We reviewed 583 adult patients without baseline renal dysfunction and who did not receive hydroxyethyl starch during surgery. AKI was defined using the Kidney Disease Improving Global Outcomes criteria according to the serum creatinine criteria. Multivariable logistic regression analysis was performed with and without oliguria and oliguria coupled with a decrease in SvO2. The performance was compared with respect to the area under the receiver operating characteristic curve (AUC). Intraoperative oliguria <0.5 and <0.3 mL/kg/h were significantly associated with the risk of AKI; however, their performance in predicting AKI was poor. The AUC of single predictors increased significantly when oliguria was combined with decreased SvO2  0.68–0.75 vs. AUC of oliguria alone 0.61; 95% CI 0.56–0.61; p < 0.0001; vs. AUC of SvO2 alone 0.66; 95% CI 0.61–0.70; p < 0.0001). Addition of oliguria coupled with SvO2 reduction also increased the AUC of multivariable prediction . Intraoperative oliguria coupled with a decrease in SvO2 may suggest the risk of AKI after LDLT more reliably than oliguria alone or decrease in SvO2 alone. Intraoperative oliguria should be interpreted in conjunction with SvO2 to predict AKI in patients with normal preoperative renal function and who did not receive hydroxyethyl starch during surgery.Acute kidney injury (AKI) is a frequent complication after living donor liver transplantation (LDLT), and is associated with increased mortality. However, the association between intraoperative oliguria and the risk of AKI remains uncertain for LDLT. We sought to determine the association between intraoperative oliguria alone and oliguria coupled with hemodynamic derangement and the risk of AKI after LDLT. We evaluated the hemodynamic variables, including mean arterial pressure, cardiac index, and mixed venous oxygen saturation (SvO The incidence of acute kidney injury (AKI) after orthotopic liver transplantation has been reported to be as high as 64% ,2,3,4. ADiagnosis of AKI is based on elevation of serum creatinine and/or decrease in urine output in the currently available KDIGO  criteria ,11. HoweThe current urine output criteria of AKI suggest that a urine flow rate of <0.5 mL/kg/h lasting for more than 6 h indicates stage 1 AKI ,11. A ra2) from pulmonary artery catheter are frequently monitored, although less invasive monitoring is increasingly used. Oliguria coupled with the deterioration in these hemodynamic variables may predict AKI better than oliguria alone because the other causes of oliguria that are not associated with AKI could be excluded. Oliguria developed from poor renal perfusion and oxygen delivery may be more strongly associated with AKI after LDLT. The etiology of acute kidney injury during surgery includes hemodynamic instability that may result in decreased renal perfusion. During LDLT, intraoperative hemodynamic variables including continuous arterial pressure, cardiac index, and mixed venous oxygen saturation , those who had baseline renal dysfunction with an estimated glomerular filtration rate of <60 mL/min/1.73m2 and/or with hepatorenal syndrome (n = 73), and those who received hydroxyethyl starch during surgery (n = 188) were excluded from the analysis. The remaining 583 patients who had undergone LDLT were analyzed. This retrospective observational study was approved by the institutional review board of Seoul National University Hospital (1608-073-784). We reviewed the electronic medical records of 1211 consecutive adult patients who had undergone liver transplantation at our institution between 2004 and 2015. The need for informed consent was waived because the study had a retrospective design. Patients who received deceased donor liver transplantation  that was placed in the right internal jugular vein. Continuous cardiac index and right ventricle-associated variables were monitored using the Vigilance II monitor . The cause of hypotension was determined on the basis of cardiac index, stroke volume variation, SvO2 and systemic vascular resistance and was treated using either (1) ephedrine and continuous dopamine, (2) phenylephrine and norepinephrine, and/or (3) epinephrine. Donor grafts were prepared using a histidine-tryptophan-ketoglutarate solution. The piggyback technique was used to anastomose the graft and donor vessels. End-to-end anastomosis of the hepatic artery and duct-to-duct anastomosis of the bile duct were carried out in succession. During surgery, immunosuppression was induced using 500 mg of methylprednisolone  and 20 mg of intravenous basiliximab . During the postoperative period, immunosuppression was induced using calcineurin inhibitors of either tacrolimus or cyclosporine with mycophenolate mofetil. During the study period, the anesthesia protocol of our institution was as follows. Anesthesia was induced and maintained using propofol, rocuronium, and sevoflurane. Volume-controlled ventilation was maintained, with a tidal volume of 6–8 mL kgWhen intraoperative oliguria occurred during the study period, we administered crystalloid solutions to increase preload when surgical bleeding is evident or preload indices including central venous pressure, pulmonary artery occlusion pressure, and/or right ventricular end-diastolic volume indicated intravascular hypovolemia. Vasopressor was used to increase renal perfusion pressure when urine output decreased with euvolemia. Diuretics were used only when intravascular volume overload was suspected with elevated central venous pressure, pulmonary artery occlusion pressure, and/or right ventricular end-diastolic volume. Diuretics were not used to treat intraoperative oliguria. The following crystalloid fluids were used to optimize the preload during LDLT before 2010: lactated Ringer’s solution, normal saline, and plasmalyte, and hydroxyethyl starch . The administration rate of crystalloid during LDLT was adjusted according to the hemodynamic preload index of central venous pressure, pulmonary artery occlusion pressure, and stroke volume variation. The hematocrit threshold for red blood cell transfusion was 20% during LDLT throughout the study period. Intraoperative diuretics  were used in patients with persistent positive fluid balance and when volume overload was suspected due to a pulmonary artery wedge pressure greater 18 mmHg. Based on previous literature, demographic and perioperative variables known to be related to postoperative renal dysfunction or AKI were collected ,20,21,222 by pulmonary artery catheter and the Vigilance II monitor were used as a baseline. Sudden decrease in mean arterial pressure, cardiac index, and SvO2 lower than 20% from baseline for at least one measurement was identified and recorded as a categorized variable. The resting arterial blood pressure before anesthesia induction was used as baseline blood pressure. The initially measured cardiac index and SvOThe primary outcome variable was postoperative AKI, as defined using the KDIGO criteria, which have been validated in patients undergoing LDLT . We detep-values < 0.05 were considered statistically significant. The Kolmogorov-Smirnov test was used to determine the normality of the data. All the continuous covariates listed in SPSS software version 23.0  and STATA/MP version 15.1  were used to analyze the data. In all analyses, 2. Third, we evaluated whether the oliguria coupled with hemodynamic derangement could enhance the AUC of the multivariable prediction model for AKI after LDLT. The following is a summary of our statistical analysis. First, we determined the cutoff of intraoperative mean urine output by multivariable logistic regression analysis. Second, according to oliguria using the cutoff, we compared the predictive ability of the oliguria alone with that of oliguria coupled with a decrease in mean arterial pressure, cardiac index, and SvOp-value < 0.20 was used to select for significant predictors in the multivariable analysis, with the backward stepwise variable selection. We also performed multivariable logistic regression analysis without stepwise variable selection. Multivariable logistic regression analysis was performed (1) to find an optimal cutoff of oliguria, and (2) to evaluate the association between perioperative variables and postoperative AKI. The following variables were considered potential risk factors of AKI after LDLT in addition to oliguria and hemodynamic variables: age, sex, body-mass index, year of operation, MELD score, CTP score, hypertension, diabetes mellitus, preoperative hemoglobin level, preoperative serum albumin, preoperative serum creatinine, ABO blood type incompatibility, operation time, graft ischemic time, preoperative diuretics use, intraoperative blood loss, intraoperative crystalloid and colloid administration, transfusion amount and total dose of diuretics administered during surgery. We did not perform any univariable screening before the multivariable analysis. A Three different cutoffs of intraoperative mean intraoperative urine flow rate including 1.0, 0.5, and 0.3 mL/kg/h were evaluated, because oliguria less than these cutoffs was significantly associated with postoperative AKI in our preliminary multivariable logistic regression analysis using perioperative baseline variables with mean urine output with different cutoffs .To compare the predictive ability of oliguria using these cutoffs with that of oliguria coupled with three hemodynamic variables, the area under the receiver operating characteristic curve (AUC) was calculated for every single potential predictor. Also, performance measurements including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were compared. Multivariable logistic regression analysis was performed again by adding the predictors of oliguria coupled with hemodynamic variables. Then, the AUCs of a multivariable prediction model with and without these oliguria coupled with hemodynamic variables were compared to evaluate whether these combined predictors could increase the predictive ability of multivariable prediction model. The comparison between AUCs was performed using De Long’ s method . p = 0.007).During the first postoperative week, AKI, as determined using the KDIGO criteria, occurred in 205 patients (35.2%), and stage ≥2 AKI occurred in 43 patients (7.4%). Patient demographics and perioperative variables were compared between the patients with and without AKI in p-values according to oliguria with different cutoffs are shown in The odds ratios, 95% CI and their 2. AUC was largest for oliguria <0.5 mL/kg/h with SvO2 reduction . The performances to predict postoperative AKI of a single variable of oliguria, a single variable of 20% decrease in hemodynamic variables, and their combined variables were compared in terms of AUC, sensitivity, specificity, PPV, and NPV . Three d2 reduction were compared in 2 20% reduction was significantly greater than all other variables . The AUCs of four single predictors of oliguria <0.5 mL/kg/h alone, oliguria coupled with mean arterial pressure reduction, oliguria with cardiac index reduction, and oliguria with SvO2 reduction are shown in R2 of the model with and without oliguria with SvO2 reduction were 0.16 and 0.39, respectively. Both models showed good calibration . The results of multivariable logistic regression analysis without stepwise variable selection are shown in The results of multivariable logistic regression analysis to predict postoperative AKI with and without including oliguria <0.5 mL/kg/h coupled with SvO2, (2) multivariable prediction with oliguria <0.5 mL/kg/h, and (3) multivariable prediction with oliguria <0.5 mL/kg/h coupled with SvO2 reduction are compared in 2 reduction: 0.87, 95% CI 0.84–0.90 vs. AUC without oliguria or SvO2 reduction: 0.68, 95% CI 0.64–0.72, p < 0.0001; vs. AUC with oliguria: 0.73, 95% CI 0.69–0.77, p < 0.0001). The AUCs of (1) the multivariable prediction without oliguria or SvO2, the AUC of a single predictor significantly increased, while oliguria coupled with mean arterial blood pressure or cardiac index failed to increase the AUC. These results suggested that oliguria accompanied by a reduction in SvO2 during LDLT may be more strongly associated with the development of AKI than oliguria or reduction in SvO2 alone. The AUC of multivariable prediction showed similar results and the model including oliguria coupled with decreased SvO2 showed significantly higher performance in terms of AUC and Nagelkerke’s R2. Although oliguria alone is not specific and has little value in predicting AKI after LDLT, oliguria coupled with a decrease in cardiac output or SvO2 could significantly increase the sensitivity and predictive ability for AKI after LDLT. However, our results should not be applied to the patients with poor baseline renal function including hepatorenal syndrome and the patients who received hydroxyethyl starch during surgery. Also, our results should be interpreted cautiously, because our oliguria was determined by the intraoperative mean value and the duration of oliguria was not considered. To our knowledge, the present study was the first to evaluate the association between intraoperative mean urine output, hemodynamic variables, and AKI after LDLT. Although there was a significant association between oliguria <1.0, <0.5 and <0.3 mL/kg/h and risk of AKI, the predictive ability of oliguria alone was relatively poor and did not add substantial additional discriminative power in multivariable prediction. However, when oliguria developed in association with decreased SvOThe urine output criteria of the RIFLE criteria  and the AKIN (AKI network) criteria are widely used to diagnose AKI . The cliSeveral studies have attempted to derive urine output thresholds that identify AKI in surgical patients ,31,32. Un = 435) showed that <1.0 mL/kg/h was not significantly associated with postoperative AKI (Along with the usual <0.5 or <0.3 mL/kg/h cutoff of oliguria, our analysis suggested significant associations between low urine flow rate of <1.0 mL/kg/h and risk of AKI after LDLT. We evaluated the cutoff of oliguria up to 3.0 mL/kg/h because previous studies reported different cutoffs of oliguria during surgery ,31,32 S. The sigtive AKI . 2 showed a slightly better performance as a single predictor, the other hemodynamic variables did not. However, oliguria coupled with a decrease in SvO2 showed a significantly better performance as a single predictor and enhanced the predictive ability of multivariable prediction when included in the multivariable logistic model.The performance of oliguria in predicting AKI defined by creatinine criteria was poor at any cutoff . AUC was2 may suggest poor oxygen delivery to the kidney [2 during LDLT reflects decreased oxygen delivery by low cardiac output to the major organs including kidney. When oliguria developed in a patient who experienced a decrease in SvO2, the oliguria of the patient is more likely to be caused by poor renal perfusion and oxygen delivery to the kidney. Meanwhile, the oliguria alone may not be associated with poor oxygen delivery to the kidney but associated with an extrarenal cause such as a transient decrease in preload or urinary tract obstruction.A low SvOe kidney . During e kidney . A low S2 during liver transplantation [However, decrease in cardiac index or mean arterial pressure combined with oliguria did not increase AUC to predict AKI after LDLT. Mean arterial pressure is not a sensitive marker to measure the cardiac output and oxygen delivery to the major organ especially in patients with significant cirrhosis or during and after reperfusion with unequal vasodilation . Cardiacantation . Several urinary or serum biomarkers were reported to be sensitive to predict AKI after surgery ,38,39. T2. However, routine use of pulmonary artery catheter has been a subject of debate. A previous multicenter trial reported no difference in mortality in high-risk surgical patients with and without hemodynamic management guided by pulmonary artery catheter [2 monitoring with pulmonary artery catheter [Hemodynamic optimization may protect renal function in surgical patient . Our rescatheter . Pulmonacatheter . There was a significant difference in gender distribution between the patients with and without AKI . The incThe present study had several limitations. Firstly, it was a single-center retrospective analysis, and urine flow rate data collected from the medical records may have been inaccurate. Furthermore, our cutoff for urine output may not be extrapolated to other institutions with different fluid management strategy and different baseline medical conditions, although multivariable adjustment was performed in this study. The intraoperative urine output may differ markedly depending on the intraoperative goal of fluid management, transfusion amount and intraoperative diuretics or hydroxyethyl starch use. Secondly, in our analysis, we used a mean urine flow rate during surgery rather than hourly urine output. However, oliguria lasting for longer than 6 h is required for the KDIGO criteria. Furthermore, there may be critical periods during LDLT, such as the anhepatic or reperfusion period, which involve unstable hemodynamics and severe metabolic acidosis . In futu2, the performance to predict AKI improved significantly and the predictive ability of multivariable prediction model was significantly enhanced. Decrease in cardiac index or mean arterial blood pressure combined with oliguria did not significantly increase the AUC to predict AKI after LDLT. Intraoperative oliguria interpreted in conjunction with a decrease in SvO2 may suggest the risk of AKI after LDLT more reliably in patients with normal baseline renal function and who did not receive hydroxyethyl starch during transplantation surgery.Intraoperative oliguria alone could not accurately predict AKI after LDLT determined by creatinine criteria, although there were significant associations using a cutoff of oliguria <1.0, <0.5 and <0.3 mL/kg/h. However, when oliguria with these cutoffs was found with decreased intraoperative SvO


Lupus nephritis (LN) is one of the most common manifestations of systemic lupus erythematosus (SLE) and is often the most serious organ complication and the cause of premature death of such a patient. Most of other organs and systems can be also affected. A typical complication is a cardiovascular involvement leading to the development of heart failure. According to current therapeutic standards, kidney transplantation is the treatment of choice in patients with renal failure in course of LN. On the contrary, a kidney transplantation in a patient with an additional heart disease poses a serious clinical challenge.We present a case of a 49-year-old woman with renal and heart failure following a long-term SLE prepared for kidney transplantation. During the SLE course, the function of the heart and kidneys gradually deteriorated. The patient required the initiation of renal replacement therapy and was dialyzed until a kidney transplantation for 4 years. In the preparation of the patient for the surgical procedure, due to the extremely low ejection fraction, it was decided to include cardioprotective treatment with Levosimendan. The postoperative period was not straightforward but successful. In the monthly and five-month follow-up, a continuous improvement of heart function with normal renal function was noted.Kidney transplantation in patients with lupus suffering from heart failure requires the involvement of a team of specialists. Patients with extremely low ejection fraction in the perioperative period should undergo careful hemodynamic supervision in the intensive care unit. Cardioprotective and thus nephroprotective Levosimendan therapy together with optimal fluid and hemodynamic therapy in the peri-transplant period may be a bridge for heart remodeling after kidney transplantation. Systemic lupus erythematosus (SLE) is a disease characterized by overactivity of the immune system manifested by the loss of autotolerance with overproduction of autoantibodies leading to multi-organ dysfunction. Kidney involvement (Lupus Nephritis - LN), is often the most serious organ complication and the cause of early death of the patient . Most ofKidney transplantation in a patient with a baseline cardiac dysfunction is a serious clinical problem. The pathophysiological interaction between the heart and the kidneys, also known as the cardio-renal syndrome (CRS), often occurs in heart failure and is associated with deterioration of renal function, as well as worse prognosis of therapy and quality of life. Considering the high risk of cardiological burdens and, thus, the possible impaired graft perfusion, there is a discussion about whether there are a validity and chance for graft durability and how high the risk of postoperative complications will be , 6. ProsLevosimendan is one of the inodilators. Its inotropically positive action is associated with a decrease in systemic resistance, which is often associated with the need to use vasoconstrictive drugs. Clinical data on the protective effect of Levosimendan on kidney function after various types of surgery are suggestive, but they are based only on a limited number of studies performed on small groups of patients , 13.regurgitant flow gradient with widened and poorly respiratory mobile inferior vena cava indicated a high probability of pulmonary hypertension. Furthermore, while preparing the patient for the surgical procedure, it was decided to include cardioprotective therapy with Levosimendan. Due to the time frame associated with the transplantation procedure, the drug infusion was started as soon as possible after cross-match results were known, immediately after the dialysis session. The infusion at a dose of 0.1 μg/kg/min was continued