At the same time, ccRCC also presented great differences in most blood indicators between males and females. In addition, patients with ccRCC had a higher probability of developing a low ratio of albumin (ALB) to globulin (GLB) (AGR < 1.2). Eight key indicators were used to classify and predict renal cell carcinoma. The area under the receiver operating characteristic (ROC) curve (AUC) of the eight-indicator model was as high as 0.932, the sensitivity was 88.2%, and the specificity was 86.3%, which are acceptable in many applications, thus realising early screening for renal cancer by blood indicators in a simple blood-draw physical examination. Furthermore, the composite indicator prediction method described in our study can be applied to other clinical conditions or diseases, where multiple blood indicators may be key to enhancing the diagnostic potential of screening strategies.Clear cell renal cell carcinoma (ccRCC) accounts for more than 90% of all renal cancers. The five-year survival rate of early-stage (TNM 1) ccRCC reaches 96%, while the advanced-stage (TNM 4) is only 23%. Therefore, early screening of patients with renal cancer is essential for the treatment of renal cancer and the long-term survival of patients. In this study, blood samples of patients were collected and a pre-defined set of blood indicators were measured. A random forest (RF) model was established to predict based on each indicator in the blood, and was trained with all relevant indicators for comprehensive predictions. In our study, we found that there was a high statistical significance ( In recent years, newly diagnosed cases of kidney cancer have increased year by year , with 90 (ccRCC) . Previou (ccRCC) . With th (ccRCC) ,5. As a  (ccRCC) . The num (ccRCC) ,8. For c (ccRCC) . ConsequIn these cases, early screening of renal cancer through simple blood tests may have a significant impact on a life-saving strategies . From a function ,23,24. Ifunction ,26. All We collected peripheral blood samples from people diagnosed with early-stage ccRCC (TNM 1) and advanced-stage ccRCC (TNM 4). After that, we measured the indicators of peripheral blood and compared them with the indicators of blood samples collected from healthy people. Meanwhile, we analysed the correlation and differences between patient’s indicators. Then, the diagnosis and prediction of ccRCC were performed using a naive Bayesian model (single blood indicator) and a random forest model (mixed blood indicators). As shown in In this study, we collected 743 blood samples from patients with, renal cancer from September 2017 to September 2022 in Dazhou Central Hospital, including 505 blood samples from patients with early-stage ccRCC (TMN 1) and 237 blood samples from patients with advanced ccRCC (TMN 4). The age of cancer patients is mainly around 57 years old, and the interquartile range is 47–65 years old. Therefore, we randomly collected samples from 500 patients aged 50–65 as the control set, with an average of 56 years old. We collected venous blood samples from patients with medically and radio-logically confirmed ccRCC, using heparin as an anticoagulant. We centrifuged the collected sample at 4 https://bioconductor.org/packages/limma (accessed on 10 October 2022)) developed by Ritchie et al. [x-variable in a sample, x-variable, y-variable in a sample, and y-variable.The clinical report was completed with the “gtsummary” package  in R lane et al. . Continut from unknown distribution T. Then, the p-value p is what the prior probability would be of observing a test-statistic value at least as “extreme” as t if null hypothesis p is as follows:For the significance analysis of statistical differences, we consider an observed test-statistic ere true . Therefox.In statistics, naive Bayes classifiers are a class of simple probabilistic classifiers based on the application of Bayes’ theorem and the assumption of strong (naive) independence between features ,31. The https://cran.r-project.org/web/packages/pROC/ (accessed on 10 October 2022)) visualizes the ROC curve and AUC of our model, where AUC is a critical index in ROC curve that tests whether positives are ranked higher than negatives. The AUC is equivalent to the Wilcoxon or Mann–Whitney U test [In model research, the ROC curve is often used to evaluate a model’s effectiveness and test whether the model has practical value ,33. The y U test  statistihttps://www.Python.org (accessed on 10 October 2022)) and the “sklearn” library ). The GridSearchCV module was used to automatically adjust the parameters of the RF model with about 100 trees, each with eight randomly selected variables and a maximum tree depth of 50 to achieve the best results for the model. We collected the results and selected the model with the best performance while measuring the prediction accuracy on the test set. At the same time, the prediction accuracy was measured on the test set. Then, the model was optimised for the number of variables selected for each tree. In this process, the over-fitting of the RF model during parameter adjustment was prevented by cross-validation, so as to keep the stability and practicability of the model. Model performance evaluation is based on the ROC curve and corresponding AUC value.We constructed a naive Bayesian classification model  to predihttps://www.r-project.org/ (accessed on 10 October 2022)) and Python 3.9. The main plot and statistical significance was visualized using the “ggplot2” package ) in R. The basic column chart and box diagram are drawn by the “matlibplot” python package ). The correlation coefficients between the data indices in the study were visualized by the “ggcorrplot” package ). A heat scatter was created using the “LSD” package ) in R. The indicator differences between male and female medical records of different cancers were visually compared by the “beanplot” package ). The visualisation of the pair plot was performed through the “seaborn” python package ). Otherwise, optimisation of colour and typesetting was completed with Adobe Illustrator (https://www.adobe.com (accessed on 10 October 2022)).Data visualisation and statistical analysis were both carried out using R  are all positively correlated with the patient’s age, indicating that the renal function indicators also increase with the increase of age. As shown in p < 0.001 statistically significant; ** means p < 0.01 is statistically significant; * means p < 0.05 is statistically significant; insignificance is denoted by ns. In terms of protein indicator results, ALB and TP indicators between healthy men and women were not significantly different. ALB and TP of early-stage ccRCC began to show statistical significance (p < 0.05), while the male and female patients with advanced ccRCC (TNM 4) showed high statistical significance (p < 0.01). On the other hand, there is a significant difference in haemoglobin between healthy men