Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease (CKD) and end-stage kidney disease worldwide. In Japan, the proportion of new patients requiring dialysis due to DKD has remained unchanged over the past five years. Early diagnosis and treatment are extremely important for the prevention of DKD progression. Albuminuria is the most promising biomarker currently available for diagnosing DKD and predicting its prognosis at an early stage; however, it has relatively poor specificity and sensitivity for DKD. Measuring the serum levels of tumor necrosis factor receptors  is an alternative for predicting the prognosis of patients with CKD, irrespective of their diabetes status. Cardiorenal risk factor management and renin–angiotensin system inhibitor usage are effective in slowing the DKD progression, although the residual risk remains high in patients with DKD. Recently, two classes of antihyperglycemic agents, sodium–glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists, in addition to nonsteroidal selective mineralocorticoid receptor antagonists, which are less potent blood pressure-lowering and potassium-sparing agents, have emerged as cardiorenal disease-modifying therapies for preventing the DKD progression. This review focused on the SGLT2 inhibitor-based therapeutic strategies that have demonstrated cardiorenal benefits in patients with type 2 diabetes. In Japan, DKD has been reported to be the most common cause of ESKD since 1998 [Diabetic kidney disease (DKD) is the main cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD) worldwide. DKD is defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 mCKD is an independent predictor of the cardiovascular disease (CVD) and mortality in patients with diabetes . TherefoPatients with diabetes require treatments that prevent cardiorenal disease development. Such interventions include intensive blood glucose control to prevent the development of microalbuminuria in patients recently diagnosed with diabetes ,7; howevSodium–glucose cotransporter 2 (SGLT2) inhibitors ,16, nons2 and the annual eGFR decline rate is −5 mL/min/1.73 m2, the patient will develop ESKD (eGFR: 15 mL/min/1.73 m2) at an age of 81 years. However, if the therapeutic intervention can halve the annual eGFR decline rate, the age at which ESKD develops can be extended to 92 years. Moreover, if the eGFR at the time of diagnosis is already 30 mL/min/1.73 m2, the patient will develop ESKD at an age of 73 years. In this case, even if the same therapeutic intervention is used, the age at which ESKD develops can only be extended to 76 years.As shown in 2 from −2.5 mL/min/1.73 m2) is achieved as during an early intervention.A graph presenting how early and late interventions affect ESKD onset. Early diagnosis and therapeutic intervention in patients with early declines in eGFR can delay further declines in renal function . Late thIdentification of patients at risk of early declines in eGFR is of great clinical importance. Circulating TNFRs (TNFR1 and TNFR2) are potential biomarkers for predicting future eGFR decline in patients with CKD, with or without diabetes ,22,23,242; DAPA-CKD: 25 to 75 mL/min/1.73 m2). Compared with the CREDENCE trial, the baseline eGFR was low and stage 4, CKD was frequent in the DAPA-CKD trial. The CREDENCE trial was the first RCT to evaluate the effects of the SGLT2 inhibitors on primary kidney outcomes in patients with T2D and macroalbuminuria  [The results of previous cardiovascular outcome trials (CVOTs) indicated that SGLT2 inhibitors improve kidney outcomes in patients with type 2 diabetes (T2D) and normal renal function, thereby leading to the initiation of multiple trials on kidney outcomes that enrolled patients with advanced CKD  ,16. As sropathy) . Moreove2, dapagliflozin only decreased HbA1c by 0.1% [In the DAPA-CKD trial, the effects of the SGLT2 inhibitors on kidney outcomes did not change in patients with CKD, regardless of their diabetes status . In pati by 0.1% . Moreove by 0.1% . Thus, t by 0.1% . TherefoIn the Dapagliflozin Effect on Cardiovascular Events–Thrombolysis in Myocardial Infarction 58 (DECLARE-TIMI 58) trial, dapagliflozin reduced the kidney outcomes with no evidence of heterogeneity in the levels of the baseline systolic blood pressure (BP) in patients with T2D . Even inIn both the CREDENCE and DAPA-CKD trials and the previous CVOTs ,35, the 2) whose baseline eGFRs were comparable with those of patients in the DAPA-CKD trial , long-term eGFR trajectory was improved in patients with >10% acute initial declines in eGFR but not in those with modest or no acute declines in eGFR. A further study is needed to investigate whether >10% acute initial declines in eGFR after initiation of the SGLT2 inhibitors has a beneficial effect on long-term eGFR trajectories. Moreover, in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial, >10% acute declines in eGFR after the initiation of the SGLT2 inhibitors in patients with heart failure (HF) with reduced ejection fraction (HFrEF), showed better composite outcomes of worsening HF and CV deaths than no decline in eGFR [SGLT2 inhibitors augment the tubuloglomerular feedback by increasing sodium and chloride delivery to the macula densa, thereby leading to acute initial declines in eGFR, resulting from the reductions in the intraglomerular pressure. This issue has increased hesitancy of clinicians to administer SGLT2 inhibitors to patients with a decreased kidney function. In the CREDENCE and DAPA-CKD trials, the proportion of patients with an initial decline in eGFR (>10%) was 45% and 49%, respectively, for the SGLT2 inhibitor treatment; an approximately three-fold higher odds ratio was obtained with the SGLT2 inhibitor than with the placebo in both the trials ,42. The  in eGFR . In real2 or more/less). Of note, the risk of ESKD in patients who develop AKI during the study period dramatically increased more than 10-fold, compared with those who did not. A meta-analysis of the data from three major CVOTs  with SGLT2 inhibitors in patients with T2D, revealed a robust reduction in the risk of AKI by 34%; however, these events were nonadjudicated [A further concern regarding the use of the SGLT2 inhibitors, is volume depletion. Although volume depletion is a relatively common adverse event associated with the use of SGLT2 inhibitors (approximately 5%), the incidence of AKI was low in both kidney outcome trials (CREDENCE and DAPA-CKD) likely due to: (1) reductions in tubular ischemia through the attenuation of sodium and glucose reabsorption; (2) improvements in anemia, leading to an improved renal oxygenation; and (3) reductions in the usage of diuretics. In the CREDENCE trial, canagliflozin decreased the risk of adverse renal events by approximately 30%, in comparison with the placebo . Howeverudicated .p < 0.01) [A decline in kidney function leads to hyperkalemia, due to the decreased potassium excretion from the kidneys. In addition, diabetes, HF, and the use of RAS inhibitors and MRAs are associated with an increased risk of hyperkalemia. Hyperkalemia, in turn, is an independent risk factor for mortality and CV events . In the  < 0.01) . In the  < 0.01) ,54. Howe < 0.01) .The data regarding the renoprotective effects of SGLT2 inhibitors in patients with CKD and normoalbuminuria are lacking. The EMPA-KIDNEY trial was stopped earlier than planned, due to the demonstrated efficacy in kidney outcomes, suggesting that SGLT2 inhibitors may expand indications for patients with CKD without albuminuria. Indeed, CVOTs in patients with T2D, also demonstrated that the renoprotective effects of SGLT2 inhibitors are independent of the amount of albuminuria . The pleIn CVOTs, evaluating the effects of the SGLT2 inhibitors in patients with T2D, the effect of the SGLT2 inhibitors on 3-point major adverse events (3P-MACE) was observed only in the secondary prevention group ; howeverIn both the CREDENCE and DAPA-CKD trials, the SGLT2 inhibitors reduced the risk of CV death or hospitalization, due to HF by approximately 30%, in patients with CKD, irrespective of the presence or absence of prior ASCVD ,63. ThisEarly diagnosis and intervention are of utmost clinical importance in DKD. In addition to eGFR and albuminuria, circulating TNFRs have the potential utility in identifying patients at risk of progressive declines in kidney function. Current clinical management of patients with diabetes comprises the correction of blood glucose, BP, and dyslipidemia with lifestyle modifications, such as appropriate exercise, diet, and cessation of smoking. The goal of treatment, particularly in patients with DKD, is the reduction in albuminuria and the preservation of kidney function while preventing CV events. However, patients with diabetes exhibit an increased prevalence of comorbidities and complications. Many previous clinical studies, mainly in patients with diabetes, have added to the existing knowledge on the risk factors and efficacious interventions for DKD and enabled the development of personalized treatment strategies that consider the comorbidities and complications in individual patients with diabetes, to reduce the residual risk of DKD. However, there remains an urgent clinical need to reduce the ever increasing number of patients with DKD using a combination of treatments, including RAS inhibitors, SGLT2 inhibitors, MRAs, and GLP-1 RAs, which are currently the four mainstay treatments for DKD .Patients with diabetes are at an increased risk of comorbidities, such as hypertension, hyperuricemia, and obesity, as well as complications, such as CKD, ASCVD, and HF. RAS inhibitors are highly recommended in hypertensive patients; however, the other three treatment agents also exhibit mild blood pressure-lowering effects (approximately 2–3 mmHg). SGLT2 inhibitors and some RAS inhibitors, such as losartan and irbesartan, exhibit mild uric acid-lowering effects. SGLT2 inhibitors and GLP-1 RAs exhibit body weight-lowering effects that differ from those of other antihyperglycemic agents. RAS inhibitors, SGLT2 inhibitors, and MRAs can be used for preventing CKD . Furthermore, GLP-1 RAs exhibit antialbuminuria effects, which are comparable to those of the other three agents, particularly in patients with diabetes and macroalbuminuria. Anemia and hyperkalemia are common complications observed in patients with advanced CKD. SGLT2 inhibitors exhibit potassium-lowering effects and have been shown to improve anemia.The abovementioned four therapeutic agents  have a demonstrated efficacy in preventing the development of ASCVD. Except GLP-1 RAs, the other three agents have a utility in the prevention of hospitalization, due to HF. GLP-1 RAs, but not SGLT2 inhibitors, have a utility in reducing the risk of cerebral infarction. Patients with prior ASCVD or HF are often hypotensive. In such cases, the use of RAS inhibitors is more challenging, due to reduced renal blood flow. Thus, patients with diabetes should receive personalized treatment that considers individual comorbidities and complications to reduce the residual risk of cardiorenal disease.SGLT2 inhibitors not only lower the blood glucose by inhibiting glucose reabsorption in the proximal tubule but also prevent kidney and HF outcomes through various pleiotropic actions. Especially in patients with impaired kidney function, SGLT2 inhibitors are more of a cardiorenal risk-reducing agent than a hypoglycemic agent. It is hoped that the SGLT2 inhibitors will be appropriately administered to as many patients at a high risk of cardiorenal disease as possible.