after surgery for a total of 24 h. The patient’s anesthesia for kidney transplantation and perioperative care included the aspect of optimizing transplanted kidney perfusion, avoiding the use of renal toxic drugs and those excreted by properly functioning kidneys, as well as the use of nephroprotective agents. Because of the patient’s cardiological burden, including recurrent episodes of extrasystole proceeding with decompensation of the circulatory system, together with the need of ICD turning off for the transplantation period, the Swan-Ganz catheter for hemodynamic assessment was not used. Anesthesia monitoring was limited the to ECG, central catheter with CVP assessment, direct blood pressure measurement from the cannula inserted into the radial artery, and cardiac ultrasound. In the perioperative period the CVP parameter was used to assess the volatility, and in the postoperative period, a cardiac ultrasound was used along with the assessment of VCI respiratory fill and motility. The therapy was aimed at the standard of fluid therapy called Goal Directed Therapy (GDT) [We present a case of a 49-year-old woman with renal and heart failure following a long-term (lasting from 13 years of age) SLE prepared for kidney transplantation. Due to LN , starting at childhood, she was treated with steroids, together with cyclophosphamide, replaced later by methotrexate and then azathioprine. Hence, the partial remission of nephrotic syndrome was achieved and from 2002 the patient did not receive any immunosuppressive therapy. She was also HBV and HCV positive. SLE involvement of circulatory system presented with early coronary atherosclerosis, ischemic heart disease, and myocardial infarction at the age of 20. In 2007, because of deterioration of kidney function with a serum creatinine concentration of 2.2 mg/dL and proteinuria of 2 g/day, the kidney biopsy was performed. The biopsy showed active and sclerotic focal proliferative lupus nephritis nevertheless immunosuppressive therapy was not introduced for the reason of active replication of HCV. The kidney function was gradually deteriorating over time. Despite cardiac intervention (PCI RCA), the patient developed severe post-infarction and dilated cardiomyopathy and required ICD implantation in primary prevention in 2009. Later, on lupus and secondary cardiomyopathic background, the patient developed severe MV and TV regurgitation. For this reason, the patient underwent mitral and tricuspid valve repair and left ventricle volume reduction surgery complicated by low cardiac output syndrome with a need for intra-aortic balloon pump use 2014). In the postoperative period, the kidney function deteriorated, requiring the initiation of renal replacement therapy. The patient has been on dialysis for 4 years. While being on active waiting list for kidney transplantation presented remission of laboratory indices of lupus  and persisting circulatory insufficiency with markedly reduced stair-climbing capacity (to one flight of stairs) with elevated BNP 619 pg/ml (n. 0–100). In transthoracic echocardiography, performed before renal transplantation, the left ventricle and the left atrium were significantly enlarged and the left ventricular systolic function was significantly reduced with LVEF 26% and GLS -3 Fig. . Due to . In the py (GDT) . During py (GDT) . In the Although in SLE patients kidney transplantations are connected with significantly lower morbidity and mortality than in SLE dialysis patients, the co-morbidities, especially circulatory system involvement remains a significant problem affecting the choice of renal replacement therapy . Unlike The pathological interaction between the heart and the kidneys, also known as the cardio-renal syndrome (CRS), often occurs in heart failure and is associated with deterioration of renal function, as well as worse prognosis of therapy and quality of life. Clinical data on the protective effect of Levosimendan are suggestive, but they are based only on a limited number of studies performed on small groups of patients. Improvement occurs through the described vasodilation, increased renal artery diameter, increased renal blood flow and simultaneous improvement of cardiac output. An equally important element of nephroprotection is the action of Levosimendan which improves the function of the right ventricle with a decrease in pulmonary hypertension and venous stasis within the kidneys , 13, 23.To conclude, kidney transplantation in patients with lupus suffering from heart failure each time requires an individual approach in the form of teamwork, which includes specialists in the field of nephrology and transplantology, cardiology and intensive care, as well as the extension of therapeutic concepts with the latest possibilities in the field of applied therapies. Patients with extremely low EF < 30% in the perioperative period should undergo careful hemodynamic supervision in the intensive care unit. Cardioprotective and thus nephroprotective Levosimendan therapy together with optimal fluid (GDT) and hemodynamic therapy in the peri-transplant period may be a bridge for heart remodeling after kidney transplantation.


Prognostic biomarkers in asthma are needed. The biomarker soluble urokinase plasminogen activator receptor (suPAR) has been associated with asthma control and with prognosis in acutely admitted medical patients. We investigated if suPAR and blood eosinophil counts at the time of admission for asthma are associated with readmission and mortality.Our cohort comprised 1341 patients  acutely admitted with a diagnosis of asthma to Hvidovre Hospital, Denmark (November 2013 to March 2017). Patients had suPAR and blood eosinophils measured at admission. Outcomes were 365-day readmission and all-cause mortality. Logistic regression analysis adjusted for age, sex, C-reactive protein, and Charlson comorbidity score was used to assess the association of the two biomarkers with readmission and all-cause mortality.n = 452, 42.3%) or died  had significantly higher suPAR concentrations (p < 0.0001) and lower eosinophil counts (p = 0.0031) at admission. The highest odds of readmission or mortality were observed for patients in either the 4th suPAR quartile (p < 0.0001) or with eosinophil counts < 150 cells/μL at admission. Increasing levels of suPAR were associated with 365-day readmission  and mortality . Eosinophil count > 300 cells/μL was significantly associated with lower odds of readmission  and lower mortality .Compared to event-free patients, patients who were either readmitted (In patients acutely admitted with asthma, elevated suPAR concentrations together with blood eosinophil count < 150 cells/μL at the time of hospital admission were associated with both 365-day all-cause readmission and mortality. Poorly controlled asthma is associated with impaired quality of life, accelerated decline in lung function, and, not least in more severe cases, repeated hospital admissions and increased mortality. The Global Initiative for Asthma estimates that half of the global asthma population has uncontrolled or only partially controlled disease , a risk Soluble urokinase plasminogen activator receptor (suPAR) is the soluble form of the urokinase plasminogen activator receptor (uPAR), a three-domain membrane receptor that is expressed on a plethora of cells ranging from mono- and lymphocytes to endothelial and smooth muscle cells. uPAR plays a central role in the plasmin/plasminogen pathway and is important for chemotaxis, immune system activation, and tissue remodeling . suPAR iIn asthma, sputum, biopsy, and serum suPAR has previously been shown to be elevated in stable asthma patients in comparison to controls –8. Plasm2 asthma, is the most prevalent asthma phenotype comprising up to 50% of asthma patients [2 asthma is seen over a wide disease spectrum from mild disease to difficult-to-control or severe asthma with high symptom burden and frequent exacerbations [2 asthma is characterized by both neutrophilic and paucigranulocytic forms, driven by neutrophils and/or mixed leukocyte populations [2 inflammation. We thus hypothesize that the two biomarkers could be used in conjunction to improve risk stratification in acutely admitted patients with asthma.Another, more intensely studied, asthma biomarker is blood eosinophil count. Eosinophilic asthma, often referred to as Tpatients . T2 asthrbations . Eosinoprbations . Howeverrbations . On the ulations . Interesulations , 15, comBased on a large, unselected cohort of acutely admitted medical patients, we identified those admitted with a diagnosis of asthma, and we tested the hypothesis that suPAR and blood eosinophil count are independent biomarkers associated with both one-year all-cause readmission and all-cause mortality.This study is a registry-based cohort comprising 29,088 medical patients acutely admitted between November 18th 2013 and March 17th 2017, including 1341 with a prevalent diagnosis of asthma. The study was carried out in the Emergency Department (ED), Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark . The ED The index admission was defined as the first admission where a patient had suPAR measured within the study period. Biochemistry data was obtained from the electronic hospital database LABKA via the Department of Clinical Biochemistry. Information on hospital admissions, length of stay, readmissions, and diagnoses were obtained from the Danish National Patient Registry. Vital status of patients was obtained from the Danish Civil Registration System . PatientBlood samples were routinely analyzed at the Department of Clinical Biochemistry. Plasma suPAR (D1D2D3 & D2D3 molecules) levels were measured using the suPARnostic AUTO Flex ELISA  on an automated Siemens BEP2000 platform according to the manufacturer’s instructions, as described in detail previously . Plasma The outcomes of interest in this study were acute all-cause readmission and all-cause mortality within 30-, 90-, and 365 days.n = 282), Q2: 1.9–2.6 ng/mL (n = 266), Q3: 2.61–3.5 ng/mL (n = 237), Q4: > 3.5 ng/mL (n = 283).Population-specific quartiles for suPAR were calculated. The suPAR quartile cut-offs were: Q1: < 1.9 ng/mL (n = 452), medium eosinophils , and high eosinophils  [For blood eosinophil counts, cut-offs were arbitrarily defined as low eosinophils  , 18, 19.Continuous variables are presented as median  and categorical variables as number (percentage).Unadjusted and multivariable adjusted logistic regression analyses were used to estimate the association between suPAR or blood eosinophil count and readmission or mortality. suPAR and blood eosinophil count were used as continuous (log2-transformed) or categorized variables (suPAR quartiles and low/medium/high blood eosinophil count groups). Results are presented as odds ratios (ORs) with 95% confidence intervals (CIs). The multivariable logistic regression