD, the average baseline creatinine was calculated using all the available creatinines for each patient from 365 days prior to 90 days after the index echocardiogram . Baseline eGFR was calculated using the CKD-EPI equation.Information on comorbidities was extracted using condition-specific diagnostic codes : hemoglobin, albumin, calcium, phosphorus, urine albumin to creatinine ratios, and brain natriuretic peptide (BNP) levels.We determined the use of angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), β-blockers, statins, aspirin, clopidogrel, and warfarin by matching the most recent outpatient medication lists with generic and brand name drugs.The following parameters were extracted from the echocardiography reports using automated text processing: LV ejection fraction, LV diastolic diameter, LV posterior wall thickness, interventricular septal thickness in diastole, LV mass (area-length method), LV mass index (corrected for body surface area), pulmonary artery pressure, right atrial pressure, left atrium diameter, aortic root diameter, concentric hypertrophy and regional wall motion abnormalities, right ventricular (RV) systolic function (preserved or reduced), and RV hypertrophy or dilatation (presence or absence). All echocardiogram reports were acquired and recorded using an American Society of Echocardiography-recommended scanning protocol with standard techniques. Although we initially planned to examine associations of diastolic dysfunction with CKD progression, tissue Doppler imaging results were image-embedded and not readily extractable.We randomly reviewed 100 patient records to check the accuracy of automated extraction of diagnoses, medication, and echocardiographic parameters. Specificity was 100% and sensitivity was between 95 and 97% for the different echocardiographic parameters (most available information was captured using regular expression searches).We retrospectively searched in the registry for available creatinine values or diagnostic codes post index echocardiography. The composite of doubling of serum creatinine, maintenance dialysis or kidney transplantation was the primary outcome because it is a standard, FDA-validated outcome. Mortality was the secondary outcome. We also analyzed associations between echocardiographic parameters and eGFR, using the latter as the exposure.Clinical outcomes were identified from RPDR using diagnostic codes. The RPDR is continuously matched to the social security death index, a national database including all deaths in the United States. For the outcome of doubling of serum creatinine, creatinine values starting 30 days after the first doubling as well as the last available creatinine were screened for repeated/confirmed doubling to rule out potential AKI. Patients were censored at the last clinical visit or lab test.2 test for categorical variables, and one-way analysis of variance or non-parametric trend tests for continuous variables.Baseline characteristics across eGFR groups were compared using the χIn order to study the association between echocardiographic parameters and eGFR, we used linear regression for continuous echocardiographic variables or logistic regression for binary variables. Normality, linearity, and homoscedasticity assumptions were confirmed using graphical methods. The following covariates were included in multivariate models on the basis of known associations with the outcomes of interest, clinical intuition, and availability in the dataset: age, sex, race, history of hypertension, diabetes, coronary disease, CHF, and use of ACEI or ARB.2 test was used to compare the different groups. To assess associations of echocardiographic parameters with clinical outcomes, multivariable Cox proportional hazards regression was used. Proportional hazards assumptions were verified using graphical methods. Patients without available creatinine values or diagnostic codes for dialysis or transplantation were considered to have stable renal function. The following parameters were included in the baseline model: age, sex, race, baseline eGFR, history of hypertension, diabetes, coronary artery disease, CHF, and use of ACEI or ARB. The various echocardiographic parameters were then added to the model. Patients with missing echocardiographic parameters were excluded from the respective survival analysis.In order to assess event-free survival, the cohort was divided into quartiles for LV diastolic diameter, LV mass, LV mass index, left atrium diameter, and pulmonary artery pressure. Categorical variables or variables reported in intervals rather than as true continuous measurements were assessed in binary categories  except for LV ejection fraction where the following cutoffs were used: < 25%, 25–39%, 40–54%, ≥55%. The incidence of the composite renal outcome was calculated for each quartile. The χWe conducted three sensitivity analyses in the following subgroups: i) outpatients only—in order to exclude individuals with echocardiograms during an acute cardiac event; ii) individuals without CHF at baseline; iii) individuals with available follow-up creatinine values or diagnostic codes.P-values < 0.05 were considered statistically significant. SPSS software  was used for all statistical analyses.2. Of these, 31,173 had at least one creatinine value available from 365 days before to 90 days after the echocardiogram. 492 patients with a transplanted heart or kidney, 268 patients on dialysis at baseline, and 1194 patients who had a baseline eGFR < 30 ml/min/1.73 m2 were excluded from the main analysis. The characteristics of the 29,219 patients with an eGFR ≥30 ml/min/1.73m2 at baseline are depicted in Table We identified 42,446 patients with at least one echocardiogram and one eGFR value between 30 and 120 ml/min/1.73m(Table ). They also had higher pulmonary artery pressures, and higher prevalence of elevated right atrial pressure. eGFR was independently associated with all echocardiographic parameters analyzed in multi-variable models .Patients with worse renal function had lower LV ejection fraction, higher prevalence of RV systolic impairment, higher LV mass index, higher LV and left atrium diameter, more regional wall motion abnormalities, and higher prevalence of RV hypertrophy or dilated RV Table . They al2. The baseline and echocardiographic characteristics according to eGFR groups of patients with CHF are shown in Additional file A total of 8183 patients had history of CHF: 1733 (21%) with an eGFR ≥90, 3369 41%) with an eGFR of 60–89, and 3081 (38%) with an eGFR < 60 ml/min/1.73m1% with aIn the subgroup of patients without CHF, prevalence of various comorbidities at baseline was lower compared with patients with CHF. In those without CHF, right atrial pressure levels were similar in all three eGFR groups. For all the other echocardiographic parameters, a significant linear trend was identified across the different eGFR groups but the prevalence of RV or LV systolic dysfunction was lower .At least one follow-up creatinine (beyond day 90 from the index echocardiogram) or diagnostic code for dialysis/transplantation were available for 20,008 patients (68%). Median follow up was 48 months (interquartile range 20–87 months). A total of 1041 composite renal events were observed: 691 events with the creatinine doubling, 273 initiations of dialysis, and 77 kidney transplantations; 282 occurred in patients with an eGFR ≥90 (0.86 events per 100 patients-years), 348 in patients with eGFR between 60 and 89 (0.73 events per 