Obesity is an important risk factor for hyperuricemia. We aimed to explore the relationship between perirenal fat thickness (PrFT) and paranephric fat thickness (PnFT) and serum uric acid (SUA) in patients with type 2 diabetes mellitus (T2DM).This was a cross-sectional study involving 257 patients with T2DM recruited from Beijing Luhe Hospital from September 2019 to May 2020. The basic and clinical information such as age, gender, duration of diabetes was collected through the medical records. All patients underwent a physical examination including height, weight, waist circumference, hip circumference, systolic blood pressures and diastolic blood pressure. The venous blood and urine samples were collected to measure SUA, fasting blood glucose, total cholesterol, triglyceride, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, serum creatinine, blood urea nitrogen and glycosylated hemoglobin. PrFT and PnFT were measured via ultrasonography. Pearson correlation test and linear regression analysis were used to analyze the association between PrFT and PnFT and SUA.P = 0.001 and P = 0.009, respectively). In addition, the PrFT and PnFT were positively associated with SUA level . Moreover, this association was stronger in males, non-obesity patients and patients with normal renal function. In the multivariate analysis, the PrFT was independently associated with SUA level after adjusting confounding factors.We found that PrFT and PnFT increased according to the tertiles of SUA level (The PrFT was independently associated with SUA level in patients with T2DM.The online version contains supplementary material available at 10.1186/s12902-022-01081-9. Serum uric acid (SUA) is the end-product of purine metabolism. In recent years, the prevalence of hyperuricemia ranged from 9.3% to 37% in different countries around the world –5. The oObesity is an important risk factor for hyperuricemia , 12–16. Few studies explored the relationship between perirenal fat and paranephric fat and SUA level. Some cross-sectional studies have shown that perirenal fat thickness (PrFT) and paranephric fat thickness (PnFT) were both positively related to SUA in diabetic patients in univariate analysis , 24. AnoThis was a cross-sectional study. A total of 257 inpatients with T2DM were recruited from Beijing Luhe Hospital from September 2019 to May 2020. As regards the criteria for inclusion, subjects enrolled were diagnosed with T2DM and were older than 18 years. Exclusion criteria included the presence of malignant tumor, present pregnancy, liver dysfunction, resistant hypertension, unstable angina, severe heart failure, severe elevated triglyceride (TG) and total cholesterol (TC) level. In addition, those who using anti-hyperuricemic agents and diuretics, undergoing major surgery, with elevated creatinine level and need renal replacement therapy , with renal morphological abnormalities or low-quality of renal sonographic images had been excluded in this study. The procedures were in accordance with the Helsinki Declaration. The study protocol was approved by the Ethics Review Committee of Beijing Luhe Hospital. Written informed consents were obtained from all participants involved in the study.α × max  −1.209 × 0.993 Age × 1.018 [if female] × 1.159 [if black]. . Renal dysfunction was defined as eGFR < 90 ml/(min*1.73m2). The BMI was calculated as weight divided by the square of height (kg/m2) and was classified into two categories: non-obesity (BMI < 27.5 kg/m2) and obesity (BMI ≥ 27.5 kg/m2) [All patients participating in our study underwent a physical examination including height, weight, waist circumference, hip circumference, systolic blood pressures (SBP) and diastolic blood pressures (DBP). The clinical information such as age, gender, duration of diabetes was collected through the medical record of each subject. The venous blood and urine samples were collected in the morning following an overnight fast for the examination of the biochemical indices. The level of SUA, fasting serum glucose (FBG), TC, TG, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), serum creatinine (sCr) and blood urea nitrogen (BUN) were measured by an auto-biochemical analyzer . The glycosylated hemoglobin (HbA1c) was quantified using high-performance liquid chromatography (HPLC) with a D10 set . The ratio of urinary microalbumin to creatinine (UACR) was determined using an early-morning first sterile urine sample with the electrochemical luminescence methods . The sensitivity and coefficient of variation of above parameters were shown in supplementary materials Table S. The eGF5 kg/m2) . The waiPrFT and PnFT were detected as previously described by our group . Brieflyhttp://www.r-project.org). Normal distribution of continuous variables was detected using histogram and Q-Q plot. Nearly normally distributed continuous variables were presented as mean ± standard derivation and the differences were compared by student’s t test. UACR, which did not fit nonnormal distribution, was presented as median and quartiles and compared by Mann–Whitney U Test. Categorical variables were presented as frequencies (proportions) and compared by Chi-square test. When the theoretical value < 1, Fisher’s exact test was used. Pearson correlation coefficient was used to assess the relationship between different parameters. Univariate and Multivariate linear regression analysis were used to evaluate the association between the SUA level and other parameters. P value < 0.05 was considered statistically significant.The statistical analysis was performed using statistical package R . In addition, the age, BMI, WHR, HbA1c, BUN, sCr and UACR in patients with higher SUA level were higher compared to patients with lower SUA level (Table P = 0.109), but with no statistical significance (Table SP = 0.023). In addition, males had higher PrFT and PnFT than that of females . In addition, the BMI, WHR, BNU, sCr, TC, TG and LDL-c were significantly and positively associated with SUA level. While age, HbA1c and HDL-c were negatively correlated with SUA level. The visualization of correlation matrix was shown in supplementary Figure SWe used the Pearson correlation coefficient to assess the relationship between SUA level and other parameters. Table 2) and eGFR < 90 ml/(min*1.73m2)), gender  and BMI (BMI < 27.5 kg/m2 and BMI ≥ 27.5 kg/m2). We further conducted Pearson correlation analysis in different subgroups. Results were shown in Table r = 0.25, P < 0.001). Moreover, the relationship between PrFT and SUA became obvious in males  and patients with normal renal function . In addition, PrFT was significantly associated with SUA level in non-obese patients  but not in obese patients . The PnFT was also positively associated with SUA level . This relationship became obvious in males  and patients with normal renal function  but not in females  and patients with renal dysfunction . In addition, PnFT was significantly associated with SUA level in non-obese patients  but not in obese patients .Considering the potential effect of multiple factors such as gender, BMI and other indices on SUA level. We stratified all subjects into different groups according to renal function  was calculated to evaluate the collinearity of variables in models. The VIF results showed that there was no existence collinearity in all models (data not show). In the Model 1, both the PrFT and PnFT were positively correlated with SUA level (β = 51.01, We conducted a cross-sectional study to explore the relationship between PrFT and PnFT and SUA level in T2DM patients. The main finding of our study was that the PrFT was independently and positively associated with SUA level in patients with T2DM. As previous studies reported, PrFT and PnFT were positively associated with SUA respectively in diabetic patients , 24, whiMoreover, we found that the level of SUA, PrFT and PnFT in males were higher than that in females, which was consistent with previous studies , 27–29. Pearson correlation analysis also showed that TC, TG and LDL-c were positively associated with SUA level and HDL-c was negatively correlated with SUA level, which was concordant with previous studies , 27. WhiSeveral hypotheses about the mechanism by which how PrFT affected the SUA level were proposed. First, when perirenal fat grows into the renal sinus, various renal structures, including the medullary vasa recta and tubules, can be compressed by the increased renal interstitial fluid hydrostatic pressure, reducing blood and tubular flow through the distensible loop of Henle. The decreased tubular transit velocity and medullary blood flow may likely promote uric acid reabsorption. These findings may likely provide an explanation for the gradual increase of SUA level . In addiOur study had several limitations. First of all, this study did not assess different lifestyles, dietary habits, which may influence the SUA level. In addition, the renal resistive index, which can reflect the hemodynamic characteristics and renal function, was not calculated in our study. Furthermore, in our study, the measure of PrFT and PnFT was not validated with computed tomography, while previous studies had reported that ultrasonography and computed tomography have a good correlation in the measure of PrFT and PnFT , 36.In conclusion, PrFT was independently and positively associated with SUA level in patients with T2DM. This indicated that PrFT maybe an important indicator of hyperuricemia in patients with T2DM. In clinical practice, the measurement of perirenal fat may be helpful to find the population with high risk of hyperuricemia. Moreover, reducing the mass of perirenal fat maybe a new therapy for the treatment of hyperuricemia.Additional file 1: Table S1. The clinical characteristics of the study population in different renal function. Table S2. The clinical characteristics of the study population in different genders. Table S3. The clinical characteristics of the study population in different BMI groups. Table S4. The sensitivity and coefficient of variation of parameters in the study. Figure S1. Ultrasound image of PrFT and PnFT. Figure S2. The correlation between the left PrFT and right PrFT. Figure S3. The correlation between the left PnFT and right PnFT. Figure S4. The visualization of correlation matrix between PrFT and PnFT and other Parameters in patients with type 2 diabetes mellitus.