analyses were adjusted for sex, age, Charlson comorbidity score, and CRP. Additionally, suPAR analyses were adjusted for blood eosinophil count and vice versa. The Charlson comorbidity score was calculated using a SAS macro as previously described , with weIn the analyses of readmission, death before readmission was considered a competing endpoint. Therefore, all patients who died before the end of follow-up were excluded from this analysis regardless of readmission or not.Cumulative probability for survival and readmission stratified by suPAR quartiles and blood eosinophil count are presented to illustrate the outcome distribution of patients over time. The discriminative ability of suPAR and blood eosinophil count to predict readmission and mortality was analyzed using Area under the Curve (AUC) for Receiver Operator Characteristics (ROC) curves.p-value < 0.05 was considered to be statistically significant.SAS Enterprise Guide 7.11 (SAS Institute) and R 3.2.3  were used for statistical analysis. R 3.2.3 was used to create the Figs. A The study was approved by the Danish Health and Medicines Authority (ref. 3–3013-1061/2) and the Danish Data Protection Agency .The datasets used and/or analyzed during the current study are available from the authors upon reasonable request, but analysis may require approvals from the Danish Patient Safety Authority and the Danish Data Protection Agency.Of 29,088 medical patients acutely admitted to the ED at Hvidovre Hospital during the study period, 1341 patients had a prevalent asthma diagnosis and were included in present study cohort  patients within 30 days, 289 (21.6%) within 90 days, and 452 (42.3%) within 365 days. The corresponding numbers for all-cause mortality were 21 (1.6%) within 30 days, 38 (2.8%) within 90 days, and 57 (5.3%) within 365 days, respectively (Table p = 0.037) between suPAR and blood eosinophil counts was found at 30 days, but not at 90- nor 365 days (data not shown).The median suPAR level was significantly elevated at the time of the index admission in patients who were readmitted within 365 days compared to patients without readmissions. Higher readmission rates were observed especially in the 4th suPAR quartile Table . A weak p = 0.044) after 365 days in the 4th quartile when compared to the 1st suPAR quartile using the multivariable model adjusted for sex, age, Charlson comorbidity score, CRP, and blood eosinophil count.   vs 2.4 ng/mL (IQR 1.8–3.1); p = 0.0002). Although 73.7% of all asthma patients who died belonged to the 4th suPAR quartile at 365 days follow-up  for suPAR in readmission prediction and 0.84 (95% CI 0.79–0.89) in mortality prediction at 365 days, see Additional file Patients with low blood eosinophil count at admission had significantly higher readmission rates at 365 days (Table p = 0.005), when compared to patients with blood eosinophil counts below 150 cells/μL in multivariable, adjusted regression analyses  (Table 50) (Tablp = 0.0007). The lowest odds of death at 365 days was seen in patients belonging to the patient group with high blood eosinophil count with OR 0.25   Table .ROC curve analyses showed an AUC of 0.53 (95% CI 0.50–0.56) for blood eosinophil count in readmission prediction and 0.72 (95% CI 0.65–0.79) in mortality prediction after 365 days, see Figs. E1 and E2 in the online data supplement.When event rates are stratified across both suPAR quartiles and groups of low/medium/high blood eosinophil count, an even distribution of patients was seen in terms of readmission Table . HoweverIn patients with an active diagnosis of asthma acutely admitted to a hospital, this study shows that the inflammatory biomarkers suPAR and blood eosinophil count are associated with hospital all-cause readmission and all-cause mortality. The highest odds of both readmission and mortality were seen in patients with suPAR concentrations > 3.5 ng/mL and in patients with low blood eosinophil counts (< 150 cells/μL).1/T17 T-cells are thought to be part of the pathogenesis of the non-T2 asthma endotypes [2 asthma [While the plasmin/plasminogen-pathway has been extensively investigated in basic research studies, little is known about the mechanistic association between asthma and suPAR. Both in vitro and in vivo studies of acute and chronic disease suggest that neutrophils are an important source of suPAR, as uPAR is shed from the surface of neutrophils, T-cells, and a subset of monocytes upon activation , 22, 23.ndotypes  which arndotypes , 25, andPrevious studies have shown that suPAR is associated with disease progression and severity, i.e., suPAR levels increase with higher disease stages and increasing severity. We have previously shown in unselected acute medical patients that suPAR levels increase with number and severity of comorbidities (Charlson score)  and withWe hypothesized suPAR concentrations to be elevated in hospitalized asthma patients due to the systemic inflammation associated with asthma, especially in uncontrolled disease . In the Mortality rates at 365 days were slightly higher than previous studies on all-cause mortality in asthma patients in Denmark , perhapsThe usefulness of blood eosinophil count as a biomarker for acute eosinophilic inflammation is still debated, and while eosinophils are extensively investigated in mechanistic studies, blood eosinophil count is commonly used as a surrogate marker for eosinophilic airway inflammation. The usage of blood eosinophil count as a surrogate marker is not without controversy, as some studies have found weak correlations between blood eosinophils and the gold standard sputum eosinophils , while oThe relationship between blood eosinophil counts and hospitalization rate has been thoroughly investigated in recent years, with some studies , 33 show2 asthma is relatively treatment refractory, resulting in frequent readmissions and death, perhaps due to a less efficient response to the initial in-hospital treatment in comparison with patients with normal or elevated blood eosinophil counts [Regarding mortality, our study showed that the median blood eosinophil count of patients who died was 30 cells/μL and 75.9% of all patients who died had a blood eosinophil count of < 150 cells/μL. The present study thus adds to the growing body of evidence that non-Tl counts –40.2 inflammation activity, while blood eosinophil counts represent T2 inflammation, but further studies regarding the different inflammatory mechanisms and their association to adverse outcomes in asthma are needed.Our study showed that in patients with low blood eosinophil counts, 31.9% of readmissions and 75.6% of mortalities belonged to the 4th suPAR quartile, suggesting that combined measurement of the two biomarkers upon admission potentially could improve risk assessment, especially in terms of all-cause mortality. With regards to inflammatory profiles, suPAR might reflect current non-TA limitation to the present study is the lack of information on patient smoking status, as suPAR is known to be affected by smoking . SmokingIn conclusion, elevated suPAR concentration and low blood eosinophil count associated with poor 365-day prognosis in this cohort of acutely admitted asthma patients. Usage of the two biomarkers at the time of acute hospitalization could allow for more precise identification of patients with a high risk of adverse events and potentially also patients with low disease control. However, further research is needed, especially effect studies of treatment on suPAR concentrations in asthma patients.Additional file 1: Fig. S1. AUC-graph for suPAR and blood eosinophil count-based 365-day Readmission Prediction Fig. S2. AUC-graph for suPAR and blood eosinophil count-based 365-day Mortality Prediction.


Chronic kidney disease (CKD) is an increasingly prevalent condition globally and is strongly associated with incident cardiovascular disease (CVD). Hypertension is both a cause and effect of CKD and affects the vast majority of CKD patients. Control of hypertension is important in those with CKD as it leads to slowing of disease progression as well as reduced CVD risk. Existing guidelines do not offer a consensus on optimal blood pressure (BP) targets. Therefore, an understanding of the evidence used to create these guidelines is vital when considering how best to manage individual patients. Non-pharmacological interventions are useful in reducing BP in CKD but are rarely sufficient to control BP adequately. Patients with CKD and hypertension will often require a combination of antihypertensive medications to achieve target BP. Certain pharmacological therapies provide additional BP-independent renoprotective and/or cardioprotective action and this must be considered when instituting therapy. Managing hypertension in the context of haemodialysis and following kidney transplantation presents further challenges. Novel therapies may enhance treatment in the near future. Importantly, a personalised and evidence-based management plan remains key to achieving BP targets, reducing CVD risk and slowing progression of CKD. CKD is 2 ) or kidn2 . Hyperte2 .2) or stage 4 (eGFR 15–29 mL/min/1.73 m2) CKD, defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines [2) [Hypertension is both a cause and effect of CKD and contributes to its progression –9. As eGines [2) , 12. Impines [2) , 14.2) and its association with hypertension is well-established [A number of mechanisms contribute to the development of hypertension in CKD and these influence its management Fig. . Increasablished . Increasablished , is implablished , and is ablished . Once hyablished , 23.Fig.In health, BP demonstrates a nocturnal dip of ~ 10 to 20%. This is controlled by several factors including diurnal variations in autonomic function, salt excretion and the RAAS . DysreguFor management of hypertension to be effective, accurate BP measurements are essential. In practice, the treatment of hypertension is often based on clinic or office BP recordings . These m24-Hour ambulatory BP monitoring (ABPM) provides a more accurate depiction of BP phenotype and is a better predictor of CVD events in those with CKD than clinic readings . 