The role of indoxyl sulfate (IS), an important protein-bound uremic toxin, in arterial stiffness (AS) in patients with chronic kidney disease (CKD) is unclear.We investigated the association between serum IS levels and AS in a cross-sectional study of 155 patients with CKD. Patients in the AS group was defined as carotid-femoral pulse wave velocity (cfPWV) value >10 m/s measured by a validated tonometry system (SphygmoCor), while values ≤10 m/s were regarded as without AS group Serum IS was measured by liquid chromatography–mass spectrometry analysis.p = 0.011), age , and SBP  were independent predictors of AS. By multivariable stepwise linear regression analysis, logarithmically transformed IS, age, DM, and SBP were significantly correlated with cfPWV. The area under the receiver-operating characteristic curve for serum log-IS was 0.677  to predict the development of AS in patients with CKD.Of these CKD patients, AS was present in 51 (32.9%) patients, who were older, had a higher rate of diabetes, higher systolic blood pressure (SBP), and higher IS levels compared to those without AS. By multivariable logistic regression analysis, IS (adjusted odds ratio [aOR] 1.436, 95% confidence interval [CI] 1.085–1.901, These finding demonstrate that in addition to older and higher SBP, a high serum IS level is a significant biomarker associated with AS in patients with CKD. Patients were staged according to 2012 Kidney Disease: Improving Global Outcomes Chronic Kidney Disease Guideline  vs. 0.88 μg/mL [IQR 0.43–1.76 μg/mL], p < 0.001), and lower estimated glomerular filtration rate (p = 0.014) compared to those without AS. There were no significant differences in sex, rate of hypertension, and use of medications between the two patient groups.p = 0.011), SBP , and age  were significant and independent predictive factors for AS , SBP , DM , and log-IS level  in patients with CKD  was significantly and positively correlated with age, DM, SBP, logarithmically transformed (log)-IS (log-IS), log-creatinine, and log-blood urea nitrogen (BUN) and was negatively correlated with eGFR. The multivariable stepwise linear regression analysis performed after adjusting for factors including DM, age, SBP, eGFR, and log-IS, cfPWV was significantly correlated with age (with CKD .p = 0.0001), with a sensitivity of 62.75% and specificity of 67.31%  with AUC as 0.677 (95%CI 0.598–0.750, f 67.31% . Figure f 67.31% .In this cross-sectional study including 155 patients with CKD, we found that, in addition to old age and hypertension, higher serum IS levels were also positively associated with cfPWV, suggesting its utility as a significant predictor of AS in patients with CKD.AS is caused by irreversible anatomical changes in vascular wall structures, accompanied with functional abnormalities and increased mechanical strain to low-impedance circulation to vital organs, which subsequently result in renal dysfunction, CVD, and mortality ,4. A stuIn vitro studies demonstrated that endothelial cells incubated with IS exhibited impaired proliferation, wound repair, nitric oxide production, and increased cell senescence and oxidative stress, indicating the adverse effects of IS on endothelial function [in vitro and in vivo studies demonstrated that IS-treated human aortic smooth muscle cells could promote aortic calcification and aortic wall thickening and enhance the expression of osteoblast-specific proteins, senescence, and calcification due to oxidative stress resulting from NADPH oxidase upregulation [in vitro [IS, which is metabolized in the liver from indole, a product of tryptophan that is produced by intestinal bacterial flora, accumulates with the deterioration of renal function and contributes to the progression of CKD ,29; IS ifunction ,34. In afunction ,34. Furtgulation ,36. In sgulation  and posigulation . Importain vitro ,37,38. Cin vitro studies. Therefore, the causal relationship between serum IS levels and AS should be evaluated with controlled dietary and nutritional supplement intake in prospective studies of larger patient cohorts and in vitro studies to clarify the harmful effects of IS on the vasculature.The present study has several limitations. First, this was a cross-sectional, single-center study including a small number of patients with CKD. Second, inflammatory markers such as C-reactive protein did not measured. Third, differences in dietary habits as well as dietary supplements can impact the colonic microbiome, which can result in fluctuations of serum IS levels; Fourth, the detailed mechanisms of IS to influence the process of AS could not be clearly deduced without In the present study, we demonstrated that, in addition to old age and elevated SBP, serum IS might also be a potential biomarker associated with AS in patients with CKD, indicating that IS might mediate the progression of AS; however, the underlying mechanisms require further investigation.


The aim of this study was to describe and analyze how T2DM patients with mild-to-severe CKD are managed by diabetologists in Greece and assess the achievement rates in glycemic, blood pressure and low-density lipoprotein-cholesterol (LDL-C) control. (2) Methods: This cross-sectional multicenter study took place from June 2015 to March 2016 and collected data from diabetes centers in public hospitals all over Greece. (3) Results: With regard to the anti-diabetes treatment, most participants were on metformin, DPP-4 (Dipeptidyl Peptidase-4 inhibitors) inhibitors and insulin. Angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers were the most prescribed medications for hypertension. For the management of dyslipidemia, most participants were on statins. For patients with DCKD, the levels of HbA1c, blood pressure and LDL-C were 7.2%, 137.7/76.9 mmHg and 95.9 mg/dL, respectively . (4) Conclusions: The outcomes of this study suggest that management of DCKD can be further improved and should be enhanced. These results may contribute to the whole health care system in Greece. In addition, the better understanding of therapeutic strategies used by diabetologists treating these patients offers educational benefits to primary care physicians, which can result in an overall more successful and efficient management of subjects with T2DM and DCKD.(1) Background: Type 2 diabetes mellitus (T2DM) is the main cause of chronic kidney disease (CKD). In Greece, in a population from hospital-based diabetes clinics ( Worldwide studies show that chronic kidney disease (CKD) is a leading cause of end-stage renal disease (ESRD) in type 2 diabetes mellitus (T2DM), which also increases cardiovascular mortality . We prev2): G1 > 90, G2 60–89, G3a 45–59, G3b 30–44, G4 15–29, G5 < 15. They were also classified into the following categories according to the Albumin/creatinine ratio (mg/gr Cr): A1 < 30, A2 30–300, A3 > 300. Categories G1A1 and G2A1 were considered normal. Given the size of our sample and the difficulty to adequately represent the 18 CKD stages, four new categories were coined as follows: normal kidney function, mild CKD, moderate CKD and severe CKD .The statistical package R (version 3.2.5-R Core Team) was used. For numerical variables, data are presented as means and standard deviations (SD). Categorical variables are described as numbers and percentages. Stages for kidney function were regrouped into four and then two categories for modelling purposes: (i) four categories: normal kidney function, mild, moderate, and severe CKD; (ii) two categories: normal kidney function vs. CKD. Univariate analysis was originally performed. Multiple analyses were then employed to associate CKD risk with treatment regimen . The proportional odds methodology was used to quantify the relationship of CKD with treatment. Significant covariates were selected using backward stepwise selection. Significance was determined at 5% level (two-tailed n = 1759), the mean age was 68 years, 54.6% were male and mean T2DM duration was 13 years. The overall prevalence of DCKD was 45% distributed to stages from mild to severe with mean CKD duration 4.1 years. Most participants  had hypertension, 1372 (77.9%) had dyslipidemia and 300 (17%) were current smokers. Mean body mass index (BMI) was 30.9 kg/m2.In the entire population (p < 0.01), longer duration of diabetes , and were more likely to be men (p < 0.01). Moreover, patients with DCKD had higher mean HbA1c and SBP (p < 0.01). For patients with DCKD, mean HbA1c, SBP, DBP and LDL-C levels were 7.2%, 137.7 mmHg, 76.9 mmHg and 95.9 mg/dL, respectively , DPP-4 inhibitors  and insulin . Metformin was most commonly administered to mild and moderate DCKD, while insulin was mostly administered to severe DCKD. Angiotensin-converting enzyme inhibitor (ACE-I) or an angiotensin II receptor blocker (ARB) were the most commonly prescribed antihypertensive medications, followed by calcium channel blockers (CCBs), B-blockers and diuretics. For the management of dyslipidemia, most participants were treated with statins , followed by ezetimibe   . Most of, 10.2%) .Pharmacological treatment of DCKD is primarily targeted towards lowering HbA1c and blood pressure . MoreoveGlycemic targets in the presence of DCKD should be personalized in accordance with the patient characteristics. Glycemic control may delay progression of DCKD, with most guidelines recommending a goal HbA1c around or below 7.0% ,14,15,162) due to DCKD have decreased insulin requirements, as insulin is cleared by the kidneys [There are several factors that predispose patients with DCKD to an increased risk of hypoglycemia. Patients with decreased GFR  taking angiotensin-converting enzyme inhibitor (ACE-1) or angiotensin II receptor blocker (ARB) therapy, those randomized to canagliflozin had a 30% lower risk (43.2 vs. 61.2 events per 1000 patient-years) of developing the primary composite renal outcome  compared with those randomized to placebo [In most, cases, metformin is the first-choice antidiabetic meditation. In our study, metformin was administered mostly to low stages of DCKD, as opposed to insulin which was mostly given to more severe DCKD. It has been reported that patients with T2DM and eGFR 45–60 mL/min/1.73 mstration . The mosstration . Howeverstration . The US /1.73 m2 . Risk of/1.73 m2 . A study/1.73 m2 . In tria/1.73 m2 . DPP-4 i/1.73 m2 . The gly/1.73 m2 . In pati placebo ,52. In p placebo ,54,55. A placebo . Finally placebo .Current evidence highlights the importance of BP reduction in the management of patients with DCKD. The rates of cardiovascular and kidney events increase when BP is elevated, whereas they progressively decrease when BP is kept within normal limits with the appropriate treatment. We should note, however, that there may be a point beyond which further BP reduction may not be helpful or even be harmful despite a reduction in proteinuria. The current KDOQI guidelines recommend a goal of BP <130/80 mmHg, whereas the Eighth Joint National Committee (JNC8) guidelines recommend a goal of BP <140/90 mmHg for most patients with T2DM and diabetic nephropathy, but with individualization ,59,60,61Because dyslipidemia is closely related to the progression of cardiovascular disease, treatment is warranted irrespective of its potential effect on diabetic nephropathy. Since the risk of cardiovascular disease is excessive in subjects with diabetes, recommendations of an aggressive lowering of LDL cholesterol