100 patients-years), and 411 in patients with an eGFR < 60 ml/min/1.73mp < 0.001), and for RV dilation 1.59 .The number of composite renal events that occurred in the 1st, 2nd, 3rd, and 4th quartile of each echocardiographic parameter is depicted in Fig. 2 (13.6 events per 100 patients-years).8780 patients died during the follow-up: 2118 (24% of deaths) among patients with an eGFR ≥90 (6.4 events per 100 patients-years), 3456 (39% of deaths) among patients with eGFR between 60 and 89 (7.2 events per 100 patients-years), and 3206 (37% of deaths) among patients with eGFR < 60 ml/min/1.73 mIn adjusted models, LV ejection fraction group, LV diameter quartile, pulmonary artery pressure quartile, and RV parameters were independently associated with mortality Table .n = 21,036, Additional file n = 20,008, Additional file Adjusted results were qualitatively similar in analyses of the 13,130 outpatients . We also identified that RV systolic function or dilation and pulmonary artery pressure are independently associated with a composite renal outcome of serum creatinine doubling, dialysis, or transplantation. Both RV and LV echocardiographic features were associated with mortality.We assessed echocardiographic characteristics of patients with preserved renal function and mild or moderate CKD in a cohort of individuals referred for echocardiography. We found that patients with CKD have a higher prevalence of structural and functional LV and RV abnormalities, which are already apparent in early CKD .More studies are needed to prospectively confirm the identified associations and carefully evaluate the right heart with comprehensive assessment of the RV including lateral tricuspid annular systolic velocity and acceleration, fractional area and long-axis change, tricuspid annular systolic excursion, myocardial performance index, and lateral free wall peak systolic strain, as well as inferior vena cava diameter and distensibility , 19. TheIn conclusion, structural and functional abnormalities of the right and left ventricle are more common in individuals with mild or moderate renal impairment and associated with mortality while RV function and structure are independently associated with CKD progression even in early stage CKD. Prospective studies with quantitative assessment of the RV are needed to validate our observations and better understand the underlying mechanisms.Additional file 1:Table S1. Condition specific diagnostic codes  (DOCX 92 kb).Additional file 2:Table S2. Crude and adjusted assessment of echocardiographic parameters and estimated glomerular filtration rate (DOCX 17 kb).Additional file 3:Table S3. Baseline characteristics of patients with CHF at baseline (DOCX 18 kb).Additional file 4:Table S4. Echocardiographic characteristics of patients with CHF at baseline (DOCX 17 kb).Additional file 5:Table S5. Baseline characteristics of patients without CHF at baseline (DOCX 17 kb).Additional file 6:Table S6. Echocardiographic characteristics of patients without CHF at baseline (DOCX 16 kb).Additional file 7:Table S7. Adjusted associations of echocardiographic parameters with composite renal outcomes and mortality in outpatients (DOCX 16 kb).Additional file 8:Table S8. Adjusted associations of echocardiographic parameters with composite renal outcomes and mortality in patients without known CHF at baseline (DOCX 16 kb)Additional file 9:Table S9. Adjusted associations of echocardiographic parameters with composite renal outcomes and mortality in patients with available follow-up creatinine values or diagnostic codes (DOCX 16 kb).


Level of inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). Visual analogue score (VAS), Ramsay sedation score (RSS), and kidney injury related indexes were evaluated at different time points. The plasma-drug concentration of patients was determined by High Performance Liquid Chromatography (HPLC) method. Compared with CG, HR, PE, and diastolic blood pressure (DBP) showed lower level while SpO2 showed higher level in IG. Furthermore, expression of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and IL-10 in IG was decreased after drug administration, the contents of β2-MG, KIM-1 and urine protein were also decreased in contrast to the CG . Besides, VAS score was decreased but Ramsay score was increased in the IG (both P<0.05). The results of HPLC showed that the half life of dexmedetomidine was about 20 min and it is speculated that the drug can be quickly metabolized within 24 h. Dexmedetomidine exerted protective effects on kidney injury of parturients with PE undergoing cesarean section.The present study aimed to elucidate the effects of dexmedetomidine on kidney injury of parturients with preeclampsia (PE) undergoing cesarean section. Total 134 cesarean delivery women with PE were randomly divided into intervention group (IG) and control group (CG). Both groups underwent combined spinal and epidural anesthesia (CSEA), the IG was treated with 0.4 μg/(kg·min) dexmedetomidine for 10 min before surgery. The CG was treated with equivalent saline. Heart rate (HR), blood pressure, oxygen saturation (SpO As a hypertensive disorder, preeclampsia (PE) usually occurs on pregnant women. Individuals suffering from PE frequently exhibit hypertension, proteinuria as well as multiple systemic lesions. At the same time, PE may even cause fetal growth retardation, prematurity, still birth, and so on. . AccumulDexmedetomidine is a highly selective α2 adrenergic receptor agonist commonly served in clinical practice, it has been proved to exert an active role in analgesia, sedation, and inhibition of sympathetic effects, thus widely applied to various kinds of operations . A studyThe present study was a prospective, randomized, double-blind, and controlled study. Ethical approval was obtained from the Ethics and Research Committee of the Department of Anesthesiology, Xuanwu Hospital of Capital Medical University. Informed consent had been obtained from all patients involved in the present study. The present study was also registered at Chinese Clinical Trial Registry and the registration number is ‘ChiCTR1800017726’.The current study involved 134 PE patients undergoing caesarean section from June 2016 to July 2017. According to the American Society of Anesthesiologists physical status (ASA-PS) classification, patients were graded as ASA I-III, aged 25–39 years, with an average age of (29.8 ± 4.3) years, gestational weeks of 34–48 weeks, with an average gestational weeks of (36.3 ± 3.1) weeks, and body weights at 59–88 kg with an average of (69.3 ± 10.1) kg. The recruited patients were then randomly divided into intervention group (IG) and control group (CG) according to random number table, with 67 patients in each group. The patients received different treatments. Randomization was computer generated centrally by School of public health, capital medical university, Beijing, China and allocations were obtained by telephone or fax from staff who were not involved in other parts of the trial. Randomization was stratified by center with minimization for age, body weight, gestational weeks, and ASA grade. Patients and investigators were not masked to treatment assignment The details with regard to the participants have been shown in a Consolidated Standards of Reporting Trials (CONSORT) flow diagram .Diagnostic criteria : PE is dPatients were fasted and taken in oxygen before surgery and 6% hydroxyethyl starch + 130/0.4 sodium chloride injection  was administered prior to