24-HourProteinuria is an important marker of renal damage and is incrementally and independently associated with CKD progression and incident CVD . QuantifBP reduction reduces proteinuria, which slows eGFR decline and reduces CVD . More inGuidelines offer the treating clinician a rapid, evidence-based, expert opinion regarding the management of certain conditions. Often criticised for a lack of flexibility, however, they are seen by some as unhelpful due to the complexities involved in clinical decision-making. Guidelines governing the management of patients with CKD are relatively few in relation to other conditions of similar prevalence. This may, in part, reflect the relative dearth of high-quality clinical trials in CKD. Despite this, guidelines outlining optimal treatment for CKD patients with hypertension are important, particularly as many of these patients are jointly managed in primary care.In their 2017 guidelines, the ACC recommended that all adults with hypertension and CKD should be treated to a target BP of < 130/80 mmHg regardless of proteinuria . The Nat2). In patients with baseline proteinuria > 1 g/day intensive BP control did slow the rate of eGFR decline when compared with standard BP control. However, no such benefit was seen in those without proteinuria [2. In this study, 1094 patients were randomised to receive either standard (MAP 102–107 mmHg) or intensive (MAP 97 mmHg) BP control with a minimum follow-up period of 3 years. Again, only patients with baseline proteinuria > 1 g/day demonstrated slowing of CKD with intensive BP control [The Modification of Diet in Renal Disease (MDRD) study was the first randomised trial to investigate the effect of standard  versus intensive (target MAP 92 mmHg) BP control on the rate of eGFR decline in a US population with CKD  study examined the effect of intensive (target systolic BP < 120 mmHg) versus standard (target systolic BP < 140 mmHg) BP control on cardiovascular outcomes  in patients with type 2 diabetes mellitus and normal renal function (serum creatinine < 133 μmol/L) . Despiten = 2646, mean GFR 47.9 mL/min/1.73 m2) intensive BP control reduced all-cause mortality with an effect size similar to that seen in the overall cohort [2 and/or proteinuria > 1 g/day were excluded from SPRINT, as were those with diabetes, who account for up to 45% of CKD in the developed world [Published in 2015, SPRINT  compared a systolic BP target of < 140 mmHg with a more intensive systolic goal of < 120 mmHg in 9361 non-diabetic patients at elevated CVD risk  . The inted world . Neverthed world , 53.decrease in kidney damage biomarkers, including ACR, anti-chitinase-3-like protein 1 and uromodulin, suggesting that benign alteration in renal blood flow, rather than pathological processes, may be responsible for the changes in eGFR observed [It should be noted that the method of BP measurement used may have a significant impact on the outcome of any trial. In SPRINT, BP was measured after participants were seated in a quiet room for 5 min with no distractions. SPRINT BPs may, therefore, not be directly comparable to our clinic BPs, which are likely to be higher. This may be why such a low target BP was found to be beneficial. Notably, the risk of developing acute kidney injury (AKI) was increased in the intensive treatment group. Additionally, in those with normal renal function at baseline, the risk of developing CKD during the study was higher with intensive treatment. An analysis by Zhang et al.  has inveobserved .The available evidence does not provide a clear consensus regarding the optimal BP target in CKD. Accordingly, guidelines vary. The 2017 ACC guidelines employed the results of SPRINT as the basis for a more intensive BP target. However, the 2018 ESC/ESH guidelines have not adopted this more intensive approach. Perhaps this could be interpreted as a prioritisation of cardiovascular protection over renoprotection by the Americans, and vice versa by the Europeans. Examining the available evidence allows understanding of the rationale behind these decisions and thus a basis on which to create individualised treatment plans that take into account CVD risk, rate of projected eGFR decline, co-morbidities and other patient characteristics. BP goals are likely to change as an individual ages or develops more advanced disease. The management of BP in CKD should therefore be considered a dynamic process.Achieving BP targets is challenging. SPRINT demonstrated that, despite intensive input including monthly medication reviews, > 50% of those in the intensive treatment group failed to achieve the target systolic BP . DespiteThere are a number of non-pharmacological treatments for hypertension in the context of CKD. A study by Slagman et al.  found th2) with CKD and proteinuria (> 1 g/24 h), a mean weight loss of ~ 4% can reduce proteinuria by ~ 30% [Weight loss is effective in reducing BP and proteinuria and may slow CKD progression . In overby ~ 30% . The benby ~ 30%  has showby ~ 30% .Despite the benefits of non-pharmacological interventions in CKD, antihypertensive medications are usually also required . As wellACE inhibitors and angiotensin II receptor antagonists (blockers) (ARBs) have both cardioprotective and renoprotective properties and are therefore of particular value in patients with CKD . RAAS blIn those with non-proteinuric CKD the superior renoprotective effect of RAAS blockade has recently been questioned. A systematic review carried out by Casas and colleagues  demonstrIn up to 50% of patients chronic ACE inhibition leads to angiotensin II reactivation with subsequent blunting of the efficacy of RAAS blockade. It has therefore been hypothesised that the addition of an ARB to those already established on ACE inhibition might improve cardiovascular and renal outcomes. ONTARGET  aimed to answer this question in patients at high risk of CVD . 25,620 2) [Potential problems associated with RAAS blockade include hyperkalaemia and the development of AKI. A rise in serum creatinine is often seen after initiation of RAAS blockade due to a reduction in intraglomerular pressure . The REN2) , 71. The2) . In cont2) .2) as this population has been largely excluded from major randomised trials. An observational study by Ahmed et al. [Further uncertainty exists regarding the use of RAAS blockade in those with advanced CKD  or a thiazide-like diuretic (such as indapamide) may have a role and should be considered as a potential for first-line therapy . TreatmeMineralocorticoid receptor antagonists (blockers) (such as spironolactone) effectively reduce BP in CKD but run the risk of exacerbating hyperkalaemia . These aBoth dihydropyridine and non-dihydropyridine CCBs are useful in the management of hypertension in CKD. Dihydropyridine CCBs (such as amlodipine) can be used as first-line therapy in non-proteinuric CKD, either alone or in combination. In proteinuric CKD their effect is inferior to RAAS blockade . HoweverThe ACCOMPLISH (Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension) trial evaluated combination therapy with amlodipine and an ACE inhibitor versus hydrochlorothiazide and an ACE inhibitor in reducing CVD mortality in those with hypertension and at high risk of CVD  . This muβ-Blockers (β-adrenoceptor antagonists) effectively reduce BP in CKD due to their effect on the dysregulated sympathetic nervous system . The carPeripherally acting α-blockers  are commonly used as part of combination therapy for the management of hypertension in CKD. This may be due to a pharmacokinetic profile that is undisturbed by declining eGFR in addition to favourable effects on glycaemic control . SeveralAs the diurnal variation of BP can be influenced by timing of antihypertensive medications, it has been hypothesised that evening dosing could reverse the non-dipping nocturnal BP seen in CKD. A study by Hermida and colleagues  exploredDespite the risks of CKD progressing to ESRD and patients requiring dialysis and/or transplantation, adherence to therapy is no better in those with CKD than in those without . AdherenThe relationship between BP and CVD outcomes in patients undergoing haemodialysis is complex. In this cohort, a lower BP does not necessarily translate into improved survival, as it does in the general population and those with pre-dialysis CKD , 108. Ev®3 now include those with CKD, but several risk calculators designed for use in the haemodialysis population have now been developed and validated [The optimal way to measure BP in patients undergoing haemodialysis is debatable. Large shifts in fluid and electrolytes mean pre- and post-dialytic BPs may differ significantly. Mayer et al.  utilisedalidated , 113.Hypertension in patients undergoing haemodialysis may be largely driven by sodium and water overload. However, hypertension often persists despite aggressive ultrafiltration . All claAs in haemodialysis, there are currently no randomised clinical trials exploring how best to manage hypertension following kidney transplantation. Hypertension is common post-transplant, with multiple factors contributing to its development Fig. . More thChoice of antihypertensive agent will depend on several factors, including time from transplantation, concomitant prescriptions including immunosuppression, and co-morbidities. Historically, RAAS blockade has been avoided in the early post-transplant period due to the potential for a transient rise in serum creatinine at this precarious time. Despite this, a systematic review by Jennings and Taber  has suggCNIs such as tacrolimus, which form the mainstay of post-transplant immunosuppression, cause afferent arteriolar vasoconstriction. There is some evidence to suggest that dihydropyridine CCBs confer particular benefit in those treated with CNIs due to their ability to cause afferent arteriolar vasodilatation in this context . Non-dihAs populations live longer and the prevalence of diabetes increases, the global burden of CKD is likely to grow . ManaginImproved survival of patients with several chronic diseases has also led to an increased incidence of CKD in these groups. For example, the life expectancy of a 20-year-old patient starting antiretroviral therapy (ART) for HIV in the UK is now almost 70 years . HIV is There remains an unmet need for therapeutic options capable of slowing progression of CKD and attenuating the associated CVD risk. Interest in sodium–glucose cotransporter 2 inhibitors (SGLT2i), such as empagliflozin, has intensified following the EMPA-REG OUTCOME  trial, which demonstrated significant slowing of CKD progression and a reduction in the composite outcome of death from CVD, non-fatal MI or non-fatal stroke in patients with type 2 diabetes and high CVD risk randomised to empagliflozin versus placebo , 135. ExFinally, there is a growing body of evidence to suggest that health literacy has a direct influence on outcomes in CKD . As the Lowering BP in CKD slows disease progression and reduces incident CVD. An understanding of the pathophysiological mechanisms leading to the development of hypertension in this patient group is useful in order to effectively target both endpoints. Existing guidelines do not offer a consensus on optimal BP targets but are created based on evidence favouring interventions for either renoprotection, cardioprotection or both. Similarly, pharmacological therapies designed to achieve these targets offer different degrees of risk reduction based on patient characteristics. One size does not fit all, therefore, and an appreciation of what is achievable with BP reduction in CKD is key to making informed, individualised decisions.


