The proteasome system is involved in several disorders. The 5′ untranslated region of PSMA6 gene contains a single nucleotide polymorphism (SNP) −8 C/G, associated with diabetes, myocardial infarction and coronary artery disease.We examined 584 patients with end-stage kidney disease (ESKD) and 430 controls. All were genotyped for −8 C/G SNP by polymerase chain reaction and restriction analysis.p = 0.0038). The odds ratio of 0.34 (95 % CI 0.26–0.45) suggests association of CG + GG with decreased risk of ESKD. We investigated the association between PSMA6 polymorphism and LVH present in 54 % of patients. There was a significant association of CG + GG genotype with LVH, with over 75 % of CG + GG in patients with LVH. This effect was independent from other common causes of LVH—age  and hypertension .We observed lower frequency of CG + GG genotypes in patients than in controls (20 vs. 42 %, We demonstrated for the first time that PSMA6 polymorphism might be a protective factor for ESKD. On the other hand, CG + GG genotypes are independently related to LVH in ESKD patients. End-stage kidney disease (ESKD) is a complex phenotype resulting from underlying kidney disease and interacting genetic and environmental factors. Despite rapid improvements in dialysis technology, the mortality rate in dialyzed ESKD patients is very high , 2. The The proteasome is a large multiple subunit enzyme complex that plays a central role in the degradation of intracellular proteins which control transcription rate, cell cycle progression and apoptosis , 6. It rThe PSMA6 gene is a single copy gene located on chromosome 14q13.2 . It codeIn this preliminary case–control study, we investigated an association between functional polymorphism −8 C/G in PSMA6 gene and end-stage kidney disease.2 associated with clinical signs of uremic syndrome requiring dialysis. ESKD resulted mainly from primary chronic glomerulonephritis (n = 183), diabetic nephropathy (n = 132), interstitial nephritis (n = 71) and polycystic kidney disease (n = 45).The study population consisted of 584 unrelated, consecutive adult patients on maintenance dialysis. All patients were Caucasians of Polish origin. Chronic kidney disease was diagnosed according to KDOQI  definition. ESKD was defined as eGFR < 15 ml/min/1.73 mCardiovascular disease was documented in 384 patients, as one or the combination of several pathological states: congestive heart failure, left ventricular hypertrophy, angina pectoris, ischemic heart disease, myocardial infarction, cerebral stroke or atheromatous lesions. There was a substantial overlap between categories. Left ventricular hypertrophy (LVH) was diagnosed by electrocardiography (ECG) and echocardiography. At the beginning of study, 426 patients were hypertensive and receiving antihypertensive medications. Hypertension was defined as a systolic blood pressure >140 mm Hg and diastolic blood pressure >90 mm Hg and/or use of antihypertensive medication.n = 430) were recruited mostly among hospital staff and blood bank donors who underwent health examination. All had normal electrocardiogram (ECG) and no clinical signs of CVD or renal disease. Subjects with a positive family history of renal or cardiovascular disease in first-degree relatives were excluded from the study.Healthy control subjects  polymorphism in the PSMA6 gene was analyzed by amplification of 343 bp DNA fragment by polymerase chain reaction (PCR). Genomic DNA (300 ng) was amplified using the following conditions: initial denaturation at 95 °C for 6 min, followed by 40 cycles of 94 °C for 30 s, annealing at 60 °C for 30 s and extension at 72 °C for 1 min. A final extension step was at 72 °C for 7 min. 10 μl of the PCR product was digested overnight at 37 °C with 5 U of Rsa I restriction endonuclease, and resulting fragments were separated on a 2.5 % agarose gel. The quality of genotyping was controlled by using blind DNA duplicates for random samples. In addition, 20 samples were randomly selected for each genotype and the PCR products were sequenced in CEQ8000 Genetic Analysis System . There was a 100 % concordance between genotyping assays.Χ2 test and Mann–Whitney test were used for comparing discrete and continuous variables. The Hardy–Weinberg equilibrium was assessed using a Χ2 test with 1 degree of freedom. Genotype distribution and allele frequencies were compared between groups using a Pearson Χ2 test of independence with 2 × 2 contingency and z statistics. For significant allelic and genotyping associations, the adjusted odds ratios (OR) with corresponding 95 % confidence intervals (CI) were calculated. Power calculations were performed with the program of Purcell et al. (available at http://pngu.mgh.harvard.edu/~purcell/gpc/). In the ESKD patient group, the frequency of the PSMA6 G allele was 0.10. The study had 99.4 % power (α = 0.05) to detect an association . Logistic regression analysis was performed to analyze the correlation of genotype and clinical characteristics, with adjustments for gender and age. Statistical significance was set at p < 0.05.Statistical calculations were performed using SPSS version 11.0 for Windows . For baseline characteristics, the normally distributed continuous variables are presented as mean ± SD. ANOVA, Pearson The genotypes of the −8 C/G PSMA6 gene polymorphism were determined in 584 ESKD patients and 430 healthy individuals. The demographic profile and clinical characteristics of studied ESKD patients and control subjects are summarized in Table p = 0.0038). The odds ratio 0.34 (95 % CI 0.26–0.45) might suggest an association of the CG + GG genotype with decreased risk of end-stage kidney disease.The frequencies of the genotypes and alleles in the control group were similar to those reported in other studies of European populations , 20, 21.p = 0.643) and hypertension .Left ventricular hypertrophy (LVH) is a strong cardiovascular risk marker in end-stage renal disease patients, so we also investigated the association between PSMA6 polymorphism and LVH present in 54 % of our patients Table . We obsep = 0.037 and OR 0.80, p = 0.036, respectively. In the Chinese population, the PSMA6 rs1048990 CG + GG genotype and G allele were protective factors for coronary heart disease [The ubiquitin–proteasome system and its gene polymorphisms are extensively studied, mostly in the cardiovascular field . The fun disease .Left ventricular hypertrophy is one of the major cardiovascular complications of end-stage kidney failure. Left ventricular mass increases progressively with duration of dialysis treatment, even in normotensive patients . Our stuAs most of the association studies, ours has some potential limitations. A survival and selection bias cannot be excluded in this retrospective case–control study. To limit this bias, we included consecutive patients and tried to adjust for known confounding risk factors, but the comorbidities might still represent a confounding factor. The strengths of the study are the fairly large size of studied groups and that all patients and controls are of the same ethnic origin. There was also an adequate statistical power of the study for the type I error at 0.05 (99.4 % for ESKD vs. controls and 98.1 % for LVH vs. no LVH subgroups). All subjects were examined in a standardized manner, with well-defined diagnostic criteria, and genotyping was performed blind with respect to case–control status. However, the occurrence of kidney diseases, diabetes and comorbidities such as CVD depends on the interaction among the different risk alleles, environmental factors and the lifestyle. The influence of single polymorphisms is rather small, and an interactive effect of several factors may lead to an underestimation or overestimation of a role of given polymorphism in determining the phenotype. These results might not therefore apply to populations with different genetic or environmental background.In conclusion, in this study we demonstrated for the first time that the PSMA6 gene polymorphism might be a protective factor for end-stage kidney disease. On the other hand, the CG + GG genotypes are independently related to LVH in end-stage kidney disease patients.