levels, given for patients with established cardiovascular disease, can also be extended to those with diabetes . In our 2, they should be referred to a nephrologist [In this setting, such therapeutic choices are not only relevant to Greece but also to other countries. It should also be stressed that patients with DCKD should avoid natural products and other over-the-counter supplements since there may be unwanted interactions with prescribed medications or other side effects. However, a collection of data on this issue was not included in our study. A previous publication from our team found a significant correlation of DCKD with retinopathy and peripheral neuropathy . Thereforologist .The occurrence and the progression of DCKD can be slowed down markedly, even in advanced stages of kidney disease. The management of CDKD is complex and should be personalized, involving the patients in the treatment process. Physicians should therefore consider the interplay between the psychosocial background, the comorbidities and the pharmacokinetic/pharmacodynamic characteristics of the anti-diabetic drugs when deciding the appropriate therapeutic regimens for their patients to achieve what is desirable and what is practically possible.The strengths of this study include the nationwide and real-world design and the enrollment of consecutive cases throughout Greece. There may be some selection bias inasmuch as subjects are restricted to diabetes units in hospitals. However, it should be pointed out that the majority of our T2DM subjects are residents of large cities and, due to the recent economic crisis, they are mostly treated in public hospitals rather than private practices [The presence of kidney disease adds an extra layer of complexity to the management of T2DM patients compared to those with diabetes alone. Optimal management of DCKD includes treatment of T2DM and hypertension, cardiovascular risk reduction and adjustments to drug dosing. The outcomes of this study suggest that management of DCKD can be further improved and should be enhanced. These results can contribute to the whole health system in Greece. In addition, a better understanding of the therapeutic strategies used by diabetologists treating these patients offers educational benefits to primary care physicians, which can result in an overall more successful and efficient management of T2DM patients with DCKD.


Applying a pneumatic tourniquet provides surgeons with a bloodless surgical field. However, application of the tourniquet induces various physiological changes. We evaluated the effect of tourniquet deflation on the intracranial pressure by using ultrasonography to measure the optic nerve sheath diameter (ONSD) in patients undergoing lower limb surgery. The ONSD was measured in 20 patients at five time points: after anesthetic induction (T0) and immediately before (T1), immediately after (T2), 5 min after (T3), and 10 min after tourniquet deflation (T4). Hemodynamic and respiratory variables were recorded. The ONSD showed significant differences at each point (P < 0.001). The ONSDs at T2 and T3 were significantly greater than that at T1 . The change in the end-tidal carbon dioxide partial pressure (EtCO2) was similar to the change in the ONSD. The change in the ONSD was significantly correlated with the change in the EtCO2 after tourniquet deflation . In conclusion, the ONSD, as an indicator of intracranial pressure, increased after tourniquet deflation in patients undergoing lower limb surgery. This was correlated with an increased EtCO2 and arterial carbon dioxide partial pressure.Trial registration: ClinicalTrials.gov (NCT03782077). However, inflation and deflation of the tourniquet induces physiological changes, including alterations in the pH, arterial oxygen partial pressure, arterial carbon dioxide partial pressure (PaCO2), potassium ion levels, and lactate levels3. In particular, tourniquet deflation causes carbon dioxide (CO2) that has accumulated during the ischemic period to be released into the systemic circulation. The resultant elevation in PaCO2 is followed by an increase in the intracranial pressure (ICP)4. Although this increase in cerebral blood flow (CBF) has not much clinical significance and it is compensated and tolerated in most healthy patients, the increase in cerebral blood volume may cause an increase in ICP in patients with decreased intracranial compliance7. Increased intracranial pressure can induce deleterious outcomes, including cerebral ischemia8. Therefore, cautious monitoring and thorough management of the ICP is required in patients undergoing lower limb surgery, who have or are at high risk of cerebrovascular disease, using a pneumatic tourniquet.Although there has been a debate on the use of pneumatic tourniquet in orthopedic surgery, they do provide surgeons with a bloodless surgical field, which improves the surgical environment. In addition, pneumatic tourniquets reduce the surgical time and intraoperative blood loss9. Increased ICP is transmitted to the subarachnoid space surrounding the optic nerve, causing optic nerve sheath expansion10. Therefore, increased ICP could be estimated based on the ONSD, which can be measured in a non-invasive manner that could be applied easily in orthopedic patients.Many studies have shown that ultrasonography of the optic nerve sheath diameter (ONSD) has good diagnostic accuracy to detect intracranial hypertensionIn the present study, we aimed to investigate alterations in the ICP using ultrasonography to measure the ONSD after deflation of the pneumatic tourniquet in patients undergoing lower limb surgery. We also evaluated the factors related to changes in the ONSD.In November and December 2018, 21 consecutive patients scheduled for undergoing knee surgery, using a pneumatic tourniquet were screened for eligibility. Among them, one refused to participate in the study, and 20 were enrolled, all of whom finished the study without drop-out. Ultimately, 20 patients were included in the final analysis. The patients’ baseline characteristics and intraoperative data are shown in Table 2) was similar to the change in the ONSD. The EtCO2 levels at T2, T3, and T4 were significantly higher than that at T1 . The PaCO2, obtained through arterial blood gas analysis, was also significantly higher at T3 than at T1 , and written informed consent was obtained from all patients. The study was conducted according to the 1964 Helsinki declaration and its later amendments. We registered the study on ClinicalTrials.gov (NCT03782077).32, (2) age between 18 and 80 years, and (3) knee surgery with pneumatic tourniquet scheduled at our center. We excluded patients with cerebrovascular, neurological, or ophthalmic diseases, as well as those who refused to participate or had any contraindication to general anesthesia or tourniquet use.The study included patients who met the following criteria: (1) the American Society of Anesthesiologists physical status I–IV2, and body temperature. General anesthesia was induced using 2 mg/kg of propofol and 50 µg of fentanyl. When the eyelash reflex was lost, 0.6–0.8 mg/kg of rocuronium was intravenously injected, and the lung was mask-ventilated using 5–6 vol% sevoflurane in 80% oxygen for 3 min. When the patients reached an adequate anesthetic depth, an appropriately sized supraglottic airway device was inserted. The esophageal temperature probe was also inserted via a supraglottic airway device to measure body temperature. Anesthesia was maintained using 1.5–2 vol% of sevoflurane in a 50% oxygen/nitrous oxide mixture at a rate of 2L/min. The concentration of sevoflurane was controlled according to the bispectral index level and minimal alveolar concentration of inhalation agent to avoid overdose sevoflurane. Mechanical ventilation was adjusted to maintain the EtCO2 level at 35 mmHg with a tidal volume of 6–8 mL/kg and a respiratory rate of 10–12/min. To eliminate the effect of self-respiration compensating hypercapnia, rocuronium was continuously infused to maintain a train of four count of 1–2 throughout the surgery. After anesthetic induction, the radial artery was cannulated for invasive arterial blood pressure monitoring and blood gas analysis. Crystalloid solution including plasmalyte was administered at a maintenance dose to maintain normovolemia. To control pain, we administered an ultrasound-guided femoral nerve and sciatic nerve block by injecting 40 cm3 of 0.3% ropivacaine. A pneumatic thigh tourniquet was applied as close as possible to the limb root, and it was inflated to a pressure of 300 mmHg. All surgical procedures were performed with the tourniquet inflated; after the surgery, the tourniquet was deflated. When the ONSD measurements were completed, the inhalation agent and rocuronium were discontinued, and the neuromuscular blockade was reversed using sugammadex. After recovery from general anesthesia, patients were transferred to the postanesthetic care unit.The recruited patients entered the operating room without any premedication. Standard monitoring was performed, including peripheral oxygen saturation, electrocardiogram, non-invasive blood pressure, EtCO33. The measurements were performed at the following five points: after anesthetic induction (T0), immediately before the tourniquet deflation (T1), immediately after the tourniquet deflation (T2), 5 min after tourniquet deflation (T3), and 10 min after tourniquet deflation (T4).The primary outcome of this study was a change in the ONSD, measured by ultrasonography after tourniquet deflation. Ultrasound imaging was performed by two investigators trained in ocular sonography using the 6–13 Hz linear probe of a single ultrasound machine . Patients were placed in the supine position with their heads in the neutral position. The probe was located on the closed upper eyelid in the transverse plane and moved slightly to identify the optimal image between the vertical hypoechoic band and the retrobulbar echogenic fat tissue. The outer diameter of the optic nerve sheath was measured 3 mm behind the optic disc . Arterial blood gas analysis was also performed to ensure accurate PaCO2 measurement at T1 and T3. In addition, the patients’ baseline characteristics and tourniquet time were recorded.MAP, respiratory variables, and body temperature were measured at the same time points. Respiratory variables included the PAP, PIAP, and EtCOBased on our clinical experiences, the mean ONSD after anesthesia induction was 5.0 ± 0.5 mm. When an ONSD change of 10% was considered significant, the calculated sample size with a power of 0.9 and an alpha-error of 0.1 was 18 patients. Considering dropout, we decided to enroll 20 patients.2 change and MAP change. P-values of < 0.05 were considered statistically significant.The data we obtained were recorded in a standardized case report form. In the analysis of repeated measured data, including ONSD, a linear mixed model was used. Furthermore, we performed multiple comparison using Scheffe’s method to compare variables between two time points. Pearson’s correlation coefficient analysis was used to analyze how the ONSD change was correlated with the EtCO