While it is well known that thyroid function may affect kidney function, the transition of the chronic kidney disease (CKD) status before and after treatment for thyroid disorders, as well as the factors affecting this change, remains to be explored. In the present study, we focused on the change in kidney function and their affecting factors during the treatment for both hyperthyroidism and hypothyroidism.Eighty-eight patients with hyperthyroidism and fifty-two patients with hypothyroidism were enrolled in a retrospective and longitudinal case series to analyze the changes in kidney function and their affecting factors after treatment for thyroid disorders.2) and an increase in eGFR in hypothyroidism (an average ΔeGFR of 7.1 mL/min/1.73 m2). The multiple linear regression analysis revealed that sex, eGFR, free thyroxine (FT4) and free triiodothyronine (FT3) could be considered independent explanatory variables for ΔeGFR in hyperthyroidism, while age, eGFR, and FT3 were detected as independent explanatory variables in hypothyroidism. In addition, the stratification by kidney function at two points, pre- and post-treatment for thyroid disorders, revealed that 4.5% of the participants with hyperthyroidism were pre-defined as non-CKD and post-defined as CKD, indicating the presence of “masked” CKD in hyperthyroidism. On the other hand, 13.5% of the participants with hypothyroidism presented pre-defined CKD and post-defined non-CKD, indicating the presence of “reversible” CKD status in hypothyroidism.Along with the improvement of thyroid function after treatment, there was a significant decrease in estimated glomerular filtration rate (eGFR) in hyperthyroidism (an average ΔeGFR of -41.1 mL/min/1.73 mWe uncovered the population of masked CKD in hyperthyroidism and reversible CKD status in hypothyroidism, thereby re-emphasizing the importance of a follow-up to examine kidney function after treatment for hyperthyroidism and the routine evaluation of thyroid function in CKD patients as well as the appropriate hormone therapy if the patient has hypothyroidism. It is well known that kidney function and thyroid function are affected by each other . Regardivia electronic-based records. Data collection was completed in 2021. For the analysis of hyperthyroidism, 972 patients were defined as having hyperthyroidism. The exclusion criteria were as follows: 1) age <18 years; 2) defective data for body mass index (BMI); 3) defective data for TSH, free triiodothyronine (FT3), free thyroxine (FT4), serum creatinine (s-Cr), and blood urea nitrogen (BUN) before and after treatment for hyperthyroidism; and 4) longer than 1 year between the pre- and post-treatment examinations. Consequently, 88 patients were enrolled in the hyperthyroid study  between January 2006 and December 2019 2) = 194 x s-Cr (mg/dL)-1.094 x Age-0.287 . CKD was defined as eGFRcre <60 mL/min/1.73 m2. Change ratio of eGFR was calculated: Change ratio of eGFR (%) = (post eGFR – pre eGFR)/pre eGFR x 100. ΔeGFR, ΔFT3, and ΔFT4 were calculated: ΔeGFR (mL/min/1.73 m2) = post eGFR – pre eGFR, ΔFT3 (pg/mL) = post FT3 – pre FT3, and ΔFT4 (ng/dL) = post FT4 – pre FT4. The presence of hypertension was defined with prior diagnosis or use of anti-hypertensive medications. Thyroid function was measured using an electrochemiluminescence assay .The following clinical characteristics were collected at the time of treatment for a thyroid disorder: age, sex, BMI, the use of angiotensin-converting-enzyme inhibitor (ACE-i), angiotensin II receptor blocker (ARB), and β-blockers, and hypertension, BUN, and s-Cr and eGFR levels. eGFR was evaluated using the equation developed by the Japanese Society of Nephrology:  and STATA V15.0 . All P-values were calculated as two-sided. Significance was defined as p-values less than 0.05. Data were expressed as n (%) for categorical variables and mean ± standard deviation (SD) for continuous variables. Categorical variables were analyzed with a chi-squared test, while continuous variables were compared by using Student’s t-test or Mann–Whitney U test, as appropriate. Correlations among ΔGFR and other variables were evaluated 2 after treatment. On the other hand, there was a significant decrease in the BUN and BUN/Cr ratio after treatment, suggesting a paradoxical laboratory change of BUN during treatment for hyperthyroidism.Eighty-eight patients met the selection criteria for the analysis , 18, 19.2. The characteristics of the stratified participants are shown in Considering the large decrease in eGFR after treatment for hyperthyroidism, we then explored the variables affecting changes to the eGFR. First, we stratified the participants into groups of ΔeGFR≥-40 (low-decrease group) and ΔeGFR<-40 (high-decrease group), considering that the median ΔeGFR of -37.4 mL/min/1.73 m2 after treatment  and ΔeGFR<5 (low-elevation group), considering that the median ΔeGFR of 4.7 mL/min/1.73 m. The characteristics of the stratified participants are shown in 2 after treatment , Okayama, Japan. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.U-MN and KT, conception and design of the work, analysis and interpretation of data, and article writing. YI, YN, EM, SF, TT, TH, KO-O, and KI, coordination of the patients’ care and revising the article. HU, SK, and JW interpretation of data, article writing, and final review. All authors contributed to the article and approved the submitted version.The work has been supported by a grant, the Japanese Society for the Promotion of Science (JSPS)/Grant-in-Aid for Young Scientists (20K17283).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Chronic kidney disease (CKD) is becoming one of the world's most prevalent noncommunicable chronic diseases. The World Health Organization projects CKD to become the 5th most common chronic disease in 2040. Causes of CKD are multifactorial and diverse, but early-stage symptoms are often few and silent. Progression rates are highly variable, but patients encounter both an increased risk for end-stage kidney disease (ESKD) as well as increased cardiovascular risk. End-stage kidney disease incidence is generally low, but every single case carries a significant burden of illness and healthcare costs, making prevention by early intervention both desirable and worthwhile. This review focuses on the prevalence, diagnosis, and causes of CKD. In addition, we discuss the developments in the general treatment of CKD, with particular attention to what can be initiated in general practice. With the addition of recent landmark findings and the expansion of the indication for using sodium–glucose cotransporter 2 inhibitors, there are now new effective treatments to add to standard therapy. This will also be relevant for primary care physicians as many patients with CKD have their family physician as their primary health care professional handling kidney function preservation. In the future, more precise and less invasive diagnostic methods may not only improve the determination of the underlying cause of CKD but may also carry information regarding which treatment to use . This could lead to a reduced number of preventive treatments per individual, while at the same time improving the prognosis. This review summarizes ongoing efforts in this area. With this paper, we aim to provide an overview of chronic kidney disease with a focus on recent developments in treatment possibilities and the need for collaboration across healthcare sectors to improve detection, treatment, and prognosis.2) estimated to be 10–15% [The prevalence of chronic kidney disease (CKD) is increasing globally, with CKD projected to become the fifth most prevalent chronic condition by 2040 . Global n = 1,120,295) [2. The risk of death from any cause was 0.76 per 100 person-years in individuals with eGFR above 60 ml/min/1.73 m2 but was 4.76 per 100 person-years in individuals with eGFR between 30 and 44 ml/min/1.73 m2. In parallel, the risk of cardiovascular events was 2.11 per 100 person-years in individuals with eGFR above 60 ml/min/1.73 m2 but was 11.29 per 100 person-years in individuals with eGFR between 30 and 44 ml/min/1.73 m2. This contributes to comorbidity and the burden of disease for many individuals with CKD, leading to an increase in both the number of medications and hospital visits. In a Scottish primary care study [The impact of CKD is multifold. Progression towards end-stage kidney disease (ESKD)  entails a concurrent substantial increase in the risk of cardiovascular disease. An analysis of the Kaiser Permanente Renal Registry , both dialysis and transplantation constitutes some of the most significant expenses in hospital-based health care. Based on annualized estimates of cost ascertained from national health care registers in Sweden, kidney disease is associated with a substantial economic burden, with costs elevated 4-fold, >10-fold, and >30-fold in patients with CKD, transplanted patients and patients on chronic dialysis, respectively . The meaSurvival in end-stage kidney disease is poor, annual mortality is estimated to be >10%, with five-year survival at approximately 50%. Cardiovascular disease continues to be the largest sole contributor to excess mortality in patients with end-stage kidney disease, with the attributable risk of cardiovascular death estimated to be >20-fold greater compared with general populations. Arrhythmias and sudden cardiac death continue to account for >30% of mortality in end-stage kidney disease, with an incidence estimated to be >25-fold greater compared with general populations. Due to the general exclusion of patients with advanced CKD from cardiovascular trials, evidence supporting current therapies remains uncertain. The implications are clear, and although a steady increase in treatment probability amongst patients with severe renal insufficiency has been noted, adherence to standard therapies in patients with CKD and cardiovascular disease including reperfusion therapy in myocardial infarction remains less implemented –17.As expected, and well-known to many clinicians, this chronic and often silent condition affects the quality of life, not only among patients but also among their caretakers. In a large French survey , health-The initial diagnosis of CKD is simple as it is based on biochemical parameters, i.e., an estimated glomerular filtration rate using a measure of plasma creatinine, with the help of an equation such as the CKD-EPI , which tCKD can be caused by many different diseases. Some are defined by distinct kidney diseases with renal pathology features (eg. glomerulopathies) while in other cases may be more of a result or a secondary complication to other acute or chronic conditions (eg. diabetes or hypertension). To help distinguish between different causes of CKD, urine analysis is important. Measurement of albuminuria/proteinuria provides essential information on the type of CKD, on prognosis, and can