Little is known about the changes in disease makers and risk factors in patients with chronic kidney disease (CKD) under nephrological care in Africa. This study aimed to evaluate the baseline level of markers of CKD and their 12-month time-trend in newly referred patients in a tertiary hospital in Cameroon.2 and/or proteinuria> 1+ and/or abnormal renal ultrasound persisting for ≥3 months. Data analysis used mixed linear regressions.This was a retrospective cohort study including 420 patients referred for CKD between 2006 and 2012 to the nephrology unit of the Douala General Hospital in the littoral region of Cameroon. Their disease and risk profile was assessed at baseline and every 3 months for 1 year. Estimated glomerular filtration rate (eGFR) was based on MDRD and Schwartz equations. CKD was diagnosed in the presence of eGFR< 60 ml/min/1.73 mOf the 420 patients included, 66.9% were men and mean age was 53.8 (15.1) years. At referral, 37.5% of the participants were at CKD Stage 3, 30.8% at stage 4 and 26.8% at stage 5. There was 168 (40%) diabetic and 319 (75.9%) hypertensive patients. After some improvement during the first 3 months, eGFR steadily decreased during the first year of follow-up, and this pattern was robust to adjustment for many confounders. Systolic and diastolic blood pressure levels significantly fluctuated during the first twelve months of follow-up. Changes in the levels of other risk factors and markers of disease severity over time were either borderline or non-significant.Patients with CKD in African settings are referred to the nephrologist at advanced stages. This likely translates into a less beneficial effects of specialised care on the course of the disease. Chronic kidney disease (CKD) is a public health problem worldwide, with growing prevalence estimated at 11 to 13% in the adult population . Main aeCKD disproportionately affects African descendants –8. This Few studies have reported the baseline profile of patients with CKD at referral and in SSA , 28, 29.This retrospective cohort study was based on registry and files of the out-patient section of the nephrology unit of the Douala General Hospital (DGH) in Cameroon. DGH is a 320-bedded public institution, serving as referral hospital for kidney disease for the Littoral region of the country and beyond. It has the largest haemodialysis unit of the country, and provides ongoing RRT to about 230 patients. The medical staff of the unit comprises two nephrologists, one general practitioner and twelve nurses. Patients with CKD referred to the unit are assigned a unique identifier and attached to one of the nephrologists, and then followed-up at intervals that are determined by the stage of the renal disease. At the first consultation in the unit, each patient has clinical assessment and laboratory tests done. The diagnosis of kidney disease was based on estimated glomerular filtration rate less than 60 ml/min and /or proteinuria. The aetiology of CKD was mostly based on clinical arguments. Patients are generally referred at the advanced stage of CKD when shrunken kidneys preclude any reliable histological diagnosis. Among those eventually eligible for such diagnosis, renal biopsy is seldom done in the unit. Ethical approval was obtained from the ethical committee board of the Douala University and administrative authorization from the DGH.In the present study, we included all patients referred for CKD between January 2006 and December 2012. We did not include patients on renal replacement therapy in this study. Socio-demographic characteristics such as age and sex, and relevant clinical data including existing hypertension, diabetes mellitus, HIV, gout, and medication at referral were recorded. Blood pressure, aetiology of CKD, biological parameters including serum urea and creatinine level, glycaemia, uric acid, lipid profile, serum albumin and haemoglobin level were noted for the baseline level and every 3 months during the first 12 months of follow-up.2 and/or proteinuria> 1+ and/or abnormal renal ultrasound , persisting for ≥3 months. Patients were classified following the Kidney Disease Improving Global Outcome (KDIGO) staging of CKD [2 with proteinuria or abnormal kidney, stage 2: 60≦eGFR< 90 mL/min/1.73m2 with proteinuria and /or abnormal kidney, stage 3: 30≦eGFR< 60 mL/min/1.73m2, stage 4: 15≦eGFR< 30 mL/min/1.73 m2, stage 5: eGFR< 15 mL/min/1.73m2. Diabetes was defined by a fasting serum glucose ≧126 mg/dL, or random glucose ≧200 mg/dL, HbA1c≧6.5%, or the use of hypoglycaemic agents. Hypertension at referral was defined as systolic blood pressure (SBP) ≥ 140 mmHg, diastolic blood pressure (DBP) ≥ 90 mmHg, or use of anti-hypertensive agents.The abbreviated version of the Modification of Diet in Renal Disease (MDRD) and Schwartz equations were used for estimated glomerular filtration rate (eGFR) in patients aged ≥18 Years and < 18 years respectively , 31. CKDg of CKD . CKD stap-value < 0.05 was used to indicate statistically significant results.Data analysis used SAS STAT v 9.1 for Windows® . We have reported baseline characteristics as count and percentages, and mean and standard deviation, and compared them across major subgroups via chi square tests and equivalents for qualitative variables, and Student’s t-test for continuous variables. Mixed linear regression models were used to examine changes in kidney function, determinants and indicators of disease complications (severity) during the first 12 months of follow-up while adjusting for baseline and changing levels of potential confounders during follow-up. Heterogeneity in the trajectories of key outcomes across major subgroups was investigated through interaction tests. Mixed linear models are suitable for handling longitudinal data with repeated measurements on continuous outcomes, particularly when there are missing data, which is rather a common situation in observational studies like this one. A p = 0.09). The mean eGFR at referral was 28.6 (17.0) ml/min/1.73m2 overall, 30.9 (17.8) in men and 24.0 (14.2) ml/min/1.73m2 in women (p < 0.0001). The staging of kidney function at referral was: Stage 1 in 0.7% of participants, Stage 2 in 4.2%, Stage 3 in 37.5%, Stage 4 in 30.8% and Stage 5 in 26.8%; with a borderline significant difference by gender (p = 0.04). There was 168 (40%) diabetic, 319 (75.9%) hypertensive and 20 (4.9%) HIV positive patients at referral. Average blood pressure (BP) and creatinine levels were high, mostly similarly in men and women , while haemoglobin level was low, and much so in women (p = 0.0006) and the distribution of other hematologic parameters, electrolytes, lipid profile showed no major gender differences. Men were more likely to be smokers (p = 0.025), alcohol drinker (p < 0.0001), physically active (p = 0.001), to have gout (p = 0.011) and less likely to be HIV positive (p = 0.009) compared with women. Treatments, including for co-morbidities did not differ between men and women  was 53.8 15.1) years, with no significant difference in age between men and women (5.1 yearsp < 0.0001), diastolic blood pressure (p = 0.0002), potassium (p = 0.002), uric acid (p = 0.028), prevalent hypertension (p < 0.0001), stage of kidney function (p = 0.013), treatment with ACE inhibitors (p = 0.011) or ARA II (p = 0.043). Compared with participants without hypertension, those with hypertension were more likely to be older, to have higher weight, creatinine, haemoglobin, albumin and phosphate levels . They were also more likely to have diabetes (p < 0.0001), to be alcohol drinkers (p = 0.033), sedentary (p = 0.005), to comprise fewer people with HIV infection (p < 0.0001), to be referred with advanced stage CKD (p = 0.002).Baseline differences were apparent between participants with diabetes and those without, with regard to age (p = 0.003); Table p = 0.013) but not in those without (p = 0.205). While there was no evidence of statistical interaction by diabetes status in the trajectories of eGFR (interaction p = 0.646), a borderline interaction was apparent in the effects by status for hypertension (p = 0.054), primarily driven by an improvement in the eGFR between 9 and 12 months of follow-up among participants without hypertension at baseline ; (Table p = 0.006); (Table p = 0.174), nor by status for hypertension (both interaction p > 0.355); (Table p = 0.09). This pattern was consistent by status hypertension, while differing trajectories were observed among participants with diabetes  and those without diabetes , with significant statistical interaction (interaction p = 0.005). Other haematological parameters, electrolytes and lipid profile did not change significantly during follow-up overall and within major subgroups of participants.; Table , with su); Table , but notIn this study, we have for the first time described the time-trend in the trajectory of kidney function, risk makers and health consequences in patients with CKD in a SSA setting. We found a deteriorating kidney function over time, which was robust to adjustment for potential confounders and broadly similar across levels of major risk factors such as diabetes mellitus and hypertension; although some late improvement was observed among non-hypertensive participants, resulting in borderline interaction by status for hypertension. We found fluctuating levels of blood pressure over time, which was significantly different by status for diabetes, but no for hypertension, and likely reflecting the difficulties to achieve and maintain adequate blood pressure control in patients with CKD. Changes in the levels of other risk factors and markers of disease severity over time were either borderline or non-significant.In its natural history, CKD progresses silently to ESKD and studies have shown that trajectories of glomerular filtration rate (GFR) over time are heterogeneous –38. The Hypertension and diabetes are well-known risks factors for the development and progression of CKD , 48, 49.We did not have data to assess the effects of glycemic control on the trajectory of kidney function in people with diabetes. However, the distribution of baseline glucose control treatment suggests that their intensity was likely not enough to achieve and maintain good glycemic control. Almost all participants with diabetes also had hypertension with differentially high uptake of reno protective drugs such as angiotensin converting enzyme (ACE) inhibitors and angiotensine receptor inhibitors among those with diabetes at baseline (in line with guidelines) , 55–57. n = 420) of patients with CKD, has provided for the first time, evidence on the trajectory of kidney function and some major risk factor over time in newly referred patients in SSA using linear regression model. An assessment of the rate of decline of renal function is important but complex because renal decline is rarely a linear phenomenon and there is no gold standard methodology. A major limitation to this study is the retrospective nature of data collection with missing follow up data for some risk markers that could have influenced our results. Also proteinuria a major progression factor for CKD was not included as follow up data in this study. We could not evaluate the association between kidney function over time with onset of ESKD and mortality. Also patient on dialysis were excluded. We did not have data on treatments uptake and changes during follow-up, and therefore, could not fully account for their possible effect on the trajectories of investigated markers. Lastly, the current study was not based on power calculation. However, we used the totality of eligible observations at our center during the study period.Our study including a representative sample size (In conclusion, our study provides additional evidence that patients with CKD in African settings are referred late to nephrologists, with an advanced stage of CKD. This likely translates into a less beneficial effect of specialised care on the course of the disease, with kidney function inexorably declining further within the first year of follow-up, regardless of underlying co-morbidities and risk factors. To what extent this progression reflects non-optimal uptake of CKD modifying therapies at baseline, and their intensification during follow-up, need to be investigated in future studies. Such information is needed to optimise the prevention of CKD progression in this setting.