and women. With the development of cancer, This may be because more advanced cancer consumes a large amount of HB. Therefore, more advanced tumours better balance the differences between men and women. This result is also reflected in hs-CRP, and there is no significant difference between men and women in advanced ccRCC patients.After comparing the correlation of blood indicators of patients in each group, we also analysed eight indicators previously showed to be involved in kidney diseases. Due to the differences between men and women in constitution, endocrinology, and normal range of blood indicators , we compp < 0.001) between male and female patients in renal function indicators, and there is a statistical significance (p < 0.05) in both healthy people and cancer patients. Another key point is that in the analysis of male and female indicators, the values of ALB, TP, HB and KAs a result, for early diagnosis, women could benefit more from the panel proposed in this study, while in case of advanced tumours, women and men are equally well performing regarding the diagnostic ability of the panel. However, there is a statistical significance (p < 0.05), while other indicators show extreme statistical significance (p < 0.001). Previous studies have pointed out that early-stage renal cancer does not affect renal function, and our results show that UA also shows consistent characteristics. In addition, ha-CRP mainly shows inflammation in patients. It can be clearly found from the indicator comparison that the inflammation indicator in cancer patients is much higher than that in the healthy population, and the hs-CRP indicator of advanced TNM 4 patients is much higher than that of early-stage cancer patients.As well as the analysis of male and female blood indicators, we compared the significance of differences between indicators in different groups of samples from healthy and cancer populations. This allows us to identify specific differences between healthy people and people with cancer. The protein groups of early- and late-stage ccRCC showed statistical significance. The protein indicators of cancer patients were significantly lower than those of the healthy population. In addition, advanced cancer consumed relatively more endogenous proteins. Therefore, ALB, TP, and HB indicators showed a significant decline. For indicators KWe systematically analysed eight related indicators of peripheral blood measurement, where TP level mainly reflects the loss of protein caused by renal lesion and serum ALB is also be greatly reduced in cancer patients. GLB is closely related to human immunity. When the human body is invaded by viruses or cancer cells, GLB will rapidly increase . As we kIn renal function indicators, CREA and BUN can reflect the degree damage to glomerular filtration function to some extent. BUN is also affected by extra-renal factors, such as a high-protein diets, gastrointestinal bleeding, dehydration, and high catabolism, which can cause BUN to increase. CREA is more accurate than BUN because it mainly depends on glomerular filtration capacity when exogenous creatinine intake is stable, and creatinine production in vivo is constant . TherefoMany correlations and interactions between indicators were challenging to mine individually. Therefore, we performed the pairwise comparative analysis on patient age and the distribution of the eight key indicators, and conducted an in-depth analysis of the indicators through the scatter diagram and density diagram. The upper part of An ROC curve is a graphical technique that is often applied to visualise classifier performance. For the single indicator prediction model, ROC was used to determine the prediction effect of the model. In this study, we tested the classification prediction performance of single indicator data of healthy population and early-stage ccRCC patients using the prediction model, as shown in Except for the fact that UA in the renal function indicators had little predictive performance, all other indicators had high AUC values, among which HB, Kof 0.932 , a sensiIn this study, the peripheral blood of early-stage ccRCC (TNM 1) was collected, and healthy people and advanced ccRCC (TNM 4) blood samples were used as control groups. After measuring the indicators of peripheral blood samples, the correlation between the indicators of early-stage ccRCC patients and the differences of healthy people were analysed. The results showed that cancer patients had lower protein levels, while renal function and inflammation indicators were higher than healthy ones. In addition, there was a high positive correlation between renal function indicators and a large difference between male and female indicators. However, more advanced tumours narrowed the difference between male and female indicators. Analysis of the blood indicators of healthy people and cancer patients can preliminarily classify the patients, with samples whose indicators exceed the standard have a higher risk of cancer. Correspondingly, we applied a naive Bayesian model (single blood index) and a random forest model (mixed blood index) to diagnose and predict ccRCC. The results are shown in Gender differences exist in the incidence of kidney cancers, hormones, blood indicators, and the prognosis of the disease ,44. NevePrediction of the clinical behaviour of cancer by artificial intelligence is a hot topic in contemporary research . The RF Our study has some limitations: the data comes from a single center, the patients’ number is limited, and all the patients belong to the same race. Moreover, the statistical data is relatively simple. We can improve the statistical power of the study in the next future, by adding more data and more variability, and by introducing more research on the patients’ follow-up.This study focused on developing a low-cost, patient-friendly, and effective strategy for kidney cancer screening. A potential clinically useful combination of eight biomarkers, all “renal” indicators detectable with a simple blood analysis, were studied through an RF prediction model, which achieved a sensitivity of 88%, a specificity of 86.3%, and an AUC of 0.932.These findings indicate that random forest-based prediction can be used as a reliable method for screening with high specificity and sensitivity, potentially acting as a low-cost liquid biopsy for ccRCC patients. This strategy, useful for early screening worldwide, could become particularly crucial in the large part of the world where more expensive screening programs are not possible and portions of the population are excluded from physical medical examinations or imaging.Additionally, the comprehensive indicator prediction method applied in our research can also be used to predict the risk of harbouring other diseases whose presence has been correlated to alterations in specific blood indicators, as is the case in kidney cancer.