also be used as a target for treatment. Additional diagnostic tools are kidney ultrasound, specific blood samples, and in selected or severe cases a kidney biopsy to provide the true pathology for CKD.For CKD in diabetes, there is some variation as to the diagnosis used. Diabetic kidney disease (DKD) is defined by elevated albuminuria, with a urinary albumin excretion rate (UACR) >300 mg/g in at least two out of three consecutive samples. The presence of retinopathy and the absence of other known kidney diseases supports the diagnosis. In addition, there is also a growing focus on persons with diabetes with nonalbuminuric impaired kidney function, perhaps with a more mixed etiology, and with less risk of progression. This is usually termed kidney disease in diabetes .Treatment for CKD can be divided into specific and general approaches . SpecifiFor the majority of patients with CKD, pharmacological treatment entails a more general approach nondependent on the pathology of CKD. The general form of treatment is rarely curative, but instead aims at slowing the progression of the disease and delaying kidney failure. Although many attempts have been made to develop new therapies for CKD, standard therapy supported by the best evidence remains blood pressure control and employment of blockers of the renin-angiotensin system (RAS), i.e., angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB). In addition to their blood pressure-lowering effects, these drugs are thought to have specific anti-inflammatory and antifibrotic effects of benefit in CKD. In various degrees of nephropathy in both types of diabetes, the collaborative group study  and the Importantly, many of these studies also demonstrated cardiovascular protection in these high-risk populations, further securing RAS-blockade as standard therapy in guidelines.2), a doubling of the serum creatinine, or death from renal or cardiovascular causes. In 2020, the DAPA-CKD study followed [In recent years, the emergence of sodium-glucose cotransporter 2 inhibitors (SGLT2i) has added results from a number of trials, with the majority being in type 2 diabetes, showing added benefit on top of standard care. The first dedicated kidney study was the CREDENCE study , testingfollowed , with a followed  as well followed . In factfollowed , 35.2 and albuminuria, and dapagliflozin has expanded its label to include CKD. There are already indications from real-world data in type 2 diabetes that the use of SGLT2 inhibitors is associated with reduced eGFR decline and a lower number of kidney-related outcomes. The findings of the CVD-REAL 3 study [SGLT2 inhibition is therefore included in recent guideline updates  as stand 3 study , a multiRecently, the nonsteroidal mineralocorticoid receptor antagonist finerenone was added to guideline-recommended  therapy It can be difficult to monitor the effect of initiated preventive treatment in CKD. To monitor eGFR requires serial measurements in stable conditions during 1-2 years for reliable assess the individual slope of kidney function decline. In proteinuric CKD however, a change in urinary albumin excretion  following initiation of treatment can be used as a prognostic indicator, as demonstrated in two metanalyses of observational and randomized controlled trials, respectively , 42. A tEven though albuminuria testing is a noninvasive, noncomplicated test that adds important knowledge for both risk prediction and for monitoring of treatment effect, there is considerable room for improvement of albuminuria monitoring in CKD. Several global reports indicate a low percentage of albuminuria measurements in populations with type 2 diabetes. A recent survey across 24 primary care organizations in the United States found that a median of 52.9% of the individuals with type diabetes had the recommended annual samples collected. In Denmark, there are signs of improved albuminuria measurements in primary care, as an analysis of repeated cross-sectional studies shows an increase in annual samples from 57.8% in 2012 to 82.7% in 2020 . In nondEven with recent updates in guidelines and significant improvements in CVD and CKD protection seen in randomized controlled trials, implementation and uptake of new therapies is slow. One example is the recent CVD protective focus on type 2 diabetes, where SGLT2i and GLP-1RA are recommended when type 2 diabetes and manifest CVD coexists. In a Danish register-based study , the uptIs this disease mongering? Disease mongering is an expression attributed to the medical journalist Lynn Payer describing a broadening of the definition of a treatable disease in order to increase demand for medicinal products and services.One could argue that health professionals pointing to a large undetected group of people with a silent but chronic condition and at the same time advocating for medical treatment, could just be trying to expand the use and indication for existing drugs. This is not our intention with this paper. Particularly earlier identification of patients with chronic illness could lead to erosion of treatment benefits due to the implementation of treatment in patients with limited risk overall. Raising awareness of the possibility of treatment leading to prevention of ensuing illness is however an important element of public health education and an invaluable means of enhancing professional and public understanding of specific diseases and promoting appropriate uptake of novel therapies. As such, an appropriate balance is indicated.In that sense, it is important to remember that the CKD classification is not age-adjusted, and widespread screening may lead to the potential overdiagnosing of elderly people with a benign prognosis . This caWe argue that end-stage kidney disease, although developing slowly and with few symptoms, is a grave condition with a severe impact on quality of life, on survival, and is associated with extensive comorbidity and health care costs. Therefore, the implementation of effective medical treatment for people at risk of developing ESKD must be considered, especially if it causes little or no harm. Whether this implementation of treatment should be accompanied by population-wide screening programs, might seem logical and tempting, but it is not clear from the literature that screening efforts lead unequivocally to a better outcome, and clearly more research is needed in this area. Few studies have examined the value of early widespread screening for proteinuria. Boulware et al. analyzed the cost-benefit of annual screening for proteinuria at age 50 years using a Markov model. They concluded that early detection of urine protein followed by treatment with an ACEi or ARB to slow the progression of CKD and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) . As a loThe cost of CKD, and especially ESKD, is high. A large study from Spain  documentIt is clear that CKD is quickly becoming one of the major chronic diseases globally, with a very silent growth that needs attention. Although it can be debated whether screening would be of benefit, it will in any case be necessary for clinicians both in primary and secondary care to try to optimize the selection of CKD patients in whom further work-up and treatment to delay the progression of kidney function decline is appropriate. Particularly, current guidance for treatment selection from the initial workup with biochemistry, urine analysis, and perhaps imaging remains limited in all but a few patients with specific symptoms and findings .Research is however ongoing with regard to identifying more specific markers for earlier diagnosis of CKD or perhaps even just the risk of developing CKD. New techniques known as “omics” or sometimes referred to as systems medicine are being explored to better understand complex metabolic pathways, often with multiple biomarkers analyzed with proteomics, metabolomics, lipidomics, or genomics . As the Earlier and perhaps more specific diagnoses could contribute to a more differentiated treatment approach. As there is variation in progression rate, there is also a need to select some for more aggressive treatment while others can be monitored solely. This distinction is currently difficult and would probably benefit from well-validated precision techniques as discussed above. Not only is there a need for guidance on which individuals to select for treatment but there is also the topic of what treatment to select. The current approach describes a few general pharmacological classes of drugs with evidence of kidney protection but is used in a very generalized way and often in the late stage of CKD. Much like antihypertensive treatment, it would be great to start therapy early to be able to prevent progression, but also to be able to select therapy in a more modern way, guided by biomarkers or a detailed understanding of the underlying pathology. In late-stage CKD the kidney biopsy is the ultimate diagnostic tool, which sometimes leads to a more targeted therapy, but widespread use is limited by safety concerns. The hope is that the kidney biopsy in the future can be replaced by a “liquid” biopsy, by use of validated use of “omics” or similar techniques and provide early and widespread guidance on CKD pathology leading to more targeted treatment choices. Randomized trials using this approach are however still lacking in CKD.In addition, the patient with little or no symptoms and therefore undetected or perhaps newly detected CKD is also challenged by the organization of health care. As an example, an individual with type 2 diabetes and diabetic kidney disease may well be involved with different principal caretakers over the many years this condition is present. Being sent back and forth between primary care, specialist diabetes care, and perhaps also the nephrologist will sometimes be complicated and confusing for the patient. A special effort to ensure alignment of patient education and sharing of medical records must be made. Indeed, joint diabetes and nephrology outpatient clinics may prove to benefit the patient, and perhaps even broaden the perspectives of the involved specialists. Joint guidelines are also helping to ensure the best care for the complicated patient with CKD and comorbidity. In the future, primary care physicians can learn from discussing shared cases with specialists, evolving their understanding of CKD, and nephrologists can perhaps develop from being “end-stage” specialists to also contribute to the prevention of CKD and related comorbidity as CVD. Notwithstanding there is much work to do to secure a future with high-quality treatment and prevention of CKD.CKD prevalence is increasing but preventive treatment has a great potential. Greater awareness and appropriate screening are necessary first steps to try to avoid a future increase in CKD morbidity and healthcare costs. A large part of this will take place in primary care settings.