Establishing which parameters to use for diagnosing malnutrition in hemodialysis patients is a challenge in clinical practice. The handgrip strength (HGS) has stood out as a method of assessing nutritional status. Thus, the aim of this study was to determine the cut-off point for HGS in the assessment of the risk of malnutrition and inflammation in HD patients, and its association with other parameters.Study carried out in hemodialysis units in the city of Curitiba, Brazil. We obtained the cut-off point of the HGS through the ROC curve, using the malnutrition and inflammation score (MIS) as a reference. We checked the relationship (Odds ratio) between the variables “MIS” and “HGS” with the other study variables using the multivariate analysis (logistic regression).We assessed 238 patients (132 men), between 18 and 87 years of age (median = 59). The HGS cut-off point for diagnosing malnutrition and inflammation according to the reference used was <14.5 kg for women, and <23.5 kg for men. According to the HGS criteria, malnourished patients were older (OR = 0.958), with lower arm circumference (OR = 1.328) and higher scores in the malnutrition and inflammation score (OR = 0.85).HGS was significantly correlated with other nutritional assessment parameters. These results suggest that HGS is a valid screening tool to identify the risk of malnutrition and inflammation in hemodialysis patients. In addition, higher MIS scores are associated with a higher risk of death and hospitalizations in HD patients.-8Despite these advantages, one of the MIS limitations is the low practicality for monitoring dialysis patients, since it uses subjective parameters, which require the evaluator’s experience, and depends on data that may not be available at a certain time. Still, since it is a test for measuring voluntary muscle strength, it is strongly correlated to body mass, making it possible to identify patients who had a significant reduction in nutritional status before any change occurred. In the scientific literature, few studies have evaluated HGS as a parameter for nutritional assessment in hemodialysis patients, and they used different measurement methods.Handgrip strength (HGS) has stood out as a method of assessing nutritional status, and it is feasible in clinical practice. Still, ccurred. In the thods.,,11In view of the aforementioned aspects, the objectives of the present study are to determine the cutoff point for HGS for men and women to identify the risk of malnutrition and inflammation, using MIS as a reference standard, and to evaluate its association with other nutritional parameters.This is a cross-sectional study carried out in four HD clinics  in the city of Curitiba, PR, Brazil. The eligible patients were over 18 years of age, of both sexes, had been on HD for at least three months and had no physical or cognitive limitations to perform the HGS measurement. The patients underwent three HD sessions per week, lasting three to four hours each, in the period between August 2016 and July 2017. We collected clinical, demographic and laboratory data from their electronic medical records . The Human Research Ethics Committee of the Paranaense Institute of Otorhinolaryngology approved this study, and all participants signed an Informed Consent Form.We measured HGS using a dynamometer, with a digital display with strength assessment measured by kilogram strength (maximum 90 kg). To use the test, the participant remained in an orthostatic position, with the elbows flexed at a 90-degree angle, with no place of support at the time of measurement. We ran the measurements after the second HD session of the week, on the upper limb contrary to the vascular/catheter access, making with three measurements and picking the maximum value of the three. which use seven components of the original SGA adding the number of years of dialysis therapy, body mass index (BMI), serum albumin level and total iron binding capacity. We learned the serum albumin values and total iron binding capacity from the electronic medical records  for the month of the evaluation. We chose a severity level for each of the ten MIS components, which could range from 0  to 3 . The sum of all these components could vary from 0  to 30 .We used the MIS according to the recommendations from Kalantar-Zadeh et al., which uinal SGA adding rished).2), with the result expressed in kg/m2. To calculate the BMI, we considered the patient’s dry weight. To measure the arm circumference (AC), we used an inelastic measuring tape, considering the midpoint between the acromion and the olecranon, with the elbow flexed at 90º, in the arm opposite to the fistula or catheter. We ran the AC measurement before the hemodialysis session, since there is no consensus on the best time for such measurement. We analyzed the results and the adequacy of the AC according to Frisancho.A trained examiner took the anthropometric measurements. We calculated the BMI using the ratio between body weight (kg) and the squared height . We ran the association between qualitative variables using the chi-square test or Fisher’s exact test.We ran the Spearman’s correlation to assess the relationship between MIS and other nutritional parameters. The correlation was weak when the values ranged from 0 to 0.29; moderate, from 0.3 to 0.69; and strong, from 0.7 to 1.0. We obtained the cutoff point of the FPM variable through the ROC curve, using the MIS classes as a reference. The variables with a significance level of up to 20%, in univariate analyzes, entered the selection of variables for logistic regression purposes.We checked the relationship (Odds ratio) between the MIS and FPM variables with the other study variables through a multivariate analysis (logistic regression). We dichotomized the MIS variable using the cutoff point of 5, already established by other authors;,19 WeWe assessed variable normality using the Shapiro-Wilk test. We assessed all the tests considering a significance level of 5%.The study included 132 men (56%), aged between 18 and 87 years (median = 59 years) and time on HD ranging from six months to 17 years (median = 25 months); 113 patients (47%) were over 60 years of age.The CKD causes were diabetes mellitus (35%), hypertension (28%), chronic glomerulonephritis (11%), polycystic kidney disease (2%), multiple myeloma (10%) and other causes (14%).We analyzed the ROC curve to establish the best cut-off point for HGS capable of identifying patients at higher risk of malnutrition-inflammation. The area under the ROC curve for HGS as a predictor of MIS was 73% (95% CI = 64% to 85%) for men, and 61% (95% CI = 49% to 74%) for women. The best cutoff point for HGS for men was 23.5 kg  and 14.5 kg for women .The estimated prevalence of malnutrition based on these cutoff points was 36% in women and 39% in men. By MIS, malnutrition was 28% for women and 21% for men.The men classified as malnourished by MIS were significantly older, with lower AC and less strength (p = <0.05). The same occurred with men classified with malnutrition by the HGS, they were significantly older and with lower AC, (p <0.05). Both malnourished men and women according to HGS had higher MIS scores. Among women, the other variables did not behave in this way and did not show statistical significance.Regarding the presence of malnutrition according to the HGS criteria , advance and also in HD individuals. The difference in HGS between men and women is mainly associated with differences in body composition, with men generally having a greater amount of muscle mass, which directly reflects greater muscle strength.We found that men had higher HGS medians than women, which corroborates the results of other studies, both in healthy individuals,20 ans.,,,,21 Thtrength.,22 was similar to that established for men in the present study, and higher than that found for women. Other studies established lower HGS cutoff points than those found in this study, for each gender, but used different reference standards other than MIS. When comparing the results of the present study with those of other authors, it is evident that, in addition to the difference in methods, considering the characteristic of the method used as a reference standard is of paramount importance, since MIS has a subjective character, which may interfere with the evaluator’s experience and does not correlate directly with the individual’s body mass.This HGS variation was evident when analyzing the results of the ROC curve that indicated different cutoff points for each gender. The HGS value with the best compensation between sensitivity and specificity was 23.5 kg in men and 14.5 kg in women. Garcia et al. suggested higher cutoff points (<18 kg for women and <28.5 kg for men), using the same methodology as this study. The value of 23.4 kg proposed for women by Silva et al.Therefore, we must use and compare the cutoff points proposed for the diagnosis of malnutrition in the population of adult and elderly patients who undergo HD three times a week, and consider the methodology and the characteristic of the reference standard used, since there is no gold standard for nutritional assessment in HD patients. In addition, we still need studies capable of proposing HGS cutoff points according to categories other than gender. These findings support the use of HGS as a simple nutritional screening tool in patients undergoing HD. Still, studies indicate that malnutrition causes greater muscle fatigue, capable of altering muscle contraction and relaxation, contributing to lower HGS. Although MIS is a comprehensive nutritional screening tool and was developed specifically for renal patients, it depends on laboratory tests that are often unavailable at the time of evaluation.In this study, the estimated prevalence of malnutrition was higher by the HGS criteria than by the MIS, for both genders. In addition, we found that HGS inversely correlated with MIS and albumin, as noted by other authors. These fwer HGS. Althoug Thus, dynamometry is a more practical nutritional screening tool that can be used in the HD patient population.CKD patients have higher levels of inflammatory biomarkers, such as C-reactive protein and interleukin 6, which have been associated with lower HGS and higher MIS. Concerning albumin, its usefulness to detect early changes in nutritional status cannot yet be confirmed. Although albumin is considered in MIS and is correlated with HGS, its low values have been discussed in the population of renal patients on dialysis, since it may be more associated with inflammation than nutritional status.,-28 Th also investigated the validity of HGS as an instrument for identifying malnutrition through correlation with MIS, and they reported that each lower HGS standard deviation was significantly associated with a two-fold increase in the probabilities of an MIS ≥ 6, among men  and women . In the present study, men with higher HGS had 5.7 times less chance of presenting malnutrition (MIS ≥ 5), which may be associated with the fact that men had greater muscle strength than women.HGS was the main variable associated with malnutrition, especially among men . Using the logistic regression model, Silva et al. also in(-)The increase in pre-dialysis serum urea was another variable associated with a lower chance of malnutrition , corroborating reports from other studies that low serum levels of urea in dialysis patients may reflect intake deficient in protein, skeletal muscle mass and related to a higher risk of death.-31 In their study, Sampaio et al, reported that the increase in age reflected the increase in MIS. Qureshi et al., reported that elderly patients were often more malnourished than younger ones, according to the ASG, in addition to having lower HGS, similar to this study. Other studies have also found negative correlations between HGS and age.In men, age was one of the variables significantly associated with malnutrition, by both criteria evaluated; malnourished men had a mean age higher than 65 years. In addition, for each year of life, men had a higher likelihood of malnutrition by 5% . This influence of age on the malnutrition outcome is associated with several factors, but especially those related to the reduction of lean mass and muscle strength resulting from the various metabolic, hormonal and nutritional disorders of CKD, contributing to the increasingly prevalent sarcopenia in the elderly population. In theio et al, reporte et al., reporteage.,,,35 Lin et al., when assessing sarcopenia in HD patients, found that patients with high MIS (≥ 7) had a 6.9-fold increase in the risk of sarcopenia when compared to those with low MIS, not differentiating between genders.Another variable associated with malnutrition was MIS, especially among women ; and the higher the MIS, the greater the odds ratio for the patient to present malnutrition according to the HGS criteria. Other authors found a significant association between HGS and MIS., Lin et  et al., when asThe variables presented and which were associated with malnutrition can be obtained in the routine nutritional assessment, enabling a quick identification of the nutritional risk. HGS, as well as the suggested cutoff points, stands out as a practical and easy instrument to use.One of the methodological limitations of this study is the lack of an acceptable reference standard for MIS. We used the MIS value > 5 as the cutoff point in this study; however, other authors propose different cutoff points, according to the population evaluated.It was not possible to assess whether there was a difference in HGS between patients who used the dominant arm or not, because we decided to use the arm without the arteriovenous fistula (AVF), to prevent the patient from applying the maximum hand grip pressure on the arm with the FAV.Considering that we held this study in HD units in a single geographic region of the country, caution should be exercised when generalizing the findings to populations in other regions. The present study did not evaluate the results proposed by differences in age range - adults and the elderly - we assessed only the differences between genders. Further studies should take into account the age group to propose cutoff points for MIS and HGS, since aging causes changes in body composition. In addition, it is of utmost importance that new studies also use methods that assess quantity and/or quality of muscle tissue, since it is directly related to HGS.The best cut-off point for HGS capable of identifying patients at risk of malnutrition and inflammation was 23.5 kg for men and 14.5 kg for women. HGS was associated with malnutrition, according to the MIS classification, significantly in both genders. The results suggest that HGS is a valid screening tool to identify risk of malnutrition and inflammation in HD patients.