Chronic kidney disease (CKD) represents a chronic proinflammatory state and is associated with very high cardiovascular risk. Apolipoprotein A‐IV (apoA‐IV) has antiatherogenic, antioxidative, anti‐inflammatory and antithrombotic properties and levels increase significantly during the course of CKD.We aimed to investigate the association between apoA‐IV and all‐cause mortality and cardiovascular outcomes in the German Chronic Kidney Disease study.2 or an eGFR >60 ml/min/1.73m2 in the presence of overt proteinuria. Median follow‐up was 6.5 years. The association of apoA‐IV with comorbidities at baseline and endpoints during follow‐up was modelled adjusting for major confounders.This was a prospective cohort study including 5141 Caucasian patients with available apoA‐IV measurements and CKD. The majority of the patients had an estimated glomerular filtration rate (eGFR) of 30–60 ml/min/1.73mp = 0.0000003). During follow‐up, each 10 mg/dl higher apoA‐IV was significantly associated with a lower risk for all‐cause mortality , incident major adverse cardiovascular events  and death or hospitalizations due to heart failure .Mean apoA‐IV concentrations of the entire cohort were 28.9 ± 9.8 mg/dl. Patients in the highest apoA‐IV quartile had the lowest high‐sensitivity C‐reactive protein values despite the highest prevalence of diabetes, albuminuria and the lowest eGFR. Each 10 mg/dl higher apoA‐IV translated into lower odds of prevalent cardiovascular disease (1289 cases, odds ratio = 0.80, 95% confidence interval [CI] 0.72–0.86, These data support a link between elevated apoA‐IV concentrations and reduced inflammation in moderate CKD. ApoA‐IV appears to be an independent risk marker for reduced all‐cause mortality, cardiovascular events and heart failure in a large cohort of patients with CKD.   Chronic kidney disease (CKD) is a major public health problem affecting more than 10% of the general population in many countries worldwide . CKD is Apolipoprotein A‐IV (apoA‐IV) is a 46 kDa glycoprotein involved in reverse cholesterol transport modulating lipid metabolism and glucose homeostasis , 10, 11.Mice transgenic for human apoA‐IV are protected against atherosclerosis by a mechanism that does not involve an increase in HDL cholesterol concentration . RecombiKidney function has a major influence on apoA‐IV concentrations. Concentrations increase with decreasing estimated glomerular filtration rate (eGFR) , 27, and2  or an eGFR >60 ml/min/1.73m2 in the presence of overt proteinuria  under regular care by nephrologists. Exclusion criteria were non‐Caucasian ethnicity, solid organ or bone marrow transplantation, active malignancy within 24 months prior to screening, heart failure New York Heart Association Stage IV, legal attendance or inability to provide consent. Patients were enrolled according to a standardised procedure by trained personnel. Blood and spot‐urine samples were collected, processed and shipped on dry ice to a central biobank where routine laboratory parameters were measured centrally, as reported previously . Second, although our analyses were extensively adjusted for traditional cardiovascular risk factors, parameters of kidney function and statin use, we cannot exclude residual confounding by unknown or unmeasured variables, which might possibly show a causal relationship with both apoA‐IV and the outcomes. Some of those unmeasured variables or confounders are other surrogate measurements for inflammation such as interleukin‐6 which, unfortunately, are not available in the GCKD study. Third, it is unclear whether our findings are also valid for non‐Caucasian ethnicities. Fourth, the study mainly recruited CKD patients in stage G3 or A3 and the findings might not be generalisable to other stages of CKD or to general non‐CKD populations. However, our earlier study in diabetic haemodialysis patients revealed results pointing in a similar direction .This large prospective study in patients with moderate CKD revealed an independent and strong association of low apoA‐IV concentrations with all‐cause mortality and significant associations with prevalent and incident major cardiovascular events as well as heart failure. These associations might be driven by the known antioxidative, anti‐inflammatory and antithrombotic properties of this apolipoprotein. Further studies are required to elucidate the value of apoA‐IV as an anti‐inflammatory and antiatherogenic parameter in the general population and various clinical settings.Johannes P. Schwaiger: conceptualization; investigation; writing – original draft; writing – review and editing. Barbara Kollerits: conceptualization; data curation; formal analysis; methodology; visualization; writing – original draft; writing – review and editing. Inga Steinbrenner: data curation; investigation; validation; writing – review and editing. Hansi Weissensteiner: data curation; methodology; software; writing – review and editing. Sebastian Schönherr: data curation; investigation; software; writing – review and editing. Lukas Forer: data curation; investigation; software; writing – review and editing. Fruzsina Kotsis: data curation; investigation; validation; writing – review and editing. Claudia Lamina: formal analysis; methodology; validation; writing – review and editing. Markus P. Schneider: investigation; validation; writing – review and editing. Ulla T. Schultheiss: data curation; investigation; methodology; writing – review and editing. Christoph Wanner: conceptualization; data curation; funding acquisition; investigation; validation; writing – review and editing. Anna Köttgen: data curation; funding acquisition; investigation; supervision; writing – review and editing. Kai‐Uwe Eckardt: conceptualization; funding acquisition; investigation; resources; writing – review and editing. Florian Kronenberg: conceptualization; data curation; funding acquisition; investigation; project administration; resources; supervision; validation; writing – original draft; writing – review and editing.Table S1 Association of apolipoprotein A‐IV with prevalent cardiovascular disease. Data are as in model 2 from Table 3 but additionally adjusted for hs‐CRP.Table S2 Association of apolipoprotein A‐IV with outcomes during the prospective follow‐up. Data are as in model 2 from Table 4 but additionally adjusted for hs‐CRP. Table S3 Association of apolipoprotein A‐IV with outcomes during the prospective follow‐up in patients free of cardiovascular disease at the time of enrollment . Data are adjusted for age, sex, eGFR, ln‐UACR, serum albumin, LDL cholesterol, smoking status, diabetes mellitus, statin use, ln‐triglycerides, BMI, systolic and diastolic blood pressure. Table S4 Association of apolipoprotein A‐IV with outcomes during the prospective follow‐up based on subdistribution hazard ratio (SHR) models. Table S5 Association of apolipoprotein A‐IV with outcomes during the prospective follow‐up when data are additionally adjusted for HDL cholesterol concentrations. For better comparison data from model 2 given in Table 4 of the main manuscript are added to this table. Table S6 Association of apolipoprotein A‐IV with outcomes during the prospective follow‐up including time‐updated covariables for eGFR, UACR, BMI, triglycerides, LDL cholesterol, serum albumin, systolic and diastolic blood pressure and statins from follow‐up examinations two, three and four years after baseline.Click here for additional data file.