Asthma is a chronic inflammatory disease that affects the lungs. Variation in whole blood cell lines is caused by the progression and severity of asthma. Common hematological abnormalities encountered during asthma include eosinophilia, neutrophilia, leukocytosis, and increased erythrocyte sedimentation rate. The main aim of this study was to assess the selected hematological abnormalities and their associated factors among asthmatic patients in Northwest Ethiopia from March to May 2021.. The bi-variable and multi-variable binary logistic regression models were used to assess the factors associated with hematological abnormalities. A p value of less than 0.05 in the multivariable logistic regression analysis was considered statistically significant.A hospital-based cross-sectional study was conducted on a total of 320 asthmatic patients in Northwest Ethiopia. A simple random sampling technique was employed to select study participants. A pre-tested structured questionnaire and a checklist were used to collect data. Blood samples were collected from asthmatic patients for complete blood count and erythrocyte sedimentation rate determination. Hematological profiles were analyzed by Unicel DxH 800 . The erythrocyte sedimentation rate was determined by using the Westergren method. The data were entered into EpiData version 3.0.4 and analyzed with a statistical package for social science version 20 softwareThe overall prevalence of neutrophilia, eosinophilia, thrombocytopenia, leukocytosis, and basophilia was 35.3%, 20%, 11.9%, 10.3%, and 4.1%, respectively. Neutrophilia was associated with a lack of physical activity  and a history of taking non-asthmatic drugs within the previous three months . Being admitted to the emergency department  was found to be associated with eosinophilia. In addition, being admitted to the emergency department  was associated with thrombocytopenia.The current study demonstrated the predominant prevalence of neutrophilia, followed by eosinophilia, among asthma patients. Therefore, hematological abnormalities should be taken into account for proper monitoring and management of asthmatic patients.The online version contains supplementary material available at 10.1186/s12890-022-02020-z. Asthma is a heterogeneous disease characterized by a chronic inflammatory condition affecting the airways of the lungs. It is a common lung disease that causes narrowing of the airways and results in breathing difficulties . ChronicAsthma is a major public health problem. Currently, asthma affects around 339 million people globally . HoweverDifferent asthma triggers can provoke an allergic reaction, which is associated with the recruitment of pro-inflammatory cells . In the The granulocytic parameters have a predictive role in asthma . PredomiNeutrophilia and eosinophilia are characteristic features of asthma , 15. IL-According to Global Initiative for Asthma (GINA), blood eosinophil count is not used for the diagnosis of asthma . HoweverPlatelets play a crucial role in the pathogenesis of asthma . The actBasophils and mast cells play essential roles in asthma pathogenesis . The masElevated erythrocyte sedimentation rate (ESR) is typical change in asthma. Basophils, mast cells, and macrophages produce IL-1 and Tumor Necrosis Factor-alpha (TNF-α), which stimulate the liver to produce acute-phase proteins. A rise in acute phase proteins like fibrinogen decreases the net negative charge of the RBC surface and enhances the rouleaux formation. Therefore, rouleaux formation increases the ESR among asthmatic patients .Asthma can affect hematological parameters due to the immune system’s response and changes in hematopoietic physiology. Progression and severity of asthma cause variations in whole blood cell lines –40. DeteAn institution-based cross-sectional study was conducted from March to May 2021 in Northwest Ethiopia at the University of Gondar Comprehensive Specialized Hospital (UGCSH) and Tibebe-Ghion Specialized Hospital (TGSH). UGCSH is located in Northwest Ethiopia, in Amhara Regional State, in Gondar Town. Currently, the hospital provides service to over 7 million people in the catchment area . The hosAll adult asthmatic patients attending UGCSH and TGSH were included in the study. Patients who already have chronic diseases like HIV/AIDS, chronic kidney disease, hematological malignancies, and tuberculosis were excluded from this study by reviewing their medical records.2(pq)/d2]. By considering the proportion of 50%, 5% marigin error, and 95% confidence interval. The total sample size was calculated as: n = (1.96)2 (0.5 × 0.5)/(0.05)2, then n0 = 384.A single population proportion formula was used to calculate sample size by [n = (Zα/2)f = n0/1 + n0/N = 384/1 + 384/1200 = 290.9, approximately nf = 291. Where d = margin of error (5%), n0 = initial sample size, N = total number of the target population, and Z α/2 = 1.96 at 95% confidence interval.However, the estimated number of asthmatic patients in two hospitals per year was 1,200 , which is less than 10,000 . A finite population correction is recommended for this situation. As a result, the sample size was adjusted to nTherefore, by adding a 10% non-response rate, the final sample size was 320. The study participants were proportionally allocated from each hospital (200 from UGSH and 120 from TGSH). A lottery-based simple random sampling technique was used to select the study participants.Asthma: any person who has ever received a diagnosis of asthma from a doctor working in internal medicine pulmonary and critical care. Diagnosis was carried out based on a history of variable respiratory symptoms and confirmed variable expiratory airflow limitation according to Global Initiative for Asthma (GINA) guideline [uideline .Admission to the emergency department: asthmatic patients who were admitted to the emergency room for health care utilization due to respiratory symptoms [symptoms .The severity of asthma was classified based on the GINA2019 guideline [uideline .Stages of asthma were classified as intermittent, mild persistent, moderate persistent, and severe persistent based on the GINA 2019 guideline [uideline .A habit of doing physical exercise: a study subject who has experience of doing physical exercise once per day for at least 20–30 min as a continuous activity [activity .Normal value: Total leukocyte (3.6–10.6 × 103/μl), neutrophil (1.6–5.1 × 103/μl), eosinophil (0.0–0.04 × 103/μl), basophil (0.0–0.2 × 103/μl), platelet (150–450 × 103/μl), and erythrocyte sedimentation rate  [0 mm/hr) .The data related to socio-demographic and behavioral characteristics of study participants were collected with a structured pre-tested questionnaire through a face-to-face interview.Clinical data of study participants such as duration of a patient living with asthma, family history of asthma, history of asthmatic drug intake before 3 months, chronic disease, severity, stages of asthma, symptoms of asthma, and history of non-asthmatic drug intake before 3 months were collected by reviewing medical records via a checklist. Anthropometric variables such as height (in meters) and weight (in kilograms) were measured by clinical nurses. Then, body mass index (BMI) was computed as weight in kilograms divided by height in meters squared. After trained clinical nurses had completed data collection through interviews, reviewing medical records, and anthropometric measurements, the study participants were sent to the laboratory room where a blood sample was drawn.A six-milliliter venous blood specimen was collected from asthmatic patients by the trained laboratory technician through venipuncture of the superficial veins of the antecubital fossa. After blood collection, 3 ml of blood was transferred into the tube containing the Ethylenediaminetetraacetic acid (EDTA) test tube and gently mixed. The left-over blood (3 ml) was dispensed into a tube containing 3.1 g/L trisodium citrate in a 1:4 ratio (1 part of trisodium citrate with 4 parts of blood) for ESR value determination.Five differential Unicel DxH 800 Coulter cellular analysis systems  were used to analyze the Complete Blood Count (CBC). This automated hematological analyzer uses principles of impedance, spectrophotometry, and VCS technology. Peripheral blood morphology assessment was done to confirm flags by the automated hematology analyzer and to check the quality of automated hematology analyzer. A thin blood smear was prepared from leftover blood from CBC. Then the air-dried smear was stained with Wright stain, and the blood cell morphological features were assessed with a 100× oil immersion by laboratory technologists.In a 3:4 ratio, whole blood was diluted with a 3.1 g/L trisodium citrate anticoagulant in a 1:4 ratio. Then a trisodium citrate diluted blood sample was left for one hour on the Westergren method of ESR determination set up. After one hour, the height of plasma was measured and reported in millimeters per hour (mm/h).A pea-sized (1 g) fresh stool specimen was obtained from every study participant in clean and labeled leak-proof stool containers. A Formol-ether concentration technique was performed to concentrate intestinal parasites. From sediment, a wet mount was prepared and examined under a microscope with 10× and 40× objectives. Laboratory tests like CBC, peripheral morphology, ESR, and stool examination were performed in the UGCSH and TGSH laboratories and recorded for every study participant using a form designed for laboratory result registration.The questionnaire was prepared in the English version and translated to the local language (Amharic) and retranslated back to the English version to check the accuracy and consistency. The questionnaire was pretested on 5% of asthmatic patients at Felege Hiwot Comprehensive Specialized Hospital, and the questionnaire was modified. The training was given to the data collectors before starting data collection to reduce technical and observer bias.Pre-analytical, analytical, and post-analytical phases of quality assurance were maintained to assure the quality of data. Quality control (QC) for working equipment and reagents was ensured by using standard controls. Low, normal, and high QC materials were run to check the functioning of the hematological analyzer. SOPs and manufacturer’s instructions were strictly followed during sample collection and laboratory procedures. The questionnaire was checked for consistency, clarity, and completeness. The results of every test were properly recorded, reviewed, and transcribed.p value of < 0.25 in the bivariable logistic regression analysis were fitted into the multivariable logistic regression analysis. The model of fitness was checked by Hosmer and Lemeshow’s goodness-of-fit