P < 0.001), age , and systolic blood pressure . Multivariable forward stepwise linear regression analysisshowed a positive association between log-transformed leptin levels and log-cfPWV . Thus, aortic stiffness is positively correlated with serum leptin levels in patients with stage 3–5 CKD.Leptin potentially exerts atherogenic effects.This study evaluated the relationship between serum leptin levels and aortic stiffness in patients with stage 3–5 chronic kidney disease (CKD). Totally 205 participants were enrolled. Fasting blood sample were checked and serum leptin were measured by enzyme immunoassay. Aortic stiffness was measured as the carotid–femoral pulse wave velocity (cfPWV). 73 (35.6%) of 205 patients showed cfPWV >10 m/s were defined as aortic stiffness group. Compared with the remaining patients, the aortic stiffness group had high prevalence of diabetes mellitus, older age, higher waist circumference, body fat mass, systolic blood pressure, fasting glucose, and higher serum leptin level. In multivariable logistic regression analysis the independent predictors of cfPWV >10 m/s included leptin levels (odds ratio [OR]: 1.061, 95% confidence interval [CI]: 1.027–1.095, Abbreviations: BUN, blood urea nitrogen; cfPWV, carotid–femoral pulse wave velocity; CI, confidence interval; CKD, chronic kidney disease; Cre, creatinine; DBP, diastolic blood pressure; DM, diabetes mellitus; eGFR, estimated glomerular filtration rate; LDL-C, low-density lipoprotein cholesterol; OR, odds ratio; SBP, systolic blood pressure; TCH, total cholesterol; TG, triglycerides Cardiovascular disease is the primarily aetiology of mortality in chronic kidney disease (CKD) patients. Many clLeptin, mainly produced by adipose tissue, is a 167-amino acid peptide hormone. It is primarily involved in the regulation of whole body energy homoeostasis and metabolism. Recent studies have suggested its role in increased cardiovascular risk associated with obesity. ,10 ActinInitially, 230 CKD participants enrolled, 25 participants were excluded on account of malignancy (n = 3), a chronic inflammatory disease (n = 3), heart failure (n = 5), or chronic obstructive pulmonary disease (n = 4), or if they refused to provide informed consent for participation (n = 10). Finally, a total of 205 patients with CKD over 18 years old without kidney transplantation or dialysis before were enrolled from the nephrology outpatient department at our medical centre in Hualien, Taiwan, between January and December 2016. All the participants were educated with detailed CKD care, focused on the salt and protein restriction, and the avoidance of nephrotoxins. This study was proved by the Protection of Human Subjects Institutional Review Board at Tzu Chi University and Hospital (IRB103-136-B), and informed consent was written before participation.2, stage 4 as eGFR = 29–15 ml/min per 1.73 m2, and stage 5 as eGFR <15 ml/min per 1.73 m2, separatively. All the participants received SBP and DBP measurement; check in the morning by using a standard mercury sphygmomanometer on right arm. Before BP measurement, they had been seated for at least 10 min. Patients who used any anti-hypertensive medications over 2 weeks, SBP ≥140 mmHg, and/or DBP ≥90 mmHg are considered hypertension disease. Either fasting plasma glucose ≥126 mg/dl or usage of oral hypoglycaemic medications or insulin is defined as DM[Estimated glomerular filtration rates (eGFRs), determined by using the Chronic Kidney Disease Epidemiology Collaboration equation, measured at least 3 months apart and used the mean value. All patned as DM.Participants were measured body weight, height, and waist circumference in light-weight clothing without shoes. Body mass index was obtained by using the body weight (kg) divided by the height (m) squared. Body fat mass was measured by bioimpedance analysis  .g immediately. Serum levels of total calcium, phosphorus, blood urea nitrogen (BUN), creatinine (Cre), fasting glucose, total cholesterol (TCH), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) were measured using an autoanalyzer . Serum leptin were measured by enzyme immunoassay with commercial kit  [Blood sample (approximately 5 ml) was taken after 8 hours fasting in the morning and centrifuged for 10 min at 3000 ×  France) .cfPWV measurement was done as previously described by applanation tonometry using a SphygmoCor system  . ParticiP value <0.05 was considered to be statistically significant. The statistical analyses were performed with SPSS for Windows version 19.0  package SPSS for Windows .The Kolmogorov–Smirnov test was used to check the normality of data distributions. We expressed normally distributed data as means ± standard deviation, and evaluated comparisons between groups by using two-tailed Student’s independent t-tests. We expressed non-normally distributed data as medians and interquartile ranges, and evaluated comparisons by using the Mann–Whitney U test. Data based on numbers of patients were expressed as the percentage (%) f study population, and evaluated by the chi-square test. Variables that were significantly associated with the aortic stiffness group were further tested for independence by multivariable logistic regression analysis. Because cfPWV, TG, fasting glucose, BUN, Cre, and leptin were not normally distributed, we had transformed the collected data to base 10 logarithmic values to achieve normality. Variables that were significantly correlated with log-cfPWV were tested for independence in a simple linear regression analysis. Variables independent in simple linear regression were then adjusted in a multivariable forward stepwise regression analysis. A P = 0.007). The aortic stiffness group were older (P < 0.001) and had higher serum leptin level (P < 0.001), systolic blood pressure , waist circumference (P = 0.012), body fat mass (P = 0.025), and fasting glucose (P = 0.049) than the control group.Comorbid conditions of the 205 participants included DM , hypertension . P < 0.001), serum leptin level , and SBP  : 1.064, 95% confidence interval (CI): 1.033–1.096, = 0.006) .Table 2.r = 0.392, P < 0.001), age , waist circumference , log-leptin level , DM , and diastolic blood pressure  were positively correlated with log-cfPWV, whereas estimated glomerular filtration rate  was negatively correlated. Multivariable forward stepwise linear regression analysis of the factors significantly associated with log-cfPWV revealed four independent predictors of log-cfPWV: SBP , age , log-leptin level , and DM .The results of the simple and multivariable linear regression analyses of the clinical variables associated with logarithmically transformed cfPWV (log-cfPWV) values are presented in Our results revealed among patients with stage 3–5 CKD, higher serum leptin levels, older age, and higher SBP were independent risk factors of aortic stiffness. In addition, higher SBP, older age, higher log-leptin level values, and the presence of DM were positively associated with log-cfPWV values.Aortic stiffness is a progressive, ageing-related process. The underlying mechanisms include vascular inflammation, activation of the renin–angiotensin–aldosterone system, insulin resistance, and neurohormonal dysfunction. Aortic 11 Second, many evidence indicate that leptin contribute to thrombosis because of platelet hyperactivity and imbalance between coagulation and fibrinolysis[Leptin is mainly producing by white adipose tissue ,25. It hrinolysis. Fourth,rinolysis. Fifth, rinolysis. Finallyrinolysis. All theSeveral studies have shown positive associations between hyperleptinemia and cfPWV, including in patients with coronary artery disease and hypertension as well as in patients who have undergone kidney transplantation or who are receiving haemodialysis . MoreoveThis was the first study to focus on the relationship between serum leptin levels and aortic stiffness in patients with stage 3–5 CKD. However, this study has several limitations. First, this study conducted at a single hospital with a limited number of patients with CKD. Second, we did not measure albuminuria in this study. It has been demonstrated that albuminuria is often followed by the development and progression of aortic stiffness and atherosclerosis. FinallyIn conclusion, this study investigated the role of leptin in aortic stiffness in patients with stage 3–5 CKD and demonstrated that serum leptin level is positively correlated with cfPWV, indicating a positive association between serum leptin level and aortic stiffness in this patient group.