Researchers have yet to investigate the specific association between 10-μm particulate matter (PM10) levels and the risk of graft failure, kidney disease, or the functional decline of transplanted kidneys, in kidney transplant recipients (KTRs). Furthermore, we know very little about the association between PM10 levels and the development of allograft rejection in transplanted kidneys. Identification of air pollution as a potential contributor to kidney disease could help reduce future disease burden, stimulate policy discussions on the importance of reducing air pollution with respect to health and disease, and increase public awareness of the hazards of air pollution. We aimed to evaluate the relationship of PM10 with the risk of graft failure, mortality, and decline of graft function in KTRs.Air pollutant data were obtained from the Korean National Institute of Environmental Research. We then investigated potential associations between these data and the clinical outcomes of 1532 KTRs who underwent kidney transplantation in a tertiary hospital between 2001 and 2015. Survival models were used to evaluate the association between PM10 concentrations and the risk of death-censored graft failure (DCGF), all-cause mortality, and biopsy-proven rejection (BPR), over a median follow-up period of 6.31 years.3. Based on 1-year baseline exposure, 1 μg/m3 increase in PM10 concentration was associated with an increased risk of DCGF (hazard ratio (HR): 1.049; 95% confidence interval (CI): 1.014–1.084) and BPR . Fully adjusted models showed that all-cause mortality was significantly associated with 1-year average PM10 concentrations .The annual mean PM10 exposure after kidney transplantation was 27.1 ± 8.0 μg/mLong-term PM10 exposure is significantly associated with BPR, DCGF, and all-cause mortality in KTRs.The online version contains supplementary material available at 10.1186/s12940-021-00741-y. Exposure to outdoor air pollution is a leading cause of global disease burden and accounts for over four million deaths each year . IncreasIn a large cohort of veterans in the United States , 9, highPrevious studies have focused only on evaluating the association between PM10 and the outcomes of kidney diseases in native kidneys. However, researchers have yet to investigate the specific association between PM10 levels and the risk of graft failure, kidney disease, or the functional decline of transplanted kidneys, in kidney transplant recipients (KTRs). Furthermore, we know very little about the association between PM10 levels and the development of allograft rejection in transplanted kidneys. The identification of air pollution as a potential contributor to kidney disease could help reduce future disease burden, stimulate policy discussions on the importance of reducing air pollution with respect to health and disease, and increase public awareness relating to the hazardous nature of air pollution.In the present study, we developed a longitudinal national cohort of KTRs and investigated the relationship between PM10 levels and the risk of biopsy-proven rejections (BPR), death-censored graft failure (DCGF), and mortality.n = 61) and double kidney transplantation (n = 85); (2) graft failure within 3 months of transplantation (n = 7), and (3) mortality within 3 months of transplantation (n = 16). Only the participants whose data included a zip code were included in the final analysis.This was a retrospective cohort study involving data generated between January 2001 and December 2015 at the Seoul National University Hospital and Seoul National University Boramae Medical Center. Initially, a total of 1531 adult participants (> 18 years) were included. However, a number of patients were then excluded for the following reasons: (1) multiple organ transplantation , the incidence of diabetes and hypertension, chronic glomerulonephritis as a cause of ESRD, the duration of renal replacement therapy (RRT) prior to transplantation, and the type of previous RRT. We also collated data relating to a range of immunological factors, including preemptive transplantation , donor status (living or deceased), ABO incompatibility, and a number of HLA-A, −B, and -DR mismatches.Across the South Korea, there are eleven different types of monitoring sites operated by the Ministry of Environment and local governments. These monitoring sites are situated across 584 locations in 114 cities and counties. This study used data arising from 373 monitoring stations situated in both urban and roadside positions.https://www.airkorea.or.kr/web). We collated hourly PM10 data from each of our 373 national monitoring sites. In addition, we used daily mean PM10 concentrations for individual study populations according to the respective district of each enrolled patient, as determined by the residential address stated on medical records.PM10 concentration data for 2001 and 2015 were provided by the Korean National Institute of Environmental Research  for categorical variables and as means  for continuous variables.To investigate the association between the clinical outcomes of transplantation patients and PM10 concentration, we calculated Kaplan-Meier estimates of survivor functions and compared survival curves between groups of patients according to a pre-determined cut-off value, which was defined as the median annual mean PM10 concentration.Next, the median PM10 concentration was used to divide PM10 data into two groups, and a log rank test was used to test the null hypothesis. We then used the Cox proportional hazards survival model to investigate the association between the 1-year mean PM10 concentrations (for the 5-year study period) before the events occurred, along with the individual and clinical outcomes. Finally, we adjusted our data to take account of covariates. As the definition of exposure was dependent on the annual mean obtained from an air monitoring station in each district, we also collated data from the year prior to the event. Additionally, subgroup analysis was performed for two groups of TCMR and ABMR according to the mechanism of occurrence of the biopsy-proven rejection event, one of the outcomes.To explore whether this association was non-linear or linear, we considered a non-linear relationship via smoothing splines. Splines are mathematical constructs made of fragments of polynomial functions that are stitched together to form a smooth curve. In order to identify a smoothing spline, we used the penalized partial likelihood method; this is known to be an effective method for survival analysis.We used models that incorporated subject-specific random effects to account for unmeasured subject characteristics that influenced the hazard of the occurrence of the outcome. In our research, these models were then extended to models that incorporated cluster-specific random effects to account for within-cluster homogeneity in outcomes. Moreover, we investigated whether different concentrations of PM10 affected the health of kidney transplant patients using the two-pollutant model of PM10 with adjustment for SO2, CO, NO2, and O3 and whether these effects differed by regions. All statistical analyses were performed using R (3.6.0) and SAS version 9.4.2. The incidence of preemptive kidney transplantation was 29.8%, while that of ABO incompatible kidney transplantation was 5.9%. The geographic locations of the participants are shown in Figure S3. The mean PM10 exposure showed a slight increase compared to the overall mean PM10 concentration between 2001 and 2009 , but then a slight decrease from 2010 to 2015 .Initially, we recruited a total of 1532 individuals. However, we then excluded 240 patients aged < 19 years, 61 patients who underwent multiple organ transplantation, and 85 patients who underwent kidney transplantation more than twice. Consequently, our final analysis featured 1146 eligible KTRs , 78 cases of DCGF (6.8%), and 549 cases of BPR (47.9%) were recorded. The Kaplan-Meier survival curves for BPR, DCGF, and mortality were significantly worse in the group exposed to higher concentrations of PM10 than in the group exposed to lower concentrations , graft failure , and mortality  in our analyses considering exposure over a 1-year period with regards to prospective clinical outcome , DCGF , and all-cause mortality . Furthermore, our result shows that there are factors that influnence the hazard of BPR. It is obvious from our results, that the districts were important  and gamma frailty with a covariance estimates of 0.05 shows that there were unmeasured districts effects present in the model.Table The underlying biological mechanisms that may explain the novel association between long-term PM10 exposure and renal outcomes in KTRs is unclear. Classically, the inhalation of particulate matters activates pulmonary inflammatory cells that may trigger a systemic inflammatory response that triggers a cascade of events, ultimately affecting the body’s cardiovascular system . Recent Other studies have investigated kidney damage following sub-chronic exposure to PM2.5 by analyzing the levels of early kidney biomarkers, histological changes, induction of the angiotensin and bradykinin system, and by measuring changes in blood pressure , 27. In Our data showed that prolonged long-term exposure to PM10 was associated with higher risks of transplant kidney rejections in KTRs. However, there is little in the current literature to explain the relationship between PM10 exposure and the risk of graft rejections. However, there is some evidence originating from studies involving the recipients of other transplanted organs, such as lung transplant recipients that suggests that PM may trigger rejection of the transplanted organ. Recent studies have reported that exposure to traffic-related air pollution independently increased the risk of bronchiolitis obliterans syndrome, a condition that is clinically correlated with chronic rejection in lung transplant patients , and alsOne particular strength of our study is that we investigated a large contemporary Korean cohort of KTRs with a long-term follow-up of 15 years. Because we had access to comprehensive long-term air pollutant data, we were able to adjust the data for multiple donors and recipient variables. Moreover, this study used BPR data as the chief outcome to evaluate the impact of PM10. However, this study also has several limitations that need to be considered. First, the study participants were mostly South Koreans; therefore, the findings may not be generalizable to other populations. Although we accounted for known confounding factors, and region with frailty survival analysis, we cannot ignore the possibility and potential effects of unknown or non-measured confounders. Therefore, if the sample size of the study was large, and subjects were evenly distributed in the sub-regional unit, it can be carefully assumed that the effect of size on the region may increase.In summary, we demonstrate a significant association between PM10 concentrations and the risk of graft failure development, all-cause mortality, and BPR in KTRs. Continued efforts to improve air quality may help to reduce the burden of renal outcome in KTRs.Additional file 1: Figure S1. Location map of the study participants. Table S1. Risk of BPR in PM 10 concentration by exposure durations from events day. Table S2. Risk of DCGF in PM 10 concentration by exposure durations from events day. Table S3.. Risk of all-cause mortality in PM 10 concentration by exposure durations from events day. Table S4. Association between average annual PM10 and SO2, CO, NO2 and O3 exposure in outcomes after kidney transplant.