Chronic kidney disease (CKD) has been closely associated with hypertension and stroke. Although studies have reported the relationship between CKD and cerebral small vessel disease (SVD), the link between CKD, hypertension, and SVD is uncertain. The aim of this study was to investigate the association between CKD and SVD in patients with strictly hypertensive intracerebral hemorrhage (ICH).2]: normal kidney function (GFR ≥ 90), mild kidney disease (60 ≤ GFR < 90), and moderate to severe kidney disease (GFR < 60).142 patients with acute hypertensive ICH were enrolled in this study. Magnetic resonance imaging was performed to assess imaging markers for SVD. Patients were categorized into three CKD groups based on the degree of kidney dysfunction [glomerular filtration rate (GFR) in milliliters per minute per 1.73 mp = 0.046) as well as the prevalence rate of overall and deep cerebral microbleed (CMB) . The stage of CKD was a significant risk factor for deep white matter hyperintensity (WMH) , overall CMB , lobar CMB , and deep CMB , even after adjustment for confounders.The prevalence rate of mild and moderate to severe CKD was 50 and 14.8%, respectively. The stage of CKD was associated with history of chronic hypertension (In patients with hypertensive ICH, the prevalence of CKD is high even at the early stage of renal function impairment and is associated with the prevalence of CMB and deep WMH. These results reinforce the notion of a link between hypertensive vasculopathy, renal function impairment, and cerebral SVD. Chronic kidney disease (CKD) is defined by a decreased glomerular filtration rate (GFR) or albuminuria. Evidence has been growing on the interactions between cerebrovascular diseases and impaired renal function. Furthermore, CKD seems to be predictive of several neurological deficits and poor functional outcomes for both ischemic and hemorrhagic stroke , 2. The Primary intracranial hemorrhage (ICH) is responsible for about 15–20% of strokes in Caucasians and with incidence twice as high in the Asians . HyperteThe term cerebral small vessel disease (SVD) describes a range of neuroimaging, pathological and associated clinical features. Features of SVD on neuroimaging include white matter hyperintensity (WMH), enlarged perivascular space (EPVS), cerebral microbleed (CMB), and lacuna , 16. TheWe performed a study of magnetic resonance imaging (MRI) in 142 consecutive patients hospitalized with acute spontaneous hypertensive ICH. Patients were enrolled after ICH located in the basal ganglia, thalamus, pons, or cerebellum was confirmed by computed tomography. Patients with lobar ICH or hematomas located in atypical location of hypertensive ICH, contraindications to MRI , irritable that needs heavy conscious sedation and those who refused to consent to participate in this study were excluded. The study was part of an integrated stroke project at Chang Gung Memorial Hospital and was approved by the Institutional Review Board of Chang Gung Memorial Hospital. All patients or their families gave their written informed consent prior to participation in the study.All data were collected using a 3 T Siemens Verio MRI system  with a 32-channel head coil. All patients were scanned within 1 month after ICH . Standard sequences included axial T2*-weighted gradient echo images ; axial fluid-attenuated inversion recovery (FLAIR) images , and axial T2-weighted (T2WI) turbo spin-echo images .Four MRI markers of SVD, including WMH, EPVS, lacuna, and CMB, have been previously described , 23, 24.Demographic data (age and gender), presence of vascular risk factors , blood pressure [initial blood pressure measured at the emergency room (ER)], previous medications (antihypertensive and antiplatelet agents), as well as other laboratory and clinical assessments  were collected for all patients. Patient outcomes, including GCS score at day 7, Barthel index, and modified Rankin Scale (mRS) score at 3 months, were also estimated.2): normal kidney function (GFR ≥ 90), mild kidney disease (60 ≤ GFR < 90), and moderate to severe kidney disease (GFR < 60).Estimated GFR according to the modification of diet in renal disease study group equation was calculated for each patient . We thenPost hoc multiple comparisons were performed with Scheffe’s method to test the difference between each group. The Kolmogorov–Smirnov method was used for tests of normality and the Kruskal–Wallis one-way ANOVA test was used when the normality assumption of continuous data was not met . Categorical variables were compared using the Pearson χ2 test or Fisher’s exact test. Multivariate binary logistic regression models were used to estimate the risk factors [odds ratio (OR) and 95% confidence interval] for SVD in hypertensive ICH patients. The interobserver reliabilities between two neuroradiologists for measuring the SVDs were tested with two-way intraclass correlation coefficients (ICC) with absolute agreement. All statistical tests were two-tailed and a p value of <0.05 indicated a significant statistical difference.All statistical analyses were performed using the Statistical Program for Social Sciences (SPSS) statistical software . Continuous variables were expressed as medium and interquartile range (IQR) and were compared by performing analysis of variance (ANOVA). p = 0.033) . Clinical history of hypertension, serum creatinine level, and GFR were significantly different between groups . The outcome measurements, including GCS at 7 days as well as mRS and BI at 3 months after ICH, were not associated with stage of renal function impairment. The ICC showed high interobserver reliability for measuring overall WMH, EPVS, CMB, and lacuna . Among the four MRI markers of SVD on MRI, patients with worse stage of CKD had a higher prevalence rate of overall CMB and deep CMB . In order to exclude patients with mixed hypertensive and CAA, the associations between stage of CKD and patients with CMB of mixed location; pure deep location as well as all patients excluding those with lobar CMBs were estimated and the results showed the trends toward associations but did not reach statistical significance .The clinical and demographic details of the patients are presented in Table p = 0.001), periventricular WMH , deep WMH , overall EPVS , centrum semiovale EPVS , and basal ganglia EPVS . Male gender was a significant risk factor for overall WMH , periventricular WMH , and deep WMH . The stage of CKD was a significant risk factor for deep WMH , overall CMB , lobar CMB , and deep CMB .To estimate the risk of CKD on SVD, multivariable binary logistic regression analysis was performed to exclude the influence of confounding risk factors including age, male gender, history of diabetes mellitus, and hypertension Table . Age wasOur study confirms the findings of previous studies that reported a high incidence of CKD in patients with primary ICH. We also showed that CKD was significantly associated with a higher presence of CMB, especially deep CMB in patients with hypertensive ICH. CKD was significantly associated with both lobar and deep CMB as well as deep WMH even after adjustment for confounders.2 was 14.8% in this study, which is similar to the previous reported prevalence rates, which ranged from 11 to 46%  and the stage of CKD was associated with past history of hypertension. A plausible explanation for these observations may include a suggestion that in Asian people, hypertensive vasculopathy develops at an earlier age, thus leading to long-term atherosclerosis with lipohyalinosis and fibrinoid necrosis of both renal and cerebral arteries. Another explanation is co-existing hypertension accelerates injuries of the cerebral arteries and leads to ICH, even in patients with early CKD. This may be also true in patients of the black race since the association between CKD and the presence and number of CMB in black patients has been reported to be greater than in non-Hispanic whites .Several studies have demonstrated the association of CKD with CMB in different cohorts , 32–34. In this study, the prevalence of MRI markers of SVD other than CMB, such as WMH and EPVS, was increased with age, and the stage of CKD was only associated with deep WMH. WMH have been reported to be associated with CKD in neurologically normal subjects , 38, 39 This study had several limitations. First, we included patients with predominantly mild to moderate severity of ICH, and patients with contraindications for MRI, major comorbidities, or requirement for emergent surgical intervention were excluded, thus resulting in selection bias. Second, we excluded patients with lobar ICH but included patients with lobar CMB. This might affect the unity of the cohort for strict hypertensive ICH. To account for this confounding factor, we also presented subgroup analysis excluding patients with lobar CMB. Furthermore, we recorded patient’s history of hypertension, blood pressure, and use of antihypertensive medication at the time of enrollment, but did not estimate if the hypertension had been well controlled or not. Thus, the causality and collinearity between renal function impairment, hypertension, and SVD can’t be well evaluated. Further longitudinal studies with large cohort and close monitoring of the renal function, blood pressure, SVD and rate of stroke or ICH are necessary to clarify this point.In conclusion, the prevalence of CKD is high in patients with hypertensive ICH. Even an early stage of renal function impairment is associated with hypertensive ICH. CKD is associated with the prevalence of CMB and deep WMH in patients with hypertensive ICH. Lobar CMB has trends to be associated with the stage of CKD, which may support that severe hypertension or renal functional impairment could be responsible for ICH or CMB in the lobar location that are generally thought to be associated with CAA. These results reinforce the notion of a link between hypertensive vasculopathy, renal function impairment, and the imaging biomarkers of SVD. Further longitudinal studies are warranted to clarify how management strategies, such as control of blood pressure and renal function, will affect the dynamic change of these imaging biomarkers and the risks of ICH.The study was approved by the Institutional Review Board of Chang Gung Memorial Hospital. All patients or their families gave their written informed consent prior to participation in the study.Y-HT: literature review, manuscript writing, and tables making. M-HL, J-TY, and L-CL: clinical data collection, cases review. S-WC and H-HW: imaging analysis. ML and Y-CH: final manuscript review and editing.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. The reviewer MP and handling Editor declared their shared affiliation.


Current guidelines recommend the measurement of arterial stiffness in terms of aortic pulse wave velocity (PWV) as an important cardio-vascular risk marker. Both aortic PWV and the aortic augmentation index (AIxao) can be measured using different techniques, e.g., the Arteriograph and SphygmoCor. A new version of the software for the Arteriograph  is now available. We wanted to determine whether this improved software differs from the previous version . We compared the estimated aortic PWV (ePWVao) and AIxao measured with both versions of Arteriograph software and analysed the agreement of these values with those measured by SphygmoCor .Eighty-seven subjects without known cardio-vascular disease (23 men and 64 women) aged 54.2 ± 8.7 years  were included in the study. Estimated PWVao and AIxao were measured by both Arteriograph and SphygmoCor. We compared Arteriograph I and Arteriograph II with each other and with SphygmoCor.P < 0.001).Estimated PWVao measured by Arteriograph II was lower than that measured by Arteriograph I, while the AIxao was higher. Divergence in ePWVao values was especially noted above 9 m/s. Estimated PWVao measured by Arteriograph II  did not differ from that measured by SphygmoCor . However, the AIao measured by Arteriograph II was significantly higher (Regularly upgraded software versions resulting from continuous technical development are needed for quality improvement of methods. However, the changes in software, even if the basic patented operational algorithm has not changed, may influence the measured values as shown in the present study. Therefore, attention should be paid to the software version of the method used when comparing arterial stiffness results in clinical settings or when performing scientific studies. Arterial stiffness, measured as aortic pulse wave velocity (PWVao) is an important marker of cardio-vascular risk and has been reported to be an independent predictor of cardio-vascular morbidity and mortality . CarotidWe have previously demonstrated a good reproducibility for the AG and SC techniques, but some differences between techniques such as higher PWV values for women, highlighting the necessity to use the same type of equipment throughout scientific studies .Although measuring arterial stiffness variables, previous methodological studies have shown some divergence between the values obtained by the AG and SC techniques –13. ThisContinuous software development and improvement within the same measurement technique usually lead to updates to new versions for the same technique. These updates constitute another possible source of variation in results. Whether changes between different software versions influence the obtained values is, however, unknown since such studies are lacking.Therefore, the aim of this study was to investigate whether values of estimated PWVao (ePWVao) and the aortic augmentation index (AIxao) recalculated by a newer software version from original raw data differed from those obtained using an earlier version of the software. For this purpose, we compared results from same raw data applying two versions of AG software introduced between 2006 and 2014.We also wanted to study the agreement of ePWVao and AIxao values obtained by the new version of AG