This cohort study compares cardiovascular and safety outcomes of chlorthalidone and hydrochlorothiazide as first-line therapies for adults with hypertension. What are the relative effectiveness and safety of chlorthalidone and hydrochlorothiazide?In this comparative cohort study of 730 255 individuals from multiple large databases, no difference in association with effectiveness between the 2 drugs was found, but a significantly worse safety profile for chlorthalidone was observed.Recommendations to prefer chlorthalidone to hydrochlorothiazide are not supported by real-world evidence. Chlorthalidone is currently recommended as the preferred thiazide diuretic to treat hypertension, but no trials have directly compared risks and benefits.To compare the effectiveness and safety of chlorthalidone and hydrochlorothiazide as first-line therapies for hypertension in real-world practice.This is a Large-Scale Evidence Generation and Evaluation in a Network of Databases (LEGEND) observational comparative cohort study with large-scale propensity score stratification and negative-control and synthetic positive-control calibration on databases spanning January 2001 through December 2018. Outpatient and inpatient care episodes of first-time users of antihypertensive monotherapy in the United States based on 2 administrative claims databases and 1 collection of electronic health records were analyzed. Analysis began June 2018.Chlorthalidone and hydrochlorothiazide.The primary outcomes were acute myocardial infarction, hospitalization for heart failure, ischemic or hemorrhagic stroke, and a composite cardiovascular disease outcome including the first 3 outcomes and sudden cardiac death. Fifty-one safety outcomes were measured.Of 730 225 individuals , 36 918 were dispensed or prescribed chlorthalidone and had 149 composite outcome events, and 693 337 were dispensed or prescribed hydrochlorothiazide and had 3089 composite outcome events. No significant difference was found in the associated risk of myocardial infarction, hospitalized heart failure, or stroke, with a calibrated hazard ratio for the composite cardiovascular outcome of 1.00 for chlorthalidone compared with hydrochlorothiazide . Chlorthalidone was associated with a significantly higher risk of hypokalemia , hyponatremia , acute renal failure , chronic kidney disease , and type 2 diabetes mellitus . Chlorthalidone was associated with a significantly lower risk of diagnosed abnormal weight gain .This study found that chlorthalidone use was not associated with significant cardiovascular benefits when compared with hydrochlorothiazide, while its use was associated with greater risk of renal and electrolyte abnormalities. These findings do not support current recommendations to prefer chlorthalidone vs hydrochlorothiazide for hypertension treatment in first-time users was found. We used advanced methods, sensitivity analyses, and diagnostics, but given the possibility of residual confounding and the limited length of observation periods, further study is warranted. Hydrochlorothiazide is the most commonly prescribed member of the class, but the guideline states that chlorthalidone is preferred on the basis of longer half-life and proven trial reduction of cardiovascular disease. However, to our knowledge there are no large, completed randomized clinical trials comparing these medications, although one is in progress.2 Indirect network meta-analyses showed superior effectiveness with chlorthalidone,4 but a large observational study showed approximately equal effectiveness.5 Short-term, small randomized clinical trials7 showed only nominal differences in safety issues such as hypokalemia, but the observational study5 showed a worse safety profile for chlorthalidone with higher rates of hypokalemia and hyponatremia.The 2017 American College of Cardiology/American Heart Association hypertension guideline8 using many negative controls to detect and correct residual bias10 and testing of the consistency among heterogeneous data sources.11 We used these techniques to compare chlorthalidone and hydrochlorothiazide on 55 outcomes in 3 large observational databases of patients from the United States.Both indirect network meta-analyses and traditional observational studies are vulnerable to bias, but recent analytic methods are providing improved strategies to mitigate this risk. These strategies include the balancing of large numbers of baseline patient covariates to make comparison groups more equivalent,12 Large-Scale Evidence Generation and Evaluation in a Network of Databases for Hypertension initiative.13 The research was approved by the Columbia University institutional review board as an OHDSI network study. The use of databases was reviewed by the New England Institution Review Board and was determined to be exempt from broad institutional review board approval because this research project did not involve human subjects research. Informed consent was also waived for this reason.This multicenter controlled cohort study was part of the Observational Health Data Sciences and Informatics (OHDSI)15 The 3 databases were deidentified.We included the 3 OHDSI databases that had at least 2500 patients with exposures to each drug who met the eligibility criteria enumerated below. The MarketScan Commercial Claims and Encounters database (CCAE)  database includes adjudicated health insurance claims and enrollment data from individuals enrolled in US employer-sponsored insurance health plans. The deidentified Clinformatics Data Mart Database   is an adjudicated US administrative health claims database with commercial and Medicare claims from inpatient and outpatient medical services, prescriptions as dispensed, and outpatient laboratory test results processed by participating large national laboratory vendors. The Optum deidentified Electronic Health Record Dataset   database comprises deidentified electronic health record data including prescriptions as prescribed and administered, laboratory results, vital signs, body measurements, diagnoses, procedures, and information derived from clinical notes using natural language processing. The databases were encoded in OHDSI’s Observational Medical Outcomes Partnership common data model version 5.16 We included all patients initiating antihypertensive treatment with chlorthalidone or hydrochlorothiazide, and we defined the index time as the first observed exposure to either drug, including only patients with a prior or concurrent diagnosis of hypertension. We excluded patients having known prior exposure to any hypertension therapies , all other drugs in the 365 days before the index date, all diagnoses in the 365 days before the index date, and the Charlson Comorbidity Index score,ISPOR) reporting guideline was followed.The primary outcomes, which we prespecified, were hospitalization for acute myocardial infarction, heart failure, ischemic or hemorrhagic stroke, and a composite cardiovascular disease outcome including the first 3 outcomes and sudden cardiac death  using a Cox proportional hazards model, accounting for time on therapy and censoring; we used Kaplan-Meier survival plots to assess the assumption of proportionality. Detailed covariate and methods information is provided in the eAppendix in the 21 The HRs and associated SEs from each of the 3 database analyses were then combined through a random-effect meta-analysis to produce a composite effect estimate.Analysis began June 2018. We conducted our cohort study using the open-source OHDSI CohortMethod R package,11 . We measured how often the true relative risks for controls were inside of their CIs (it should be 95% of the time for 95% CIs), and we calibrated all HR estimates, their 95% CIs, and their 2-sided P values so that approximate 95% coverage was achieved for the controls.We estimated residual bias using 76 negative control outcomesTo address multiplicity concerns, we indicate which estimates remain statistically significant after a Bonferroni correction for 55 hypotheses. However, we report all differences.Outcomes may differ in timing: electrolyte imbalances may occur quickly while cardiovascular outcomes may take longer to occur, issues that were identified after the prespecified analyses. We therefore performed a post hoc analysis with risk period starting 91 days after the first drug exposure. This both ensured that all recorded days at risk had at least a 91-day exposure to the drug and shifted the median time at risk to longer time than for the primary analysis.Only the electronic health record database, PanTher, had systolic and diastolic blood pressure readings recorded to assess baseline blood pressure. We repeated the analysis on that database with last systolic and last diastolic blood pressures in the year prior to index treatment included in the propensity score model using cubic splines.PanTher also had appropriately timed blood potassium levels for some patients. We compared the last potassium level up to a year before first drug dose with the last potassium level 30 to 90 days after the first dose. In the largest database, CCAE, we addressed differences in dosing and potency by restricting the analysis to patients whose dose was 12.5 mg of chlorthalidone or 25 mg of hydrochlorothiazide for the entire on-treatment period.21 for CCAE, demonstrating sufficient between-group equipoise. For CCAE, there were 14 104 individuals receiving chlorthalidone and 287 390 individuals receiving hydrochlorothiazide; for Optum there were 7696 and 189 834, respectively; and for PanTher there were 15 118 and 216 113, respectively. We found no statistically significant differences in risk of acute myocardial infarction, hospitalized heart failure, stroke, or the composite cardiovascular outcome between individuals receiving chlorthalidone and hydrochlorothiazide . The calFurthermore, the event rates for hypokalemia were substantial. In CCAE, the rates per patient were 6.3% and 1.9% for chlorthalidone and hydrochlorothiazide, respectively. The Kaplan-Meier curves  for the delayed risk period, which was similar to that for the original period, which was 0.96 .We assessed balance on baseline blood pressure in the PanTher database. Before any stratification, the standardized difference of the mean for blood pressure was 0.200 for systolic and 0.168 for diastolic. After propensity score stratification, but without including blood pressure in the model, the differences were 0.126 and 0.094, respectively. Therefore, without knowing blood pressure, balancing on the other 60 535 PanTher covariates resulted in marked improvement in balance on blood pressure. When we included blood pressure in the propensity model, the differences improved to 0.046 and less than 0.001 for systolic and diastolic blood pressure, respectively, with good balance among all other covariates  and calibrated HR of 1.57 , passing the Bonferroni threshold . Visualization of the changes reveals a greater downward shift in chlorthalidone . Other electrolyte abnormalities were also more frequent.Our study is the largest multisite analysis of real-world evidence to address this comparison, with 36 918 records of individuals prescribed chlorthalidone and 693 337 prescribed hydrochlorothiazide across the 3 databases. We found consistent results across our 3 databases, excellent balance on more than 60 000 covariates after stratification, little bias based on our controls, little sensitivity to changes in time at risk, to inclusion of baseline blood pressure or to initial dose, and confirmation