We examined the effect of oral functional tongue pressure stimulation against the anterior palatal mucosa on cerebral activation using NIRS in 13 adults. Tongue pressure stimulation caused significant changes in cerebral blood flow in some areas compared with controls (p < 0.05). We performed a correlation analysis (p < 0.05) between MTP60% and changes in oxygenated hemoglobin in all 47 NIRS channels. MTP60% triggered activation of the right somatosensory motor area and right dorsolateral prefrontal cortex and deactivation of the anterior prefrontal cortex (APFC). TPM balloon-probe insertion in the oral cavity activated the bilateral somatosensory motor area and deactivated the wide area of the APFC. Moreover, MTP60% via the TPM balloon probe activated the bilateral somatosensory and motor cortex areas. Tongue pressure stimulation changes cerebral blood flow, and NIRS is useful in investigating the relationship between oral stimulation and brain function.Tongue pressure measurement (TPM) is an indicator of oral function. However, the association between tongue pressure and cerebral activation remains unclear. We used near-infrared spectroscopy (NIRS) to examine the correlation between cerebral cortex activation and tongue pressure stimulation against the anterior palatal mucosa. We measured voluntary maximum tongue pressure (MTP) using a TPM device; a pressure value of approximately 60% of the MTP was used for the experimental tongue pressure (MTP In ageing societies, cognitive decline and physical deterioration pose serious health-related challenges and are symptomatic of various diseases. Among physical challenges, oral functional deterioration is a cause of mortality owing to its relationship with both dysphagia  and respNoninvasive functional neuroimaging techniques have been developed to assess human brain function. Cerebral functional activity is detected using surrogate biomarkers such as neural electromagnetic activities, CBF, and oxygenation. In particular, CBF- and oxygenation-based neuroimaging techniques have been developed to elucidate cerebral function based on neurovascular coupling .Fox et al.  first reIn contrast, near-infrared spectroscopy (NIRS) is based on the biopermeability of near-infrared light. NIRS can detect the hemodynamics of the cerebral cortex caused by neurovascular coupling. In 1977, Jöbsis  first noThe purpose of this study was to examine regional CBF induced by tongue pressure against the anterior palatal mucosa and OFT with TPM stimulation. We used NIRS due to its greater flexibility in task assignments compared to other functional neuroimaging techniques and evaluated the potential of NIRS as an on-site, objective indicator of the rehabilitation effect of tongue pressure OFT.Thirteen healthy adult volunteers , 29.3 ± 3.6 years) were recruited. The participants had no unstable illness, were not taking any medication, had not consumed alcohol, and provided written informed consent after they were given information about this study. All procedures were approved by the appropriate Ethics Committee of Hiroshima University Hospital, Hiroshima, Japan, on 10 January 2017 (authorization number: E-173).60%), considering the effects of overshooting, artifact, fatigue, and struggling to perform the task , was evaluated using a balloon-type TPM device . The participants were seated on a chair with a backrest and instructed to hold the plastic pipe of the TPM device at the midpoint of their central incisors with their lips closed. Participants were asked to lift their tongue against the anterior palatal mucosa around the palatal rugae. The mean MTP was calculated from three measurements. The experimental tongue-pressure stimulus was determined at approximately 60% of the mean MTP  to measure changes in cerebral hemodynamics using two wavelengths of near-infrared light (695 and 830 nm) and the accompanying 47 channels (Chs). The measurement probe had an array of 3 × 11 optical fibers, and the distance between the light-emitting unit and detector unit was 30 mm. We used an NIRS head-holder, with the emitter and detector arranged along the 3 * 5 line, and set the lower line of the NIRS head-holder along the T4-Fpz-T3 line according to the International 10–20 method of electroencephalography (EEG) electrode placement. All measurements were conducted in a silent room at the Hiroshima Innovation Center of Biomedical Engineering and Advanced Medicine .Continuous-wave NIRS is the most used type , in whicWe determined the arrangement between the probe and cerebral prefrontal surface using the virtual registration method ,24. The The task paradigm consisted of a block design. Each block consisted of a 30 s stimulation period and a 40 s recovery period. The experimental stimulus was applied with the tongue three times for 5 s against the anterior palatal area during the 30 s stimulation period via a TPM balloon-type probe . The tas(1)Task 1: resting tongue position for control.(2)60% against the anterior palatal mucosa .Task 2: MTP(3)Task 3: insertion of the TPM probe.(4)60% via the TPM probe .Task 4: MTPContinuous NIRS measurement was integrated with the baseline determined using the mentioned parameters .We calculated the Oxy-Hb values for all 47 Chs within the stimulation period during the task blocks (10–40 s). The mean value of the change in the Oxy-Hb concentration (from baseline) was determined using the area under the curve. The baseline for each task was the line connecting the average of the 10 s pre-time and the 5 s post-time. After Benjamini and Hochberg’s false-discovery-rate processing of the subcurve values for each of the 47 channels, multiple comparison analysis with Dunnett’s post hoc comparison was used to examine the tasks and identify the channels that significantly changed blood flow. Statistical analyses were performed using SPSS version 21 .t-test was performed on the subcurve values of each of the 47 channels in the men’s and women’s groups.In order to examine whether there was a difference in the variation in CBF owing to sex, a statistical test using a paired 60% and changes in Oxy-Hb (ΔOxy-Hb) levels in each Ch was analyzed using correlation analysis. Statistically significant Chs are depicted on the cortical surface map in The relationship between MTP60% was used in our analysis. There was no significant difference in the mean MTP between the men’s and women’s groups  in Task 3 and Ch 42 (p = 0.043) in Task 4 showed a significant difference.We used a corresponding 60% and ΔOxy-Hb revealed significant channels: Ch 26  and Ch 39 . The correlation analysis between MTP60% via the balloon-type probe of TPM and ΔOxy-Hb revealed significant channels: Ch 45  and Ch 39   .60% against the anterior palatal mucosa was predominantly localized to the right temporal cortex. In a previous study, oral stimulation of the first transverse palatine ridge resulted in bilateral activation of the primary somatosensory cortex [This study showed that tongue pressure against the anterior palatal mucosa and TPM have various effects on regional CBF. MTPy cortex . Howevery cortex ,27,28.The participants were examined for blood flow fluctuations in the cerebral cortex when tongue pressure was applied, and these data may serve as a basis for excluding the effects of unconscious tongue pressure in an fNIRS study.60% via the TPM balloon-type probe activated the bilateral primary sensory and motor cortices, which is consistent with oral ball-rolling tasks [The TPM balloon-type probe activated the bilateral temporal lobes and deactivated the wide area of the PFC, which is in line with previous findings . MTP60% ng tasks . This st60% and ΔOxy-Hg values at the channels over the left DLPFC and right MTG. The DLPFC plays an important role in emotional and motivational tendencies , and thSince CBF responses may be altered by ageing, we examined changes in CBF in the cerebral cortex in young, healthy individuals. Based on our findings, there is a need to study the effects of both ageing and brain diseases. Furthermore, since NIRS signals are affected by many physiological systemic functions, such as heart rate, respiratory rate, blood pressure, skin blood flow, motion artifacts ,32, and NIRS may detect emotional conditions in conjunction with other physiological biomarkers ,37,38. F60% via the TPM balloon probe activated the bilateral somatosensory and motor cortex areas. These findings expand our understanding of brain hemodynamics during oral function. The development of a clinically feasible NIRS protocol during oral rehabilitation could facilitate the visualization and digitization of oral function from a cerebral perspective.This study demonstrated that tongue pressure against the anterior palatal mucosa elevates Oxy-Hb levels in the right somatosensory motor area and showed the deactivation of the PFC with passive, nontaste oral tactile stimulation. TPM probe insertion in the oral cavity activated the bilateral somatosensory motor area and deactivated the wide area of the APFC. Moreover, MTP