anesthesia. Patients were kept in left lateral position, CSEA was then performed in the spinal L3–L4 intervertebral space. Total 1 ml Ropivacaine Hydrochloride  diluted by 1 ml cerebrospinal fluid was injected into the patients’ spinal canal. The acupuncture method was utilized to determine the epidural block plane, and it was controlled in the T8–T10 segment of the spine, then the cesarean section was performed. Total 5 mg/(kg·h) propofol and 0.15 μg/(kg·min) remifentanil were injected in veins to retain anesthesia during operation. The bispectral index (BIS) was kept at 40–50 during operation.The IG was intravenously and slowly injected by 0.4 μg/(kg·min) dexmedetomidine for 10 min before surgery , whereas the CG was injected with equal 0.9% normal saline for 10 min. Two anesthesiologists blinded to the experimental protocol were responsible for patient care and data collection during the surgery.2 of two groups of patients were measured by Philips MP60 Monitor , at 0 h (pre-operation), 1 h (postoperation), 3, 6, 12, and 24 h after administration.Levels of HR, SBP, DBP, and SpOTotal 3 ml venous blood of upper limb of the patients was drawn at 0 h (preoperation), 1 h (postoperation), 3, 6, 12, and 24 h after administration respectively. After standing for 15 min, serum samples were centrifugated at 3000 rpm/min for 15 min, then the supernatant was collected, and preserved in −80°C refrigerator. Levels of TNF-α, IL-6, and IL-10 were detected using TNF-α Quantikine ELISA Kit , IL-6 Quantikine ELISA Kit , IL-10 Quantikine ELISA Kit  respectively. The operating procedures were as following: first the reference standards (containing 50 μl reference standards) and samples (containing 10 μl sample under study + 40 μl sample dilution solutions) were constructed. Total 100 μl Horseradish Peroxidase (HRP)-conjugated antibody was added into the reference standards and samples, then the reaction pore was sealed off by closure plate membranes. The samples were bathed with water, which followed by the discard of liquid. Filled each well with washing solution and rest for 1 min. Discard the washing solution and dried the plate by using bilbulous paper, such washing procedure was repeated for five times. Total 50 μl substrates A and B were added to each well respectively and then the well was further incubated for 15 min in the dark. Subsequently, 50 μl stop solution was added into each well, a Microplate Reader  was then applied for optical density (OD) detection at a value of 450 nm.Urine of parturients was respectively collected at 0 d (preoperation), 1, 2, 3, 4, 5, 14, 21, and 42 d after the drug administration. The Automatic Biochemical Analyzer  was utilized to detect the blood urea nitrogen (BUN), uric acid (UA), creatinine (Cr), β2-microglobulin (β2-MG), kidney injury molecule-1 (KIM-1), urine albumin (Alb) and total protein (TP) at various time points, the percentage of urine protein content was calculated.Visual analogue score (VAS) and Ramsay sedation score (RSS) were used to evaluate the pain and sedation of the patients at 0 h (preoperation), 1 h (postoperation), 2, 3, and 4h after drug administration. The score of the VAS: 0 mark as painless, 10 mark as extremely painful. The score of the RSS: 1 mark as anxious, agitated, restless, 2 mark as cooperative, oriented, and tranquil, 3 mark as drowsiness and responsive to commands, 4 mark as sleeping and responsive to stimulus, 5 mark as sluggish response to stimulus, 6 mark as deep sleep and no response to stimulus.18. Methanol: 0.5% formic acid solution (60:40) was set as mobile phase, the flow rate was 0.3 ml/min and column temperature was 35°C, volume of sample injection was 10 μl and the bottle temperature was 5°C. Sample treatment: 100 μl sodium hydroxide (1 mol/l) was added to 0.5 ml patient plasma, 20 μl dexmedetomidine (10 ng/ml) was set as internal standard. After mixing, 5 ml anhydrous ether was added, shaken for 3 min, and then centrifuged at 7000 rpm for 10 min. Discard the supernatant and the lower sediment was frozen at –80°C for 20 min. Subsequently, 150 μl mobile phase was added to dissolve the sediment. Then the solution was centrifuged at 1300 rpm for 10 min, 10 μl supernatant was collected and sampled. The determination of serum concentration was performed at 0, 10, 20, 30, 60, 120, 180, and 240 min after drug administration.High performance liquid chromatography (HPLC) assay was adopted to determine the blood concentration of PE treated with dexmedetomidine. The chromatographic condition was set up as following: Kromasil 60-5CN column was set as chromatographic column and the precolumn is Phenomenex Security Guard™ CThe vital signs of the patients were monitored and recorded within 72 h after cesarean section. Major adverse reaction included bradycardia (<45 beats/min), hypotension (<60 mmHg), hypertension (>160 mmHg), localized pain, dry mouth, vomiting, and headache.The Apgar scores  of newborns in 1, 5, and 10 min were recorded after delivery. 8–10: no asphyxia, 4–7: mild asphyxia, 0–3: severe asphyxia.t test, and multigroups were examined by one-way analysis of variance. (ANOVA). Enumeration data were expressed as a percentage and analyzed using a chi-square test, Comparisons amongst multiple groups were examined by ANOVA and homogeneity test of variance was performed, when there was a significant difference in variance analysis, q test was further conducted for pairwise comparison; in case of heteroscedasticity, non-parametric rank-sum was performed.SPSS 21.0 software  was utilized for data analyses. Measurement data were expressed as mean ± S.D. The comparison between two groups was analyzed by The sample size analysis performed using Power Analysis and Sample Size 19.0.1 indicated that 42 patients were needed per group to detect a between-group difference with a power of 80%, α of 0.05, and an allocation ratio of 1:1 (based upon previous experience). So 67 patients in per group were included in the study.P>0.05).The maternal and surgical characteristics of the two group patients were shown in 2 value between the two groups at preoperative stage (both P>0.05). With the increase of time after injection, the values of SBP, DBP, and HR of the two groups were decreased, while the level of SpO2 was increased. Compared with the CG, the above indexes of the IG showed more obvious change (both P<0.05).As indicated in P<0.05). With the increase of time after injection, levels of TNF-α, IL-6, and IL-10 showed a decline. Compared with the CG, IG showed the most obvious change .The levels of TNF-α, IL-6, and IL-10 in peripheral blood of the two groups at different time points were shown in P>0.05). As time went on, the contents of Cr, UA, BUN, β2-MG, KIM-1, and urine protein were all declined, no significant difference was found in albumin and total protein content (P>0.05). Compared with the CG, the levels of β2-MG, KIM-1, and urine protein dropped more significantly at each time point after administration (P<0.05).The expressions of kidney injury related indexes of the two groups at different time points were shown in P>0.05). In IG, VAS was gradually decreased with the increase of time after drug injection, but the RSS was gradually increased (both P<0.05), whereas VAS and RSS in the CG were fluctuating. Compared with the CG, the VAS of the IG was decreased at each time point after drug administration, but the RSS was increased .The VAS and RSS of the two groups of parturients were shown in HPLC method was utilized to detect