of differences in potassium by laboratory measurement.Chlorthalidone use was associated with a higher rate of electrolyte and renal disorders, with an increase in hypokalemia, hyponatremia, acute renal failure, and chronic kidney disease. Based on the electrolyte findings, chlorthalidone’s association with an increase in rate of type II diabetes may be associated with potassium depletion or to dehydration. Chlorthalidone’s lower rate of abnormal weight gain may be associated with more effective diuresis.23 looked at cardiovascular outcomes vs placebo for low-dose diuretics; there were nominal differences, but the 2018 European Society of Cardiology/European Society of Hypertension guideline24 interpreted the results as roughly equivalent for the 2 drugs. The indirect meta-analysis by Roush et al4 showed an improved relative risk for composite cardiovascular events for chlorthalidone compared with hydrochlorothiazide of 0.79 . The real-world evidence study by Dhalla et al5 estimated an HR for chlorthalidone vs hydrochlorothiazide of 0.93 , although 1 dose subgroup did reach statistical significance without adjustment for multiple hypotheses. An observational study of the MRFIT cohort by Dorsch et al25 showed a relative HR for chlorthalidone vs hydrochlorothiazide of 0.79 , but the doses for both drugs were high. A randomized clinical trial comparing hydrochlorothiazide with chlorthalidone currently in progress2 may provide more definitive information to inform drug choice.To our knowledge, there have been no completed large head-to-head randomized clinical trials comparing chlorthalidone and hydrochlorothiazide on cardiovascular effectiveness. An indirect meta-analysis by Thomopoulos et al13 which used the same methods and databases and had the same follow-up times, was able to discern differences in effectiveness. Third, indirect network analysis is subject to bias26 if the underlying trials differ in populations of patients, in physician behavior, or in study design, and, similarly, our observational study may be subject to residual bias. A fourth factor, failure to account for differences in baseline blood pressure between the 2 drugs, does not appear to be a source of the disagreement based on the PanTher database results. Fifth, our 95% CI for the composite cardiovascular disease HR is 0.85 to 1.17, which does not rule out some superiority in either direction, although it does exclude the previous indirect network analysis results.Several factors may be contributing to the discordance between our effectiveness results and those of previous indirect network analyses. First, because we focus on first-time use of antihypertension drugs, we likely have higher proportion of patients with milder disease with less baseline cardiovascular disease risk than the randomized clinical trials included in the network analyses. Second, our time-at-risk periods may be shorter, but our sensitivity analysis showed no difference as we increased time at risk, and our previous study of hypertension drug classes,28 could underlie some of the observed differences in toxicities, but our dose-sensitivity analysis still revealed higher hypokalemia for chlorthalidone at a 1:2 chlorthalidone:hydrochlorothiazide dose ratio. Furthermore, if clinicians treat to similar blood pressure levels, then they may titrate the doses to levels with similar blood pressure reduction, explaining our lack of differences in effectiveness but not our differences in safety. Ernst et al6 found better chlorthalidone nighttime blood pressure control at a 1:2 dose ratio, which could explain some increased safety signals.A simple difference in effective dose, with chlorthalidone known to have a greater-per-milligram potency for lowering blood pressure levels than hydrochlorothiazide,6 found little difference in potassium. At a 1:1 dose ratio, Bakris et al7 found no statistically significant difference in the hypokalemia rate although with only 5 events, the study lacked power. The network meta-analysis by Ernst et al29 found a small difference in potassium reduction. Two analyses of the MRFIT cohort30 showed increased reduction of potassium for chlorthalidone when both drugs were used at high doses (50 mg-100 mg). A study of real-world evidence by Dhalla et al5 showed odds ratios around 3 for hypokalemia, matching our results well, even in the 2 strata in which chlorthalidone was half the dose of hydrochlorothiazide; it also found an HR of 1.68 for hyponatremia.The literature inconsistently points to a difference in hypokalemia between the 2 drugs. At a 1:2 dose ratio, Ernst et alOur main limitation is the possibility of residual confounding including confounding by indication, differences in physician characteristics that may be associated with drug choice, concomitant use of other drugs started after the index date, differences in blood pressure measurement error, and informative censoring at the end of the on-treatment periods. To minimize this risk, we used newer methods to account for bias and to detect residual bias through our negative and positive controls.Our findings based on currently available data and the most recent advances in observational research do not support the use of chlorthalidone over hydrochlorothiazide. This study found that chlorthalidone use was not associated with significant cardiovascular benefits when compared with hydrochlorothiazide, while its use was associated with greater risk of renal and electrolyte abnormalities. We acknowledge the possibility of residual confounding despite our analytic approach and diagnostics and look forward to the results of the ongoing randomized clinical trial.


The purpose of this study is to explore the underlying functional network brain activity changes of patients in middle‐aged with retinitis pigmentosa (RP) and the relationships with clinical features such as depression scale and visual functioning using voxel‐wise degree centrality (DC) method.t‐tests, gender and handedness were compared using chi‐square test). We use the voxel‐wise DC method to assess spontaneous brain activity. Receiver operating characteristic (ROC) curve analysis was performed to distinguish between RP patients and HCs. Correlation analysis was used to examine the relationships between mean DC values in various brain regions and clinical features  in RP patients.We included 16 patients with RP  and 16 healthy controls . Participants were matched in terms of age, weight, gender and handedness  and the relationships with clinical features such as depression scale and visual functioning using voxel‐wise degree centrality (DC) method. The inclusion criteria for RP were as follows: (a) diagnosed with RP based on relevant medical history, symptoms, and visual function check and ophthalmoscopy; (b) no abnormality of the cerebral parenchyma on cranial MRI; and (c) no other ocular diseases in either eye . The exclusion criteria were: (a) eye diseases, trauma or ophthalmic surgery; (b) mental illness , cardiovascular disease, brain disease ; or (c) abnormality of cerebral parenchyma on cranial MRI.Sixteen healthy controls  were recruited from Nanchang in Jiangxi Province in China. They were matched with the RP group in terms of gender, age, weight, and handedness. All HCs met the following criteria: (a) no eye disease; (b) no mental illness ; (c) ability to undergo MRI scans .All research protocols were written in accordance with the Helsinki Declaration. All subjects participated voluntarily and understood the purpose, content, and risks of the study before providing written consent.2.2A Siemens Trio 3.0 T scanner  with an 8‐channel phased‐array head coil was applied to perform MRI scanning of all subjects as previously described  was used to classify functional data and remove incomplete data. The remaining data were preprocessed by DPARSFA software , including digital imaging and communication form conversion in medicine, slice timing, head motion correction, spatial normalization, and Gaussian kernel of full width at half maximum (FWHM) of 6 × 6 × 6 mm2.4z‐score graph: Zi¼DCi – mean /SD .On the basis of the individual voxel function network, we generated DC values by calculating the number of significant super‐threshold correlations (or degrees of binary adjacency matrices) for each subject. Using the following equation . Differences were considered statistically significant at p < .05. At the same time, functional data were compared with two‐sample t‐tests using REST software. The statistical threshold of voxel level for multiple comprehensive comparisons was set at p < .05 after using Gaussian random field theory. Alphasim corrected at a cluster size >40 voxels and p < .01.We compared the clinical variables and demographic of both groups using independent sample We generated receiver operating characteristic (ROC) curves to classify the mean DC values regions of the cerebrum distinct between the RP and HC groups. Clinical Parameters and Data collections The association DC and clinical features of RP patients should be evaluated though separate linear regression models which included age, gender and Duration of RP(y) as nuisance covariates. Correlation analysis was performed to assess the relationships between DC and clinical features of RP patients.2.6p < .05.REST software was used to classify encephalic regions with DC differences between the two groups as ROIs, after which the mean DC value was calculated for each by averaging all voxels. The relationship between behavioral performance such as depression scale and visual functioning and the mean DC value in each ROI was analyzed using linear correlation analysis in the RP group. Differences were considered statistically significant at 2.7t‐tests (differences significant at p < .05).Cumulative clinical measurements  of RP patients were recorded and analyzed with independent sample 33.1p = .781), weight (p = .836) or IOP  as shown in Table SD) of RP duration was 12.43 ± 5.41 years. The details are presented in Table No statistically significant differences were observed between two groups in age p = .78, weight 3.2p > .05).Compared to HCs, middle‐aged patients with RP showed significantly reduced DC values in the right medial frontal gyrus, bilateral cuneus, bilateral precuneus, and bilateral superior frontal gyrus Figure  and sign3.3r = −.869, p < .001), and the mean DC value in the bilateral precuneus were positively correlated with the Visual Functioning Questionnaire‐25 score  indicated the diagnostic cutoff. In this study, the AUCs were clearly shown in Table 4To our knowledge, this is the first study to investigate functional network brain activity using DC methods in middle‐aged patients with RP. We found that this group showed significantly reduced DC values compared to HCs in the right medial frontal gyrus, bilateral cuneus, bilateral precuneus, and bilateral superior frontal gyrus and significantly increased DC values in the right cerebellum posterior lobe, left inferior temporal gyrus, and right fusiform gyrus Figure .4.1We know that the medial frontal gyrus plays an important role in cognitive and attentional function  17. The cuneus receives significant input from the lower visual field Cohen,  correspoThe precuneus (BA7) is a part of the superior parietal lobule ; Natural Science Key Project of Jiangxi Province (No: 20161ACB21017); Youth Science Foundation of Jiangxi Province ; Key Research Foundation of Jiangxi Province ; Education Department Key Project of Jiangxi Province (No: GJJ160020); Teaching Reform of Degree and Graduate Education Research Project of Jiangxi Province (No:JXYJG‐2018‐013); Grassroots Health Appropriate Technology “Spark Promotion Plan” Project of Jiangxi Province (No:20088003); Health Development Planning Commission Science Foundation of Jiangxi Province (No: 20175116); Health Development Planning Commission Science TCM Foundation of Jiangxi Province (No:20150823).https://publons.com/publon/10.1002/brb3.1983.The peer review history for this article is available at