Renal fractional flow reserve (rFFR), measured by pressure guidewire, may distinguish the patients who may benefit from revascularization by identifying physiologically significant stenoses. However, the role of usage of both OCT and rFFR is not well-studied. We herein report a 17-year-old male with renovascular hypertension due to FMD. Angioplasty of drug-coated balloon (DCB) guided by OCT and FFR favorably achieved blood pressure (BP) control. In conclusion, the utility of both OCT and FFR may be useful for the appropriate selection of patients with renal FMD.Fibromuscular dysplasia (FMD) is the second common cause of renovascular hypertension. With the advent of endovascular therapy, angiography has become a diagnostic gold standard for FMD. Optical coherence tomography (OCT) by reflecting  Fibromuscular dysplasia (FMD) is a non-atherosclerotic arterial disease, which is characterized by abnormal cellular proliferation and distorted architecture of the arterial wall . FMD mosThe diagnosis and classification of renal FDM were mainly based on angiographic characteristics, among which the “string of beads” appearance was the most striking feature . HoweverOn the other hand, the revascularization criteria of RAS remain debatable. Based on the latest consensus, the pressure gradient could provide further information to identify with hemodynamically significant stenosis, even though, which was validated on studies of atherosclerotic RAS . HoweverA 17-year-old male who presented with hypertension for 1 month was admitted to the cardiology department, whose ambulatory blood pressure (ABPM) showed an average blood pressure (BP) of 160/98 mm Hg despite anti-hypertensive therapy consisting of bisoprolol and nifedipine. A smoking history for 7 years was noticed. Physical examination was unremarkable, and abdominal bruit and peripheral edema were absent. ABPM showed elevated mean BP of 154/93 mmHg . An ECG showed sinus rhythm with left ventricular hypertrophy, and echocardiography revealed a left ventricular ejection fraction (LVEF) of 71.6%. Laboratory examination revealed a normal result of a full blood cell count, renal, and liver function. Since the young age of the patient, without a family history or risk factors for hypertension, investigation for secondary hypertension was first considered. Initial workup noted elevated aldosterone level and plasma renin activity both beyond the upper limit of reference, which posed a strong suspicion of renovascular hypertension. The stenosis of the main branch of the right renal artery was finally revealed after repeated ultrasound examinations. CT angiography was also performed, which demonstrated the stenosis in the initial segment of the anterior segmental artery of the right kidney. Possible involvement of other vascular beds was ruled out with Doppler ultrasound and enhanced CT. The kidney ultrasound and urinalysis of the patient were normal. A radionuclide renal scintigraphy showed mild impairment of the function of the right kidney and normal function of the left kidney. Thyroid-stimulating hormone, the circadian rhythm of cortisol, level of serum catecholamines, and metanephrines were all normal, and other causes for secondary hypertension were ruled out. Autoimmunity screening was negative, which ruled out underlying vasculitis diseases. The lipid profile was normal with low-density lipoprotein cholesterol (LDL-C) of 2.25 mmol/L. Based on these findings, we tentatively diagnosed the patient with renovascular hypertension secondary to RAS, and FMD was highly suspected due to his young age, smoking history, and no further atherosclerosis evidence.2 and the wavy endothelium of the right renal artery in longitudinal reconstruction and luminal stenosis due to intimal hyperplasia in cross-sectional imaging, which was compatible with pathognomonic for FMD ' legal guardian/next of kin for the publication of any potentially identifiable images or data included in this article.YL, BZ, MC, and JL contributed to the clinical treatment of this case. YL and XW contributed to manuscript writing. WM contributed to the review of the manuscript. All authors listed have contributed sufficiently to the project in order to be included as authors and approved the final version of the manuscript for publication.This manuscript was funded by the Youth Clinical Research Project of Peking University First Hospital (No. 2018CR05).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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The association between homocysteine (Hcy) and IgA nephropathy (IgAN) is not well understood. We aimed to investigate the relationship between Hcy and clinicopathologic features in IgAN patients.A total of 337 IgAN patients and 150 sex- and age- matched healthy controls were enrolled in this single-center retrospective study. According to Hcy ≤ 10 μmol/L or > 10 μmol/L, patients were divided into low and high Hcy groups. Multivariate logistic regression was performed to explore the risk factors for elevated Hcy.P < 0.001], unanimously in the subgroup of 156 patients with a normal estimated glomerular filtration rate (eGFR) (≥ 90 ml/min/1.73 m2) . Compared to the low Hcy group, serum creatinine (Scr), blood urine nitrogen (BUN), uric acid (UA), endocapillary hypercellularity (E) and tubular atrophy/interstitial fibrosis lesion (T) were higher in the high Hcy group. Hcy levels were positively correlated with Scr, BUN, UA, 24-h urine protein, and E and T lesions, but negatively correlated with eGFR and superoxide dismutase (SOD). In the subgroup with normal eGFR, patients with higher Hcy were persistent with higher Scr, BUN and T lesions. A multivariate logistic regression model showed that the risk of elevated Hcy in patients with pathological T increased by 2.87-fold. T lesions could better predict high Hcy, with an odds ratio (OR) of 14.20 in the subgroup with normal eGFR.Serum Hcy was higher in IgAN patients than in healthy controls [11.6  vs. 8.8  μmol/L, Pathologic T was an independent risk factor associated with elevated Hcy, especially at the early stage of IgAN.The online version contains supplementary material available at 10.1186/s12882-021-02632-3. Homocysteine (Hcy) is a sulfhydryl amino acid situated at a branch point of methionine metabolism that is metabolized via two interrelated processes of remethylation and transsulfuration . NumerouIgA nephropathy (IgAN) is the most common primary glomerulonephritis . Approxi2).In this study, we investigated the relationship between Hcy and clinicopathologic characteristics in IgAN patients in our center, especially at an early stage with a normal estimated glomerular filtration rate (eGFR) (≥ 90 ml/min/1.73 mThis was a single-center retrospective study. Patients (age ≥ 14 years) with biopsy-based diagnosis of primary IgAN between April 2014 and March 2021 in the Sun Yat-sen Memorial Hospital of Sun Yat-sen University were enrolled. Patients with secondary IgAN, such as systemic lupus erythematosus, Henoch-Schönlein purpura, anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis, diabetic nephropathy or hepatic diseases were excluded from the study. Patients with fewer than 8 glomeruli in biopsy samples, incomplete data and CVDs such as stroke, coronary atherosclerotic heart disease, aortic aneurysm, and aortic dissection, were also excluded. Patients with Hcy ≤10 μmol/L and Hcy > 10 μmol/L were classified into the low Hcy group and high Hcy group, respectively . A totalDemographics and clinicopathologic data were retrieved from the medical record system. All laboratory indicators, including serum Hcy, were collected and measured at the time of biopsy and retrospectively analyzed. Demographic data included sex, age, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and history of hypertension (HBP). Laboratory indicators included 24-h urine protein, Hcy, serum creatinine (Scr), blood urine nitrogen (BUN), uric acid (UA), hemoglobin (Hb), serum albumin (ALB), fasting glucose (Glu), cholesterol (CHOL), triglyceride (TG), low-density lipoprotein-cholesterol (LDL), high-density lipoprotein-cholesterol (HDL), superoxide dismutase (SOD), high sensitivity C reaction protein (hsCRP), erythrocyte sedimentation rate (ESR), immunoglobulin A (IgA), immunoglobulin M (IgM), immunoglobulin G (IgG), complement 3 (C3), and complement 4 (C4). MAP was calculated as DBP plus a third of the pulse pressure. HBP was defined as SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg or requirement for antihypertensive therapy. The eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation . Blood sRenal biopsy specimens were examined by light, immunofluorescence, and electron microscopy. Two pathologists independently evaluated histopathological manifestations according to the Oxford classification system of IgAN . MesangiP value for multiple comparisons was corrected according to the Bonferroni method. Spearman’s rank correlation was applied to detect the association between Hcy and clinicopathological features in IgAN patients. Univariate and multivariate logistic regression analyses were performed to identify the risk factors for elevated Hcy. A multivariate logistic regression model was created using stepwise forward LR to identify the variables that were independently associated with elevated Hcy selected from the variables with P < 0.1 in univariate logistic regression analysis. We further carried out analysis in the subgroup with normal renal function patients based on eGFR ≥90 ml/min/1.73 m2 to modify the effect of renal impairment. The data were analyzed using the SPSS 25.0 package . All the P values were two-tailed, and P < 0.05 was considered significant in all statistical tests.Continuous variables with a normal distribution are expressed as the mean ± standard deviation and were compared via Student’s t test. Skewed distributed continuous variables were expressed as medians (interquartile ranges) and compared with the Mann–Whitney U test or the Kruskal–Wallis test. Categorical variables were expressed as frequencies (percentages) and compared via the chi-squared test. The n = 135) were male. The age of the healthy controls was 36.0  years, and 42.7% (n = 64) were male. The median levels of eGFR and MAP were 88.1  ml/min/1.73 m2 and 94.7  mmHg, respectively. The median level of 24-h urine protein was 0.6  g/24 h.A total of 337 IgAN patients aged 34.0  years entered the study, and 40.1%  μmol/L in CKD stage 1 patients, which was still higher than that in healthy controls (P < 0.001). The median Hcy levesl of CKD stage 1-5 patients were 9.9 , 11.1 , 15.7 , 24.4 , and 23.8  μmol/L, respectively , respectively. Compared with patients without endocapillary hypercellularity (E0), those with endocapillary hypercellularity (E1) had significantly elevated Hcy , lower eGFR , higher ALB , and pathologic T  independently increased the risk of elevated Hcy in IgAN patients.The logistic regression analysis results are shown in Table 2. Seventy-four patients were in the high Hcy group, with a higher proportion of male patients, and a history of HBP, SBP, Scr, BUN, ALB, and pathological T lesions and a lower eGFR and 24-h urine protein than those in the low Hcy group. The results of the subgroup analysis are presented in Supplement Table P = 0.015) in the subgroup of patients with eGFR ≥90 ml/min/1.73 m2.A total of 156 patients had normal renal function with eGFR ≥90 ml/min/1.73 m2.In this study, we found that the serum Hcy of IgAN patients was significantly higher than that of healthy controls in our center. IgAN patients with elevated Hcy displayed more severe T lesions, even in subgroups of patients with normal renal function. Multivariate logistic regression analysis showed that pathologic T was an independent risk factor for elevated Hcy in IgAN patients and persisted in a subgroup analysis according to eGFR ≥90 ml/min/1.73 mP < 0.001], which was similar to a previous study [In this study, we found that Hcy was positively correlated with age in the whole cohort of 337 IgAN patients. A serious shortage of vitamin B12 and vitamin B6 was common in elderly populations, and a lack of cofactors reduced the metabolism of Hcy. In addition, the decline in renal function with aging also caused elevation of Hcy . Signifius study , 16. Morus study . In addius study . As prevus study , patientus study . HoweverFrom the results in this study, it can be seen that serum Hcy was closely related to kidney function. A previous study demonstrated that serum Hcy was very likely elevated in patients with CKD and gradually increased with the progression of CKD stage . Hcy wasP = 0.018) was an independent risk factor for elevated Hcy in IgAN patients, even after adjustment for eGFR and in the subgroup with normal renal function . Zhang et al. observed the association between Hcy and pathologic T lesions in IgAN [It has been demonstrated that the kidney is a major site for the removal of plasma Hcy and plays an important role in the regulation of plasma Hcy levels . In our  in IgAN . Given i in IgAN . Li et a in IgAN . When tu2. A longitudinal prospective study showed that elevated plasma Hcy levels may be a predictor of accelerated decline in renal function and future incidence of CKD [The Oxford classification score is a well-regarded prognostic indicator for IgAN. Tubular interstitial lesions are the most valuable histological parameter and a final pathway for most progressive kidney diseases. T lesions are common in IgAN patients even with normal renal function; however, factors associated with T lesions in IgAN have not been elucidated. Possible mechanisms to explain the T lesions are that with aggravating renal impairment, renal units will be damaged accompanied by fibrosis, resulting in loss of normal excretory function and reduced clearance of Hcy. On the other hand, IgAN is an inflammatory disease, and Hcy is related to the inflammatory response and stimulates the production of cytokines and proinflammatory molecules, which may be related to renal fibrosis. We found that nearly half of IgAN patients had elevated Hcy levels and displayed more severe clinicopathologic characteristics, even in patients with normal renal function with eGFR ≥90 ml/min/1.73 me of CKD . An anime of CKD . In bothe of CKD , 28. A pe of CKD . In facte of CKD .2O2. Hcy directly inhibits the activity of antioxidants, thereby disrupting SOD. On the other hand, elevated Hcy could induce oxidative stress, resulting in excessive superoxide production and SOD consumption [In addition, serum Hcy was positively correlated with hsCRP and ESR, but negatively correlated with SOD in the whole cohort of IgAN patients. Gori et al. revealed that interleukin-6 and interleukin-1 were independent predictors of Hcy concentrations in elderly individuals . Decreassumption . The clisumption , which c2 to modify the effect of renal impairment. Our study showed consistent results that higher Hcy was associated with higher Scr, BUN, UA, ALB and T lesions but lower eGFR and HDL. However, there were opposite results in the correlation between Hcy and age, 24-h urine protein, and ESR at the early stage of 156 IgAN patients, which might be partially explained by the small sample size.Of note, we investigated the relationship between Hcy and clinicopathologic characteristics in the whole cohort of 337 IgAN patients and then in the subgroup with eGFR ≥90 ml/min/1.73 mTo date, whether Hcy is just a marker or plays a causal role in IgAN remains to be elucidated. The main strength of this study was that we assessed the association between serum Hcy and clinicopathologic characteristics in IgAN patients with normal renal function. We observed that elevated Hcy displayed more severe clinicopathologic characteristics, and pathologic T was an independent risk factor for elevated Hcy even in the early stage of IgAN. Our study prompted clinicians to pay more attention to Hcy levels in IgAN patients, especially at early stages. Previously, a randomized controlled trial in China suggested that Hcy-lowering therapy can significantly delay the progression of renal impairment among patients with mild-to-moderate CKD . FurtherThe present study had some limitations. First, because of the cross-sectional design of this study, we cannot obtain any causal inferences from the data. Second, as a single-center study, our study could not exclude the limits of races and regions, and its external validity may be limited. Third, the serum Hcy cutoff points differed among the previous studies , 11, 36.IgAN patients with elevated serum Hcy displayed more severe clinicopathologic characteristics. Pathologic T was an independent risk factor associated with elevated Hcy in IgAN patients, especially at the early stage of IgAN.Additional file 1: Supplement Table 1. Clinicopathologic characteristics comparison in the subgroup of IgAN patients with eGFR≥90 ml/min/1.73 m2. Supplement Table 2. Correlations between Hcy and clinicopathologic parameters in the subgroup of IgAN patients with eGFR≥90 ml/min/1.73 m2. Supplement Table 3. Clinicopathologic features as factors of elevated Hcy by univariate and multivariate logistic regression analysis in whole populations with "Enter" method. Supplement Table 4. Clinicopathologic features as factors of elevated Hcy by univariate and multivariate logistic regression analysis in patients with eGFR≥90 ml/min/1.73 m2 with "Enter" method.