In hospitalized COVID-19 patients, disease progression leading to acute kidney injury (AKI) may be driven by immune dysregulation. We explored the role of urinary cytokines and their relationship with kidney stress biomarkers in COVID-19 patients before and after the development of AKI. Of 51 patients, 54.9% developed AKI. The principal component analysis indicated that in subclinical AKI, epidermal growth factor (EGF) and interferon (IFN)-α were associated with a lower risk of AKI, while interleukin-12 (IL-12) and macrophage inflammatory protein (MIP)-1β were associated with a higher risk of AKI. After the manifestation of AKI, EGF and IFN-α remained associated with a lower risk of AKI, while IL-1 receptor (IL-1R), granulocyte-colony stimulating factor (G-CSF), interferon-gamma-inducible protein 10 (IP-10) and IL-5 were associated with a higher risk of AKI. EGF had an inverse correlation with kidney stress biomarkers. Subclinical AKI was characterized by a significant up-regulation of kidney stress biomarkers and proinflammatory cytokines. The lack of EGF regenerative effects and IFN-α antiviral activity seemed crucial for renal disease progression. AKI involved a proinflammatory urinary cytokine storm.  The kidney damage induced by SARS-CoV-2 is multifactorial; it can directly infect the kidney podocytes and proximal tubular cells, and based on an angiotensin-converting enzyme 2 (ACE2) pathway, it can lead to acute tubular necrosis, protein leakage in Bowman’s capsule, collapsing glomerulopathy and mitochondrial impairment , but virAcute kidney injury (AKI) is a heterogeneous group of conditions characterized by a sudden decrease in glomerular filtration rate (GFR), manifested by an increase in serum creatinine (sCr) concentration or oliguria, and classified by stage and cause . AKI occConsidering that cytokines have been described in the plasma of patients with COVID-19-associated AKI, here we explored these molecules in the urine of patients with subclinical AKI who developed AKI on subsequent days. This way, we were able to describe the immunoregulatory proteins affecting the kidney before and after the development of AKI. Therefore, this longitudinal study was aimed at exploring the role of urinary cytokines and their relationship with the kidney stress biomarkers neutrophil gelatinase-associated lipocalin (NGAL), the tissue inhibitor of metalloproteinases-2 (TIMP-2) and the insulin-like growth factor binding protein 7 (IGFBP7) in a cohort of patients with severe COVID-19 and subclinical AKI.During the period between May and August 2020, a total of 420 individuals were admitted to critical areas of the National Institute of Respiratory Diseases (INER). Of those, 69 were negative for SARS-CoV-2 infection; in 44 SARS-CoV-2 infection could not be confirmed; 60 remained in the emergency room due to hospital saturation and 20 died there. Informed consent could not be obtained from 196 patients. We thus included 51 patients who provided informed consent for participating in the study . p = 0.01), and had a higher SOFA score (4 in the AKI group (IQR: 3–7) vs. 3 in the non-AKI group .Of those, 30 were males (58.8%), the median age was 53 years (IQR: 40–61), 14 had systemic arterial hypertension (27.5%), 16 had diabetes (31.4%), and 21 were obese (41.2%). Of the 51 individuals studied, 28 had subclinical AKI (elevation of kidney biomarkers in the absence of changes in sCr and urine output) on admission to critical care areas (day 1) and developed AKI within the following 48 h , and 23 did not develop AKI . The AKI group had a higher frequency of hypertension  in the AKI group vs. 0.07 (ng/mL)2/1000 (IQR: 0.04–0.11) in the non-AKI group (p = 0.045); and NGAL 54.7 ng/mL (IQR: 36.4–117.4) in the AKI group vs. 32.4 (IQR: 14–40.05) in the non-AKI group (p = 0.002). In contrast, renal function had similar values in both groups on day 1 and became significantly lower in the AKI group on day 5, as indicated by sCr 0.79 mg/dL (IQR: 0.67–1.13) in the AKI group vs. 0.60 mg/dL (IQR: 0.51–0.75) in the non-AKI group (p = 0.01), and CKD-EPI 99 mL/min/1.73m2 (IQR: 69.5–109.5) in the AKI group vs. 110 mL/min/1.73m2 (IQR: 103–121) in the non-AKI group p = 0.01, q = 0.14), and lower level of epidermal growth factor (EGF) in the AKI group since day 1  and NGAL at a cutoff of 40 ng/mL , specificity and accuracy values, the cytokines and biomarkers with the best performance for the prediction of AKI were EGF at a cutoff of 4600 pg/mL : 0.597–0.979, p = 0.037), and EGF > 4600 pg/mL was associated with a lower risk of AKI . After adjusting for possible confounding variables, only EGF > 4600 pg/mL remained associated with a lower risk of AKI  and with NGAL .We explored the relation of urinary EGF and RANTES with kidney stress biomarkers on day 1. EGF had an inverse correlation with [TIMP2] × IGFBP7]  of cytokines indicated that the first five principal components (PC) had eigenvalues > 2  and explained > 70% of the accumulated variance 73.43%, . p = 0.017) and the PC4 (encompassing IL-12 and macrophage inflammatory protein (MIP)-1β) was associated with higher odds of AKI  on day 1. The PC1 was also associated with lower odds of AKI on day 5  and the PC2 (encompassing IL-1 receptor (IL-1R), granulocyte-colony stimulating factor (G-CSF), IP-10 and IL-5) was associated with higher odds of AKI -α) was associated with lower odds of AKI  in various clinical conditions ; and immOn day 5 of hospitalization, that is, when more than half of the patients had developed clinical AKI, we found that EGF and IFN-α were still associated with a lower risk of AKI, and IL-1R, G-CSF, IP-10 and IL-5 were associated with a higher risk of AKI. The IL-1R is primarily responsible for transmitting the inflammatory effects of IL-1; G-CSF stimulates the survival, proliferation, differentiation, and function of neutrophils and stimulates mobilization of hematopoietic stem cells to the bloodstream; IP-10 is a chemoattractant of monocytes, macrophages, T cells, NK cells and dendritic cells, and promotes T cell adhesion to endothelial cells; and IL-5 is a chemotactic and activating factor for B cells and eosinophils . Thus, tAn important limitation of our study was the small sample size. Another study limitation was that patients with incomplete clinical files or those who were transferred to other hospitals due to the scarcity of intensive care beds were not included in the study, and this may represent a selection bias. In addition, our study was conducted at a national referral center for respiratory diseases receiving disproportionately more patients with severe COVID-19, and this represents a potential source of referral bias. The lack of pre-hospital baseline sCr measurements was also a study