statistic. A p value of less than 0.05 was considered statistically significant in any condition.The collected data was entered into Epi-data software (Version: 3.0.4), then cleaned and exported into a Statistical Package for Social Science version 20  for analysis. Descriptive statistics such as frequencies and percentages were used to summarize the data. The Kolmogorov–Smirnov test and histogram were used to check the normal distribution of data. The values of selected hematological parameters were presented with median and interquartile range (IQR). Non-parametric mann–Whitney U tes was used to compare median difference in hematological parameters among groups. The data was presented using tables, charts, and graphs. Bivariable and multivariable logistic regression analysis was done. Crude odds ratio (COR) and adjusted odds ratio (AOR) with a 95% confidence interval (CI) were used to observe the strength of the association between the predictors and the outcome. The backward selection method was used to select the important variables. The variables with a Ethical clearance was obtained from the ethical review committee of the School of Biomedical and Laboratory Science, College of Medicine and Health Sciences, University of Gondar, with letter reference number SBMLS-2748/2021. A support letter from the Department of Hematology and Immunohematology was submitted to UGCSH and TGSH. Permission was obtained from the UGCSH and TGSH directors.Informed written consent was obtained from each study participant after the objective of the study was explained. For illiterate study subjects, informed consent was obtained after information was read to the study participants by the data collectors. Then a fingerprint signature was taken from each illiterate study participant. To maintain confidentiality, the study participants were identified by using codes rather than individual identifiers, and unauthorized persons were not able to access the collected data. The results and information of the study participants were kept confidential. Study participants with hematological abnormalities were linked to the UGCSH and TGSH chest clinic departments for proper management. All methods were performed in accordance with the relevant guidelines and regulations (Declaration of Helsinki).A total of three hundred twenty (n = 320) adult asthmatic patients were enrolled in this study. There were 178 (55.6%) females among them. The age of study participants ranged from 18 to 65 years, with a median and interquartile range (IQR) of 50 (38–60) years. 206 (64.4%) and 204 (63.8%) of the participants were older than 40 years old and living in urban areas, respectively. Regarding the educational status of study participants, 140 (43.8%) were unable to read and write. Among study participants, 109 (34.17%) were housewives, and 213 (66.6%) were married  were current cigarette smokers, 54 (16.9%) had a habit of doing physical exercise, and 75 (23.4%) had the habit of drinking alcohol. Of those who had a habit of drinking alcohol, about 51 (15.9%) were frequent drinkers. Among study participants, 56 (17.5%) had a high BMI (Table .6% were About 107 (33.4%) of study participants had a family history of asthma, 127 (39.7%) had been living with asthma for less than five years, 234 (73.1%) had asthma with moderate severity, and 204 (63.8%) had a moderate persistent stage of asthma. Regarding symptoms of asthma, 119 (37.2%) of study participants experienced shortness of breath, and 105 (32.8%) had a cough. About 261 (81.6%) of the study participants had taken asthmatic drugs in the previous three months. Among the study participants, about 89 (27.8%) were admitted to the emergency department (Table lumbricoides was found in 35 (66%), followed by Taenia species 5 (9.4%)  were infected with one or more intestinal parasites. Among those who had a parasitic infection, Ascaris 4.7% wereThe majority of study participants had neutrophilia, 113 , followed by eosinophilia, 64 . About 38  had thrombocytopenia, leukocytosis, 33 , and basophilia, 13 .. The median and IQR values of the selected hematological parameters are WBC, 6.6 (4.8–8.75), neutrophil count, 3.94 (2.4–5.87), eosinophil count, 0.2 (0.07–0.4), basophil count, 0.03 (0.00–0.1), platelet, 229 (183–287), and ESR, 20 (5–43). In addition, an increased ESR value was observed among 163 (50.9%) of the study participants.p < 0.04). Also, the eosinophil count was significantly lower among asthmatic patients who had taken ICS than among patients who had not taken ICS (p < 0.03). In addition, the absolute basophil count showed a statistically significant median difference among patients who used SC and those who had not taken SC (p < 0.05). However, platelet and absolute neutrophil counts did not show a statistically significant median (IQR) difference among any of the groups  and taking drugs other than asthmatic drugs before three months  were found to have a statistically significant association with neutrophilia  and SC use  only showed a statistically significant association with eosinophilia in multivariable logistic regression analysis Table .Table 4BIn bivariable logistic regression analysis, residence, alcohol drinking habit, duration of a patient living with asthma, SC use, and admission to the emergency department were associated with thrombocytopenia. In multivariable binary logistic regression analysis, being admitted to the emergency department  and living in an urban area  showed a statistically significant association with thrombocytopenia  of asthmatic patients. Even though the magnitude of leukocytosis was not reported, different studies indicated that leukocytosis is a common feature among asthmatic patients , 41, 48.Based on the findings of this study, the most common hematological abnormality was neutrophilia, with a prevalence of 35.3% (95% CI 30.1–40.8%). Similar studies conducted in Turkey , PakistaUnlike eosinophils, neutrophils are the first cell type to enter the lung following an allergen challenge . MoreoveIn the present study, the prevalence of eosinophilia was 20% (95% CI 15.8%‒24.8%). This finding is in line with the study conducted in the USA (18.5%) , the UK Moreover, eosinophilia is considered a prognostic marker and can be associated with frequent asthma exacerbations , 60. HigThrombocytopenia was observed in 11.9% (95% CI 8.5–15.9%) of asthmatic patients. A similar study was done in Jimma and showed that mean values of platelet count were lower in asthma patients than in healthy controls  but the Basophilia was observed in 4.1% of asthmatic patients. This finding was lower than a similar study done in Mexico (37.7%) . The posIncreased ESR values were observed in 50.9% (95% CI 45.3–56.5%) of asthmatic patients. Although the percentage was not reported, similar studies were done in India  and JimmBased on the findings of this study, the study participants who were diagnosed with intestinal parasitic infection had significantly higher absolute eosinophil count than those who were not infected with intestinal parasitic infection. This finding was supported by different studies , 63. TheThis study also determined the association between hematological abnormalities and their associated factors among asthma patients. We have done a multivariable logistic regression analysis for leukocytosis. But any of the variables did not show a statistically significant association with leukocytosis.. showed that physical activity had a protective effect on asthma [Asthmatic patients who do not have the habit of doing physical exercise were three times more likely to develop neutrophilia when compared to patients doing physical exercise. This might be due to the fact that poor exercise worsens asthma outcomes. A worsened asthma state causes frequent asthma attacks and increases asthma exacerbation . In addin asthma .Study participants who had taken non-asthmatic drugs before three months were 3 times more likely to develop neutrophilia than patients who had not taken non-asthmatic drugs. This might be due to the effects of drugs. Different drugs (like glucocorticoids) can cause neutrophilia by inducing the release of neutrophils from the bone marrow .The study subjects who were admitted to the emergency department were less likely to develop eosinophilia. This might be due to patients admitted to the emergency department being treated with high doses of ICS (according to GINA guidelines) . ICS is Asthmatic patients who had taken SC were less likely to develop eosinophilia. This finding was supported by different studies –74. The Study participants who were admitted to the emergency department were 5 times more likely to develop thrombocytopenia. The possible explanation may be due to patients admitted to the emergency department having more severe asthma attacks. When inflammation increases (severe asthma), platelets become activated and are recruited to the pulmonary .Study participants who lived in urban areas were 2.79 times more likely to develop thrombocytopenia. This might be due to the fact that the outdoor air of urban areas is polluted due to high traffic and industry-related emissions that can increase the risk of asthmatic attacks. Thus, patients who live in urban areas might have more asthma attacks than patients living in rural areas. An increase in the severity of asthma can be linked with peripheral thrombocytopenia.This study had some limitations. The cross-sectional nature of the study makes it difficult to establish a cause-effect relationship between hematological changes and associated factors . Another limitation is that important cytokines that mediate pro-inflammatory cell recruitment  were not analyzed due to a lack of testing materials.In the present study, neutrophilia was the most frequent hematological abnormality identified, followed by eosinophilia and thrombocytopenia. The hematological abnormalities were common among asthmatic patients. Therefore, considering selected hematological abnormalities should be important for the proper monitoring and management of asthmatic patients.No habit of doing physical exercise and taking non-asthmatic drugs before three months was associated with neutrophilia. On the other hand, being admitted to the emergency department was associated with eosinophilia and thrombocytopenia. Checking the hematological profiles of asthmatic patients would be important for reducing the risk of emergency department admission and further complications. Further longitudinal studies will be encouraged to see the effect of systemic corticosteroid use and other drugs on hematological parameters among asthma patients.Additional file 1. Socio-demographic characteristics of asthmatic patients in Northwest Ethiopia, 2021 (n = 320).