The IOP difference between immediately before the first intervention and after finishing the final intervention was also greater in the AG and EG than in the SG in both eyes . In conclusion, IOP was reduced at 60 min after acupuncture or electroacupuncture was performed at BL1 and EX-HN7. Additionally, IOP was reduced after finishing four acupuncture or electroacupuncture sessions. Therefore, our results suggest that acupuncture and electroacupuncture are beneficial for lowering IOP in glaucoma patients. This trial is registered with NCT04157530.Glaucoma is characterized by the degeneration of retinal ganglion cells that cause progressive optic neuropathy, finally resulting in changes to the optic nerve head. Lowering intraocular pressure (IOP) is the only method proven for treating glaucoma. Several studies have discovered that acupuncture can reduce IOP and also increase ocular perfusion and ocular blood flow. Therefore, the present study investigated the effect of acupuncture on IOP in glaucoma patients. We conducted a single-blinded, randomized, controlled trial involving 45 glaucoma patients. The results indicated that the difference between the IOP 60 min after the intervention and IOP immediately before the intervention was greater in the acupuncture group (AG) and electroacupuncture group (EG) than in the sham group (SG) for all four of the interventions performed and in both eyes (all  Glaucoma is a leading cause of blindness after cataract; it is an optic neuropathy with a specific structural finding in the optic disc and causing a specific functional deficit in automated visual field examinations . AccordiGlaucoma is characterized by the degeneration of retinal ganglion cells, causing progressive optic neuropathy and finally resulting in changes to the optic nerve head . The maiAcupoints Jingming (BL1) and Qiuhou (EX-HN7) are located in the periorbital region, and according to traditional Chinese medicine theory, BL1 can communicate yin and yang and nourish and clear eyes, whereas Qiuhou (EX-HN7) can transport qi, activate the blood, and achieve free-flowing meridians and clear eyes. The present study investigated the effect of acupuncture at BL1 and EX-HN7 on IOP in glaucoma patients. We designed a single-blinded, randomized, controlled clinical trial.NCT04157530). The purpose of the study and all procedures of the trial were explained to the participants, and informed consent was obtained prior to the trial. The inclusion criteria were as follows: (1) glaucoma diagnosis at least 3 months previously; (2) use of one or no intraocular hypotensive drugs; (3) age ≥20 years; (4) female or male; and (5) clear consciousness that enabled the participant to sign the informed consent form and cooperate with the trial procedure. The exclusion criteria were (1) comorbidity with other chronic diseases, such as hypertension and diabetes, and taking multiple drugs; (2) laser surgery for either glaucoma or myopia; (3) pregnancy or lactation; (4) intolerance to acupuncture treatment; (5) allergy to acupuncture needles; and (6) refusal to sign the informed consent form.The study participants were patients with glaucoma that had been diagnosed by an ophthalmologist from Dashe Shun Ming Eye Clinic, Kaohsiung, Taiwan. Acupuncture was performed at the Chi-Sin Chinese Medicine Clinic between March and October 2018 by a Chinese medicine doctor with at least 10 years of acupuncture practice experience. The research protocol was reviewed and approved by the Research Ethics Committee of China Medical University Hospital  and ClinicalTrials.gov  of 0.05, 39 people (13 in each group) were required to achieve a statistical power of 90%. Assuming a dropout rate of 5%, 45 people (15 in each group) were needed.The present study was designed as a single-blinded, randomized, placebo-controlled, three-armed trial. Each participant was treated with sham acupuncture, acupuncture, or electroacupuncture (EA) twice weekly for 2 consecutive weeks (four interventions), each intervention was 20 min. IOP was evaluated at four time points for each treatment. Assuming an effect size of 0.50 and a type I error  the sham group (SG), to which the seeds of Wang Bu Liu Xing, a Chinese herb, were applied to the skin surface at BL1 and EX-HN7 for 20 min at a time; (2) the acupuncture group (AG), to which an acupuncture needle  with a spherical needle head was inserted into BL1 and EX-HN7 with Der-qi; and (3) the electroacupuncture group (EG), to which needles were inserted similarly as in the AG group, but the needles were then connected to an EA machine after Der-qi, with the frequency of stimulus being 6 Hz and the intensity of stimulus enough to produce a minimal visible muscle twitch.Four stages of IOP assessments were performed for all the participants. The first IOP assessment (V1) was conducted before the sham, acupuncture, or EA intervention; the second assessment (V2) was conducted immediately after the intervention; the third assessment (V3) was conducted 30 min after the intervention; and the fourth assessment (V4) was conducted 60 min after the intervention. Quality of life was assessed using the World Health Organization Quality of Life brief , Taiwanese version; the scale was administered before the intervention and after the fourth intervention.The primary outcome was IOP, and the secondary outcome was the change in the score of WHO Quality of Life-BREF, Taiwanese version.BL1 is located in the depression between superomedial parts and inner wall of the orbit. EX-HN7 is located at the junction between the outer 1/4 and medial 3/4 of the inferior margin of the orbit when the subject is in a sitting position and looking upwards .A Canon fully automatic tonometer  was used by a well-trained individual to measure IOP. In the present study, the average of three measurements was used. The IOP was measured from 9:00 a.m. to 11:30 a.m. to prevent the effects of diurnal intraocular pressure changes.The visual field index (VFI) represented as % and mean defect (MD) represented as dB were measured by using a Humphrey Field Analyzer II-i  in the Dashe Shun Ming Eye Clinic  in some case.The checklist of Consolidated Standards of Reporting Trials  was compp value of less than 0.05 was considered statistically significant. All statistical analyses were performed using SAS 9.4  and SPSS Statistics 24 .Categorical data were displayed in numbers and percentages, whereas continuous variables were given as means ± standard deviations. Differences in continuous variables were tested using the analysis of variance or Kruskal–Wallis test and differences in categorical variables were tested using the chi-square test or Fisher exact test among groups. The repeated measures analysis of variance was used to compare the IOP differences between the four time points (V1–V4) for four interventions among different groups. A A total of 44 glaucoma patients completed the trial: 15 patients in the SG, 14 in the AG, and 15 patients in the EG. One patient withdrew because he/she was afraid of the air that was suddenly ejected from the IOP measurement device .p > 0.05; The basic characteristics of the participants, their sex, age, height, body weight, blood pressure (systolic and diastolic blood pressure), IOP (right and left eyes), and latanoprost use for lowering IOP, showed no significant differences between the SG, AG, and EG  assesses overall quality of life, overall health satisfaction, the physiological domain, the psychological domain, social relationships, the social relationship domain (Tw), environment, and the environmental domain (Tw). For this scale, scores obtained before any of the interventions and after any of the interventions did not show significant differences , and latanoprost use showed no significant differences between the SG, AG, and EG. Therefore, these results demonstrate that acupuncture or EA at BL1 and HX-EN7 lowers IOP in glaucoma patients. The pathogenesis of glaucoma is increased IOP and ischemia of the optic nerve head, influencing the retinal ganglion axon. An ocular perfusion pressure below the lower limit of autoregulation or failure of neurovascular coupling results in secondary insults . Reductiglaucoma . Taken tOur results also indicated that IOP was greater at V2 (immediately after the intervention) than at V1 (immediately before the intervention), suggesting a stress response immediately after sham, acupuncture, or EA treatment, especially for EA; however, this stress response had disappeared 30 min after the intervention. Our results showed good agreement with those of another study discovering that acupuncture temporarily increased IOP .Although our results also indicated that the VFI and MD increased 6 months after acupuncture and EA interventions in the AG and EG, but reduced in the SG, only three cases could not be concluded, and future studies are needed to increase the number of cases.Our results also indicated that the changes in all component scores and the total scores for the WHOQOL-BREF (Taiwanese version) showed no significant differences between the groups, suggesting that to investigate changes in quality of life, a longer investigation may be required. The intervention period in our study was only 2 weeks.As for the duration of acupuncture or EA, and when is the best time for acupuncture or EA intervention to reduce intraocular pressure. According to the results of the present study Tables  and 4, wNo bleeding, ecchymosis, or side effects such as shock occurred after acupuncture or EA was applied to BL1 and HX-EN7 around both eyes in this study. This suggests that applying acupuncture or EA to BL1 and HX-EN7 for a 2-week glaucoma treatment is safe in lowering intraocular pressure, but longer-term observation is required in the future. Taken together, we considered that acupuncture or EA is a better method in lowering IOP than medical therapies, such as latanoprost as one of the prostaglandin analogues because prostaglandin analogues may induce ocular side effects including blurred vision, dry eye, and hyperemia .This study had some limitations: (1) the sample was small, the intervention period was short, and there was no long-term follow-up; therefore, larger samples, longer interventions, and follow-up are required in future research. (2) This was a single-blinded, randomized, controlled study; a double-blinded, randomized, controlled study should be designed in the future. (3) This study only assessed the effects of acupuncture or EA on IOP; how they affect visual acuity and the visual field should be determined in future studies. (4) Finally, this study did not differentiate between primary and secondary or open-angle and closed-angle glaucoma; classification of the glaucoma type is required in future research.In conclusion, IOP was reduced 60 min after acupuncture or EA at BL1 and HX-EN7, and IOP was also reduced after finishing four acupuncture or EA sessions, suggesting that acupuncture and EA are beneficial for lowering IOP in glaucoma patients. In addition, acupuncture and EA at BL1 and HX-EN7 were discovered to be safe for 2 weeks.