limitation because baseline sCr values were an estimation. The lack of sCr measurements prior to hospital admission often impairs the identification of underlying CKD and creates challenges for the reliable detection and staging of AKI. One study in which baseline sCr measurements were available, reported that 35% of patients with COVID-19-associated AKI had underlying CKD . AnotherTaken together, our findings indicate that AKI was frequent in our cohort of hospitalized patients with COVID-19. Subclinical AKI was characterized by lower regenerative and antiviral protection conferred by EGF and IFN-α, in the context of proinflammatory cytokines. The lack of protective effects of EGF and IFN-α seemed to be crucial for the progression of renal disease. Up-regulation of NGAL and [TIMP-2] × [IGFBP7] was already significant, indicating that these kidney stress biomarkers may be useful for the diagnosis of subclinical AKI in patients with COVID-19. After the clinical manifestation of AKI, we observed an evident profile of inflammatory cytokines characteristic of the cytokine storm leading to disease progression, together with indicators of decreased renal function. Large randomized controlled clinical trials are required to further explore the role of kidney stress biomarkers and cytokines in critically ill patients with COVID-19.2 using the CKD-EPI equation [2/FiO2) <300 mm Hg, and a positive result for SARS-CoV-2-real-time reverse transcription–polymerase chain reaction (rRT-PCR) assay in a nasopharyngeal swab [This prospective, longitudinal cohort study was conducted at the INER, the largest third-level institution designated by the Mexican Government for COVID-19. The Institutional Review Board approved the study  and written informed consent was obtained from all participants. We included individuals that were admitted to intensive care with the diagnosis of severe pneumonia that was caused by SARS-CoV-2; who were 18 years of age or older; without AKI when a urine sample was collected; and with no history of chronic kidney disease (CKD) as indicated by interrogation of patients about CKD medical history and by an estimated eGFR greater than 60 mL/min/1.73mequation . Pregnaneal swab . The recThe baseline sCr level was defined as the minimum inpatient value during the first 7 days of admission . DiagnosThe urine samples were collected on day 1 and on day 5. The urine was frozen at −80 °C within the first 30 min after sample collection. The urinary concentrations of TIMP-2 and IGFBP7 were determined using commercially available ELISA kits  following manual instructions. The ELISA plates were read at O.D. of 450 and the calculations were done according to the signal that was given by the standard curve of each kit. NGAL determinations were done using the NGAL kit  according to the manual instructions and using the Abbott ™ ARCHITECT™ Analyzer .The concentrations of cytokines and chemokines in urine were measured with a Luminex 200 instrument  using xMAP  technology. Data were analyzed by Milliplex Analyst software to determine cytokine concentrations . The Milliplex Human Cytokine Reagent Kit  was used to measure a cytokine panel consisting of fibroblast growth factor (FGF), G-CSF, granulocyte/macrophage-colony stimulating factor (GM-CSF), RANTES , MIP, monocyte chemoattractant protein-1 (MCP-1), EGF, hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), IFN-α, IP-10, monokine induced by IFN-gamma (MIG), eotaxin; interleukin (IL)-1β, IL-1R, IL-10, IL-13, IL-6, IL-12, IL-17, IL-15, IL-5, IL-2, IL-7, IL-2R, IL-4 and IL-8.We performed descriptive statistics, including means and standard deviations for normally distributed continuous variables; medians and interquartile ranges (IQR) for non-parametric distributions and proportions for categorical variables. The comparisons of the group developing AKI during hospitalization vs. the group without AKI were made using a chi-squared test for categorical variables and Mann–Whitney U for continuous variables. The significantly different cytokines between groups were identified. The correlation of identified cytokines with kidney stress biomarkers was explored using the Spearman test. Given the large number of assessments for each group, we used the false discovery-based q-value statistic to correct for multiple hypothesis testing . p values ≤ 0.05 were considered statistically significant.For each biomarker, the AUC with 95% CI was calculated, as well as the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the accuracy at three different cutoff values using urine samples that were collected on day 1. The cutoffs for each biomarker were selected based on the highest AUC, specificity, and accuracy for the prediction of AKI. Combinations of the top biomarkers were also explored. When combinations had no significant added value, the individual biomarkers were preferred. For all analyses, two-sided p-values of ≤0.05 were considered statistically significant. Logistic regression analysis was used to identify the association between relevant covariates with AKI. We obtained age-stratified estimates considering 60 years and older as a vulnerable population. The variables were entered into the models when the alpha level of the risk factor was <0.20 in the univariate analysis. Age and gender were entered into the models regardless of the alpha level. All statistical tests were two-sided, and two-sided Values of cytokines outside the ranges specified by the Luminex manufacturer were treated as missing values in the data set. Missing values were imputed according to a practical guide for multiple imputation of missing data in nephrology , using Pp values ≤ 0.05 were considered statistically significant. The PCA was conducted using R Studio 1.4.1717 .Principal component analysis was performed to compress and simplify the size of the data set by keeping the most important information and analyzing the structure of the observations and the variables . We reta