the concentration of dexmedetomidine in blood of the IG at different time points. As indicated in the , the conP<0.05). After relevant measures, the patients were improved and returned to normal. In addition, Apgar scores of neonates within 1, 5, and 10 min after delivery were not significantly different between two groups(both P<0.05).The incidence of adverse drug reactions in patients 72 h after cesarean section and Apgar scores of newborns in 1, 5, and 10 min were shown in A study designed by Awowole IO demonstrated that 40% of kidney damage of parturients was associated with PE . Patient2 after surgery compared with the CG , suggesting the value of dexmedetomidine in effectively improving hypertension of PE parturients. This finding is also confirmed by the research conducted by Hariharan et al [It has been confirmed that dexmedetomidine exerts notable positive effects in inhibiting plasma norepinephrine levels and inhibiting sympathetic nerves; thus, it was widely used in perioperative analgesia and sedation for various types of surgeries . In recean et al . Dexmedean et al . In addian et al . At the an et al . In the et al. applied dexmedetomidine in cisplatin-based cancer chemotherapy and it was found that apart from promote to keep calm and dexmedetomidine can also exert protective effects in kidney damage induced by cisplatin. The regulation of apoptosis and immune responses may involved in the underlying mechanisms [P<0.05), indicating that dexmedetomidine plays a protective role in improving kidney injury of PE parturients during cesarean section. Futhermore, the response of an overall pro-inflammatory systemic environment is verified to be closely related to the morbidity of PE, the excessive release of inflammatory factors could contribute to the progression of PE, heart and kidney damage of patients [Cr and urinary protein contents are critical indicators for clinical diagnosis of kidney injury and their enhancements in expression are considered to be closely correlated to the extent of renal trauma . In addichanisms . In the patients . In presIn conclusion, the aforementioned findings of the study strongly support the standpoint that dexmedetomidine cannot only promote analgesia and sedation, alleviate the symptoms of PE, but also contributes to down-regulating the levels of β2-MG, KIM-1, and urine protein, exerting a significant protective effect on kidney injury in PE parturients. Our study is of guiding significance in medicine application for PE parturients undergoing cesarean section.The study was in accordance with the Helsinki Declaration and it was discussed and approved by the Ethics Committee of the Xuanwu Hospital of Capital Medical University. Patients volunteered to participate and signed informed consent forms. The trial was registered at Chictr.org.cn (ID ChiCTR1800017726).


The dramatic increase in prevalence of chronic kidney disease (CKD) with ageing makes the recognition and correct referral of these patients of paramount relevance in order to implement interventions preventing or delaying the development of CKD complications and end-stage renal disease. Nevertheless, several issues make the diagnosis of CKD in the elderly cumbersome. Among these are age related changes in structures and functions of the kidney, which may be difficult to distinguish from CKD, and multimorbidity. Thus, symptoms, clinical findings and laboratory abnormalities should be considered as potential clues to suspect CKD and to suggest screening. Comprehensive geriatric assessment is essential to define the clinical impact of CKD on functional status and to plan treatment. Correct patient referral is very important: patients with stage 4–5 CKD, as well as those with worsening proteinuria or progressive nephropathy (i.e. eGFR reduction > 5 ml/year) should be referred to nephrologist. Renal biopsy not unfrequently may be the key diagnostic exam and should not be denied simply on the basis of age. Indeed, identifying the cause(s) of CKD is highly desirable to perform a targeted therapy against the pathogenetic mechanisms of CKD, which complement and may outperform in efficacy the general measures for CKD. In the last two decades there has been a tremendous increase in the number of elderly patients with CKD and end-stage kidney disease: older adults over 65 years encompass the most rapidly growing subset of the end-stage renal disease (ESRD) population, while there was also a significant increase in the prevalence of CKD from 10.3 to 13.1% of the population, with the greatest percentage increase in those older than 70 years of age, rising from a prevalence of 37–47% .Therefore, we aimed at summarizing the evidence about differences between physiologic aging of the kidney and progressive kidney disease, as well as challenges in diagnosing kidney disease among older patients. In particular, we addressed the confounding role of comorbidity and multimorbidity and diagnostic clues to be considered in clinical practice. Finally, we described the CKD diagnostic process, including patient referral, clinical assessment and use of imaging and renal biopsy, in an attempt to promote a strict collaboration between nephrologists and geriatricians in clinical management of older patients.The content of this article represents an expert opinion shared between nephrologists and geriatricians and not the result of a formal consensus process generating guidelines.Aging may variably affect structures and regulatory functions of the kidney, and these changes may increase the propensity to develop acute kidney injury (AKI) and progressive chronic kidney disease (CKD).Overall, although renal ageing and failing kidney share some pathophysiological and clinical characteristics, very gradual changes observed in the aging kidney are clearly different from those observed in CKD, where mechanisms of progressive genetic, immune, or toxic injury are involved. Current evidence suggests that an imbalance between blunted protective factors  and stress factors  may contribute to the activation of pathways commonly involved in kidney inflammation and fibrosis characterizing CKD. This lead to enhanced senescence and microvascular rarefaction which maintain the damage and promote progression . AdvanceGFR declines slowly as a function of age , and theThe aged kidney shares with the failing kidney two main functional characteristics: a low GFR and a diminished ability for tubular salt and water reabsorption. On the other hand, in healthy older people the proximal tubular function is preserved, serum levels of calcium, magnesium and phosphorus are normal, and the same is also true for serum erythropoietin and hemoglobin levels . Else, e4 elimination peaks later than in the adult in response to an acute acid load. Accordingly, plasma pH and PaCO2 may take longer to be restored after an acid load in the aged.Older people also show tubule-interstitial changes such as tubular diverticuli and atrophy, fat degeneration, interstitial fibrosis and medulla hypotonicity; both sodium reabsorption and potassium secretion are to some extent impaired . In factThus, normal age-related changes in kidney function might be clinically relevant in the older patients, even in the absence of a clinically evident nephropathy, mainly in the context of conditions, such as a volume overload or a severe acidosis, impacting the renal functional reserve.Clinicians should be able to distinguish normal ageing kidney from true renal disease Table , and