Morbidity and mortality due to chronic kidney disease are increasing among hypertensive patients in Sub-Saharan Africa. The majority of hypertensive patients with chronic kidney disease are not diagnosed at an early stage because of poor knowledge. However, to the best of our knowledge, there is no study conducted in Ethiopia about knowledge of hypertensive patients towards prevention and early detection of chronic kidney disease. Thus, the aim of this study was to assess knowledge towards prevention and early detection of chronic kidney disease and associated factors among hypertensive patients at Jimma town public hospitals, Ethiopia. P value of less than 0.05 were considered.  A hospital-based cross-sectional study was conducted among 332 hypertensive patients using an interviewer-administered questionnaire and medical record reviewing from April 5 to May 21, 2019. Study participants were selected using simple random sampling. Data were collected by using a standardized questionnaire. Data were entered into Epidata version 3.1 and analyzed by SPSS version 23. Descriptive statistics and bivariable and multivariable logistic regression were applied. To identify factors, a 95% confidence level and P = 0.014), higher education , working in private sectors , taking three and above drugs per day , and having a family history of kidney disease  were significantly associated with knowledge. Conclusion and Recommendation. Near to half of the study participants had good knowledge towards prevention and early detection of chronic kidney disease. Attending secondary education and above, working in private sectors, taking three and above drugs per day, and having a family history of kidney disease were independent predictors of knowledge. Hypertensive patients should be encouraged to be aware of risk factors of CKD, and health care providers should educate hypertensive patients about the prevention and early detection of chronic kidney disease. Over half (59.6%) were males, and the mean (±SD) age of participants was 54.92 (12.91) years. Among the total participants, more than half of them (47.9%) had good knowledge. Attending secondary education (AOR = 2.9,  Chro3 months . The norNowadays, developing countries including Ethiopia are disproportionally affected by both communicable and noncommunicable diseases (double burden disease) . In EthiIn Sub-Saharan Africa (SSA), the prevalence of CKD in the general population is 13.2%  and the In most of SSA, patients cannot get treatment for kidney failure because of huge cost, shortage of skilled health care providers, and limited service settings for renal replacement therapy. As a result, patients' quality of life is decreased and health expenditure is increased; ultimately, premature death can occur . LikewisThe majority of patients with renal dysfunction are not aware of having CKD until 90% of kidney function becomes lost . BecauseLimited studies were conducted regarding knowledge towards prevention and early detection of CKD in SSA –23. HoweThe study was conducted in Jimma town public hospitals from April 5 to May 21, 2019. Jimma town is located 352 kilometers far apart from Addis Ababa, the capital city of Ethiopia. Jimma University Medical Center and Shenen Gibie Hospital are public hospitals in Jimma town. Jimma University Medical Center is a teaching hospital with 659 beds and serves more than 18 million people. Shenen Gibie Hospital is a general hospital. Chronic illness care is one of the services in which both hospitals provide to the community within and outside Jimma town. According to 2019 registration, there were a total of 1520 hypertensive patients in Jimma University Medical Center and Shenen Gibie Hospital.A hospital-based cross-sectional study was conducted.All hypertensive patients who had to follow-up at Jimma University Medical Center and Shenen Gibie Hospital chronic illness follow-up clinic were the source population. Hypertensive patients who had to follow-up at Jimma University Medical Center and Shenen Gibie Hospital chronic illness follow-up clinic during the data collection period were taken as the study population.All adult (age ≥ 18 years) hypertensive patients and registered in the list of hypertensive patients until the commencement of data collection were included in the study. On the contrary, hypertensive patients who were already diagnosed with CKD obtained from medical record reviewing and seriously ill patients were excluded.α value), 95% confidence interval, 5% margin of error, and 50% proportion. Because of the absence of a previous study, 50% is taken as a proportion. Since the source population is less than 10,000, a correction formula was utilized. By adding a 10% nonresponse rate, the final sample size was 338. Simple random sampling (lottery method) was used to recruit study participants using their medical record number. After that, participants were interviewed and their medical records are reviewed when they came for medication refill and medical checkup at a chronic illness follow-up clinic.The sample size was determined using a single population proportion formula by considering 1.96 for the standard normal variable with a 5% level of significance  and clinical factors , number of drugs, family history of kidney disease, family history of diabetes mellitus, and family history of cardiac disease).Knowledge: awareness of hypertensive patients about CKD and measured by calculating the mean score of 24 items.Good knowledge: if participants scored ≥mean score of knowledge questions.Poor knowledge: if participants scored <mean score of knowledge questions.Prevention: range of health promotion actions that are geared towards limiting the development of CKD.Number of drugs: drugs taken by hypertensive patients for a long period of time and classified as <3 and ≥3 drugs per day.The data were collected by a structured interviewer-administered questionnaire and medical record reviewing using data abstraction format. The questionnaire had three parts. The first part was about the sociodemographic characteristics of participants. The second part assessed clinical factors, and the third part was the chronic kidney disease screening index tool. The knowledge questionnaire was adopted from the CKD screening index which was validated, and its reliability was checked in the previous studies. In the previous studies, its internal consistency was 0.87 and 0.8 in Palestine  and JordThe questionnaire was pretested on 5% of the sample at Agaro Hospital to check acceptability and consistency two weeks prior to actual data collection. After reviewing the result of the pretest, modification of the questionnaire was performed for clarity, sensitiveness, and completeness of the questionnaire. Training was given for data collectors and supervisors for one day on the objective of the study. Data collectors were fluent speakers of local languages (Afan Oromo and Amharic). Continuous supervision and daily checking of the collected data were performed by investigators.P value < 0.25 in the bivariable analysis were fitted into a multivariable logistic regression to control for the possible effects of confounding. Then, multivariable logistic regression using the backward likelihood ratio method was done to see the associations between outcome and independent variables. Odds ratio and 95% CI were used to identify the presence and strength of association, and P value < 0.05 was declared as statistically significant at the final model. Model fitness was checked by the Hosmer-Lemeshow test.The collected data was numerically coded, checked, and entered into Epidata version 3.1 and then exported to SPSS version 23.0 for analysis. All independent variables having Out of a total of 338 hypertensive patients, 332 participated in the study yielding a response rate of 98.2%. More than half, 198 (59.6%), of participants were males. The mean (±SD) age of participants was 54.92 (±12.91) years, 204 (61.4%) were living in urban, and 233 (70.2%) were married .More than one-third, 125 (37.7%), of hypertensive patients had lived with the disease between five and ten years, and half, 167 (50.3%), of hypertensive patients were treated by one or two drugs. Three hundred three (91.3%) patients had no comorbidities, and 279 (84%), 289 (87%), and 303 (91.3%) had no family history of kidney disease, diabetes mellitus, and cardiac disease, respectively .After computing the answers of 332 participants, normal distribution was checked using a histogram and the distribution was normal. The mean (±SD) score of knowledge among study participants was 11.18 (±4.64). Participants who scored ≥11.18 were classified as having good knowledge, and participants who scored <11.18 were classified as having poor knowledge. Based on this, 173 (52.1%) of participants had poor knowledge and 159 (47.9%) had good knowledge. The majority (69.3%) of the study participants did not know the function of the kidney. Only near to one-fourth of the respondents (23.5%) knew that the kidney releases hormones to regulate blood pressure. With regard to risk factors of CKD, 222 (66.9%) of the respondents reported that being old is a risk factor. Being a smoker is reported as risk factors for CKD by half (50.6%) of the respondents. Moreover, having kidney stones and recurrent urinary tract infections, being obese, and having high blood pressure were reported as risk factors by 180 (54.2%), 197 (59.3%), and 195 (58.7%) of participants, respectively. However, most (78.6%) of the participants did not know the relationship between CKD and having a family history of CKD. One hundred forty (42.2%) of participants knew the importance of checking creatinine and serum urea nitrogen tests. Near to three-fourth, 257 (77.4%), of participants identified swollen feet and ankle and puffiness around the eye as symptom/sign of CKD. Most, 221 (66.6%), did not know that the final stage of CKD (ESRD) needs dialysis as a lifelong treatment .P value < 0.25 and entered into multivariable logistic regression. However, in multivariable logistic regression analysis, only educational status, occupation, taking three and above drugs per day, and having a family history of kidney disease showed significant association with good knowledge at P value < 0.05. Participants who had attended higher education were 5 times more likely to have good knowledge as compared to participants with informal education ) ) .It is crucial for hypertensive patients to discover the level of knowledge to develop health education to prevent major complications including chronic kidney disease. Thus, the current study was aimed at assessing the knowledge of hypertension patients towards prevention and early detection of chronic kidney disease.In this study, 47.9%  had good knowledge about chronic kidney disease. This finding was higher than studies done in Tanzania 38.5% , NigeriaHowever, this finding was lower than a study done in Jordan , where mIn this study, being old is reported as a risk factor by 66.9% of the participants. This was in line with a study conducted in Jordan (66.6%) . More thEducational status was significantly associated with knowledge towards prevention and early detection of chronic kidney disease. Accordingly, participants who had attended secondary education and above were three times and five times, respectively, more likely to have good knowledge as compared to participants who had no formal education. This finding was supported by other studies conducted in Palestine, Nigeria, Australia, Malaysia, and Singapore , 26–28. Occupational status was associated with knowledge. The current finding showed that those participants who had worked in private/NGOs were four times more likely to have good knowledge as compared to farmers. This finding was consistent with a study done in Cameron , where rIn this finding, a number of drugs had a significant association with knowledge. Participants who had taken three or more drugs a day were 45% less likely to have good knowledge as compared to participants who had taken less than three drugs. The possible explanation could be pill burden, and side effects might compromise patients' adherence to their medication and might stop taking medication.Another, having a family history of kidney disease was associated with good knowledge. Participants who had a family history of kidney disease were two times more likely to have good knowledge as compared to those participants who had no family history of kidney disease. This finding was in line with a study done in Australia . This coSince the study design is cross-sectional, it did not show a temporal relationship between cause and effect. Knowledge was assessed by an interview technique; this might lead to recall bias. Another is that comparison of study findings was held with other countries because of the limitation of literature on this topic in Ethiopia, where the health facility setup, health policy, and socioeconomic status of the population might differ across the country.In conclusion, the current study showed that near to half of the study participants had good knowledge towards prevention and early detection of chronic kidney disease. Attending secondary education and above, working in private sectors, taking three and above drugs per day, and having a family history of kidney disease were independent predictors of knowledge. Hypertensive patients should be encouraged to be aware of risk factors of CKD, and health care providers should educate hypertensive patients about the prevention and early detection of chronic kidney disease.