software with those obtained using SC.th-75th percentile)), renal disease, known hypertension or was taking any medication affecting the cardio-vascular system. The study group was recruited from a population of 96 participants  in a study previously described in detail [Eighty-seven non-smoking subjects (23 men and 64 women) without known cardio-vascular disease, age range 33–68 years , were included in the study. No subject had diabetes mellitus  mmol/L, median , a cuff is placed on the patient’s upper arm; pressure variations in the arm influence pressure receptors in the cuff and are transferred via an infra-red port to a computer. The systolic blood pressure (SBP) and diastolic blood pressure (DBP) in the upper arm were measured at the first cuff inflation, Arterial pulse waves measured by SC  were registered with a single high-fidelity tonometer . The tonometer connected to the SC equipment was gently pressed onto the artery of interest. The arterial pulse waves were processed by the system software, and the corresponding aortic pressure waveform was generated from the radial artery waveform using a validated transfer function , 5. The The arterial blood pressure was measured in both arms, after 30 min of supine rest, using a digital automatic blood pressure monitor . The mean values of the SBP and the DBP in both arms were calculated.th–75th percentile. The tests were two-tailed and a P-value of < 0.05 was considered significant. The Wilcoxon signed-rank sum test was used to test differences between the methods and software versions. The Bland–Altman test was used to evaluate the variability between the software versions and methods [Statistical analyses were performed using Statistica . Data are expressed as mean ± SD or median and 25 methods . In our  methods . In this2, SBP 122 ± 14 mmHg and DBP 77 ± 8 mmHg. Vascular data obtained using SC, AG I and AG II are presented in The mean body mass index (mean ± SD) of the participants was 23.6 ± 3.16 kg/mP < 0.001). No significant differences were seen for ePWVao measured by SC  and AG II . However, AIxao measured by SC  was lower compared with that measured by AG II  (P < 0.001).We found significant differences between AG I and AG II for PWVao and AIxao values  of the software. We also compared these values with those obtained using SC. Our main findings were that on average, ePWVao values obtained using the updated software version AG II were closer to the values obtained using SC than those obtained using AG I, but the scatter was not improved. Furthermore, AIxao values obtained using AG II were significantly higher than those obtained using AG I, and differed even more from the values obtained by SC. This difference might be caused by the new algorithms used in the updated AG II. The return time, RT/2, calculated with AG II was higher than that calculated by AG I; this leads to a decreased ePWVao and better agreement with values obtained using SC. Increased PWVao has been reported to be associated with a higher incidence of cardio-vascular mortality, stroke and coronary heart disease events in older adults , and preBesides software related factors that can cause errors or methodological discrepancies, there are known limitations when collecting pulse waves from carotid and femoral arteries. Obesity may cause a difficulty obtaining an adequate signal in some individuals and may also cause errors in distance measurement and estimation of transit length. The distance should be measured precisely, because small inaccuracies in centimeter may influence the absolute value of PWV. For SphygmoCor, the shorter the distance is between two recordings sites, the greater the absolute error in determining the transit time . The samThe primary determinant of augmentation index is central pulse pressure, which was not measured in this study, and is not directly reflected in peripherally measured blood pressure. Estimation of central BP through transformation algorithms therefore constitutes a potential source of error. Peripherally measured SBP is higher than aortic  SBP in young healthy individuals, while the DBP and mean blood pressure remain almost steady throughout the arterial tree . The difIn this study we compared the two most frequently used pulse wave techniques for estimation of arterial stiffness. Recently imaging techniques, such as magnetic resonance imaging have emerged that allow evaluation of arterial stiffness and may become a future reference method . ReproduThe results from our investigation should encourage further studies on variability of PWVao and AIxao measurements between different software versions of the other methods available. This would apply even for “reference” methods. From clinical and scientific communities there are also expectations on the manufacturers to provide detailed information on the characteristics of new software upgrades and possible consequences for systematic changes in measured values.An advantage of the present study was the possiblity to use the same raw data for calculations by two software versions for the Arteriograph. We did not have the possibility to do similar recalculations and compare software versions for SphygmoCor.Regularly upgraded software versions resulting from continuous technical development are needed for quality improvement of methods. However, the changes in software, even if the basic patented operational algorithm has not changed, may influence the measured values as shown in the present study. Therefore, attention should be paid to the software version of the method used when comparing arterial stiffness results in clinical settings or when performing scientific studies.S1 File(XLSX)Click here for additional data file.


Lower within-individual visit-to-visit variability in blood pressure readings in the amlodipine/perindopril combination treatment arm of the ASCOT study has been shown to account for the more effective stroke reduction rate with this combination compared to atenolol and diuretic-based therapies, despite overall similar blood pressure lowering.This finding was presented at the late-breaking clinical trial session of the American College of Cardiology congress and was published simultaneously in the Lancet Neurology edition online.1‘These findings have major clinical implications for the management of patients with hypertension’, said Peter Sever, FRCP, a professor of clinical pharmacology and therapeutics and co-director of the International Centre for Circulatory Health, Imperial College, London. ‘This data convincingly demonstrates that patients with more variation in their blood pressure levels are at greatest risk of future heart attacks and strokes, and that reducing variability is a key goal of treatment.’2For the ASCOT-BPLA study, researchers recruited 19 257 patients with high blood pressure, averaging 164/95 mmHg at rest. Patients were randomly assigned to treatment with the calcium channel blocker amlodipine with or without the ACE inhibitor perindopril, or to treatment with the beta-blocker atenolol with or without the diuretic bendroflumethiazide.During 5.5 years of follow up, blood pressure variability was determined by comparing multiple blood pressure readings taken at each visit and at several different visits.The Medical Research Council (MRC) trial of 4 396 elderly hypertensive patients treated with atenolol, a diuretic combination, or placebo, were also evaluated for blood pressure variability and the results were included in this study.3Researchers found that between-visit blood pressure variability was significantly greater among patients treated in the atenolol arm than those in the amlodipine/perindopril arm of ASCOT. In addition, when researchers compared patients at the highest one-tenth for between-visit blood pressure variability to those at the lowest one-tenth, they found a strong link with increased risk of stroke.In the beta-blocker group, patients with high blood pressure variability faced a risk of stroke 4.06 times that of those with low blood pressure variability. In the amlodipine/perindopril group, the risk of stroke was 3.8 times higher among patients with high blood pressure variability.A similar pattern linked high blood pressure variability to an increased risk for heart attack and other coronary events. The overall risk of stroke was 22% lower among patients treated with amlodipine/ perindopril when compared to those treated with the beta blocker/thiazide diuretic, a difference that could be entirely explained by differences in blood pressure variability, researchers found.In the ASCOT-BPLA trial, the researchers were also able to look at within-visit variability and variability on 24-hour ambulatory blood pressure monitoring (ABPM). In the ABPM substudy, reduced variability in daytime systolic blood pressure (SBP) in the amlodipine group (p < 0.0001) partly accounted for the reduced risk of vascular events, but reduced visit-to-visit variability in clinic SBP had a greater effect.In the MRC trial, all measures of within-individual visit-to-visit variability in SBP were increased in the atenolol group compared with both the placebo and diuretic groups during initial follow up . Subsequent temporal trends in variability in blood pressure during follow up in the atenolol group correlated with trends in stroke risk.‘The greater reduction in variability among patients treated with amlodipine and perindopril may be best explained by their more profound effects on blood vessel relaxation, compared to beta-blockers’, Sever said. He and his co-investigators believe that clinical guidelines and future drug trials must take into account the importance of blood pressure variability in the management of patients, not simply the extent to which a drug lowers average levels of blood pressure. This aspect will need to be reported on in more detail in future trials.The hypothesis that erratic blood pressure levels could be an important factor in determining the risk of future strokes was originally proposed by Peter M Rothwell, MD, PhD, of the Stroke Prevention Research Unit, University Department of Clinical Neurology, John Radcliffe Hospital, Oxford, UK.


Vasopressors are frequently used to increase blood pressure in order to ensure sufficient cerebral perfusion and oxygenation (CPO) during hypotensive periods in anaesthetized patients. Efficacy depends both on the vasopressor and anaesthetic protocol used. Propofol–remifentanil total intravenous anaesthesia (TIVA) is common in human anaesthesia, and dexmedetomidine is increasingly used as adjuvant to facilitate better haemodynamic stability and analgesia. Little is known of its interaction with vasopressors and subsequent effects on CPO. This study investigates the CPO response to infusions of norepinephrine and phenylephrine in piglets during propofol–remifentanil and propofol–remifentanil–dexmedetomidine anaesthesia. Sixteen healthy female piglets (25–34 kg) were randomly allocated into a two-arm parallel group design with either normal blood pressure (NBP) or induced low blood pressure (LBP). Anaesthesia was induced with propofol without premedication and maintained with propofol–remifentanil TIVA, and finally supplemented with continuous infusion of dexmedetomidine. Norepinephrine and phenylephrine were infused in consecutive intervention periods before and after addition of dexmedetomidine. Cerebral perfusion measured by laser speckle contrast imaging was related to cerebral oxygenation as measured by an intracerebral Licox probe  and transcranial near infrared spectroscopy technology (NIRS) .During propofol–remifentanil anaesthesia, increases in blood pressure by norepinephrine and phenylephrine did not change cerebral perfusion significantly, but cerebral partial pressure of oxygen (Licox) increased following vasopressors in both groups and increases following norepinephrine were significant . In contrast, cerebral oxygen saturation (NIRS) fell significantly in NBP following phenylephrine (P = 0.003), and following both norepinephrine (P = 0.02) and phenylephrine (P = 0.002) in LBP. Blood pressure increase by both norepinephrine and phenylephrine during propofol–remifentanil–dexmedetomidine anaesthesia was not followed by significant changes in cerebral perfusion. Licox measures increased significantly following both vasopressors in both groups, whereas the decreases in NIRS measures were only significant in the NBP group.Cerebral partial pressure of oxygen measured by Licox increased significantly in concert with the vasopressor induced increases in blood pressure in healthy piglets with both normal and low blood pressure. Cerebral oxygenation assessed by intracerebral Licox and transcranial NIRS showed opposing results to vasopressor infusions.The online version of this article (10.1186/s13028-018-0362-z) contains supplementary material, which is available to authorized users. Vasopressors are frequently used to increase blood pressure in order to ensure sufficient cerebral perfusion and oxygenation (CPO) during hypotensive periods induced by e.g. anaesthesia or septic shock –4. Two o1) and β-(β1 and β2) adrenergic-receptors, whereas phenylephrine is a highly selective α1-agonist. The cerebral veins are more sensitive to sympathetic activation than cerebral arteries, and vasoconstriction are more specifically mediated by α2 rather than α1 adrenoceptors . Following washout MAP was not significantly different to pre-treatment levels in either group (P = 1) with median differences of 1 mmHg  for LBP and 7 mmHg  for NBP.Phenylephrine administration significantly (P = 0.03) increased MAP in the LBP group  but not in the NBP group   but not norepinephrine   increased significantly following norepinephrine (P = 0.02) but not phenylephrine (P = 0.06) in the LBP group  and 11 mmHg , respectively). A similar response was observed in the NBP group with a significant increase following norepinephrine  but not phenylephrine   fell significantly in the LBP group following both