Exercise is advised for young adults with elevated blood pressure, but no trials have investigated efficacy at this age. We aimed to determine whether aerobic exercise, self-monitoring and motivational coaching lowers blood pressure in this group.2. The study took place in the Cardiovascular Clinical Research Facility, John Radcliffe Hospital, Oxford, UK. Participants were randomized (1:1) with minimisation factors sex, age  and gestational age at birth  to the intervention group, who received 16-weeks aerobic exercise training  change from baseline to 16-weeks on an intention-to-treat basis. Clinicaltrials.gov registered on March 30, 2016 (NCT02723552).The study was a single-centre, open, two-arm, parallel superiority randomized clinical trial with open community-based recruitment of physically-inactive 18–35 year old adults with awake 24 h blood pressure 115/75mmHg-159/99 mmHg and BMI<35 kg/mn = 102 in the intervention group; n = 101 in the control group), 178  completed 16-week follow-up and 160  completed 52-weeks follow-up. There were no group differences in awake systolic  or awake diastolic ambulatory blood pressure . Aerobic training increased peak oxygen uptake  and peak wattage  at 16-weeks. There were no intervention effects at 52-weeks follow-up.Enrolment occurred between 30/06/2016-26/10/2018. Amongst the 203 randomized young adults (These results do not support the exclusive use of moderate to high intensity aerobic exercise training for blood pressure control in young adults.Wellcome Trust, British Heart Foundation, National Institute for Health Research, Oxford Biomedical Research Centre. We completed a search from inception up to June 2019 with no language restrictions . Search terms included but were not limited to “physical activity”, “exercise”, “aerobic exercise”, “blood pressure” and “hypertension”. Our first published meta-analysis suggested scarce evidence on the effects of exercise on blood pressure in younger adults and the observed pooled intervention effect on blood pressure reduction was short-term (6 months) and dominated by studies with complex interventions including exercise, dietary and weight loss components. Our second published meta-review indicated variation in blood pressure response to type of exercise and level of blood pressure and that the young adult age group remained under-investigated.To the best of our knowledge, this is the first trial to exclusively investigate effectiveness of aerobic exercise intervention to lower blood pressure in young adults. The study design removes the confounding of dietary and weight loss intervention observed in previous studies and provides resting and ambulatory blood pressure measures up to 1 year following exercise intervention in young adults.Aerobic exercise may not be a reliable first line intervention to target blood pressure reduction in young adults. The available evidence suggests need for personalisation of intervention with short-term tracking and refinement of lifestyle intervention dependent on blood pressure response. Overall, further research is required to improve understanding of how best to lower blood pressure in young adults.Alt-text: Unlabelled box,,,,,,in utero developmental history including preterm birth or pregnancy hypertension, which have been related to unique cardiovascular phenotypes.Based on current guidelines, up to 40% of young adults may have elevated blood pressureThe study was a single-centre, open, two-arm, parallel superiority randomized (1:1) controlled trial with open community-based recruitment. The study took place in the Cardiovascular Clinical Research Facility, John Radcliffe Hospital, Oxford, UK. The trial protocol2; were not on, and had not previously been prescribed, hypertension medications; had a verifiable birth history of preterm birth (<37 weeks) or full-term birth (≥37 weeks); and had the ability to access and use a computer and the internet. Participants could not take part: if they were pregnant; if they participated in structured exercise more than once per week or maintained high cardiovascular fitness; if they were unable to provide consent; had any contra-indications to exercise; were unable to walk briskly on the flat for 15 min; had any evidence of cardiomyopathy, inherited cardiac abnormalities or other significant cardiovascular disease. Participants were recruited through invitation from hospital birth registers, GP records, open recruitment, targeted online advertising via Facebook, Instagram and Twitter, and invitation following participation in previous studies. Participants gave written informed consent. Enrolment occurred between June 30, 2016, and October 26, 2018; final follow-up January 9, 2020.Persons were eligible for inclusion if they were: 18 to 35 years old; had 24 h awake ambulatory systolic and/or diastolic blood pressure >115/75 mmHg, but <159/99 mmHg; had a body mass index <35 kg/mFollowing completion of baseline study measures, participants were randomly assigned through minimisation with a probabilistic element using an online randomization program  to one of two groups in a 1:1 ratio – a control group or an aerobic training and physical activity intervention. Minimisation factors were sex, age  and gestational age at birth . Due to the nature of the intervention, participants and those delivering the intervention were not masked. The outcome assessors were not involved in randomisation or intervention delivery and remained blinded until after completion of final analysis.,Participants were asked to complete three aerobic training sessions per week, aiming for 60 min exercise at 60–80% peak heart rate measured at baseline. Participants were encouraged to attend supervised sessions offered by the study team. The intervention replicates strategies identified during systematic review of exercise intervention that reduced blood pressure in older age groups.The primary outcome was change in 24 h ambulatory awake blood pressure (systolic and diastolic) from baseline to 16 weeks. Secondary outcomes included change in nocturnal and resting clinic blood pressure, change in peak cardiorespiratory fitness, peak exercise wattage, submaximal ventilatory anaerobic threshold, insulin resistance, cholesterol HDL ratio, glucose and vascular stiffness at 16 and 52 weeks. Additional secondary outcomes reported in the trial protocol will be presented in future manuscripts and include additional blood pressure, CPET and blood sample measures, as well as cardiac echocardiographic outcomes, cell culture data, wrist-worn accelerometery activity and walking speed, retinal imaging and in a subgroup of participants, dermal capillary measures, molecular and vascular cell function and heart, brain and liver MRI outcomes. Full details of the study objectives, outcomes and measurement procedures are detailed in the published study protocol.p = 0.05) required a total sample of 164 participants and to observe a similar effect on diastolic blood pressure required a sample of 114 participants, based on pooled SD from previous systematic review of 11 mmHg for systolic and 8 mmHg for diastolic pressures.To observe a treatment effect on systolic blood pressure of 5 mmHg powered to 80%  within a multivariate mixed effects model to estimate the primary outcome of change in blood pressure at 16 weeks. This model accounted for person as a random effect, and time (16 or 52 weeks), treatment, and the minimisation factors  as covariates. Baseline blood pressure was included as a continuous variable. A treatment by time interaction was also included in the model to allow 16-week specific treatment effects to be calculated. This estimate of the 16-week treatment effect is the primary outcome estimate. The primary analysis was intention-to-treat  and the mixed model used all available data at each time point.Secondary continuous outcomes analysed at 16 and 52 weeks were analysed using the same ANCOVA mixed effects model as the primary analysis but adjusting for their corresponding baseline variables.Exploratory subgroup analyses according to gestational age, sex and BMI were performed using an interaction term to define the subgroups in an ANCOVA model with blood pressure measured at 16 weeks as the outcome . These analyses were restricted to participants with non-missing subgroup data.A sensitivity analysis was carried out using the per-protocol population including only those considered compliant as per the definition given in the intervention section. Post-hoc exploratory sub-group analysis was also performed to understand whether there was difference in effect related to volume of supervised or unsupervised exercise sessions completed. Two missing data sensitivity analyses on the primary analysis were performed. Details and results of these analyses are given in the supplementary material.The trial statistician completed all primary, pre-specified 16-week and 52-week secondary, sensitivity and pre-specified sub-group analyses. Other 52-week secondary and post-hoc exploratory analyses were completed by a study team investigator blinded to participant identifier, with results verified by a second research team member. There was a data and safety monitoring committee. Clinicaltrials.gov registration number NCT02723552, prospectively registered March 30, 2016.The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. WW, AL, WL, and AO, JH had direct access to the data. All authors agreed on decision to submit for publication.Enrolment occurred between June 30, 2016, and October 26, 2018; final follow-up January 9, 2020. Baseline characteristics of participants are presented in A total of 82 of 102 participants allocated to exercise received the intervention (79%). Activity data over the 52 weeks is not shown but across the 82 exercising participants the median volume of supervised moderate to vigorous exercise per week was 140 min per participant (IQR 110 to 160) at an intensity of 76% (SD 5) of maximum heart rate. Median daily wear of the Fitbit Charge HR was 105 days, with daily wear on 87% of available wear days across 16 weeks of the structured exercise programme. Using the Fitbit, participants registered a median of 337 min (IQR 213 to 462) of bouts of physical activity longer than 7 min at or above moderate intensity per week. The median daily step count in the first 16 weeks was 10,559 steps . Total daily wear of the Fitbit dropped to less than 62% of available wear days between 16 and 52 weeks. In the last 60 days of the follow up period, total daily wear was 55% of available wear days and daily step count declined to a median of 9651 steps . On average step count was 1442 steps per day (SD 2458) lower at the end of the 52 week follow up than during the 16 weeks structured exercise.n = 76 mean 126·9 mmHg [SD 11·5] vs control group n = 84 mean 125.8 mmHg [SD 10·0]; adjusted mean difference 0·0 ; P = 0·98). There were no between group differences in 16-week awake diastolic ambulatory blood pressure .  and increase in peak wattage . At 52 weeks there were no between group differences for peak oxygen uptake or peak wattage. There was a larger submaximal oxygen uptake at the ventilatory anaerobic threshold (VAT) in the aerobic training group at 16 weeks , this difference was not sustained at 52 weeks. There were no between group differences in 16-week or 52-week insulin resistance, cholesterol HDL ratio, blood glucose levels, or vascular stiffness (pulse wave velocity). There were also no differences for secondary measures of awake ambulatory blood pressure at 52 weeks or asleep ambulatory systolic and diastolic blood pressure, nor seated clinic systolic pressure, at 16 weeks or 52 weeks. Seated clinic diastolic blood pressure was higher in the intervention group at 16 weeks  but this difference was no longer evident at 52 weeks , both systolic and diastolic awake ambulatory blood pressure were lower at 16 weeks in the intervention group. Furthermore, awake ambulatory diastolic blood pressure was higher in those born full term after 37 weeks’ gestation. There were no significant differences between the randomised groups for other clinical subgroups (Supplement). Exploratory subgroup analysis found no difference related to whether the participant undertook supervised or unsupervised exercise sessions (Supplement).In pre-specified, exploratory subgroup analysis, blood pressure response to intervention varied in relation to gestational age at birth . In the There were two adverse events reported, both in the training group, an ankle sprain and toe injury. Injuries were self-limiting and activity adapted to allow continued participation in the intervention.The per protocol analyses on awake systolic and diastolic blood pressure found no difference between groups at 16-weeks. The two sensitivity analyses completed to examine the robustness of the primary results against missing data showed no change from the main findings, implying the strategy used in the primary analysis was robust. Missing data results are presented in supplemental material.In this trial involving young adults with elevated blood pressure, aerobic training and physical activity self-monitoring did not reduce ambulatory awake blood pressure compared to lifestyle education alone. The lack of effect was despite achieving an improvement in cardiovascular fitness in the training group. This is not in accordance with our hypothesis, which was based on previous studies that reported short-term benefit of aerobic exercise intervention on blood pressure.,The observed increase in cardiorespiratory fitness at 16 weeks is comparable to benefits observed in older adult hypertensive populations.,,The pre-specified exploratory subgroup analysis did indicate a potential heterogeneity in blood pressure response related to gestational age at birth. Those born very preterm had an improvement in both systolic and diastolic blood pressure profile at 16 weeks. By contrast, the intervention was associated with an increase in awake ambulatory diastolic blood pressure in those born at term, in keeping with the higher seated diastolic pressure after intervention in the whole group analysis. These findings would be consistent with cardiovascular differences described in young adults born peterm.21There were limitations to this single centre study. The study excluded participants with moderate to severe obesity so results may not be generalised to all young adult clinical populations. The wrist-worn device is commercially available and therefore the investigators did not have control over any additional features or behavioural prompting. The sample size calculation was adjusted for 18% loss to follow-up on 24 h ambulatory blood pressure. On completion of data cleaning ambulatory blood pressure was only available on 79% of participants at 16 weeks. Incomplete data related to lack of participant comfort during recording, disturbed sleep and reduced wear time. Whilst this means we did not reach our intended sample size, the study still had an overall power larger than 80% due to a smaller than expected observed standard deviation. Nevertheless, this study highlights compliance with ambulatory monitoring may limit feasibility and reliability as an outcome measure. Furthermore, the results could be biased in the event that data lost during follow-up were not missing at random but the sensitivity analyses do not suggest this is the case. Reassuringly, clinic blood pressure and cardiopulmonary exercise data was available on 88% of the randomized participants at 16 weeks and 79% of the randomized participants at 52 weeks. Due to the large number of secondary outcomes, there is a high chance of false positive results being discovered. Finally, it was also not possible to mask participants to trial group.In conclusion, aerobic exercise training had no significant benefit in lowering awake ambulatory blood pressure in physically inactive young adults with elevated blood pressure compared to lifestyle education. Furthermore, benefits of aerobic training on other indicators of cardiovascular risk such as low submaximal and peak oxygen uptake only persisted during the aerobic exercise intervention. Motivational coaching and use of wrist-worn activity monitors had no sustained effects on maintenance of increased cardiovascular fitness achieved during training. Further work is required to understand whether different modes of exercise, alternative lifestyle interventions or pharmacological approaches are effective, safe and sustainable strategies to lower cardiovascular risk in young adults with elevated blood pressure.WW wrote the first draft of the manuscript with input from all other authors in subsequent drafts. AO did the statistical analysis. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication. WW, AL, WL, and AO, JH have accessed and verified the data.Wellcome Trust, British Heart Foundation, National Institute for Health Research, Oxford Biomedical Research Centre.Trial data and materials are available to be shared subject to data sharing agreement and will be reviewed on a case by case basis. Please contact the corresponding author for requests.RM has received BP monitors for research from Omron and is working with them to develop a telemonitoring system. He does not personally receive payment for this. The other study investigators declare no competing interests.