Hypertension (HTN) is a chronic disease that affects more than 972 million people throughout the world, which is usually associated with endothelial dysfunction. Scientists are closely investigating endothelial dysfunction and have recently discovered the endothelium-derived relaxing factor (EDRF) known as NO (nitric oxide), which is derived from a semi-essential amino acid, L-arginine, by the action of endothelial nitric oxide synthase (eNOS). Production of adequate amounts of NO by vascular endothelial cells is essential to maintain normal blood pressure and prevent the development of HTN. Asymmetrical dimethylarginine (ADMA) is an endogenous NOS inhibitor that is increased in those with HTN especially in patients with renal dysfunction. In the present review, the role of L-arginine, arginine transporters, and ADMA in the pathobiology of HTN and their potential clinical significance are discussed. In 2000, a total of 972 million adults were affected with hypertension . HyperteHypertension and endothelial dysfunctionHypertension can be caused by the inactivation of NOS and salts, which gradually increases and stimulates blood pressure. Coleman and Guyton conducted an experiment that shows the effect of salts on hypertension in dogs by salt loading, and they concluded that dogs who were salt-loaded acquired an elevation in blood pressure of the arteries, unlike normal dogs .The endothelium, the inner coating of blood vessels, moderates the tone of the vascular smooth muscle by releasing relaxing and contracting factors . NO and L-arginine and vasodilationIn 1998, Robert Furchgott, Louis Ignarro, and Ferid Murad were honored with the Nobel Prize in Physiology of Medicine as they discovered the identity of endothelium-derived relaxing factor (EDRF) as NO. It was an important discovery that led to a long series of papers and clinical trials relating to the endothelium vasodilator . NO is pL-arginine is a semi-essential amino acid as it is present in many dietary proteins and produced from another amino acid, L-citrulline. Therefore, an increase in L-citrulline leads to an increase in L-arginine, which leads to an enhancement in NO production. A recent study was done on 17 young men with normal blood pressure who were given citrulline supplementation for four weeks . The resCellular L-arginine transportersExtracellular L-arginine needs special transport channels in the plasma membrane to get in the cell. There are two main transport systems, y+ and y+L, which are responsible for transporting L-arginine and cationic and neutral amino acids through the plasma membrane. Cellular L-arginine transport can be affected by extracellular concentration of L-arginine, cationic or neutral amino acids . Both y+Although the y+ transport mechanism is considered the most vital in epithelial cells, both y+ and y+L transport mechanisms mediate L-arginine uptake. On the other hand, both cationic and neutral amino acids are transported by system y+L. System y+ is a family of cationic transporters that are encoded as CAT1, CAT2A, CAT2B, and CAT3.29-32. The y+l mechanism, which is present in endothelial cells, is connected with CD/984F2 heavy chain. Cationic amino acids of sodium can be independently transported by y+ and y+l systems. However, uptake of neutral amino acids is related to y+l transporters, which depend on sodium [m in the L-arginine transport seems to be greater than that of the latter, this increase was noted as insignificant [L-arginine transport in endothelial cells is seen to be affected by the concentrations of insulin and glucose. In a research by Sobrevia et al., results showed an augmentation in L-arginine transport due to an elevation in the glucose levels. Insulin was also noted as an important modulator of L-arginine transport. Human insulin stimulated the L-arginine transport in the cells with lower glucose levels while decreasing the transport of L-arginine for the cultured cells with higher levels of glucose. Although Knificant .Inhibition of nitric oxide synthesisADMA is L-arginine’s methylated isomer derived from proteins. ADMA is a competitive inhibitor of NOS. Impaired NO synthesis leads to many conditions . ResearcIn healthy middle-aged humans, L-arginine has proved not to be a limiting factor; therefore, it does not correlate with blood significantly . In patiRole of the kidney in hypertensionThe main factors of developing renal hypertension are related to the disturbance of the relationship between the renal fluid and renal perfusion pressure and sodium excretion . These rMost endogenous L-arginine synthesis occurs in the kidney. The kidney acquires approximately 80% of the intestinal citrulline, which is released from glutamine metabolism, for L-arginine production . The bioL-arginine and angiotensin II-induced hypertensionIt has recently been discovered by Rajapakse et al. that an exogenous L-arginine can dramatically reduce angiotensin II (Ang II)-induced hypertension in Sprague Dawley rats . This, wWhile the direct relation of exogenous L-arginine in NO synthesis is still unconfirmed, L-arginine has been discovered to increase renal plasma flow (RPF) in healthy humans by 12%-15% . HoweverA recent trial on 10 healthy males studied the effects of L-arginine on angiotensin-converting enzyme (ACE) . An intrOral administration vs. intravenous administrationResearches have shown us the variation in the results of administrating L-arginine. In Higashi et al.’s trial, 10 healthy males were intravenously (IV) induced with L-arginine (500 mg/kg over 30 min) . As a reAlthough the hypotensive effects of L-arginine are not yet confirmed, there is an evident, modest decrease in blood pressure when a patient is administered with L-arginine. A greater decrease in blood pressure is seen in hypertensive patients or patients with endothelial dysfunction. Cellular L-arginine transport can be affected by extracellular concentration of L-arginine, cationic or neutral amino acids. Also, L-arginine transport in endothelial cells is seen to be affected by the concentrations of insulin and glucose. The kidney plays a major role in the synthesis and excretion of L-arginine in terms of reducing blood pressure by acquiring the intestinal citrulline. It is found that L-arginine is better at decreasing blood pressure by reversing the causes of hypertension such as ADMA and Ang II than at improving the blood pressure at regular conditions. L-arginine supplementation has also shown great effects regarding renal hypertension. Individuals with hypertension tend to have a poor endothelial function, a condition that can be recovered by the supplementation of L-arginine. Furthermore, studies show an improvement by supplementation of L-arginine in patients with diabetes mellitus and congestive heart failure. For future references, larger clinical trials must be made to enforce the acknowledgment of the effects of L-arginine. More trials with a specific type of patients would help further understand and explore the effects even more.


Chronic kidney disease (CKD) is now an enormous worldwide health problem. The incidence and prevalence of CKD is high and still increasing, mainly owing to obesity and diabetes, and is associated with growing morbidity and mortality . OverallCurrent management of CKD includes blood pressure control, treatment of albuminuria with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, nutritional intervention, avoidance of potential nephrotoxins and obesity, drug dosing adjustments, and cardiovascular risk reduction. Recent progress in our understanding of CKD pathophysiology together with the development of novel therapeutic agents has led to a renewed attention on the treatment of CKD and its associated metabolic complications which are now amenable to intervention. It is this point that led to the creation of this relevant Special Issue. I am happy to know that scientists from several parts of the world responded with enthusiasm to the opportunity, sending papers which involve genetics, pathophysiology and epidemiology together with the novel therapeutical approaches to CKD.d-mannosidase (MANBA) is an exoglycosidase involved in the sequential degradation of the N-glycosylproteins glycans. Recently, the MANBA gene was proposed as a kidney disease severity gene. In this issue, Hye-Rim Kim et al.  disease is a leading cause of morbidity and mortality in patients with CKD and in those on hemodialysis [HD]  and is sHyperphosphatemia is a common complication of CKD. Even if severe hyperphosphatemia is clinically asymptomatic, it is associated with morbidity and poor outcome. Hyperphosphatemia is an emerging cardiovascular risk factor in CKD, by contributing to vascular calcification. However, mechanisms by which hyperphosphatemia is associated to CV complications are not clearly understood. Abbasian et al.  studied 2 in patients with diabetes mellitus, after performing multivariate regression analysis. In addition, they found that pre-HDBP at the start of the week, post-HDBP at the end of the week, and weekly averaged BP (WABP) were independently associated with LVMI on univariate regression analysis of follow-up. Multiple BP measurements taken before, during and after dialysis were confirmed to be the most accurate assessment format, a finding which suggests that multiple measurements of BP should be performed and then averaged in this clinical setting.Both in CKD and HD patients, volume and pressure overload ultimately lead to LVH, a significant predictor of increased CV events . Althoug+ excretion has been represented by sodium polystyrene sulfonate, a cation-exchanging resin. Recently, new drugs able to promote gastrointestinal potassium elimination, namely patiromer and sodium zirconium cyclosilicate, have been developed and studied in large trials, proving their efficacy and safety in different clinical contexts. In this review, Esposito et al. , in CKD stage 3–5, and in patients with diabetes mellitus. Among CKD patients, those requiring dialysis represent a group at particularly high risk of hyperkalemia. For a long time, the only therapeutic option for increasing fecal Ko et al.  have revn = 105) patients on conservative therapy , or renal replacement therapy (HD = 32 pts or PD = 36 pts), for at least 3 months. A total of 173 patients, with a median age of 76 years, was studied. The median duration of all the hospitalizations was 6 days and the number of deaths was 33. MPI significantly correlated with days and number of hospitalizations per year. According to the findings, MPI was associated with outcomes in patients with renal disease, suggesting that a multidimensional evaluation should be implemented in this clinical context.Assessing cognitive, nutritional and functional status in elderly subjects with CKD is emerging as a new tool to stratify the risk to develop ESRD and death . In addiMany of the important issues dealing on prevention and treatment of CKD are addressed in this volume. We thank the writers, the large number of investigators and the MDPI staff for their leadership in producing this Special Issue. We hope the readers will enjoy and benefit from new insight.