norepinephrine and phenylephrine  and in the NBP group SbrO2 fell significantly following phenylephrine  but not norepinephrine  , NBP: P = 0.01, median increase 48 mmHg ]. Following washout MAP was not significantly different to pre-treatment levels in either group (P = 1.0) with median differences of − 6 mmHg  for LBP and − 1 mmHg  for NBP.Phenylephrine administration significantly increased MAP in both groups  ]  increased significantly in the LBP group following both norepinephrine and phenylephrine . In the NBP group, a similar response was seen with significant increases seen following norepinephrine  and phenylephrine   did not fall significantly in the LBP group following either norepinephrine  or phenylephrine . In contrast, the NBP group experienced significant decreases following both norepinephrine  and phenylephrine   was found to increase during vasopressor challenges when assessed by Licox, while cerebral oxygen saturation (SbrO2) decreased when assessed by NIRS. Cerebral perfusion (LSPU) was not found to change significantly in concert with the vasopressor induced increases in MAP. This pattern of findings was similar in both groups and during both TIVA protocols  and cerebral partial pressure of oxygen values (PbrO2) are not directly comparable in absolute values, since NIRS reflects levels of oxygen-saturated haemoglobin in the venous, capillary and arterial blood [brO2 in the grey matter of the cerebral cortex, whereas Licox measures PbrO2 in the less metabolically active white matter of the CNS, areas with different metabolic activity and blood flow [The increase in Pd brains  and traud brains . In the s in CBF . Decreasups Fig. a, b. Thenephrine  or phenynephrine , 52, 53 pressure , 55. Sompressure , while opressure , 56–59. al blood  and Licoal blood , 61, 62.al blood , 63. Traal blood , was notood flow , 66.The differences in cerebral oxygenation assessment by Licox and NIRS could indicate that vasopressor treatment affects the cortex and the white matter differently. Whether this is a normal response attributable to a preserved cerebral autoregulation  or relatIn summary, the CPO response to vasopressor challenge in piglets was found to be qualitatively similar for the two TIVA protocols used, and the concern regarding the potential additive vasoconstrictive effect of dexmedetomidine during vasopressor infusions could not be confirmed in this study.The current study was strengthened by omission of premedication on the day of experiment, by avoiding a possible vasoactive effect of premedication on CPO, and by using animals of the same sex and with a narrow age span since both age and gender may influences CBF in porcine models –70. The aCO2 (represented by EtCO2 in this study) might however have increased the variability of the perfusion data, which would make the non-significant findings expected. In general, PbrO2 showed greater variability and a tendency to increase in the NBP group than in the LBP group, especially after addition of dexmedetomidine. Finally, the supplemented inspiratory oxygen levels were also relatively high in this study, with a FiO2 of 0.8 for all animals  increased the risk of type II error. Confidence intervals were therefore reported for both significant and non-significant changes, permitting a more nuanced interpretation.Non-significant P values following Holm-Bonferroni correction were noted for several parameters despite their confidence intervals for the change in medians not including zero. The small sample size and large variability for some parameters ; NIRS: Near infra red spectroscopy; LSCI: Laser speckle contrast imaging; MAP: mean arterial pressure; EtCO2: End-tidal carbon dioxide; FiO2: Fraction of inspired oxygen; (T): data corrected for body temperature; PaCO2: Partial pressure of arterial carbon dioxide; PaO2: Partial pressure of arterial oxygen; HCO3: Hydrogen bicarbonate; Hct: Haematocrit; THbc: Total haemoglobin concentration.


Delayed graft function is a main complication after deceased donor kidney transplantation that adversely affects graft outcome. Difficulties in prediction and early detection of delayed graft function have hindered the ability to perform proper therapeutic interventions. We investigated whether measuring urinary interleukin 18 and neutrophil gelatinase-associated lipocalin as markers of ischemia reperfusion injury could predict delayed graft function in deceased donor kidney transplant patients.We studied 69 patients undergoing kidney transplantation from deceased donor during early October 2013 to December 2014 at the Urology Research Center, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran. Serial urine samples at 2, 24, and 48 h after transplantation were analyzed for interleukin 18 and neutrophil gelatinase-associated lipocalin levels.P=0.003), 24 (P<0.001) and 48 h (P=0.018) points. The levels of neutrophil gelatinase-associated lipocalin to urine creatinine ratio were significantly higher in the group with delayed graft function at the 24 (P=0.004) and 48 h (P=0.015) points. The receiver–operating characteristic curve analysis suggested that both urinary biomarkers at 24 h after transplantation had better accuracies for prediction of delayed graft function. In multivariate analysis, only urinary interleukin 18 to urine creatinine ratio improved the ability of clinical model for predicting delayed graft function.Thirteen patients (18.9%) developed delayed graft function. Urine interleukin 18 to urine creatinine ratio was significantly higher in patients with delayed graft function compared to those with non-delayed graft function, at 2 (Urinary interleukin 18 to urine creatinine ratio at 24 h post-transplantation, along with traditional markers such as relative fall in serum creatinine, urine output and other risk factors for delayed graft function, increased the ability to predict delayed graft function. Kidney transplantation is a cardinal method and the most cost-effective treatment modality for patients with end-stage renal disease . IschemiAccording to the United States Renal Data System (USRDS) in 2009, the incidence of DGF in deceased donor kidney transplants ranges from 20% for standard criteria donors to 31% for extended criteria donors . Different definitions based on creatinine, urine volume, and the need for dialysis have been provided for DGF, the most common of which is the need for dialysis in the first week after transplantation. The dependence of DGF diagnosis on non-critical variables such as creatinine and medical decision-making on the need for dialysis has made DGF diagnosis a big challenge for kidney transplants to date. Although various scoring systems have been designed to predict DGF according to the donor and recipient parameters , replaciThere is not enough information on which biomarker has a better predictive value, time of measurement, and cut-off value. In addition, previous studies have been conducted among different populations, in terms of the cause of brain death and duration of cold ischemia. Therefore, we aimed to evaluate the role of urinary biomarkers in predicting DGF, among patients undergoing kidney transplantation from a deceased donor.This prospective cohort study was carried out on adult patients undergoing first time kidney transplantation, from deceased donors during early October 2013 to December 2014 at the Urology Research Center, Sina Hospital, Tehran, Iran with the aim of evaluating the role of urinary biomarkers in predicting DGF. The study was approved by the Ethics Committee of Tehran University of Medical Sciences and the patients were enrolled after giving written informed consents. Patients with graft impairment caused by renal artery thrombosis or bleeding from the graft vascular anastomosis were excluded.The primary endpoint was DGF. Delayed graft function was defined by need for dialysis within the first week after transplantation or when serum creatinine level decreased by less than 10% per day immediately after transplantation. To measure the levels of urinary biomarkers at 2, 24, and 48 h after transplantation, 5 ml of urine samples were collected directly from the patients’ catheters. The urine samples were centrifuged at 5000 × g at room temperature and stored at -80 °C. The IL-18 and NGAL levels were measured in a blind approach to patients’ information using the Human IL-18 ELISA Kit and Human NGAL ELISA Kit . The inter-assay variability coefficient was less than 12% for the biomarkers. Urinary biomarkers were normalized to urinary creatinine concentration, in order to account for the differences in glomerular filtration rate and resultant urinary flow.The immunosuppressive regimen involved induction with daily anti-thymocyte globulin (ATG), at a dose of 1 mg/kg for 5 d, followed by triple-drug immunosuppressive therapy. All patients received methylprednisolone 500 mg intraoperatively, 250 and 100 mg on the second and third day post-transplant, then converted to prednisone and tapered to 5 mg daily after several months. Mycophenolate mofetil was administered at a dose of 1g twice daily, starting the day of transplantation. Oral administration of cyclosporine started after transplantation at a dose of 6 mg/kg/day, divided twice daily.The clinical data were collected from the patients’ records and the National Kidney Transplantation Registry database. Recipient variables included age, sex, body mass index, cause of end-stage renal disease, time on dialysis pre-transplantation, hemodialysis time before transplantation procedure, daily serum creatinine until discharge and daily urine output within the first week after transplantation. Donor variables included age, sex, cause of brain death, serum creatinine and duration of cold ischemia.t tests or cross-tables and Fisher’s exact test. If the statistical assumptions for parametric analysis of interval variables were not met, Mann–Whitney’s two-independent samples test was used. The biomarker levels between patients with DGF, and non-DGF were compared using unpaired two-sample t tests. The receiver–operating characteristic (ROC) curve analysis was performed to compare the accuracy of IL-18, and NGAL at each time point, for the prediction of DGF. The associations between biomarkers and DGF were evaluated in a multivariate logistic analysis while adjusting the variables selected by univariate analysis and risk factor for DGF. Multivariate stepwise multiple logistic regression and integrated discrimination improvement (IDI) analyses were performed to assess added values of urinary biomarkers for predicting DGF. A value of P<0.05 was considered statistically significant. Analyses were conducted using the SPSS version 19 . IDI has been calculated using the package PredictABEL in R .Patient demographic information and baseline characteristics were summarized using descriptive statistics. The recipient, donor, and transplant parameters were compared using unpaired two-sample Seventy-five (75) patients were enrolled in this study. Of these, six patients were excluded due to surgical site/anatomical complications. The characteristics of donors and recipients, as well as findings in patients DGF and non-DGF are given in In this study, urine was selected as a source for determining graft function biomarkers, although it was not possible to determine the levels of urinary biomarkers before transplantation, since the majority of the patients were anuric or oliguric. Two patients with DGF had post transplantation anuria so were excluded from multivariate analysis because of the absence of urinary sample.P=0.003), 24 (P <0.001) and 48 h (P=0.018) after transplantation. The levels of NGAL to urine creatinine ratio (NGAL/Cr) were significantly higher in the group with DGF at the 24 (P=0.004) and 48 h (P=0.015) points (The mean urine IL-18 to urine creatinine ratios (IL-18/Cr) were significantly higher in patients with DGF compared to those with non-DGF, at 2  points . From thROC curve analyses were performed to determine which biomarker and time point was a better predictor of DGF. Logistic regression models and integrated discrimination improvement (IDI) analysis were used to assess the added value of 24 h post-transplant urinary IL-18/Cr and NGAL/Cr to clinical variables in prediction of DGF. First, variables including the first 24 h UOP, the relative fall in serum creatinine at 24 h post-transplant, and standard risk factors for DGF  entered as a clinical model . Next, IDelayed graft function is associated with worse long-term graft outcome . Timely In this research, the incidence of DGF was 18.9%, but according to USRDS in 2009, the rate in patients undergoing transplants from deceased donors has been between 20 and 31% (Based on ROC analysis, urinary IL-18/Cr and NGAL/Cr were better at discriminating DGF from non-DGF at 24 h. When AUCs of urinary NGAL/Cr and IL-18/Cr for 24 h in our study were compared with the results of the previous studies -13, urinAdding IL-18/Cr, significantly improved the prediction of the clinical model for the diagnosis of DGF, but NGAL/Cr did not improve the prediction ability of the model. This is in contrast to previous studies where the 24 h urinary NGAL/Cr, increased the ability of clinical variables to predict DGF , 12-15. The small sample size is the main limitation of this study. The DGF was determined in the first week after transplantation based on the need for dialysis. However, the clinical judgment of practitioners on the need for dialysis may overestimate the rate of DGF and result in a possible bias.A measure of IL-18/Cr at 24 h post-transplantation, along with traditional markers such as relative fall in serum creatinine, UOP and other risk factors involved in DGF, increased the ability to predict DGF. Measuring urinary NGAL/Cr at 24 h post-transplantation did not help in the diagnosis of DGF. In this study, the concurrent measurement of urinary IL-18/Cr and NGAL/Cr than IL-18/Cr alone, did not lead to an increase in the predictive power of DGF.