theThe initial step, i.e. the diagnosis of true renal disease deserves attention and critical thinking. Reduced GFR represents the most relevant feature of kidney failure, while increased albumin-to-creatinine ratio (ACR) is a marker of kidney damage . These v2. Conversely, CKD is characterized by albuminuria in only 19% of cases among older patients [2 without proteinuria had an estimated number needed to treat of 2500 to prevent ESRD in one patient [The role of albuminuria also deserves to be mentioned. In young adults, 75% of CKD is usually characterized by albuminuria, while only 25% presents with eGFR < 60 ml/min per 1.73 mpatients . In healpatients . Thus, cpatients , thus su patient . Thus, cCKD usually coexists with other chronic diseases due to a pathogenetic link, e g diabetes and atherosclerosis as the cause of CKD, and to the sharing of risk factors (e.g. age and smoking habits) and pathophysiological pathways described above. Recurrent and highly prevalent clusters of diseases including CKD are the rule according to the multimorbidity approach, which defines the main associations between and among diseases without any hierarchical assumption. According to such approach, Formiga et al.  reported2 and further increases in patients given metformin or potentially nephrotoxic drugs as well as in those having anemia, diabetes mellitus, CHF and hypotension, which clearly are age-related conditions [Not unfrequently, acute kidney injury due to contrast medium unravels CKD –33. Indenditions .Noteworthy, CKD occurs in 26–53% of patients with heart failure with preserved ejection fraction (HFpEF)  and worsWith the many caveats due to confounding by multimorbidity, symptoms are the main clues to suspect CKD, but biological clues are also worthy of consideration. Indeed, the kidney has a primary endocrine and paracrine role besides being the main regulator of the water and electrolyte balance. As a consequence, a new onset hypertension or an important increase in the requirement of antihypertensive drugs may reflect a renal dysfunction, and sympathetic overtone may be secondary to decreased renalase activity. Water retention, with its clinical  and laboratory or instrumental manifestations  may be a further clue to CKD. However, CKD may occasionally associate with dehydration in the context of decreased responsiveness to ADH and depressed thirst. Analogously, anemia without a demonstrable deficit of hemopoietic factors may suggest CKD, not only in stage IV, but even in stage III, given that, mainly in diabetic CKD, the renal synthesis of erythropoietin may decline faster than expected on the basis of eGFR . FurtherOn these bases, a systematic screening of renal function is mandatory in a variety of clinical and laboratory conditions Table .Furthermore, it is highly recommended also in the asymptomatic and healthy elderly because kidney function relies upon a huge functional reserve which is consistent with well being until a critical threshold deficit is achieved. However, it is unclear how frequently renal function should be checked for in this subject. Based on the age-related yearly risk of new onset CKD, a yearly check seems recommendable, but a widespread consensus on this topic is lacking.The screening of renal function includes the measurement of eGFR and albuminuria.KDIGO still recommend the CKD-EPI equation  to estimFurthermore, the widespread use of CKD-EPI in the adult population allows compare different populations and observe very long-term trends. The albuminuria may be assessed by single spot analysis and, only in the event of a positive result, by confirmatory assessment of the 24 h proteinuria.Identifying CKD allows treat it, and the interventions are effective at any age. This is true either for causal therapy or for the overall therapy of CKD . InteresThus, even in the very old CKD should not a priori considered as the effect of vascular and/or metabolic diseases. Furthermore, many other interventions are made possible by the awareness of CKD.Optimizing the choice of drugs and tailoring their doses to the renal function. The high incidence of ADRs to water soluble drugs in older patients with concealed CKD and the proved effectiveness of dedicated prescribing strategies found this measure.Choosing the antihypertensive treatment in order to preferentially contrast the sympathetic overtone or the water retention, as indicated on individual bases.Downsizing the insulin therapy in severe CKD.Providing erythropoietin and/or D3 vitamin, if needed.Planning interventions aimed to improve nutritional status and provide individualized diet regimens.Providing alkalinizing therapy in tubular acidosis.Providing effective strategies for preventing contrast induced nephropaty in at risk patients , 46.Replacing B12 vitamin, if needed, through methyl and hydroxocobalamin and not through cyanocobalamin due the potential rise in serum cyanide in CKD . Indeed,Planning and performing the immunization against selected viruses and bacteria. Given CKD is associated with immune depression, immunization against Hepatitis B virus should be provided in the early stages of CKD and, then, repeated in the end stage .Overall, there is circumstantial evidence that a comprehensive approach to CKD can improve both survival and quality of life in aged populations .When evaluating the epidemiology of kidney diseases in geriatric population, at least three main selection bias should be considered:the lack of overt symptoms and/or misleading laboratory parameters;elderly patients showing early signs of renal disease are rarely referred to a Nephrologist;elderly patients under the Nephrologist’s care rarely undergo a renal biopsy.Many nephrological conditions are clinically silent up to the onset of late complications, especially in the elderly. On the other hand, very frequently abnormal laboratory findings remain neglected and do not induce the general practitioner to ask for a nephrological opinion . Not unf2 should be labeled as having kidney disease, since this may be part of physiological aging. The universality of eGFR thresholds for diagnosis of CKD independent of age is still matter of debate. The lack of an age calibration for CKD diagnosis has been considered as an inherent and potentially serious weakness that might lead to substantial over-diagnosis of CKD in otherwise healthy populations of older subjects [2), which predominantly affects older persons and is seldom progressive in the absence of significant proteinuria [2 has been proposed for older patients, but it would only be applicable to those who do not have any other corroborating signs of kidney disease such as proteinuria [2) should be screened regularly for functional impairment and malnutrition to identify those needing an in-depth assessment and intervention.Obviously, as recently outlined by a joint initiative of European nephrologist and geriatrician , not allsubjects . The mosteinuria . Moreoveteinuria . Howeverteinuria . Indeed,teinuria . Additioteinuria . In gene2.As regards the second selection bias, main criteria for nephrologist referral are reported in Table CKD regression may occur in one-fourth of patients receiving outpatient nephrology care, especially in the absence of high proteinuria, hypertension and diagnosis of CKD . CKD regA careful history taking is mandatory to acquire the clinically relevant information. Informal support may be very useful . MedicatBMI should not be considered a universally reliable index