Previous research has been highly suggestive that patients of African ancestry are less responsive to beta-blockers and angiotensin converting enzyme inhibitors. However, clinical practice within Ethiopia has continued to recommend all drugs for treatment of hypertension despite the lack of evidentiary support. Therefore this study aims to compare the effectiveness of the three major antihypertensive drugs currently prescribed in an Ethiopian health care setting to further the potential for evidence based prescribing practices.A prospective, randomized, open label comparative study was used to determine the mean reduction in blood pressure (primary outcome) and assess cardiovascular events (secondary outcomes) among patients receiving one or more of three common antihypertensive drugs  in routine clinical practice between November 2016 and April 2017. Patients were followed for three months. Analysis was based on an intention-to-treat approach. One way analysis of covariance was used to compare the difference in therapeutic effectiveness in reducing blood pressure.A total of 141 patients were randomized to one of three recipient groups—nifedipine (n = 47), enalapril (n = 47) or hydrochlorothiazide (n = 47). Three months after randomization, 44 patients in each group completed the follow-up. Patients randomized to nifedipine had significantly higher mean reduction in systolic blood pressure than those randomized to enalapril(p = 0.003) or hydrochlorothiazide(p = 0.036). The mean reduction in systolic blood pressure was -37.35 in the nifedipine group; -30.3 in patients receiving enalapril; and -32.1 in patients assigned hydrochlorothiazide. However, nifedipine did not have a significance difference in reduction of mean diastolic blood pressure compared than those receiving enalapril (p = 0.57) or hydrochlorthiazide (p = 0.99).This study revealed that amongst the three drugs nifedipine was found to be the most effective drug in reduction of systolic blood pressure. Hydrochlorothiazide and enalapril did not show a difference in reduction of mean blood pressure. Further, long term randomized trials are highly recommended to inform revision of Ethiopia-centric hypertension treatment guidelines. The mean (SD) baseline heart rate was 82.4(10.7) with no difference in distribution (p = 0.76).Table 3). After two months follow-up nifedipine was added to four hypertensive patients randomized to HCT initially and to two patients assigned to enalapril, while enalapril was added to two patients randomized to nifedipine; and HCT was added to one patient commenced on nifedipine. There was one treatment shift in a patient randomized to ACE-I due to adverse effect of dry cough.Regarding time to BP control, with patients assigned to HCT showed the fastest BP control in 2.5(2.3) weeks followed by nifedipine 3.26(3.2) weeks and, finally, enalapril 3.7(3.8) weeks, there was no significant difference between the study drugs (P = 0.22). At the end of the study, mean heart rate was reduced to 75.9(9.4), 78.02(11.1) and 78.5(8.8) bpm in the nifedipine, enalapril and HCT groups yielding no significant difference in the study arms (p = 0.42). Few patients 4 (3%) reported side effects like dry cough, headache, and nasal stiffness. By the end of the follow up BP was controlled in the majority of patients 122(91.7%). Dose escalation occurred in nearly one third [44(32.5%)] of patients . Only one cardiovascular event occurred in a single case of heart failure  and DBP (P = 0.007) was significantly associated with mean reduction in BP. Other variables did not have significant association.On preliminary checks to ensure that there was no violation of the assumptions of normality, linearity, homogeneity of variances, and reliable measurement of the covariate, there was no violation in all parameters. Interaction was also checked between the independent variables and outcome variable in the study drugs by including an interaction term in the ANCOVA model, which yielded no significant interaction.Table 4).After adjusting for age and baseline SBP, there was a significant difference between the three drug groups in mean reduction of SBP, F = 4.89, P = 0.009, partial eta squared = .072 which indicates a moderate effect size according to Chen’s 1988 estimation . There wAdjusted for baseline SBP and age those randomized nifedipine, had significantly higher mean reduction in SBP. The mean reduction in SBP was -37.35 in groups assigned to nifidipine, -30.3 in patients assigned to enalapril and -32.1(CI:-35.-29.3) in patients assigned HCT. The mean SBP reduction was -7.03 mmHg higher [which is mean in those randomized to nifedipine—Mean in those randomized to enalapril] in those randomized to nifedipine than those randomized to enalapril(p<0·003).Table 5).The mean difference of in reduction of SBP in the nifedipine groupwas -4.88 higher than those assigned to HCT. There was a significance difference in reducing SBP between nifedipine and HCT (p = 0.036). But there was no significant difference between HCT and enalapril (P = 0.34) (Table 6).After adjusting for age and baseline DBP, there was no a significant difference between the three drug groups in mean reduction of DBP, F = 4.7, P = 0.8, partial eta squared = 0.003 which indicates a small effect size according to Chen’s 1988 estimation . There wTable 7).The mean reduction in DBP was -15.66 in groups assigned to nifedipine, -14.8 in patients assigned to enalapril and -15.62 in patients assigned HCT. The mean difference between nifedipine and enalapril was -0.83 while it is -0.014 between nifedipine and HCT . There was no a significant difference in reducing DBP between nifedipine and HCT (P = 0.99), nifedipine and enalapril(P = 0.57)  but with respect to DBP no significant difference in effect was evidenced (P = 0.57).No published evidence compared the effects of first line antihypertensive drugs in Ethiopia, resulting in reliance on evidentiary extrapolation from other studies and populations. There are few trials which were conducted in an African context as evidenced in a recent meta-analysis . GuideliThe findings in this study align with the guidelines on the effect of CCB in SBP but it contradicts the recommendations respecting HCT and enalapril in Ethiopia and Africa –13,16,23Variation in reducing BP could be due to genetic variation of study participants compared to African Americans and other sub-Saharan Africans or due to environmental factors. The study findings suggest that nifedipine was most effective in reducing SBP while enalapril had a similar effectiveness profile to HCT, which contrasts with previous guidelines ,13 and fCCB, particularly nifedipine, were effective to decrease BP in this study population. Nifedipine is metabolized extensively by CYP 450 enzymes, specifically CYP 3A4 enzyme . GeneticIn contrast to the current practice, our study population had lower response to HCT when compared with nifedipine and similar response when compared with enalapril. This remained valid on subgroup analysis by stage I and II hypertension. Thiazide diuretics are evidenced as the most effective drugs to reduce BP in African patients; hence, they are widely prescribed in routine clinical practice. This pattern is attributed to persons of African ancestry reported to have a tendency to retain salt ,32, whicThe relatively lower effect of HCT compared to nifedipine could be related to genetic polymorphism as reported before  and, recAs was hypothesized, enalapril was not relatively effective in reducing BP compared to nifedipine. Previously it was predicted that a low response of ACEI is due to low rennin level and high salt retention tendencies in African people ; althougInhibition of ACE-Is not the only mechanism that works but also ACEI promote NO synthesis in the endothelium . StudiesNevertheless, it is unclear why HCT and nifedipine were not statistically different from enalapril in reduction of mean DBP and with HCT in decreasing SBP. This clearly indicates a need for further molecular and human studies.In this study, the mean reduction in both in SBP& DBP was generally higher when compared to previous studies ,31,39,40The mean reduction in SBP in the nifedipine group was higher compared to previous studies ,31; althDiuretics were also as good as CCB in reduction of BP compared to other studies . AlthougIn our investigation, the mean reduction in SBP and DBP by enalapril was -30.3 and -14.8 respectively. This is higher than a previous trial which compared effect of enalapril against control group resulting in a reduction of SBP by -7.1(13.2) versus 0.0(13.2) and DBP of -6.2(8.0) versus 0.0(8.0) . In geneThis study was an initial comparative effectiveness research with prospectively collected data and follow- up of patients established a baseline of reliable and valid data. Randomization, multi-site, and multi-practitioner involvements strengthened the reduction of bias. Furthermore, the result of randomization indicated distribution of baseline characteristics were almost balanced across the study groups which indicates the success of randomization. However, there was a difference in baseline SBP which may overestimate the effect of nifedipine.The major weaknesses of this study were small sample size and short period of follow up, limiting the determination of cardiovascular events as a direct indicator for effectiveness antihypertensive drugs. Nevertheless, mean reduction in BP is a good predictor of cardiovascular event. In addition, the study was not blinded and concealment of medication allocation was not complete, which may impact on estimation of effect size.This study revealed that nifedipine was superior in reduction of BP in our target population of newly diagnosed Ethiopian primary hypertensive patients. This finding showed significance in reduction of SBP compared to HCT and enalapril. In reduction of DBP there was no significant difference but nifedipine was the topmost in decreasing the magnitude of mmHgs. In contrast to previous guidelines and recommendations, HCT and enalapril had similar effect in reduction of BP through this study. This finding warrants a multi-year, large sample size, longitudinal or experimental study to enhance evidence informed Ethiopian hypertension treatment guidelines.


Background and Objectives: Chronic low back pain (CLBP) is the most common occupational disorder due to its associated disability and high risk of recurrence and chronicity. However, the mechanisms underlying physical and psychological variables in patients with CLBP remain unclear. The main objective of this study was to assess whether there were differences between physically active patients with nonspecific CLBP compared with asymptomatic individuals in sensorimotor and psychological variables. Materials and Methods: This was an observational cross-sectional design with a nonprobabilistic sample. The sample was divided into two groups: individuals with nonspecific CLBP (n = 30) and asymptomatic individuals as a control (n = 30). The psychological variables assessed were low back disability, fear of movement, pain catastrophizing, and self-efficacy. The sensorimotor variables assessed were two-point discrimination, pressure pain threshold, lumbopelvic stability, lumbar flexion active range of motion, and isometric leg and back strength. Results: Statistically significant differences between the groups in terms of catastrophizing levels (p = 0.026) and fear of movement (p = 0.001) were found, but no statistically significant differences between groups were found in self-efficacy (p > 0.05). No statistically significant differences between the groups in any of the sensorimotor variables were found (p > 0.05). Conclusion: No sensorimotor differences were found between patients with asymptomatic and chronic low back pain, but differences were found in the psychological variables of catastrophizing and fear of movement. Low back pain (LBP) is the most prevalent musculoskeletal problem and one of the most common reasons for medical consultations ,2. ReseaPrevious studies have determined that the chronicity of the symptoms could involve, at the neurophysiological level, a processing alteration at the central level. This alteration contributes to the generation of neuroplastic maladaptive changes at the medullary and the supramedullar levels in which psychological, somatosensory, and motor factors can be affected. ,5. It haIn addition, central sensitization mechanisms could be associated with psychosocial factors, which play a significant role in patients with CLBP. Regarding the influence of psychosocial factors in individuals with nonspecific CLBP, there is an important body of evidence demonstrating that negative psychosocial attributes are strongly associated with a greater perception of pain and disability . Thus, iIn recent years, new lines of research have emerged to identify the mechanisms underlying the associations between physical and psychological variables in patients with nonspecific