So far, there is no sufficient evidence to support the routine monitoring of rSO2c during general surgical procedures in children. We aimed to find out the frequency of cerebral desaturation 20 % or more from baseline and to identify possible predictors of change in cerebral oxygen saturation during neonatal and infant general surgery.Cerebral oxygen saturation (rSO2), heart rate (HR), endtidal CO2, expired fraction of sevoflurane and rectal temperature were recorded. The main outcome measure was rSO2c value drop-off ≥20 % from baseline. Mann-Whitney U-test, chi-squared test, simple and multiple linear regression models were used for statistical analysis.Forty-four infants up to 3 months of age were recruited. Before induction of anesthesia, two pediatric cerebral sensors were placed bilaterally to the forehead region and monitoring of regional cerebral saturation of oxygen was started and continued throughout the surgery. Simultaneously, mean arterial blood pressure (MAP), pulse oximetry (SpO2c from baseline occurred in 8 (18.6 %) patients. There were no differences in basal rSO2c, SpO2, HR, endtidal CO2, expired fraction of sevoflurane and rectal temperature between patients with and without desaturation 20 % or more from baseline. But the two groups differed with regard to gestation, preoperative mechanical ventilation and the use of vasoactive medications and red blood cell transfusions during surgery. Simple linear regression model showed, that gestation, age, preoperative mechanical ventilation and mean arterial pressure corresponding to minimal rSO2c value during anesthesia (MAPminrSO2c) were associated with a change in rSO2c values. Multiple regression model including all above mentioned variables, revealed that only MAPminrSO2c was predictive for a change in rSO2c values  -0.28 (−0.52–(−0.04)) p = 0.02).Forty-three infants were analyzed. Drop-off ≥20 % in rSOCerebral oxygen desaturation ≥20 % from baseline occurred in almost one fifth of patients. Although different perioperative factors can predispose to cerebral oxygenation changes, arterial blood pressure seems to be the most important. Gestation as another possible risk factor needs further investigation.NCT02423369. Retrospectively registered on April 2015.The international registration number The online version of this article (doi:10.1186/s12871-016-0274-2) contains supplementary material, which is available to authorized users. Due to improved medical care many seriously ill neonates and infants survive. However, adverse neurodevelopmental outcome of survived infants still exists , and theThe assessment of adequate cerebral perfusion in small children is commonly based on routine clinical parameters, whereas, invasive measurement techniques requiring central venous and/or arterial catheter access, such as jugular bulb oxygen saturation or central venous saturation are quite risky . SeveralPerioperative period in newborns and infants carries the risk of cerebral perfusion disturbances due to potential hemodynamic or metabolic derangements as a consequence of patient, surgery and anesthesia-related factors . FurtherThis prospective observational study was performed in Lithuanian University of Health Sciences, Kaunas Clinics, the department of Anesthesiology from 2013 May to 2015 November. Ethics approval was obtained from the Local Ethics Committee . The patients described in this study constitute the part of the patients of the internationally registered study no NCT02423369. Informed written parental consent was obtained before enrollment of every patient.th class. Patients were fasted as indicated by the surgical condition or according to ASA fasting recommendations appropriate for age. After arrival to the operating room, continuous electrocardiography, pulse oximetry (SpO2), non-invasive blood pressure monitoring was started before anesthesia as per standard of care. All patients underwent general anesthesia with tracheal intubation and controlled ventilation. Anesthesia was induced with an inspired fraction of sevoflurane up to maximum 6 in 50 % O2/air. Muscle relaxants were administered to facilitate orotracheal intubation (7 patients were on positive pressure ventilation before surgery). Anesthesia was maintained with sevoflurane up to 1 minimal alveolar concentration, additional doses of fentanyl (1 mcg∙kg−1) and muscle relaxant. During anesthesia positive pressure controlled ventilation using circle breathing system was performed to maintain endtidal CO2 (etCO2) between 35 and 45 mmHg, whenever possible; positive end-expiratory pressure of 4 mmHg was used in all patients. Intraoperative infusion therapy was given as per standard of care and consisted of 5 % glucose 4 ml∙kg−1∙hour−1 and isotonic crystalloid 6–20 ml∙kg−1∙hour−1. According to the decision of responsible anesthesiologist hemodynamic support with additional boluses of isotonic crystalloid 10 ml∙kg−1 and/or vasoactive medications were administered based on assumption that hypotension was defined as mean arterial blood pressure (MAP) less than gestational age in weeks for premature newborns and less than 38 mmHg for term newborns and infants [We recruited 44 term and preterm infants younger than 3 months old, undergoing general, thoracic or urologic surgery for congenital anomalies or disease. Exclusion criteria were: cardiac surgery, any evidence of neurosurgical disease, sepsis, renal or hepatic insufficiency, hyperbilirubinemia and physical status of the patients corresponding to American Society of Anesthesiologists (ASA) classification 5 infants . Blood p2c). Before induction of anesthesia, two pediatric cerebral sensors were placed bilaterally to the forehead region and rSO2c monitoring started. Data were captured with a sampling interval of 5 s and when stable for a period of 1–2 min, baseline value was noted. Throughout the surgery rSO2c monitoring was used continuously with information recorded every 5 min. Simultaneously, MAP, HR, SpO2, etCO2, expired fraction of sevoflurane and rectal temperature were recorded. As the rSO2c monitoring is not a standard care in our unit, clinical decisions during anesthesia were not based on rSO2c readings. After surgery, NIRS sensors were removed, and all patients were transferred to the intensive care unit for artificial lung ventilation, sedation and analgesia.A near-infrared spectrometer  was used for measurement of regional cerebral saturation of oxygen  rSO2c value of every patient, when SpO2 was ≥90 % for premature newborns and ≥94 % for term newborns and infants [2c value drop-off 20 % or more from baseline [2c value drop-off 20 % or more from baseline formed desaturation group. The normal group was formed from the patients without this criterion. Repeated measures analysis of variance (ANOVA) was used to compare normally distributed (Kolmogorov-Smirnov test) rSO2c values during anesthesia in normal and desaturation groups.Mean rSO infants  was compbaseline . Patient2, etCO2, expired fraction of sevoflurane and rectal temperature was calculated for each patient.Mean intraoperative value of MAP, HR, SpOU-test. Categorical variables were summarized using frequencies and percentages (%) and compared between the groups using chi-squared test. Spearman correlation coefficient was calculated to demonstrate the relationship between % change in cerebral oxygen saturation and MAP corresponding to minimal rSO2c value during anesthesia (MAPminrSO2c). Parametric t-test, was used to compare normally distributed (Kolmogorov-Smirnov test) cerebral oxygenation values corresponding to MAP values during anesthesia.As some demographic, preanesthetic and anesthetic characteristics of patients were distributed abnormally nonparametric statistics was used. Continuous variables were summarized using median  and compared between the groups  using Mann-Whitney minrSO2c were included into a simple linear regression model as predictive factors for a % change in cerebral oxygen saturation during surgery. As all included parameters were significant for a % change in cerebral oxygen saturation, they all were included into multiple linear regression model. Regression coefficients β and 95 % confidence intervals were calculated.Patient demographic characteristics (variables) , preoperative mechanical ventilation and MAPThe level of statistical significance was set at 0.05. All statistical tests were two-sided. The statistical analysis was performed by using IBM SPSS statistical software (SPSS v.20 for Windows).2 (<90 %), thus 43 (14 preterm and 29 term) infants were analyzed. Demographic and clinical characteristics of the patients are shown in Table Forty-four patients were enrolled in this study. One patient was excluded due to the low mean perioperative SpO2c from baseline during surgery was (−12.1) (+12.7–(−36.6)) %. Drop-off 20 % or more from baseline occurred in 8 (18.6 %) patients (desaturation group). In desaturation group absolute minimal rSO2c value was 66 % (41.5–71 %), whereas in normal group was 76.5 % (60.5–90 %); (p = 0.0004). In desaturation group duration of desaturation ranged from 5 to 90 min. Absolute minimal rSO2c value below 50 % for a period of 50 min was observed in one infant, who had basal rSO2c of 65.5 %. With regard to % change from baseline in normal (mean 9.27 %) and desaturation (mean 26.15 %) groups, and combined standard deviation 9.9 %, statistical power of our study was calculated to be 0.989.Median (range) % change in rSO2c values during anesthesia in normal and desaturation groups are shown in Fig. p = 0.041) by ANOVA).Intraoperative rSO2c values and the majority of anesthetic parameters were not different between the groups compared. The groups differed with regard to gestation, weight, preoperative mechanical ventilation and intraoperative use of vasoactive drugs and red blood cell transfusions.Comparison of demographic and clinical characteristics between infants with and without cerebral oxygen desaturation events is shown in Table minrSO2c was included into simple linear regression model as a predictor. Simple linear regression model showed, that all included predictors were associated with a % change (decrease) in rSO2c values during surgery compared to baseline (Table a)). However, multiple regression model revealed that only MAPminrSO2c was predictive for a % change (decrease) in rSO2c values (Table b)). Relationship between % change in rSO2c values during surgery and MAPminrSO2c is shown in Fig. 2c values were higher than rSO2c values when MAP ≤30 mmHg ) . The use of intraoperative vasoactive agents and red blood cell transfusions were not included because were applied in response to reduced circulation. Instead, MAPp = 0.000). Two of these patients were premature, all three had undergone cardiorespiratory resuscitation after birth. Two patients from normal group subsequently died due to unfavorable course of surgical disease.On the in-hospital follow-up which ranged from 14 days until 6 months decline in neurological function  was observed in 3 patients in desaturation group, compared to none in normal group  for a period of 50 min and a simultaneous hypotension  for a period of 80 min. In the early postoperative period subependymal hemorrhages were noticed bilaterally, but, improving over time. Long term outcome, though, of this patient is still unknown.The great majority of our patients were term and preterm neonates under 28 days of life. Appropriate blood pressure in neonates still remains a question for debate. We observed that NIRS values were lower, when MAP was 30 mmHg or less, compared to higher MAP values , respiratory insufficiency due to increased intraabdominal pressure (n = 2), obstruction of the upper airway by tumor (teratoma) (n = 1). This might be a possible cause for bias as low rSO2c values could be linked with artificial ventilation especially when airway pressures are high, as was demonstrated in infants with respiratory distress syndrome [During neonatal and infant anesthesia important issue is appropriate pulmonary ventilation as cerebral blood flow is affected by blood PaCO2 levels . We aimesyndrome –21. Preo2c monitoring is not a standard care in our unit, clinical decisions during anesthesia were not based on rSO2c readings. However, cerebral oxygenation monitoring was not blinded, therefore we cannot exclude that it might have influenced anesthesia management in certain cases.Important finding is that there were differences in anesthesia management between patients with and without cerebral oxygen desaturation 20 % and more from baseline. More patients in desaturation group received vasoactive agents and red blood cell transfusions compared to normal group patients. As the rSO2 in small children is not accurate. Blood gas analyses to assess PaCO2 would have been more precise. However, due to the ease of application and non-invasive character etCO2 is a part of standard monitoring during anesthesia. 