Pregnancy results in many changes, including reduced hand grip strength (HGS). However, good HGS is required for physical functions such as carrying and breastfeeding the baby after birth. The aim of this study was to determine the factors that may predict HGS during pregnancy.The study was a cross-sectional study approved by the Research Ethics Committees of Kano State Ministry of Health and Aminu Kano Teaching Hospital in Kano, north-west, Nigeria. Pregnant women at the designated hospitals were included in the study if they had no serious comorbidities or any known neurological condition that affects the hands and the neck. Demographic characteristics and independent (predictor) variables  of each of the participants were recorded by experienced therapists. The data were analysed using descriptive statistics, t-test, Pearson correlation coefficient and standard multiple regression.2 = 0.081, p = 0.300 . In the final model, none of the variables significantly predicted HGS. However, systolic blood pressure contributed to the model more than any other variable (Beta = -0.155). For the non-dominant hand, the total variance explained by the whole model was not significant, 33.1%, F = 1.675, R2 = 0.111, p = 0.089 . In the final model, only systolic blood pressure  significantly predicted hand grip strength.One hundred and sixty-one pregnant women with mean age, 25.04 ± 4.83 years participated in the study. In the dominant hand, 120 participants (74.5%) had weak grip strength. In the non-dominant hand, 135 participants (83.9%) had weak grip strength. For the dominant hand, the total variance explained by the whole model was significant, 28.5%, F = 1.187, RCardiovascular events or changes during pregnancy (such as change in systolic blood pressure) may be related to HGS in pregnant women. It is therefore, important for clinicians to pay attention to this, in planning rehabilitation strategies for pregnant women.The online version contains supplementary material available at 10.1186/s12884-021-04003-0. Pregnancy can cause physiological, psychological and physical changes in women. Some of the physical changes include musculoskeletal changes such as reduced hand grip strength (HGS) , 2. ReduReduced HGS may help indicate health outcomes. This is because hand grip strength is an indicator of many health outcomes such as physical strength, cognition, functional status, mobility, pulmonary function, and cardiovascular health , 8–11. CReduced HGS is characterised by pain, numbness, difficulty in grasping objects, muscle weakness and tendency of things to drop from the hand , 20. HowThe study used a cross-sectional research design. The population of the study was pregnant women attending antenatal clinics at Aminu Kano Teaching Hospital (AKTH), Murtala Muhammad Specialists Hospital (MMSH) and Muhammad Abdullahi Wase Specialist Hospital (MAWSH), all in Kano, Nigeria. The study was approved by the Research Ethics Committees of AKTH (AKTH/MAC/SUB/12A/P-3/VI/2392) and Kano State Ministry of Health (MOH/Off/797/T.I/740). Participants were included if they were pregnant , and had neither movement restriction in the upper limbs nor positive history of any neurological disorder. The participants were consecutively recruited into the study. In addition, all participants provided written informed consent for their participation in the study.2) = 0.15 . We included maternity leave status as one of the independent variables because it may affect the participants’ level of physical activity, which may also affect HGS. Data for this study was collected using a proforma for demographic and other independent variables, a portable weighing scale for body weight, tape measure  for height, Camry electronic hand dynamometer  for HGS and sphygmomanometer, and stethoscope  for blood pressure. An electronic hand dynamometer is an affordable and a reliable instrument for measuring of hand grip strength [The minimum sample size for the study was 143. This was calculated using G power software . The calstrength , 24.2, normal weight = BMI from 18.5 kg/m2 to 24.9 kg/m2, over weight = BMI from 25 kg/m2 to 29.9 kg/m2 and obese = BMI above 30.0 kg/m2 [Body weight was measured with the participants in minimal clothing and without shoes. The measurement was carried out in kg to the nearest 0.5 kg using a portable weighing scale . Height .0 kg/m2 .For the measurement of HGS, the participants were seated comfortably in a chair with the arm resting on the arm rest. They were then made to hold the test arm of the dynamometer at a 90° elbow flexion, with the forearm placed in a neutral position and the hand parallel to the forearm. Thereafter, the participants were asked to squeeze the dynamometer to the best of their ability three times. This was carried out for both hands starting with the dominant hand, followed by the non-dominant with two minutes interval between them. The measurements were recorded in kilograms and the mean of the three trials was taken as the measure of  HGS. The three trials were carried out with each of the hands with one minute rest period between them.th June, 2018 and 30th August, 2018.Similarly, to measure blood pressure (BP), the participants were seated comfortably in a chair with the arm resting on the arm rest. The  BP was measured using a mercury sphygmomanometer and was undertaken twice on each arm (for both the dominant and non-dominant hands). One-minute interval was allowed between each measurement. We chose one minute interval because blood pressure can change with time. Therefore, we decided on a short interval. Following the measurements, the average was obtained and used as the BP value. All measurements were carried out in a conducive and well ventilated environment to avoid overestimating or underestimating the measurement since temperature can affect blood pressure. In addition, an appropriate cuff size was used, and the correct placement of the cuff was achieved  in order to obtain accurate readings. The diaphragm of the stethoscope was placed over the brachial artery. The participants were also instructed to relax and avoid any thought or activity that could raise their level of anxiety prior to the measurement. Data at the three study sites were collected by experienced physiotherapists (one in each study site) who were blinded from the aim of the study. The data collection took place between 4The data obtained were analysed using Statistical Package for Social Sciences (SPSS) version 20.0 and a p-value of < 0.05 was considered significant in the analysis. The normality of the data distribution was assessed using Kolmogrov-Smirnov statistics which showed normal data distribution (p > 0.05). Consequently, parametric statistics (Pearson product moment correlation) was used to analyse the relationship between the independent and dependent variables; and between the independent variables. In addition, the difference in HGS between trimesters was analysed using analysis of variance (ANOVA). The difference between trimesters was determined using ANOVA because the measurement was carried out once in each trimesters. Therefore, the rationale was to determine the variance between trimesters especially that there were differences in the number of participants between trimesters. Furthermore, descriptive statistics of mean, frequency, distribution tables, and standard deviation were used to describe the data.Finally, standard multiple regression analysis was carried out to determine whether the independent variables age, BMI, maternity leave status, number of abortuses, number of live births, number of termed deliveries, number of preterm deliveries, trimester, heart rate, systolic BP, diastolic BP, inter arm systolic BP difference and inter arm diastolic BP difference could predict HGS in pregnant women. Standard multiple regression analysis means the independent variables were entered into the model to help determine the variable or variables that predict HGS better or more than the others without considering the order of entry of the variables into the model.A total of 161 pregnant women with age range, 17 to 39 years participated in the study  had weak grip strength. In the non-dominant hand,  135 participants (83.9%) had weak grip strength. Overall, the dominant and non-dominant hands’ mean HGS was 20.46 ± 4.61 kg and 7.87 ± 4.40 kg respectively, indicating reduced grip strength. The normal values of HGS for the left and right hand are 30.8 (27.2 to 34.5) kg and 33.8 (29.5 to 38.1) kg respectively .The result also showed no significant difference (p > 0.05) in grip strength between trimesters. The result is presented in Table For both the dominant and non-dominant hands, HGS is correlated with the independent variables. See Tables 2 = 0.081, p = 0.300 . In the final model, none of the variables significantly predicted HGS. However, systolic blood pressure contributed to the model more than any other variable (Beta = -0.155). See Table For the dominant hand, the total variance explained by the whole model was not significant, 28.5%, F11, 161) = 1.187, R1 = 1.1872 = 0.111, p = 0.089 . In the final model, only systolic blood pressure  significantly predicted hand grip strength. See Table For the non-dominant hand, the total variance explained by the whole model was not significant, 33.1%, F = 1.675, Rrd trimester. Therefore, we conducted a posthoc analysis to determine whether age, BMI, maternity leave status, number of preterm deliveries, number of abortuses, systolic blood pressure, diastolic blood pressure, inter arm systolic BP difference (IASBP), inter arm diastolic BP difference (IADBP), and heart rate will significantly predict HGS during the 3rd trimester. The result showed that, for the dominant hand, the total variance explained by the whole model was not significant, 34.0%, F = 1.060, R2 = 0.116, p = 0.402 . In the final model, only systolic blood pressure  significantly predicted HGS. See Table Although, there was no significant difference in HGS between trimesters, but majority of the participants (n = 92) were within the 32 = 0.116, p = 0.396 . In the final model, none of the independent variables significantly predicted HGS. See Table For the non-dominant hand, the total variance explained by the whole model was not significant, 34.1%, F10, 92) = 1.068, R2 = 1.068The main aim of this study was to determine HGS and its predictors in pregnant women. The result of the study showed that only systolic blood pressure significantly predicted HGS. Both reduced grip strength and increased blood pressure have been reported to be caused by hormonal changes, increased protein level and fluid retention in pregnant women , 30, 31.Similarly, it may help reduce fatigue and deconditioning during pregnancy and after delivery –41. TherIn addition, in the present study, the result showed no significant difference in HGS between trimesters. However, in a recent study, it was reported that, weak grip strength was more prevalent in the third trimester . This mard trimester was analysed, systolic blood pressure also significantly predicted HGS in the dominant hand . Long standing high systolic blood pressure could probably lead to inefficiency in the pumping of blood by the heart, which will ultimately lead to fluid retention. Fluid retention may worsen the pathophysiology of reduced HGS [In a previous study, HGS was shown to have no significant association with blood pressure in the elderly; but it has a significant association with the middle-aged participants . Althouguced HGS , 7. Addiuced HGS . Consequuced HGS , 46. Theuced HGS .Another variable in the literature that is related to HGS is BMI, and is said to exist regardless of hand dominance , 49. SimFull-term deliveries appear to be the best predictor of HGS even though it is not significant. This indicates that the more gravidity and the more pregnancy is to term, the more physiological changes occur in the body, leading to symptoms that cause reduced HGS. However, this study has some limitations or weaknesses. One of its weaknesses is the lack of use of qualitative inquiry to explore the pregnant women’s experience with their HGS during pregnancy. In addition, lack of assessment of mobile phone use during pregnancy, and the level of physical activity of the study participants were some of the other potential weaknesses of this study. This is because, mobile phone usage, and physical activity level can affect HGS , 52. MorCardiovascular events or changes during pregnancy (such as change in systolic blood pressure) may be related to HGS in pregnant women. Therefore, it is important for clinicians to monitor pregnant women with reduced HGS for fluctuations in systolic blood pressure or vice-versa. This will help them design novel exercises or rehabilitation strategies that can be used to combat the effects of reduced HGS and high blood pressure capable of endangering the lives of the expectant mother and the foetus or the baby after birth. In addition, future studies should determine how long post-delivery does it take for a person to regain  HGS; and whether strength and conditioning exercise protocol is beneficial post-delivery.Additional file 1.