of nutritional status and the measurement of arterial blood pressure may be biased by arrhythmias and vascular rigidity.Besides increasing the risk of ESRD, morbidity and mortality, CKD also affects outcomes relevant to older people, including subjective physical function, limitations in activities of daily living (ADL) and worsening disability, impaired objective measures of physical performance, frailty, cognitive impairment, depression, impaired sensory function, nutritional disorders and sarcopenia .The systematic use of comprehensive geriatric assessment (CGA) allows to identify medical, psychosocial, and functional limitations of a frail older person in order to develop a coordinated plan to maximize overall health with aging , and botLaboratory investigations for kidney diseases do not change with age. While specific eGFR equations have been developed for older people , 53, theAlthough urine abnormalities are the most representative findings in geriatric nephrology, they are still now the least investigated. Isolated hematuria is frequently due to urological conditions, but it may also reflect a renal disease such as thin basement membrane nephropathy or papillary necrosis. On the other hand, isolated proteinuria is never due to ageing kidney, but it may be the first sign of renal damage induced by diabetes, hypertension and so on .Two main reasons clearly support the use of ultrasonography (US) in the geriatric field: lack of potentially nephrotoxic contrast media and ease of use in geriatric common conditions. Thus, US currently qualifies as a routine investigation of obstructive nephropathy, renal mass, malignancies.In elderly patients, both renal function and kidney volume are often reduced . As intrThe overall rate of native kidney biopsy varies throughout the world, from over 250 pmp in Australia to less than 75 pmp in the United States , being hAt least two main studies focused on the risk of a misdiagnosis carried by a pure clinical diagnostic path. The former showed that only the histological diagnosis allowed the patients to be properly treated and to be protected from unnecessary and potentially harmful therapy . The latFinally, glomerular diseases are far from being rare in advanced age, and it is important to define them : incidenIn conclusion, histology is essential to precisely characterize the Glomerular Diseases with nonspecific clinical pictures, and to optimize the therapeutic strategies, also in elderly. Elderly patients should be offered the same chance of therapy that adult patients are usually given, and the higher rate of drug side-effects should not deter the treatment. A closer monitoring of the therapy is more suitable in this setting. The role of renal biopsy in the diagnostic workflow aimed at distinguishing normal aging of the kidney from CKD and at characterizing CKD is proposed in Fig. Nephrologists and geriatricians are more and more involved in diagnosing and caring older patients with CKD. Sharing diagnostic methodologies is particularly relevant when guidelines recommendations are lacking, as is the case of older people. Renal diseases are a major problem in the elderly, but also a treatable and, to some extent, preventable one. The complexity characterizing the elderly patient could mask kidney disease or account for several modifiable factors affecting kidney function. Thus, recognizing the renal disease and its causes as well as planning a tailored treatment requires an in depth knowledge of the patient, which frequently is out of the reach of the traditional nephrologic approach. Involving primary care physicians may help to obtain early identification and correct referral of older CKD patients. Furthermore, providing a comprehensive care of the health status implies that its many components and determinants be properly recognized. All this makes a truly multidimensional approach to this kind of patient mandatory. A strict cooperation between nephrologists and geriatricians is needed to select the best tools for the comprehensive geriatric assessment and to provide practical therapeutic recommendations. Indeed, a nihilistic attitude would carry the risk of leaving a treatable condition untreated and, then, prone to deterioration. On the other hand, a too aggressive and untailored approach might be harmful. Thus, a renewed diagnostic and therapeutic process is expected to stem from a positive and reciprocal contamination of the nephrological and geriatric cultures.


In Latin America, there is scarce information about severe asthma (SA) according to the ERS/ATS 2014 criteria. This study aimed to compare the demographic, socio, clinical characteristics, treatment, and use of healthcare resources between SA and non-severe asthma (NSA) patients in Argentina, Colombia, Chile and Mexico.A cross-sectional study was conducted including 594 asthma patients from outpatient specialized sites. A descriptive analysis was performed comparing SA patients and NSA. Chi-square and Mann Whitney tests were used to assess associations between asthma severity and outcome variables.p < 0.001) and had higher proportion of uncontrolled asthma than the NSA patients . SA patients reported a significantly higher proportion of both hospital admission and emergency room (ER) visits due to asthma in the last year, compared with NSA patients, 8.7% vs. 3.7% (p = 0.011) and 37.0% vs. 21.7% (p < 0.001), respectively.Using ERS/ATS 2014 criteria, 31.0% of the patients were identified as SA. SA patients were older at diagnosis , there was still a higher proportion of uncontrolled disease.The online version of this article (10.1186/s12890-019-0871-1) contains supplementary material, which is available to authorized users. Asthma is a chronic inflammatory disorder of the airways  and its Approximately 2–10% have some form of severe asthma (SA) , 7. AccoIn Latin America, there is a lack of information related to SA epidemiology and the burden of SA following implementation of the ERS/ATS 2014 criteria. Essentially, most of the Latin American studies that have assessed the SA population in the region had also included untreated patients , 11 or fThe Asthma Control in Latin America (ASLA) study was a cross-sectional multisite study. Patients were consecutively enrolled between December 2013 and December 2015. The 16 recruiting sites were located in Argentina (five sites); Chile (five sites), Colombia (three sites), and Mexico (three sites) .The study included 594 diagnosed and treated asthma patients who were recruited during routine care at specialized outpatient sites, aged over 12 years old, under pneumologists follow up, with at least one prescription of asthma medication and one medical visit for asthma within the last 6 months. Individuals were excluded if they were participating in a clinical trial at the time of the study or were unable or not willing to comply with the study requirements. This study was conducted in accordance with the amended Declaration of Helsinki . WrittenDuring the course of a scheduled medical visit, the participating patients were asked to complete the Asthma Control Test (ACT) , which wAsthma severity was operationally defined using an algorithm based on answers to questions relating to the ERS/ATS 2014 criteria. SA was defined as asthma that required step four or five treatment  regardless of ICS doses). Four treatment categories did not fulfil the ERS/ATS 2014 criteria for SA and NSA and were reviewed by a panel of three pneumologist experts on asthma to allocate a group  was calculated in adults as weight divided by the square of height, and the nutritional status categorized as: underweight < 18.5 Kg/mlsewhere  and the A total of 594 asthma patients were studied: 154 subjects from Argentina, 154 from Chile, 163 from Mexico and 123 from Colombia. Overall 72.7% were women and 50.8% white, with a median age of 47 years old at the time of the study visit and an age of 25 at the time of asthma diagnosis. According to the ERS/ATS 2014 criteria, 31.0% of the patients had SA (Table p < 0.001).Differences in socio-demographic and clinical factors by SA and NSA are shown in Table p = 0.013).Figure p = 0.011) and almost two times higher proportion for ER visits due to asthma ) in the last year, compared with NSA patients.Table p = 0.015 and 14.1% vs 7.3%, p = 0.009). The same pattern was observed when considering the mean number of clinically significant asthma exacerbations .Regarding the hospital admission and emergency visits due to other causes, SA patients also had a significant higher proportion of both events than NSA patients