2. We recorded data every 5 min, although rSO2c values were captured every 5 s. Therefore, we might have missed short desaturation episodes during anesthesia. 3. We performed rSO2c monitoring only in the forehead region and did not register oxygenation of other tissues, thus we could not compare overall tissue oxygenation to cerebral tissue oxygenation. However, blood lactate concentration did not differ between patients in normal and desaturation groups pre- and post-operatively, implying that overall perfusion was similar in both groups.The major limitation of our study is that our patient population was not homogenous. Although all patients were hemodynamically stable before surgery, they were different regarding gestation and age, and birth history, the known risk factor of cerebral lesions in infants . Thus, nCerebral desaturation ≥20 % from baseline may occur in almost one fifth of patients. Recognition and avoidance of risk factors for potential decrease in cerebral oxygenation is the crucial task for every anesthesiologist. Although different perioperative factors can predispose to cerebral oxygenation changes, arterial blood pressure seems to be the most important. We were not able to provide strong evidence, but prematurity, as another possible risk factor cannot be ignored. Therefore, further studies are required to clarify this issue and to link cerebral desaturation episodes to patient outcome.


COPD and asthma are important chronic inflammatory disorders with a high associated morbidity. Much research has concentrated on the role of inflammatory cells, such as the neutrophil, in these diseases, but relatively little focus has been given to the endothelial tissue, through which inflammatory cells must transmigrate to reach the lung parenchyma and cause damage. There is evidence that there is an abnormal amount of endothelial tissue in COPD and asthma and that this tissue and its’ progenitor cells behave in a dysfunctional manner. This article reviews the evidence of the involvement of pulmonary endothelium in COPD and asthma and potential treatment options for this. Chronic obstructive pulmonary disease (COPD) is an important smoking related condition with 10.1% prevalence (with Forced expiratory volume in one second (FEV1) < 80%) in adults over 40 years worldwide . COPD isAsthma is a chronic respiratory condition characterised by variable airflow obstruction and airway hyper-responsiveness (AHR) in the presence of typical symptoms such as wheeze or cough . ApproxiBoth asthma and COPD are disorders associated with increased inflammation , 8. Ther2 [The pulmonary vasculature is critical to gas exchange in the lung, with a total pulmonary vascular surface area of 90m2 . Endothe2 . Finally2 , 13. A dTransendothelial migration (TEM) is a mechanism by which the endothelium may play a role in asthma or COPD. Neutrophils play an important role in the inflammatory response in COPD . In ordeTEM appears to be upregulated in COPD and macrophage-1 antigen (MAC-1), a protein involved in TEM is upregulated in neutrophils from COPD patients . MAC-1 bTEM also appears to be of importance in asthma. For example, mice deficient in cell adhesion molecules L-selectin and ICAM-1 show a reduced influx of inflammatory cells into the lung and a reduction in AHR on exposure to an ovalbumin challenge . In addiThe absolute level of adhesion molecules may not be the only factor of importance in TEM in asthma. Different alleles of adhesion molecules may predispose to asthma. For example the PECAM-1  125 Val/leu polymorphism is more frequent in asthma patients in comparison with controls .In addition to inflammation and endothelial dysfunction, another possible mechanism of increased TEM in asthma is upregulation of chemokines. Endothelial cells in asthma appear to increase production of chemokines to attract and activate circulating eosinophils. For example, Eotaxin messenger ribonucleic acid (mRNA) expression is increased in endothelial cells from bronchial biopsy specimens in asthmatic patients and levels are associated with AHR . PulmonaIn summary, TEM appears to be upregulated in obstructive lung diseases and an increase in endothelial adhesion molecules is seen in both COPD and asthma. This is likely to play a role in the increased influx of inflammatory cells seen in both conditions and therefore may be important in the development of inflammation and the pathogenesis of obstructive lung disease.Apoptosis (programmed cell death) is a highly ordered process which eliminates damaged or unwanted cells . In the Animal studies provide support for apoptosis of endothelial cells resulting in emphysema. For example, it is possible to induce emphysema in rodents by deliberately causing endothelial apoptosis by blockade of vascular endothelial growth factor (VEGF) . When thIn addition to VEGF other mechanisms have been proposed for the development of endothelial apoptosis in COPD patients. For example, Noe et al. demonstrated that Cystic Fibrosis Transmembrane Regulator (CFTR) in human pulmonary endothelial cells was required for stress-induced apoptosis. CFTR inhibition resulted in the attenuation of endothelial apoptosis in response to treatment of cells with staurosporine or hydrogen peroxide . Alpha-1Whole lung gene expression studies which have demonstrated that gene expression appears to differ between emphysematous tissue and normal lung have shown that angiogenesis-related genes are down-regulated in emphysema. Also, SERPINF1 (an antiprotease) was elevated in severe emphysema and this acts as an angiogenesis inhibitor by inducing endothelial cell apoptosis . TherefoIn conclusion, vascular atrophy due to endothelial apoptosis may contribute to the destruction of alveoli and consequently the development of emphysema. It may therefore be an important mechanism of COPD pathogenesis in this subgroup of patients.Senescent cells are unable to progress through the cell cycle and divide, but remain metabolically active . SenesceA reduction in endothelium in patients with emphysema may be caused by reduced levels of Vascular Endothelial Growth Factor (VEGF) . VEGF isInterestingly, similar studies looking at the expression of HIF-1α and VEGF in patients with chronic bronchitis (rather than emphysema) have shown HIF-1α and VEGF are increased in this patient group . This suThere is also evidence that vasculature may be altered in the airways of patients with COPD, in addition to their peripheral lung tissue – several groups have shown an increased vascular area in the airways of patients with COPD , 53. It Patients with asthma also demonstrate increased VEGF expression in a similar way to chronic bronchitis patients. For example, VEGF mRNA levels are increased in endobronchial biopsies in patients with asthma in comparison to normal controls . VEGF isAgain, in a similar way to chronic bronchitis, patients with asthma have increased vasculature in their airways which might be important in the development of airway narrowing . BronchiIn addition to altered levels of endothelium in patients with COPD, the endothelium appears to behave in a dysfunctional manner. Endothelial dysfunction is defined as disturbed endothelial dependent vasodilatation. It results in a breakdown of the microvascular endothelial barrier and loss of the anti-adhesive and anti-thrombotic functions of the endothelium . Animal Endothelial dysfunction was previously measured by arterial catheterization to identify the response of the artery to acetylcholine. Patients with endothelial dysfunction respond with vasoconstriction rather than vasodilatation as expected . HoweverIn addition to FMD endothelial dysfunction can also be measured by serum markers. For example, one can look at the blood level of von Willebrand factor (vWF) as an indication of endothelial dysfunction . This isNitric oxide (NO) is reduced in endothelial dysfunction due to a reduction in production and/or inactivation of NO synthase by ROS . Maricic123I-metaiodobenzylguanidine (123I-MIBG) is an analogue of guanethidine and is actively taken up and metabolized by the lungs through a sodium-dependent channel into the pulmonary endothelium. Therefore, scintigraphic analysis of 123I-MIBG in the lungs can be used to provide information on how well the pulmonary endothelium is functioning. The washout rate of 123I-MIBG is reduced in COPD patients suggesting injury to the microvascular pulmonary endothelium. Interestingly 123I-MIBG washout rate was also correlates with the severity of COPD (using FEV1 and DLCO) providing further support for endothelial damage underlying COPD development [elopment .Finally, endothelial dysfunction of the airways can be measured specifically using airway blood flow (Qaw) measurements which should increase in response to inhaled albuterol. Patients with COPD have reduced response to albuterol suggesting endothelial dysfunction in their airways. The responsiveness to albuterol does increase after exposure of fluticasone/salmeterol for 4–6 weeks suggesting that current inhaled therapy might help improve underlying endothelial dysfunction .It is known that the prevalence of cardiovascular disease in patients with COPD is greater than controls. The risk of cardiovascular mortality also appears to be increased in COPD patients . It is nThe evidence for endothelial dysfunction in asthma is not as great as that in COPD. However, one study has demonstrated that asthma patients have reduced FMD levels in comparison to controls . FMD wasQaw is increased in patients with asthma which is likely related to the increased vascularity seen in the airways in asthma –95. HoweEndothelial progenitor cells (EPCs) act to repair endothelial injury and replace dysfunctional endothelium after being mobilized from the bone marrow to circulating blood . TherefoThere is also evidence that EPCs do not function normally in patients with COPD. EPCs isolated from COPD patients had reduced proliferation rates and formed fewer clusters in vitro compared to control patients. EPCs from COPD patients had reduced chemotaxis levels and were less able to form tubular structures (in Matrigel angiogenesis studies) than control EPCs suggesting that their ability to repair endothelium was reduced. Expression of platelet/endothelial cell adhesion molecule-1 (PECAM-1), an adhesion molecule necessary for endothelial migration and junctional integrity on the surface of EPCs was also reduced in COPD patients further suggesting their dysfunctional nature. This was supported in animal studies by the same group who showed that fewer EPCs from COPD patients attached to injured arterial intima in mice compared to controls . Human sIn contrast to COPD EPCs appear to be upregulated in patients with asthma . EPCs deSmoking is known to have widespread effects on the microcirculation and may result in microvascular disease in various organs such as the eye, heart and kidney . It has