The time-dependent effect of diastolic blood pressure levels associated with living environment was not statistically significant, indicating a sustained difference in diastolic blood pressure associated with living environment changes at baseline after three years. The effect of living environment changes on diastolic blood pressure increment was also evident in men without antihypertensive medication use during the study period and in men who were current drinkers at baseline. There were no associations between living environment changes and diastolic blood pressure levels among women. Sudden changes in living environment due to the disaster had an impact on the long-term effects of higher diastolic blood pressure among middle-aged men.The Great East Japan Earthquake occurred on 11 March 2011, forcing Fukushima Prefecture residents to change their living environment. Such sudden changes possibly have long-term effects on cardiovascular-related diseases. We therefore sought to identify temporal relationships between living environment changes and blood pressure levels over three years following the earthquake. Participants included 14,941 men and 21,533 women aged 16 years or older who answered self-administered questionnaires, including questions on living environment changes at baseline (2012). Blood pressure levels were measured each year from 2012 to 2015. Linear mixed-effects models were used to analyze associations between living environment changes and blood pressure levels. Men with changes in living environment  showed significantly higher diastolic blood pressure levels than those who lived in their home at baseline (77.3 mmHg vs. 77.8 mmHg;  The Great East Japan Earthquake that occurred on 11 March 2011 in Japan was catastrophic. The earthquake and subsequent tsunami damaged the Fukushima Daiichi Nuclear Power Plant (NPP), releasing hazardous radiation into Fukushima Prefecture, particularly the coastal regions, and forcing more than 160,000 residents to evacuate the area. This natural disaster and the subsequent evacuation led to changes in living environments; loss of family, friends, and relatives; physical injuries; loss of property and jobs; disruption of social networks; and reduced dietary conditions, thereby inducing psychological stress in the evacuees . Immediaa priori hypothesis that living environment changes might increase blood pressure levels. Moreover, we aimed to identify the temporal relationships between sudden changes in the living environment and systolic and diastolic blood pressure levels over the three years (2012–2015) following the earthquake.Therefore, our present study investigated the association between sudden changes in the living environment due to the earthquake and changes in blood pressure levels after the earthquake in Fukushima Prefecture residents. We examined our In the questionnaire on mental health and lifestyle, we asked the participants “Where did you live after the earthquake?” to measure living environment changes. Respondents could choose one of six possible answers: “shelter”, “temporary housing”, “rented apartment”, “relative’s house”, “own house”, or “other”. In this study, people belonging to the categories of shelter, temporary housing, rented apartment, relative’s house, and other were together considered as “persons with living environment changes”. People belonging to the category of own house were regarded as “persons without living environment changes”; this category was used as a reference .Blood pressure measurements in this study were carried out in accordance with the “Specific Health Checkup/Specific Health Guidance Guideline”, which is used in the specific health examinations conducted by the Ministry of Health, Labor and Welfare in Japan . Specifi2). Socks and light clothing were included during height and weight measurement at baseline and follow-up. We calculated the body mass index (BMI) for all participants by dividing weight (kg) by height , HDL cholesterol (mg/dL), triglycerides (mg/dL), blood glucose levels (mg/dL), and risk factors for cardiovascular diseases were measured at the annual health examination. Diabetes was defined as fasting glucose ≥ 7.0 mmol/L (126 mg/dL) or casual blood glucose ≥ 11.1 mmol (200 mg/dL) and/or on treatment for diabetes or HbA1c ≥ 6.5%. We used the Kessler 6 (K6) scale  for measWe used the question about sleep quality sourced from the Athens Insomnia Scale  for measTo assess whether participants performed regular physical exercises, we asked them “How often do you usually exercise?” and offered the following response options: “almost every day”, “2–4 days a week”, “1 day a week”, or “almost never”. This questionnaire was used in the specific health examinations conducted by the Ministry of Health, Labor and Welfare in Japan. Specific health checkups are nationwide checkups for people aged 40 to 74 that focus on metabolic syndrome to prevent lifestyle-related diseases . MissingInformed consent from community representatives was obtained to conduct an epidemiological study based on the guidelines of the Council for International Organizations of Medical Science. This study was approved by the Ethics Committee of Fukushima Medical University (29064) and the Ethical Review Board of Juntendo University Faculty of Medicine (2017142). T-tests and chi-square tests were used to compare sex-specific means and proportions of various lifestyle and psychological factors of baseline characteristics.ijY represents systolic and diastolic blood pressure levels for an individual i taken at time j, β0 is the overall intercept, pβ is the effect of living environment changes considered as constant across time, Tβ represents the intercept and slope of the linear relationship between systolic and diastolic blood pressure levels and time at which the outcome was measured, and PTβ is the effect of living environment changes on the slope describing the linear relationship between blood pressure levels and time (blood pressure changes per year). Model coefficients were estimated through maximum likelihood using the SAS MIXED procedure and specifying a compound symmetry structure for the covariance matrix ; p = 0.03), whereas men who changed their living environment showed no significant change in systolic blood pressure levels over time (time-dependent effect). β = 0.63 mmHg ; 77.3 mmHg vs. 77.8 mmHg; p < 0.001). No significant time-dependent effect was observed . These results revealed that diastolic blood pressure levels, which increased after the earthquake, had not decreased over the three years in men who had living environment changes due to the earthquake. For women, diastolic blood pressure levels did not change at baseline or over the three years in any group.Men with living environment changes had significantly higher diastolic blood pressure levels immediately after the earthquake than those without these changes  and diastolic blood pressure levels . Systolic blood pressure levels decreased after the three years . However, no significant difference in diastolic blood pressure levels was observed during the follow-up period in men without antihypertensive medication use . β = –0.97 mmHg ; 135.7 mmHg vs. 135.5 mmHg; p = 0.02) than men without living environment changes. However, no significant difference in diastolic blood pressure levels was observed at baseline and over the three years in men with antihypertensive medication use.Among men with antihypertensive medication use, those with living environment