Age (P < 0.001) and gender (P = 0.022) were significantly different across the BP categories. Weight (P < 0.001), height (P < 0.001), BMI (P < 0.001), pulse pressure (P = 0.020), history of stroke (P = 0.012), hemoglobin level (P = 0.002), red blood cell count (P = 0.031), creatinine (P < 0.001), and (estimated glomerular filtration rate) eGFR (P = 0.002) was also significantly different across the three BP categories. After adjustment, the significantly associated factors of RSH in the SCD patients were age , male gender , BMI . After adjustment, the independent variables significantly associated factors of Hypertension in the SCD patients were age , male gender , BMI . Creatinine was significantly associated with RSH . SCD patients with RSH or hypertension maybe at increased risk of renal dysfunction. We found relatively high prevalence of RSH and hypertension (20.8%) in SCD patients in Cameroon. Tailored Interventions that consider major risk factors  may lower BP pressure and prevent severe complications.Increased blood pressure (BP) has been associated with higher risk of stroke and mortality in Sickle Cell Disease (SCD). We investigated risk factors associated with Relative Systemic Hypertension (RSH) or systemic hypertension in SCD patients in Cameroon. Using R, Multivariate multinomial logistic regression modeling was used to examine the effects of the demographic, anthropometric, clinical, and laboratory factors to determine risk factors. A total of 815 individuals with SCD, including 380 (46.6%) males were analyzed. At baseline, the median age [interquartile range] was 18.0 [12.0–25.0] years, ranging from 3 to 66 years. Approximately three-quarters of the patients ( Sickle cell disease (SCD) patients, generally, have lower systolic, diastolic, and mean blood pressure compared to age and sex-matched controls , 2. TherBlood pressure is a potential modulator of clinical severity in SCD patients, recent studies showed that relative systematic hypertension (RSH), defined as BP 120–139/70–89 mmHg, and Systemic Hypertension (BP >140/>90), considerably increased the risk of pulmonary hypertension and renal dysfunction . All patients older than 18 years signed consent forms, while informed consent was given by the parents or guardians for participants younger than 18 years old, in accordance with the Declaration of Helsinki. This study was approved by the National Ethical Committee of the Ministry of Public Health of Cameroon (No 193/CNE/SE/15).Written and signed informed consent forms were obtained from adult participants and parents/guardians of minor patients. An assent was also obtained from the participants of more than 7 years old.All SCD patients with complete socio-demographic, clinical, laboratory variables, and complete systolic and diastolic blood pressure measurements were included in the study. The data were obtained from a cross-sectional study conducted in Cameroon from May 2016 to July 2018. The data were collected from nine hospitals from five cities in Cameroon, including Yaoundé, Douala, Bafoussam, Bertoua, and Maroua. Patients who have not experienced a painful crisis a month before, and who had not received a blood transfusion in the past 6 months, were recruited irrespective of age and gender.Sickle cell disease patients with a SBP within the range of 120–139 mmHg and/or DBP within the range of 80–89 mmHg is defined as having RSH. Systemic hypertension is further defined as SBPs greater than 140 mmHg or DBPs greater than 90 mmHg. Participants who had incomplete/out of range blood pressure readings were excluded from the analysis.Information on demographics, including age, residential location, sex, ethnicity, educational level, marital status, and household income status, was collected using a standard questionnaire involving the household and individual levels. Clinical information and laboratory information were also collected. Those who had incomplete/out of range relevant information such as age, gender, BMI, demographic, clinical, laboratory information were also excluded from the dataset.All our analysis was analyzed using R (version 4.0.2). Continuous variables were presented as median and interquartile range (IQR) and categorical variables as percentages (%).X2-test or Fisher exact test if the expected count in a cell was less than five while continuous variables were compared according to BP category with the Kruskal–Wallis test.Categorical variables were compared using Multivariate multinomial logistic regression modeling was used to examine the effects of the demographic, anthropometric, clinical, and laboratory factors to determine the potential independent risk factors for RSH and Systemic hypertension.P < 0.05. The findings presented as crude and adjusted odds ratios with their 95% confidence intervals (CI).A final model was created that included all the predictors and interactions that were significantly associated at the level of P < 0.001) and gender (P = 0.022) were significantly different across the BP categories, with age increasing with BP. Weight (P < 0.001), height (P < 0.001), BMI (P < 0.001), pulse pressure (P = 0.020), history of stroke (P = 0.012), hemoglobin (P = 0.002), red blood cell count (P = 0.031), creatinine (P < 0.001), and eGFR (P = 0.002) were also significantly different across the three BP categories.P < 0.001), patients >18 years (P < 0.001), weight (P < 0.001), height (P < 0.001), BMI (P < 0.001), pulse pressure (P = 0.046), creatinine (P < 0.001), eGFR (P < 0.001) and hemoglobin (P = 0.020) , P = 0.002] were independent risk factors for high BP values in SCD patients with RSH compared with SCD patients with normal BP values  . MultivaP values .P < 0.001), patients >18 years (P = 0.013), male gender (P = 0.019), weight (P < 0.001), BMI (P < 0.001), pulse pressure (P = 0.019), hemoglobin (P < 0.001), creatinine (P < 0.001) and Red blood cell count (P = 0.03) , P = 0.042], BMI  were independent risk factors for higher BP values in SCD patients with hypertension compared with SCD patients with normal BP values  . MultivaP values .Additionally, This study determined the role of demographic, anthropometric, clinical and laboratory factors associated with RSH and hypertension among SCD patients in Cameroon, one of the rare attempts from Africa. The main findings, from this relatively large dataset are as follows. Approximately one quarter of our 815 SCD patients were classified in either RSH or systemic hypertension group. At baseline, we observed statistically significant differences in age, gender, weight, height, BMI, pulse pressure, a history of stroke, hemoglobin, and red blood cell count across our three BP groups . We found that age, BMI, creatinine, and male gender were independently associated with an increased risk of RSH and systemic hypertension after adjusting for other variables.The nearly 19% prevalence of RSH reported in this study was similar to that of 17% reported in studies from North America by Becker et al.  and BodaUnsurprisingly, this study also found that age was significantly associated with BP in SCD patients, SCD patients with RSH and systemic hypertension were older than SCD patients with normal BP values suggesting that advancing age contributed to their higher BP values. This finding corroborates with previous reports in developed countries; , 8 and iPegelow et al.  demonstrConsistent with previous studies, Oguanobi et al.  in Niger2), showed a 32.6% fat composition, indicating high levels of adiposity. Since fat accumulation and adipocyte secretion are responsible for many hormonal changes playing a role in the development of vascular dysfunction and hypertension in the general population, this could be the case in SCD patients too, even if BMI values are normal. Therefore, further studies are needed to better understand the relationship between BMI; hormonal status and BP in SCD.Furthermore, measuring BMI alone, in SCD, is sufficient to screen for adiposity and obesity. Previous reports show the body composition of SCD patients with normal mean BMI . All patients older than 18 years signed consent forms, while informed consent was given by the parents or guardians for participants younger than 18 years old, in accordance with the Declaration of Helsinki. This study was approved by the National Ethical Committee of the Ministry of Public Health of Cameroon (No 193/CNE/SE/15). Written and signed informed consent forms were obtained from adult participants and parents/guardians of minor patients. An assent was also obtained from the participants of more than 7 years old. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.AW conceived the study. AN, VN, GM, and AW made substantial contributions to the conception, design of the work, methodology, analysis, data interpretation, and wrote the final manuscript. AN and GM analyzed and interpreted the data. AN issued the first draft of the paper. AN, VN, KM, GM, VN, AK, and AW critically revised successive drafts of the manuscript. VN, GM, AK, and AW supervised the project and compiled the revisions. All authors have read and agreed to the published version of the manuscript.This work was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health (Award Number U24HL135600) and (Award Number 1U24HL135881).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.