Angiopoietins and their receptors (Tie-1 and Tie-2) are involved in the late phases of angiogenesis. Angiopoietin 1 (Ang-1) is proangiogenic and acts in the development of vascular networks . Ang-2 aAngiopoietins also appear to play a role in asthma. Levels of both Ang-1 and Ang-2 in sputum are increased in stable asthmatic patients in comparison to controls. Smoking also increased angiopoietin levels in the asthma group . AngiopoIn conclusion, the endothelium appears to behave in an abnormal fashion in COPD and asthma. Multiple pathways involving the endothelium may have importance in both conditions. In some cases such as TEM, pathways appear to behave in a similar fashion in COPD and asthma. However, other pathways behave differently depending on the phenotype of the patient. For example, increased angiogenesis in asthma/chronic bronchitis and decreased angiogenesis in emphysema. A summary of the mechanisms involved in endothelial dysfunction in COPD and asthma can be seen in Fig. Endothelial dysfunction may be a result of the increased levels of oxidative stress seen in COPD. Patients with COPD and low levels of FMD show improvements in FMD when given anti-oxidants . The RhoAs systemic inflammation is increased in COPD patients studies have been performed to investigate whether the level of inflammation seen in these patients is related to endothelial dysfunction. Eickhoff et al. demonstrated that FMD was associated with C-reactive protein and leukocyte levels suggesting an underlying association between inflammation and endothelial dysfunction . HoweverInsulin resistance may also have a role in the development of endothelial dysfunction in patients with COPD. One study followed up COPD patients over the course of a year. During this time FMD decreased and fasting blood glucose increased. FMD was significantly negatively correlated with fasting blood glucose suggesting that patients with worse glucose control also had worse endothelial function . InteresThere is a lack of evidence for why patients with asthma might develop endothelial dysfunction. However, one study demonstrated that vascularity in bronchial biopsy specimens was reduced in asthma patients after a 6 month course of inhaled corticosteroids (ICS) . This suMany of the above pathways have potential treatments associated with them. For example, as above, patients with COPD and reduced FMD have shown improvement in FMD with the use of anti-oxidants . Ginkgo It is possible that some of the treatments already available for COPD might be able to improve endothelial functioning. For example, one study observing endothelial function in COPD patients demonstrated that patients with improved 6MWT scores had improved FMD levels . TherefoOther studies have focused on treating the increased levels of endothelial apoptosis seen in patients with emphysema. For example, one study demonstrated that CSE induced apoptosis and decreased prostacyclin synthase levels in human umbilical vein endothelial cells (HUVECs) in vitro . ProstacAs previously mentioned, targeting the inflammation seen in asthma using ICS can reduce VEGF expression and airway vascularity , 132. AnAnother potential treatment option is to target EPCs in asthma. When a chemokine receptor antagonist (AMD3100) was given to mice sensitized to ovalbumin airway pulmonary EPCs, eosinophil accumulation, vascularity and AHR was reduced . HoweverFinally, reducing TEM may be another treatment option for patients with asthma. Theophylline (a methylxanthine drug with bronchodilator and anti-inflammatory properties) was added to HUVECs in vitro. This reduced adhesion of eosinophils to the HUVECs and also reduced the expression of endothelial adhesion molecules such as ICAM-1 . This suPulmonary endothelium in asthma and COPD patients appears to be altered in comparison to control subjects. There is evidence that in some COPD patients with the subtype of emphysema apoptosis of the endothelium may result in alveolar destruction and reduced gas transfer. In patients with asthma or chronic bronchitis increased VEGF and vascular remodelling in the airways may have a more important role. The endothelium also behaves in a dysfunctional manner in COPD and endothelial progenitor cells appear to be less effective at repairing the damaged and dysfunctional endothelial tissue. There is some evidence that endothelial dysfunction also occurs in asthma and endothelial progenitor cells are upregulated in these patients.Multiple mechanisms such as inflammation may explain the underlying alteration in the endothelium in these patients and some already existing treatments could target these mechanisms and improve underlying endothelial function. Very few studies looking into treatment of endothelial dysfunction in COPD and asthma exist and more work is required to evaluate whether or not mechanisms of endothelial dysfunction researched in vitro will lead to promising treatment strategies in COPD and asthma.


Kidney impairment constitutes severe risk for cardiovascular disease, stroke and all-cause mortality, and early identification and prevention of kidney impairment is critical to effective management of prognostic risk in community residents. Previous studies have validated that carotid-femoral pulse wave velocity (cfPWV) is a significant factor associated with chronic kidney disease. However, whether cfPWV is associated with moderately reduced glomerular filtration rate (GFR) remains unclear. This analysis was designed to examine the association of moderately reduced GFR with cfPWV and central pulse pressure (cPP) in Chinese middle-aged and elderly community residents.There were 875 community residents enrolled in this analysis, and then cfPWV and cPP were assessed in all participants following the standard procedure.P < 0.05 for all). Logistic regression analyses indicated that cfPWV and cPP had the significant association with moderately reduced GFR .Entire cohort had a median (range) age of 66 (45–88) years, and 65.4% were women. Both cfPWV and cPP differed significantly between participants with and without moderately reduced GFR (This analysis demonstrated the significant association of cfPWV and cPP with moderately reduced GFR in Chinese middle-aged and elderly community residents. Kidney impairment constitutes severe risk for cardiovascular disease, stroke and all-cause mortality, and early identification and prevention of kidney impairment are critical to effective management of prognostic risk in community residents. Recently, more and more attention has been given to the association of arterial stiffness and central hemodynamics with kidney impairment, especially early kidney impairment . PreviouSeveral reports have indicated the evidence of CKD present in patients with abnormal central hemodynamics indicated by elevated central pulse pressure (cPP) –7. Moreo2. Therefore, this analysis had 875 participants. This analysis was approved by Ethics Committee of Chinese People’s Liberation Army General Hospital . Written consent was obtained from each participant.There were 937 participants aged 45 years and older in this analysis. According to the stratified cluster sampling design of health check-up program from May 2007 to July 2009, all participants were permanent residents of four communities in three districts  of Beijing, China. Of those participants, 62 participants had GFR below 60 ml/min/1.73 mFollowing the standard procedures, peripheral blood pressure was measured on brachial artery with mercury sphygmomanometer . Blood pressure was measured in duplicate and averaged. Pulse pressure (PP) was calculated as systolic blood pressure minus diastolic blood pressure. Participants with systolic blood pressure ≥ 140 mmHg, diastolic blood pressure ≥ 90 mmHg or hypotensive drugs were regarded to have hypertension. Arterial stiffness was evaluated by a device designed for automatic cfPWV analysis . Radial artery pressure waveform was evaluated by a device designed for automatic pulse wave analysis , and the corresponding cPP was calculated with its transfer function. Their technical characteristics have been described previously [-1.234 × age (year)-0.179 × 0.79  [2 to 89 mL/min/1.73m2. Laboratory examination was completed by qualified technicians without knowledge of clinical information.Blood sample was drawn in the morning after the overnight fasting and examined by central laboratory on the same date. Concentrations of fasting plasma glucose (FPG), triglyceride, high-density lipoprotein-cholesterol (HDL-c), low-density lipoprotein-cholesterol (LDL-c) and serum creatinine were examined with enzymatic assays . Diabetes mellitus referred to those with FBG ≥ 7.0 mmol/L or hypoglycemic treatment. Chinese modified Modification of Diet in Renal Disease equation was used as an evaluation of GFR: 175 × serum creatinine (mg/dL) female) . Range o2 test for categorical data. Pearson’s correlation for continuous variables with normal distribution and Spearman’s correlation for categorical variables were used to evaluate their simple correlation of GFR with cfPWV and PP. Logistic regression analysis (Enter) was used to evaluate multivariate association of cfPWV and PP with moderately reduced GFR after adjustment of age, HDL-c and LDL-c. Age, HDL-c and LDL-c, rather than gender, hypertension, diabetes mellitus, FPG and triglyceride, were significant in univariate analysis with moderately reduced GFR, and included as the adjustment of multivariate analysis with moderately reduced GFR. Two-sided P value < 0.05 was accepted as significant.Statistical analysis was implemented with Statistical Package for the Social Science version 17 . Categorical data were reported as number and percentage. Continuous data were reported as mean and standard deviation for variables with a normal distribution, and median and interquartile range for non-normally distributed variables. Difference between groups was assessed by Student’s t-test for continuous data with a normal distribution, Mann–Whitney U test for non-normally distributed data and xP < 0.05 for all). cfPWV differed significantly between participants with and without moderately reduced GFR (P < 0.05). Both cPP and pPP had the significant difference between participants with and without moderately reduced GFR .Entire cohort had a median (range) age of 66 (45–88) years, and 65.4% (572 participants) were women. Prevalence of hypertension and diabetes mellitus were 52.7% (461 participants) and 24.3% (213 participants), respectively. Characteristics of the study cohort with and without moderately reduced GFR were depicted in Table P < 0.001 for all; cfPWV and cPP: r = 0.368; cfPWV and pPP: r = 0.374; cPP and pPP: r = 0.797) . Simple correlation and multivariate association of cfPWV and PP with moderately reduced GFR were shown in Table P < 0.05 for all). cfPWV had the significant association with moderately reduced GFR (P < 0.05). There was the significant association of cPP and pPP with moderately reduced GFR .Either two of cfPWV, cPP and pPP were significantly correlated with each other (This analysis had two main findings in Chinese middle-aged and elderly community residents: firstly, cfPWV was significantly associated with moderately reduced GFR; secondly, both cPP and pPP had the significant association with moderately reduced GFR.cfPWV is a noninvasive representative of central arterial stiffness , 4. In pCentral and peripheral hemodynamics are commonly assessed by cPP and pPP, respectively. Previous researches have realized that increased cPP rather than pPP correlated with reduced kidney blood flow and GFR in patients with CKD, and even in those after kidney transplantation –8. HowevThis analysis demonstrated the significant association between cfPWV and moderately reduced GFR. Meanwhile, both cPP and pPP were significantly associated with moderately reduced GFR in Chinese middle-aged and elderly community residents.