CLBP . TraditiTherefore, the main objective of this study was to assess differences between physically active patients with nonspecific CLBP compared with asymptomatic individuals in terms of sensorimotor and psychological variables, with both groups composed of physically active people currently participating in a general exercise program. The secondary objective was to analyze the association between sensorimotor variables and psychological variables in both groups.An observational cross-sectional study with a nonprobabilistic sample was designed. Participants were allocated into two groups, with the first group composed of patients with nonspecific CLBP, and asymptomatic individuals comprising the control group (CG). The procedures were planned following the ethical considerations of the Helsinki Declaration. The study was approved by the Local Ethics Committee of the La Salle University Centre for Advanced Studies, Madrid, Spain . This study followed the Strengthening the Reporting of Observational Studies in Epidemiology statement guidelines . All parA consecutive, nonprobabilistic convenience sample of 30 patients with nonspecific CLBP and 30 asymptomatic individuals for the CG were recruited between April 2017 and July 2017. The sample was recruited from clients of a physical fitness center and patients of a physical therapy clinic, both located in Pozuelo de Alarcón, Spain. The inclusion criteria for the CLBP group were (a) low back pain in at least the prior 6 months; (b) low back pain of a nonspecific nature; (c) men and women older than 18 years; and (d) participating in at least 1 moderate exercise session per week. The exclusion criteria were as follows: (a) neurological signs; (b) specific spinal pathology ; (c) having had back surgery; and (d) signs of acute inflammation. The CG was recruited from among the clients of the previously mentioned fitness center using posters, email newsletters, and social media. Asymptomatic individuals were examined and included in the study if they met the following criteria: (a) individuals who had not had low back pain in the last 6 months; (b) men and women older than 18 years; (c) participating in at least 1 moderate exercise session per week.There were common exclusion criteria for both groups: (a) cognitive deficiencies that impede correct execution of the tests; (b) illiteracy; (c) understanding or communication difficulties or no comprehension of the Spanish language.The Spanish version of the Roland Morris Disability Questionnaire (RMDQ) has demonstrated acceptable psychometric properties in measuring the perceived limitation of daily activities as a result of low back pain, and it has a Cronbach’s alpha ranging between 0.84 and 0.93 ,27. The Fear of movement was assessed using the Spanish version of the Tampa Scale for Kinesiophobia (TSK-11), whose reliability and validity have been demonstrated  . The TSKPain catastrophizing was assessed using the Spanish version of the Pain Catastrophizing Scale (PCS). The PCS has demonstrated good psychometric properties . This scThe Spanish version of the Chronic Pain Self-Efficacy Scale (CPSS) has acceptable psychometric properties  in assesResearch has shown that individual clinicians can reliably assess the 2-point discrimination (TPD) threshold at the neck, the back, the hand, and the foot using mechanical callipers . Partici2. The researcher instructed the individuals to express pain by saying “yes”. This procedure has shown excellent reliability for the low back (ICC 0.86 to 0.99) and moderate to excellent reliability for the tibia (ICC 0.53–0.90). The evaluator took 3 measurements, and the mean was employed in the data analysis [Algometers are devices that can be used to identify the pressure and/or the force eliciting a pressure pain threshold (PPT). Participants were positioned in prone decubitus, and the evaluator marked at 2 different points: the tibia and the erector spinae muscle. The evaluator then pressed against the tissue vertically, increasing the force at a constant rate of 1 kg/cmanalysis ,38.To assess the ability of the participants to voluntarily control the motion of the lower back, we selected the Hip Flexion Test measured with a “Pressure Biofeedback Unit” (PBU). A validation study concluded that trained examiners can reliably perform PBU measurements for patients with chronic LBP . For this test, the participant lay supine with the hips and knees extended, and the PBU was positioned under the lumbar spine so that the inferior border of the device was aligned with the posterior superior iliac spine marks. After the participant was positioned, the PBU was inflated to 40 mm Hg pressure. The participant was then asked to flex their dominant hip, moving the knee towards the chest without touching the table with the foot. Once the maximum hip flexion was achieved, the pressure registered in the PBU was recorded by the assessor. The mean of 3 measurements was used in the analysis.To collect this measurement, a mobile device goniometer called “Goniometer Records” was used. It has shown high intrarater reliability with an ICC greater than 0.80  . It can The clinician held the mobile device over the participant’s sacrum and maintained a slight pressure while the participant performed a “waiter’s bow” movement. The mean of 3 measurements was employed in the data analysis.To measure the isometric strength (IS) of the leg and the back extensor muscles, a portable dynamometer was used. The reliability of this device has been validated and can be used for determining leg and back strength in maintained positions, provided that the measurement protocol is standardized . It is aFor the measurement, the participants let their arms hang straight down to hold the bar with both hands with the palms facing towards the body. The chain was then adjusted so that the knees were bent at approximately 110 degrees. Then, without bending the back, the participant pulled against the weight steadily as much as possible, trying to straighten their legs and keeping the arms straight. The evaluator took 3 measurements, and the mean was employed in the data analysis.The participants’ levels of physical activity were measured by using the International Physical Activity Questionnaire (IPAQ), which divided the participants into 3 groups according to their level of activity: high, moderate, and low or inactive . This quFor this study, both patients with nonspecific CLBP and the CG performed the same procedure following the same instructions. The assessor delivering the physical tests ignored whether the participant performing the test was from the CG or the CLBP group.Once the participants signed the informed consent document, they received a sociodemographic questionnaire, which collected sex, date of birth, education level, and work situation. In addition, physical activity levels were assessed using the Spanish version of the IPAQ . Once thFollowing the completion of the self-reported measures, the participants were instructed to perform the sensorimotor tests in the same order , lumbar flexion active range of motion (LF-AROM) and IS). The sociodemographic and the clinical variables of the participants were analyzed. The data were summarized using frequency counts, descriptive statistics, summary tables, and figures. t-test was used for the group comparisons. Cohen’s d effect sizes were calculated for multiple comparisons of the outcome variables. According to Cohen’s method, the magnitude of the effect was classified as small (0.20–0.49), medium (0.50–0.79), or large (0.80). The data analysis was performed using the Statistics Package for Social Sciences . The categorical variables are shown as frequencies and percentages. The quantitative results are represented by descriptive statistics . For all variables, the z-score was assumed to follow a normal distribution based on the central limit theorem because all the groups had more than 30 participants ,46. StudThe relationships between psychological measures as well as between physical measurements were examined using Pearson’s correlation coefficients. A Pearson’s correlation coefficient greater than 0.60 indicated a strong correlation, a coefficient between 0.30 and 0.60 indicated a moderate correlation, and a coefficient below 0.30 indicated a low or very low correlation .p > 0.05) except for weight (p = 0.016). There were no statistically significant differences in age, sex, height, education, or physical activity levels (p > 0.05). p = 0.026), including helplessness (p = 0.036) and magnification (p = 0.01) subscales of the PCS questionnaire and fear of movement (p = 0.001) in both subscales of the TSK-11 (activity avoidance and harm) (p < 0.01). No statistically significant differences between groups were found in any of the subscales of the CPSS, showing high levels of self-efficacy in both groups (p > 0.05).p > 0.05). p < 0.01). In the CG, a positive correlation was also found between higher FSE and higher LF-AROM  and low back pressure pain threshold (PPT-LB) . In the nonspecific CLBP group, a higher SSE was positively correlated with higher PPT both in the tibia  and the low back . Finally, a positive correlation between higher scores in the PPT-LB and the RMDQ was found .The primary objective of this study was to determine the differences between psychological and sensorimotor measures between two physically active populations, one group with nonspecific CLBP and another group that was asymptomatic. Our results suggest no significant differences in somatosensory and functional variables. There were statistically significant differences in catastrophism and kinesiophobia but not in self-efficacy.Numerous studies support the influence of various psychological factors in patients with chronic pain conditions. Among the most influential is the fear of movement, which, according to the fear avoidance model, is associated with catastrophic conditions and disability. Thus far, it has been determined that physical activity can act as a mediator, reducing disability and pain and therefore the fear of movement. Previous studies have shown that interventions based on physical activity can lead to changes in the fear of movement variable, despite the fact that the size of the effect has been small to medium. ,49 On thOur results showed no significant differences between groups for the psychological variable of self-efficacy or for somatosensory and functional variables. This unusual characteristic of the nonspecific CLBP group can be explained by the socioeconomic context of the participants. Our sample reflects an active population with higher sociocultural and economic levels and patients who did not seek help for their condition. A higher socioeconomic status has been associated with lower disability in patients with CLBP . The samAccording to our findings, patients with various conditions of chronic musculoskeletal pain who seek help present an external locus of control, which could be correlated with a lack of self-efficacy . In addiAs for the results of the correlation analysis, only one large-magnitude association was found in our analysis. In healthy individuals, the greater the precision in controlling the lumbopelvic movement was, the less fear of movement existed. Physical activity, including motor control exercises, produces hypoalgesic effects . The posWith respect to the nonspecific CLBP group, the strongest positive correlations were found between PPTs and lumbar disability and between PPTs and coping with symptoms subscales. Along these lines, Immura et al. found a correlation between PPTs in the lumbar region and the level of disability in patients with nonspecific CLBP . In addiThe most important limitation of this study is its cross-sectional design. Our findings are valid for suggesting new hypotheses but not for establishing causal relationships. In addition, no corrections have been made for multiple comparisons, which should be considered in the interpretation of the results. Future longitudinal research is recommended to confirm the hypothesis of this study. Therefore, other sensorimotor measures such as dynamic trunk movement, acceleration, or resistance would be necessary to obtain more consistent conclusions and to confirm these results. It would also be interesting to increase the sample size to confirm whether the obtained results could be extrapolated to larger populations. The results of the present study suggest no sensorimotor differences between asymptomatic and physically active patients with CLBP. However, differences were found in the psychological variables of catastrophizing and fear of movement. No significant correlation was found between sensorimotor and psychological variables except for lumbopelvic stability and less fear of movement in healthy individuals. These results highlight the relevance of psychological variables in patients with CLBP and suggest that these variables should be considered clinically for the management of these patients.