Increasedcancer (CA) incidence and survival rates, easier access to health care and themultiplicity of chemotherapy regimens all contribute to the increase in the diagnosis ofcardiovascular complications in patients with CA. The increase in CA prevalence andmortality, as well as its cardiovascular complications, is the price that nations payfor the aging of their populations in an oncogenic environment.2 Reportsof toxicity previously presented with other chemotherapeutic agents had also beenconfirmed with the new class of anthracyclines. The novelty was the real possibility ofcure. In the risk-benefit evaluation, adverse effects were neglected on behalf of thedecision to use it.3 Warnings on thecardiotoxicity of doxorubicin (DOXO) came with the description of the classic ‘von Hoffcurve’, where the risk of heart failure incidence at cumulative doses above 500mg/m2 wasdemonstrated.4The discovery, in the 1960s, in the Adriatic Sea coast, of a red pigment produced by afungus with great cytotoxic power has changed paradigms and introduced the concept ofcure in clinical cancerology.5 Other mechanisms of cellular aggression did not become clear untilrecently, when the action on the mechanical properties of cancerous and healthy cellswas demonstrated, especially their effect on the cellular membrane.6Initially, the mechanism was said to be an oxidative effect of the chemotherapeuticagent. Later, it was demonstrated that DOXO had a blocking effect on topoisomerases IIalpha (neoplastic cells) and beta (cardiomyocyte), as well as its consequence to thestructure of DNA, which caused cell death.7 investigates the relationships between arterial stiffness andventricular dysfunction in patients undergoing DOXO and cyclophosphamide.Today, there is a pertinent criticism about the lack of studies using judiciousmethodology and satisfactory casuistry in cardio-oncology. Indeed, there is a lack ofbasic science research addressing the aggression mechanisms in cardiovascular disease inCA patients. The study published in Arq Bras Cardiol8,9 The decision to study DOXO is justified by the highprevalence of its use in solid tumors such as breast cancer and hematologicaltumors.Theoretically, the cytotoxic impairment of DOXO could affect the endothelium, withconsequences to blood pressure variables, secondarily becoming one of the multipleventricular myocardial aggressions. Actually, there are no significant clinical reportsof arterial hypertension in DOXO users, unlike patients undergoing angiogenesisinhibitors that act by blocking one of several endothelial growth pathways.In the cohort studied, which comprised 24 middle-aged women, high global cardiovascularrisk was clearly observed. On average, the women were hypertensive and obese. There wasno change in blood pressure variables in left ventricular function according tomeasurements by pulse wave velocity and two-dimensional echocardiography. The negativeresult should not be viewed with dismay. We need all the information we can find onthese mechanisms. It is urgent to understand the pathophysiology of these cardiovascularaggressions. Only then will we be able to design ethical clinical trials with thehighest possibility of results that might interfere with the reduction of cardiovascularlesions and, above all, with the improvement of survival of patients with cancer.


Background: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is increasingly diagnosed during childhood by the presence of renal cysts in patients with a positive familial history. No curative treatment is available and early detection and diagnosis confronts pediatricians with the lack of early markers to decide whether to introduce renal-protective agents and prevent the progression of renal failure. Neutrophil Gelatinase-Associated Lipocalin (NGAL) is a tubular protein that has been recently proposed as an early biomarker of renal impairment in the ADPKD adult population.Methods: Urinary NGAL (uNGAL) levels were measured in 15 ADPKD children and compared with 15 age and gender matched controls using parametric, non-parametric, and Bayesian statistics. We also tested the association of uNGAL levels with markers of disease progression, such as proteinuria, albuminuria, blood pressure, and Total Kidney Volume (TKV) using correlation analysis. TKV was calculated by ultrasound, using the ellipsoid method.Results: No difference in mean uNGAL levels was observed between groups . Moreover, no correlation was found between uNGAL and proteinuria (P = 0.51), albuminuria (P = 0.69), TKV (P = 0.68), or mean arterial pressure (P = 0.90). By contrast, TKV was positively correlated with proteinuria (P = 0.04), albuminuria (P = 0.001), and mean arterial pressure (P = 0.03).Conclusion: uNGAL did not confirm its superiority as a marker of disease progression in a pediatric ADPKD population. In the contrary, TKV appears to be an easy measurable variable and may be promising as a surrogate marker to follow ADPKD progression in children. PKD1 gene concern around 85% of the ADPKD population and are associated with a more severe renal impairment and disease progression. Given the fewer cyst burden and later age at diagnosis among PKD2-related ADPKD, PKD1-associated ADPKD is over-represented in pediatric patients  is the most prevalent inherited monogenic kidney disease and affects 1/500 individual worldwide. It represents up to 5–10% of total end-stage renal disease . Its diapatients .Until recently, ADPKD was considered mainly as an adult disease. However, clinical manifestations may already occur during early childhood. Developments in ultrasound technology have led to an increase in the prenatal and infant diagnosis of ADPKD  and, conEven in the early stages, 60% of ADPKD children present impaired urine concentration capacity several years before the decline in the glomerular filtration rate (GFR) . The estCurrent biomarkers used to evaluate renal function in children at a stage of normal GFR highlight the difficulty for clinicians to determine whenever it is beneficial to introduce renal-protective agents. Albuminuria and proteinuria are routinely used as follow-up biomarkers in pediatric ADPKD patients, but they may not be present during the early stages of the disease. New biomarkers are required to detect the impact of the disease on kidney function. Glomerular hyperfiltration has been shown to be associated with a significantly faster decline in renal function and higher rate of kidney enlargement over time . In adulHere we assessed the predictive value of uNGAL as an early tubular biomarker of renal function and impairment in ADPKD pediatric patients and compared values with a gender- and age-matched control group. We also investigated whether there was an association between uNGAL and well-recognized clinical markers of the disease, such as proteinuria, albuminuria, blood pressure, and TKV.d = 3.73), we estimated that a sample size of 15 ADPKD patients and 15 controls would be sufficient to show uNGAL differences between groups.Based on the data reported by Bolignano et al.  , and normal blood pressure. Any congenital disease was an exclusion criterion.The study was performed between December 2015 and July 2017 at Geneva University Hospitals  among 15 ambulatory ADPKD patients aged <18 years old. The diagnosis of ADPKD was made using the typical ultrasound findings of renal cysts  associated with a positive familial history. Two patients had been genetically tested before the study. Both of them had a The protocol was approved by the local ethical committee of human research in Geneva (CER-15-230). The study was conducted in accordance with the principles of good clinical practice, the Declaration of Helsinki, and all local regulations. Written informed consent was obtained from parents and children >12 years old before participating in the study.NGAL measurement: 10 mL urine were collected on the day each participant came for an outpatient visit. The urine sample was therefore taken at a random time during day and was rapidly transferred to the laboratory where it was immediately centrifuged and stored at −80°C until assayed. NGAL was measured using an ELISA method on a commercial kit  according to the manufacturer's instruction. All measurements were made in duplicate and in a blinded manner. NGAL levels were expressed as pg/mL and converted to ng/ml to make the comparison easier with the values found in the medical literature.Proteinuria and albuminuria: in the ADPKD patient group, urine samples were also tested for albuminuria and proteinuria as standard care follow-up, calculated on the ratio of urinary albumin or total urinary proteins and urinary creatinine, respectively. Significant albuminuria was defined as >2.5 mg/mmol and significant proteinuria as >20 g/mol.3. Two controls had their last normal ultrasound prior to the study and TKV was therefore not included in our analysis. The values in both groups were compared to standard kidney volume in children  was calculated upon the ultrasound image by the same pediatric radiologist using the ellipsoid method based on the length, width and depth (kidney volume = length × width × thickness × [π/6]) . The TKVchildren . The TKVSystolic and diastolic blood pressure were measured in both groups during the consultation and adjusted to age and height percentiles to determine the individual blood pressure percentile . A mean t-tests  were used to compare continuous variables between groups. When relevant, we confirmed null effects using JZS Bayes factor tests to estimate the ratio of the likelihood probability of the null and alternative hypothesis . We also checked for linear associations between uNGAL concentrations and clinical parameters of renal impairment, such as proteinuria, albuminuria, blood pressure and TKV, using Pearson's correlation. We used a significance level of alpha = 0.05.Analyses were performed with the R software  includint(26) = 0.05; P = 0.96; Bf = 0.34], weight percentiles  or height percentiles  were observed between the two groups : ±4.3; range: 4–17]) and 15 age- and gender-matched controls  participated in the study. No differences in age     . As pred = 0.02] . When co= 0.005] .2 = 2.40, P = 0.30] or diastolic blood pressure percentiles  were observed between the two groups.Among the ADPKD group, 3 patients had systolic blood pressure, diastolic blood pressure or both >90th percentile when corrected for age and height percentiles at consultation . None wet(13) = 0.41; r = 0.11; P = 0.68], ht-TKV , mean arterial pressure , proteinuria  or albuminuria  (t(12) = 2.25; r = 054; P = 0.04 and t(12) = 2.47; r = 0.58; P = 0.02, respectively]. A similar relation was observed between albuminuria and TKV or ht-TKV  as well as mean arterial pressure   is frequently proposed as an early marker for renal progression in ADPKD adult patients. Similar to a previous study conducted in the adult ADPKD population by Vareesangthip et al. , we founKawano et al.  have expIn our ADPKD group, uNGAL concentrations were compared to other clinical markers used to assess disease progression in children, such as proteinuria, albuminuria, mean arterial pressure, and TKV. No correlation was found between albuminuria, proteinuria, and uNGAL. However, significant proteinuria and albuminuria concerned only a few of our patients. Previous studies in children and adults demonstrated that proteinuria and albuminuria were associated with a more rapid progression toward more severe renal disease . HTN is n = 54) had greater protein excretion than patients with moderate disease   with ADPKD and preserved renal function where the degree of albuminuria correlated with TKV and kidney volume growth rate, measured by magnetic resonance imaging sequences ( n = 49) . When co n = 49) .TKV has been recently demonstrated as a marker of disease progression and therapeutic efficacy –16 in th2). Different urinary biomarkers were dosed and tested for an association with the estimated GFR and Ht-TKV. No association was found between uNGAL and the estimated GFR or Ht-TKV . Bring together, these observations strongly support the idea that more subjects would not have led to a significant result. Another limitation is the variability in uNGAL values observed between participants. We argue that this cannot explain the absence of a significant difference between groups for the following reasons. First, the absence of a significant difference persisted following outlier removal, using a well-described method for data exclusion (1.5-fold IQR). Second, the uNGAL values in our population were within the normal range values proposed by Bennett et al. . Thus, tGFR is usually normal in children with ADPKD , 39. In PKD1 or PKD2 mutation. We can assume that PKD1 was predominant in our patients as patients with PKD2 mutation express cysts later and PKD1 is over-represented in pediatric ADPKD population (Finally, our ADPKD population was not genetically tested to identify pulation .Our results demonstrate the absence of interest of uNGAL as an early biomarker of renal function in the pediatric population. Interestingly, we showed a significant correlation between TKV and markers of disease progression, such as proteinuria, albuminuria, and mean arterial pressure. TKV is easy, measurable and low cost and may be a surrogate marker to follow ADPKD progression disease in children. More studies on early markers of renal impairment and disease progression in children are needed.The datasets generated for this study are available on request to the corresponding author.MT and PP designed the study. MT, AW-B, and AG developed the methodology and collected the data. MT, MS, LM, and PP performed the analysis, and interpreted the results. MT and PP wrote the initial draft of the paper and all authors provided critical review, edits, and approval for the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.