It is not yet clear if blood pressure and renal function changes evolve differently in children with a congenital or acquired solitary functioning kidney. This study aims to assess if there are any differences between these two types of solitary kidney patients.Current research is a retrospective study assessing the evolution of glomerular filtration rate, proteinuria, and blood pressure in clinical records of 55 children with a solitary functioning kidney . We used the medical records of children who had been assisted, in our unit of pediatric nephrology, for a period of 14 years (168 months), from the time of diagnosis, between January/1997 and December/2015.2, p NS) and proteinuria  demonstrated no significant change. However, after 14 years of follow-up 76.4% of patients had increased levels of arterial hypertension with values over the 90th percentile for gender, age, and height. Specifically, children with an acquired solitary functioning kidney mainly developed hypertension [T0 2/17 (12%) vs T14 9/17 (52.9%) p < 0.025], whereas children with a congenital solitary functioning kidney mainly developed pre-hypertension [T0 3/38 (7.9%) vs T14 17/38 (44.7%) p < 0.0005].During the study period, glomerular filtration rate (T0 128.89 ± 32.24 vs T14 118.51 ± 34.45 ml/min/1.73 mThe renal function of children with solitary functioning kidneys remains stable during a follow-up of 14 years. However, these children should be carefully monitored for their tendency to develop arterial blood pressure greater than the 90th percentile for gender, age, and height. In the 1980s, Brenner et al.  theorizeTherefore, Siomou  highlighPresent study conducted a retrospective approach in a population of SFK children, in order to assess changes in renal function (glomerular filtration rate and proteinuria) and arterial blood pressure according to the congenital or acquired nature of the diseases. Patients were followed over a 168-month observation period.This is a retrospective study based on the clinical records of pediatric patients with congenital or acquired SFK, with an observation time of 14 years (168 months). Current study aimed to assess if the nature of SFK  has a different influence on blood pressure and renal function.We enclosed all children referred to our center with a diagnosis of SFK that were aged between 3 months and 18 years at diagnosis; and followed them at our day hospital for 14 years. SFK subjects were divided into two groups: congenital SFK (cSFK) and acquired SFK (aSFK).2 at Tc-99 m DTPA renal scintigraphy, and no history of surgical nephrectomy.The cSFK group included patients with one kidney found absent or significantly smaller at ultrasound, with no detectable renal function or glomerular filtration rate (GFR) <10 ml/min/1.73 mThe aSFK group included SFK patients with complete absence of one kidney due to previous mono-lateral total nephrectomy due to trauma.Exclusion criteria included previous treatment with drugs potentially affecting renal function, documented orthostatic proteinuria, congenital anomalies of the urinary tract and SFK due to previous nephrectomy for causes other than trauma.We measured proteinuria in 24-h urine collections as described previously . In caseWe used the Tc-99 m DTPA renal scintigraphy to measure the GFR of the two kidneys separately 2 [2/24 h [As normal values, we assumed: GFR >90 ml/min/1.73 m2 , 12 and  [2/24 h .For the evaluation of renal functionMeasurement, evaluation, and classification of blood pressure:In children less than 1 year, the tables for diagnosis of neonatal hypertension were used In children between 1 and 18 years, we used “the Fourth Report on the Diagnosis, Evaluation and Treatment of High Blood Pressure in Children and Adolescents” . as it sClinical blood pressure classification:The updated recommendations for the standard assessment of ABPM in children and adolescent were applied  which coas it separates 1) normal blood pressure, 2) hypertension, and 3) prehypertension, 4) masked hypertension, and 5) with white coat hypertensionABPM classification:In children between 0 and 18 years:The guidelines set by the European Society of Cardiology for the assessment of clinical blood pressure and ABPM were followed .as it separates adults with In 1) normal blood pressure, 2) hypertension, and 3) prehypertension, 4) masked hypertension, and 5) with white coat hypertensionIn patients older than 18 years:In children <120 cm in height we only took blood pressure manually with a mercury sphygmomanometer . In children ≥120 cm in height we added a 24-h ambulatory blood pressure monitoring (ABPM) applying the technical modalities described previously . For allFor each patient, glomerular filtration rate, proteinuria, and blood pressure at the time of first admission (T0) and at 14 years (T14) were extrapolated from the records stored in our center for pediatric nephrology.The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki as revised in 2000 [χ2) test for data expressed as percent. For the data expressed as mean ± standard deviation we tested the approximation to normal of the distribution of the population by Kolmogorov-Smirnov One-Sample Test and statistics for kurtosis and symmetry. As results were asymmetrically distributed, non-parametric tests were used (Wilcoxon test).For statistical evaluation, we used a dedicated software: JMP  e GraphPad 5.0 . We expressed the qualitative variables as percent and the quantitative as mean ± standard deviation. We analyzed the differences between the groups using the chi-square  during 14 years after diagnosis at our center. Among them, 6 patients were excluded. Two of them had nephrectomy secondary to Wilms tumor, and four were affected by vesicoureteral reflux. Among remaining 55 patients , 38 patients had congenital SFK and 17 of them experienced acquired form.p < 0.001) in the cSFK group (6.24 ± 3.55 months) compared to the aSFK group (95.11 ± 33.12 months). Causes of cSFK included unilateral renal agenesis in 21, congenital aplasia/hypoplasia in 8, and multicystic kidney disease in 9 children.The mean age at diagnosis was significantly lower (In Table p < 0.003). This value remained stable in aSFK patients during the course of follow-up (T0 4/17 vs T14 5/17 p NS).The number of subjects with renal scar was similar at T0 in both groups (cSFK 10/38 vs aSFK 4/17 p NS); while it was significantly increased at T14 in subjects with cSFK (T0 10/38 vs T14 24/38 Table p <0.0001); which 22 (40%) of them were prehypertensive and 20 (36.4%) were hypertensive (Table p <0.0005), as well as a significant increase of hypertension (Hyp) in the aSFK group (T0 2/17 vs T14 9/17 p <0.025) , equally divided between prehypertensive (11%) and hypertensive (11%). At T14 (end of the study period) the number of children with blood pressure >90th centile had increased to 42 (76.4%) p < 0.047 Congenital solitary functioning kidney, 2/38 at T0 and 9/38 at T14 In particular, subjects with renal scars and hypertension where distributed as follows:In our study we did not detect any subjects with masked hypertension or white coat hypertension.Current study showed that during a 168-month follow up of children with congenital or acquired solitary functioning kidney, renal functions did not change significantly and blood pressure increased up to over the 90th centile in 76.4% of the studied population. These findings are in agreement with the results of Siomou et al. , 6 outliHowever the higher incidence of subjects with hypertension as shown in our study, albeit higher, is in agreement with those of the KIMONO study 21%) [% 21, 2222. We beWe measured the blood pressure with ABPM at T0 and T14 whenever feasible, i.e., when the child height is ≥120 cm. This was always the case with SFK patients acquired type, but SFK patients congenital type where first observed at a very young age, and ABPM could not be used at T0. It was therefore necessary to compare the IV Report classification  with theOur data differs from a later report by Westland et al.  showing Furthermore, our findings have distinct characteristics compared to the reports by Seeman et al. . This stCurrent study also highlights the presence of prehypertension in 40% of the cases; a condition that we believe requires a close observation. Since prehypertension state is prone to develop into hypertension , 27, itsIn view of the significant increase in blood pressure over a 14 year follow-up, we suggest prolonged mandatory follow-up of blood pressure every 6 months in children with both acquired and congenital SFK; in view of the higher incidence of prehypertension and hypertension that we found in this population, we consider it more appropriate than the yearly control suggested by Westland et al. . The scrSpecific attention should be given to the screening of patients for suspect prehypertension; as these children could definitely benefit from simple changes in life style and the early institution of an adequate medical therapy, that effectively prevent the clinical consequences and contrast the progression to hypertension .