Hypertension is considered as a main risk factor for chronic kidney disease development and progression. Thus, the control and evaluation of this disease with new software and devices are especially important in patients who suffer from chronic kidney disease.This study aimed to validate the QardioArm mobile device, which is used for blood pressure (BP) self-measurement in patients who suffer from chronic kidney disease, by following the European Society of Hypertension International Protocol 2 (ESH-IP2) guidelines.A validation study was carried out by following the ESH-IP2 guidelines. A sample of 33 patients with chronic kidney disease self-measured their BP by using the QardioArm and Omron M3 Intellisense devices. Heart rate (HR), diastolic BP, and systolic BP were measured.The QardioArm fulfilled the ESH-IP2 validation criteria in patients who suffered from chronic kidney disease.Thus, this study is considered as the first validation using a wireless upper arm oscillometric device connected to an app to measure BP and HR meeting the ESH-IP2 requirements in patients who suffer from chronic kidney disease. New validation studies following the ESH-IP2 guidelines should be carried out using different BP devices in patients with specific diseases. Increased afferent sympathetic activation may be an early event in patients who suffer from chronic kidney disease . VariousActive involvement is required in patients with hypertension to get a successful management of this disease. Encouragement of home BP monitoring is considered as one of the main measures that increased patient compliance with their treatment, showing a great potential to improve hypertension control rates -9. To geThe Association for the Advancement of Medical Instrumentation published a protocol to validate electronic and aneroid sphygmomanometers in 1987. In 1990, the protocol of the British Hypertension Society appeared as a new guideline. Afterward, both protocols were revised in 1993 ,11. On tThe hypothesis of this study was that QardioArm (Atten Electronics Co) would be valid for self-measurement of BP and heart rate (HR) in renal patients according to the ESH-IP2 guidelines. Hence, the purpose of this study was to validate the QardioArm for BP self-measurement in patients who suffer from chronic kidney disease, following the ESH-IP2 guidelines.This study was a descriptive investigation study to validate the QardioArm device for the measurement of BP and HR in patients with chronic kidney disease according to the ESH-IP2 guidelines . It was The Institutional Research and Ethical Committee at the University of Extremadura , with the code 151/2019, approved this study. This study adhered to the Declaration of Helsinki [IntelliSense technology to acquire a comfortable controlled inflation without pressure presetting or reinflation.The Omron M3 Intellisense  was considered as the gold standard in this study. This device was validated in the general population  and in pThe QardioArm was selected as the test device in this study. QardioArm is a fully automatic, noninvasive, wireless BP monitor. QardioArm comprises a BP measurement system intended to assess the diastolic BP and systolic BP and HR in the adult population .This device used an inflatable cuff that was wrapped around the upper arm. Cuff circumference ranged from 22 to 37 cm.KitKat (or later) was required, being compatible with iPod, iPhone, Apple Watch, iPad, and Android phones and tablets.A specific free Qardio app was downloaded from the Apple App Store or Google Play Store. A device with Bluetooth 4.0, iOS 7.0 (or later), and Android 4.4 Furthermore, the QardioArm provided an automatic screen, including graphics, to facilitate visual data interpretation. This app is configured by issue reminders and warnings, and the measurements and progress are real time shared with other users.Fresenius Medical Care dialysis clinics in Plasencia (Extremadura) and signed the written informed consent.All patients were recruited from the Following the ESH-IP2 guidelines , 33 patiA total of 2 nurses with experience in BP measurement carried out all assessments. The measurement room provided an adequate temperature without any factor that could have influenced the measurements, such as noise and distractions ,13.2), and the arm circumference was measured to ensure the adequate cuff size.Each participant self-reported birth date, sex, height, weight, and body mass index . BP coinciding with the HR was measured on the right arm in 30 patients with chronic kidney disease, whereas BP was assessed on the left arm in 3 patients because of the presence of an arteriovenous fistula on the right arm (n=2) and right hemiplegia (n=1). A total of 9 consecutive measurements were carried out following the ESH-IP2 guidelines ,13, alteBP A—entry BP using the standard deviceBP B—device detection BP using the test instrumentBP 1—using standard deviceBP 2—using the test instrumentBP 3—using standard deviceBP 4—using the test instrumentBP 5—using the standard deviceBP 6—using the test instrumentBP 7—using the standard deviceAt the same time of measurement, the patients remained quiet, calm, sitting and without moving, placing the back straight, maintaining the feet over the floor in parallel position, without crossing their legs, and resting the arm over a flat surface, with the hand palm upward and the elbow in a slightly flexed position to place their fist at the height of the heart. The interval time between BP measurements varied from 30 to 60 seconds . All meaStatistical analysis was performed by using IBM SPSS Statistics, version 19 (SPSS Inc). Results were described in mean (SD).The device accuracy following the ESH-IP2 guidelines was based on a comparison between the measurements of the reference (Omron M3) and test device (QardioArm).For each patient, the device measurements such as BP 2, BP 4, and BP 6 were first compared with the measurements such as BP 1, BP 3, and BP 5, respectively, and also with the measurements such as BP 3, BP 5, and BP 7, respectively. Comparisons that were more favorable to the device were used.Indeed, differences were classified separately for both diastolic BP and systolic BP, depending on whether their values were within 5, 10, or 15 mm Hg , and forResults were analyzed and detailed according to the ESH-IP2 requirements to conclude if the used device passed or failed to pass the explained validation protocol. Parts 1 and 2 of the validation protocol concern the differences in number of the requested ranges for each individual measurement (99 measurements) and each individual patient (33 patients), respectively .Furthermore, Bland and Altman graphs were used to illustrate the relationship between systolic BP differences (systolic BP and device-reference) and mean systolic BP (device and reference), diastolic BP differences (diastolic BP and device-reference) and mean diastolic BP (device and reference), or HR differences (HR and device-reference) and average HR (device and reference).A sample of 35 patients with chronic kidney disease were recruited to assess 33 participants who met the ESH-IP2 inclusion criteria, and 2 of them were excluded because of device failure (n=1) and arrhythmias (n=1).The remaining sample (n=33) was screened. There were 15 females and 18 males. The characteristics of the patients, such as age, height, weight, body mass index, and arm circumference, are presented in Validation findings for the QardioArm BP device following the 2010 ESH-IP2 are presented in The measurement numbers differing from the standard device Omron M3) of 5, 10, and 15 mm Hg or less were presented in  of 5, 10Mean differences between the test device and standard device were 2.43 mm Hg (SD 4.15) for diastolic BP and 4.03 mm Hg (SD 4.42) for systolic BP.From these analyses, of 99 measurements, 81 differences for systolic BP and 85 differences for diastolic BP showed an absolute difference within 5 mm Hg (compared with at least 65 differences for diastolic BP and 73 differences for systolic BP according to the ESH-IP2 criteria). Furthermore, 92 comparisons for systolic BP and 95 comparisons for diastolic BP showed an absolute difference within 10 mm Hg (compared with at least 81 differences for diastolic BP and 87 differences for systolic BP according to the ESH-IP2 criteria).In addition, of 99 differences, 96 for systolic BP and 95 for diastolic BP exhibited an absolute difference within 15 mm Hg (compared with at least 93 for diastolic BP and 96 for systolic BP according to the ESH-IP2 criteria). Indeed, the validation of part 1 of the device was successfully completed.According to part 2 of the 2010 ESH-IP2 criteria, of 33 patients, 29 patients showed a minimum of 2 of 3 comparisons within a 5 mm Hg difference for systolic BP, and 30 patients showed a minimum of 2 of 3 comparisons within a 5 mm Hg difference for diastolic BP (compared with at least 24 patients for systolic BP and diastolic BP according to the ESH-IP2 criteria). Nevertheless, 2 patients showed their 3 differences outside 5 mm Hg for systolic BP, and no patients showed their 3 differences outside 5 mm Hg for diastolic BP (compared with a maximum of 3 patients for diastolic BP and systolic BP according to the ESH-IP2 criteria). Owing to these 2 described conditions, validation of part 2 of the device was successfully completed.Therefore, part 3 of the QardioArm device validation was completed, as both parts 1 and 2 were validated for diastolic BP and systolic BP.Validation results of QardioArm—Part 3Result: PassValidation findings for the QardioArm HR device following the 2010 ESH-IP2 are presented in Measurement numbers differing from the standard device Omron M3 of 3, 5, and 8 beats per minute or less are detailed in From these analyses, of 99 differences, 85 showed an absolute difference within 3 beats per minute, 94 differences showed an absolute difference within 5 beats per minute, and 95 differences showed an absolute difference within 8 beats per minute. Thus, part 1 device validation was successfully completed for the HR.According to the part 2 of the 2010 ESH-IP2, of 33 participants, 29 showed a minimum of 2 of 3 comparisons within 3 beats per minute difference for HR. Nevertheless, 1 participant showed 3 differences outside 3 beats per minute. As these 2 detailed conditions were validated, the part 2 device validation was successfully completed.Therefore, part 3 of the QardioArm device validation was completed, as both parts 1 and 2 were validated for HR.Indeed, the QardioArm device met the validation criteria of the ESH-IP2 for the diastolic BP, systolic BP, and HR for patients who suffered from chronic kidney disease.The prior findings coincided with the Bland and Altman graphs that visually showed the differences between QardioArm device measurements and Omron M3 measurements for systolic BP , diastolValidation results QardioArm—Part 3Result: PassGlobally, the use of home BP monitoring is increasing in several countries, being a useful complement to clinic measurements with significant acceptance by patients with hypertension with several advantages ,9,18,19.The main disadvantage of automated home sphygmomanometers is their inaccuracy, although their accuracy is progressively improving . This inNevertheless, there is a lack of research studies, which validate devices in patients with chronic kidney disease ,24-27. FThis research is considered as the first study investigating the validation of a wireless upper arm oscillometric device connected to an app to measure HR and BP in chronic kidney disease patients. This validation has been carried out following the ESH-IP2 guidelines, although a validated noninvasive oscillometric upper arm device was used as a reference instead of a mercury sphygmomanometer.QardioArm has been previously validated for the general population in the first place by our team  and lateAccording to the results of our prior works, the number of differences included in each category according to the ESH-IP2  for systolic BP and diastolic BP was similar in the 3 validations -30, as pFollowing the ESH-IP2 guidelines, the findings of this study showed that the QardioArm device successfully passed the validation requirements for patients with chronic kidney disease . NeverthThe findings of this study are relevant because it is considered as the first validation to show that a device connected to an app to measure BP and HR met the requirements of the 2010 ESH-IP2 in the patients who suffer from chronic kidney disease.Besides, the ESH-IP2 guidelines should stress on validating the BP devices in other specific populations by publishing explicit criteria for such a validation in these populations.Finally, it is highly recommended to determine the accuracy of this device in other populations with specific diseases such as pregnant women, elderly people, or arrhythmic patients.