Hyperuricemia is a state in which the serum levels of uric acid are elevated. As such it has a pronounced effect on vascular and renal function with their consequences, while also showing some antioxidant effects that show to be beneficial. Hyperuricemia has shown to have a J-shaped relationship with mortality, is frequently associated with development and progression of heart and kidney disease, and is correlated with malnutrition-inflammation-atherosclerosis syndrome, although several Mendelian studies have failed to show an association with morbidity and mortality. Hyperuricemia is usually associated with gout flares and tophi development but can also present as asymptomatic hyperuricemia. It is still uncertain whether asymptomatic hyperuricemia is an independent risk factor for cardiovascular or renal disease and as such its treatment is questionable. Some possible tools for future decision making are the use of noninvasive techniques such as pulse wave analysis, urinary sediment analysis, and joint ultrasound, which could help identify individuals with asymptomatic hyperuricemia that could benefit from urate lowering therapy most. Some of it is ingested in the form of various purine rich foods, while some purines are endogenous: from synthesis or catabolism of nucleic acids. Nevertheless, purines are metabolized by xanthine dehydrogenase or xanthine oxidase to form uric acid ,2. Humannd MRP4) .Even though SUA is an end product of purine metabolism, it still has a biological effect, primarily affecting renal and vascular function. Experimental studies suggest that hyperuricemia causes kidney damage due to systemic and glomerular hypertension. One of several mechanisms suggested is inhibition of nitric oxide synthesis, which leads to arterial vasoconstriction. Another is induction of oxidative stress and inflammation ,5,9–13. 2.One of the problems in dealing with hyperuricemia is no consensus on the definition of hyperuricemia. A practical value would seem to be SUA concentrations higher than 405 µmol/L (6.8 mg/dL) as this is urate’s solubility point measured using automated enzymatic methods in laboratories . Other rOn the other hand, asymptomatic hyperuricemia is a condition, where patients have elevated levels of SUA, yet do not exhibit symptoms or signs of monosodium urate crystal deposition, such as gout attacks, urolithiasis, or uric acid nephropathy. Campion et al. reported that during a follow up of 15 years, the annual incidence of gout for initially healthy men with their SUA between 420 and 470 µmol/L (7 and 7.9 mg/dL) was 0.5%. They concluded that most patients with hyperuricemia remain asymptomatic [3.Effect of lifestyle and therapy on SUA levels is summarized in 3.1.The first line of hyperuricemia treatment is undoubtably using a low-purine diet, which can reduce SUA levels by 10–15%. It is wise to avoid meat, sea foods, soft drinks, fructose rich beverages, honey, and alcohol. Some agents have also proven to be effective in lowering SUA, such as vitamin C, so diets rich in vegetables and fruit can be helpful. Furthermore, bing cherry, coffee, low-fat dairy products, and folic acid have shown to be protective. Additionally, weight loss and physical activity are recommended ,11,17.2 [A study on Bangladeshi adults has reported a significant positive relationship between SUA and obesity . Further2 . Another2 ; however2 .Lactobacillus strains have shown to lower SUA with beneficial effects on hypertension and renal disease [Recently, studies on mice have shown that probiotics could reveal to be an additional therapeutic option.  disease ,27.3.2.The main pharmacologic agents used for ULT are xanthine oxidoreductase (XOR) inhibitors. XOR inhibitors reduce SUA levels by inhibiting uric acid synthesis . AllopurOther possible ULT agents are uricosurics such as probenecid, benzbromarone, lesinurad and recently a selective urate reabsorption inhibitor (SURI) named dotinurad ,33. CurrThe 2016 EULAR recommendations on management of gout recommend starting treatment with allopurinol. If target SUA cannot be reached, they recommend use of febuxostat, a uricosuric or a combination of a uricosuric with a xanthine oxidase inhibitor. Pegloticase is recommended for refractory gout .3.3.Another option for treating hyperuricemia is the use of medications with secondary SUA lowering capabilities such as losartan, atorvastatin, calcium channel blockers, sodium-glucose co-transporter 2 (SGLT-2) inhibitors, fenofibrate, sevelamer, metformin, and angiotensin-II/neprilysin inhibitors (ARNI). Some medications that should be considered for discontinuation because of their known effect to raise SUA are acetylsalicylic acid, cyclosporine, theophylline, mycophenolate, beta- and alpha-1-adrenergic antagonists, and angiotensin-converting enzyme (ACE) inhibitors ,15,41–44post hoc analysis on diabetes mellitus (DM) patients [Interesting data were found regarding medications with urate lowering capabilities as a secondary effect. Use of losartan has decreased the chance of renal disease by 6% for every 0.5 mg/dL decrease in SUA levels, which was also observed in a patients ,31. An apatients ,45.Regarding the use of statins, a meta-analysis showed urate lowering effects observed only with use of atorvastatin and simvastatin, but not others . With atLastly, SGLT-2 inhibitors have been observed to lower SUA. A meta-analysis has shown empagliflozin to be superior to others in this regard and better results were achieved during early DM. However, the effect was abolished in patients with CKD . In comp4.Currently, there is still no consensus whether to pharmacologically treat asymptomatic hyperuricemia. Some have suggested ULT in cardiovascular (CV) prevention strategies, but no official recommendations have been made. Pharmacotherapy is warranted only in patients receiving radiotherapy or chemotherapy, patients with hereditary enzyme deficiencies, or in patients with extreme values of SUA ,19. Neve5.It is still uncertain whether asymptomatic hyperuricemia is an independent risk factor for CV disease. In several epidemiological and observational studies, hyperuricemia has been linked to CV events, AH, and DM, but Mendelian randomization studies do not seem to show an association ,54–58. HAllopurinol use was associated with only a small reduction in blood pressure in adults of 3.3 mmHg systolic and 1.3 mmHg diastolic, while febuxostat has managed to lower systolic pressure in CKD patients for 7.2 mmHg and diastolic pressure for 5.1 mmHg ,63. HoweThe ongoing URRAH  project has identified several SUA cutoff values for prediction of total mortality (4.7 mg/dL), CV mortality (5.6 mg/dL), and fatal myocardial infarction (5.7 mg/dL) .6.Patients with known gout have a twofold risk for developing kidney stones compared to healthy individuals. However, it remains unclear whether hyperuricemia is an independent risk factor for incident kidney stones, even though some evidence is revealing an association . Epidemi2 compared to placebo, which was observed in other meta-analyses on CKD patients as well [Several meta-analyses have been carried out to test the effect of using ULT on CKD progression. A recent meta-analysis regarding use of allopurinol has shown a mean difference in lower eGFR decline of 3.2 mL/min/1.73 m as well . A study as well . Similar as well ,83–88. O as well . Recentl as well . A head  as well . All met as well ,83. Howe as well . Patient as well . Additio as well . Chou et as well .Recently, and open label study was published evaluating anti-albuminuric effects of topiroxostat in patients with diabetic nephropathy, where treatment with high dose (160 mg) topiroxostat reduced albuminuria compared to low dose (40 mg) .7.Researchers have suggested the use of urinary sediment analysis for the presence of urate crystals, which indicates supra-saturation values in the kidney, and musculoskeletal ultrasound for identification of urate deposition on joints in patients with asymptomatic hyperuricemia. Studies should evaluate the cost–benefit of testing to reveal patients that could benefit most and guide clinical practice. Others have suggested ultrasound of the first metatarsal joint in patients with family history of gout. ULT should be initiated and SUA followed-up, if pathologic findings are present ,38. A piAs atherosclerosis is one of the main causes of CV morbidity and mortality, and could be associated with hyperuricemia in all patients, future research in this area could also benefit from use of noninvasive tools for CV assessment such as pulse wave analysis and pulse wave velocity. A study has shown that higher SUA was associated with a greater increase in pulse wave velocity, pointing toward arterial stiffness in patients with SUA ≥ 370 µmol/L (6.2 mg/dL), which is more frequently reached in men ,95. NoveAccording to the review from Pascart and Richette , several8.Even though the topic of hyperuricemia is as old as most medications used for its treatment, controversy remains. As we wait for further trials to complete and give us a definitive answer whether we should start treatment of asymptomatic hyperuricemia, further thought should be given into individualizing patient treatment and substituting certain medications with others that have a similar primary end goal with additional effects regarding lowering of SUA. Time will also tell whether countries that have already begun with a more aggressive approach toward treatment will show better outcomes for patients, in the meantime use of musculoskeletal ultrasound and urinary analysis might guide the rest of us.