changes immediately after the earthquake had significantly lower systolic blood pressure levels . For women with antihypertensive medication use and living environment changes, diastolic blood pressure levels were significantly higher  immediately after the earthquake and decreased during the follow-up period . For women, systolic blood pressure levels decreased significantly over time, regardless of antihypertensive medication use  showed significantly higher diastolic blood pressure levels than those who continued to live in their own home at baseline. For men, the time-dependent effect of diastolic blood pressure levels associated with the living environment was not statistically significant during the study period, which indicated that the difference in diastolic blood pressure associated with living environment changes at baseline remained after three years. The effect of living environment changes on diastolic blood pressure increment was also evident in men without antihypertensive medication use and in those who were current drinkers at baseline.Some possible mechanisms can explain the adverse effect of living environment changes due to the earthquake on blood pressure, for example, psychological distress and adverse lifestyle changes. A relationship between disasters and blood pressure levels has been documented in review articles based on the mechanisms and management of disaster hypertension . Changesp < 0.001). As we found in the present study, observing and treating diastolic blood pressure in the younger generation of people who have recently experienced sudden living environment changes due to disasters is vital for reducing the risk of cardiovascular events. The difference in time-dependent changes between systolic and diastolic blood pressure levels in this study may be due to the mechanisms and characteristics of increased blood pressure levels. An increase in systolic blood pressure levels is caused by age-related decreases in aortic compliance, while an isolated increase in diastolic blood pressure levels is caused by reduced peripheral vascular compliance. Isolated diastolic blood pressure increment is mostly noted in young and middle-aged people, male sex, those with poorer lifestyle practices , and those with hypercholesterolemia, hypertriglyceridemia, hyperglycemia, metabolic syndrome, and sleep apnea . IsolateStudies have found various impacts of the Great East Japan Earthquake on residents and evacuees who have changed their housing type, such as shelters and temporary housing. These studies have reported significant differences in motor function , physicaWe found no significant association between living environment changes and blood pressure changes in women. Women with living environment changes were relatively younger than men (55.0 years vs. 58.2 years). Women had lower mean systolic (123.5 mmHg vs. 128.8 mmHg) and diastolic blood pressure levels (73.4 mmHg vs. 77.4 mmHg) at baseline than men, which made detecting any adverse effect of living environment changes on blood pressure difficult. Moreover, the proportion of respondents with problem drinking, calculated using the CAGE questionnaire , was 20.We considered that mental stress due to the earthquake and aging may also increase systolic blood pressure over time. However, both men and women who had changed their living environments and were not using antihypertensive medications tended to exhibit decreased systolic blood pressure over time. One explanation is that the mean age of persons (both men and women) with living environment changes was significantly lower than that of persons without living environment changes. Furthermore, we did not consider further changes in the living environment, negative emotional status, and lifestyles from 2012 to 2015 in our analyses. Housing prospects for persons in temporary housing were associated with psychological distress one year after the earthquake . These mA strength of the present study is a prospective design with a large sample size to detect the association between changes in the living environment and blood pressure levels over the three years following the Great East Japan Earthquake. Most participants (75.2%) had more than one blood pressure measurement. Moreover, no significant difference was observed in baseline characteristics between the participants who had more than one blood pressure measurement and those with only one baseline measurement . TherefoThe present study has several limitations. First, the proportion of participants who responded to the questionnaire on mental health and lifestyle conducted at the baseline in 2012 was 34.9%, and the remaining 65.1% of residents who did not respond could not be considered. Second, this study did not evaluate socioeconomic factors other than living environment changes as potential confounders. We did not collect information about other environmental or socioeconomic factors, such as education status, job status, and marital status, so we could not rule out the possibility of residual confounding factors. Third, we had no information on the salt intake of participants. After the disaster, foods containing salt, such as cup noodles, were delivered to residents in shelters, which resulted in excessive salt intake among daily eating habits . HoweverIn conclusion, the present longitudinal observational study showed that sudden living environment changes caused by the earthquake led to increased diastolic blood pressure levels immediately after the earthquake among middle-aged men. The increased diastolic blood pressure did not subsequently decrease in men during the three years following the Great East Japan Earthquake. The effect of living environment changes on diastolic blood pressure increase was also evident in men without antihypertensive medication use during the study period and in men with a current drinker status at baseline. Thus, the sudden change in the living environment after the disaster incurred long-term effects on increased diastolic blood pressure. By 2021, 10 years had passed since the Great East Japan Earthquake, and while reconstruction is in progress, many Fukushima residents  are still living in changed environments due to the nuclear power plant accident. Continuous antihypertensive treatment, active blood pressure monitoring after the disaster, and interventions consisting of antihypertensive medications are pivotal for adequately controlling blood pressure among residents. Along with hypertension management, psychological interventions and early housing prospects are considered crucial and useful for preventing high systolic and diastolic blood pressure levels, as well as for controlling mental stress, especially in the younger generation.


Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to exert cardiorenal protective effects in diabetic patients and are widely used clinically. In addition, an increasing number of reports now suggest these drugs may even be beneficial in non-diabetic patients. However, SGLT2 inhibitors are rarely prescribed for kidney transplant recipients due to the risk of renal graft damage and urogenital infections.We report the cases of 5 renal transplant recipients with chronic kidney disease G3a-4 and metabolic syndrome who were administered the SGLT2 inhibitor empagliflozin, which yielded beneficial results in 4 cases. With the exception of one patient with an initial estimated glomerular filtration rate (eGFR) of less than 30 ml/min/1.73 m2, administration of empagliflozin elicited beneficial metabolic effects. There were no significant reductions in eGFR before or after empagliflozin administration, and no dehydration or urogenital infections were observed during the treatment course.Empagliflozin showed some positive effects in 4 cases with better renal function than CKD stage 4. Further studies will be required to clarify the efficacy and safety of SGLT2 inhibitors in a larger group of patients with similar medical conditions. Post-transplantation diabetes mellitus (PTDM) refers to diabetes present after transplantation, irrespective of the timing of the diagnosis or whether it was present but undetected before transplantation . AccordiHere we present the results from 5 patients treated with empagliflozin for metabolic syndrome following living-donor kidney transplantation Table. The ageThis case report has several limitations. First, this report is a single-center study with a small number of cases. The fact that all patients were male was considered a factor in the absence of urinary tract infections. The observation period was short, ranging from 8 to 24 months.PTDM is defined as a post-transplant diabetic condition, regardless of the timing of diabetes onset . Long-tefunction or if the dose is adjusted appropriately with more significant chronic kidney disease. Because of these factors, as well as evidence that they do not affect immunosuppressant levels, DPP-4 inhibitors are increasingly used for treatment of PTDM without significant safety concerns identified. . SGLT2 i2, and both doses significantly decreased HbA1c, body weight and systolic blood pressure as compared to placebo. In 5 other studies [Despite the efficacy of SGLT2 inhibitors in non-transplanted patients, administration of SGLT2 inhibitors to renal transplant patients remains controversial , 17, 18. studies –29, SGLT2 (CKD stage 4) before empagliflozin administration, and no useful effect of this drug was observed. In this case, the excretion of urinary sugar induced by empagliflozin was considered to be insufficient due to advanced renal dysfunction, and no good effect was obtained. In the other 4 cases, however, empagliflozin administration led to weight loss, decreased blood pressure, decreased ALT or γ-GTP, decreased HbA1c, and/or decreased UACR. In case 2, the patient exhibited decreases in both ALT and γ-GTP after empagliflozin administration. We suggest that these decreases in ALT and γ-GTP were due to improvement in this patient’s fatty liver disease [In case 3 in the present study, the patient had an eGFR of 25.9 ml/min/1.73m disease .The only randomized clinical trial (RCT) of SGTL2 inhibitor treatment in patients with PTDM is Halden et al . They coRecently, Jenssen reviewed the efficacy and safety of SGLT2 inhibitors in patients with PTDM . JenssenIn this report, we describe the efficacy and adverse effects of empagliflozin administered to 5 Japanese patients with CKD G3a-4 and metabolic syndrome after renal transplantation. Empagliflozin showed beneficial effects in 4 patients with better renal function than CKD 4. No adverse events, including deterioration of renal function, were observed in any patient. The number of cases in the literature so far is small, ranging from 8 to 22, and we believe that RCTs with a larger number of patients are needed to determine the efficacy and safety of SGLT2 inhibitors in KTR. Our case series is also small, only five cases, but there are still very few reports worldwide, and we hope that this presentation will trigger further research.


Despite massive research guidelines, high blood pressure remains a major public health concern since barriers to treatment and control are on the rise. Lack of awareness is one of the serious impediments to managing hypertension. Therefore, this study is designed to gauge awareness, beliefs, and practices related to hypertension amongst diagnosed subjects.A total of 425 hypertensive patients were recruited from the wards and outpatient department of Jinnah Medical College Hospital located in Korangi district, Karachi. Data was obtained regarding socio-demographics, comorbidity, duration of HTN, current BP readings, and BMI. Additionally, awareness, practices, treatment, and control of hypertension were also assessed. Using IBM SPSS version 25.0, a chi-square test was run for categorical variables to analyze the differences in demographic variables, awareness, practices, and treatment between controlled and uncontrolled hypertensive patients. Multivariate regression model was used to identify the risk factors associated with uncontrolled hypertension. A p-value of less than 0.05 was considered significant.65.6% of the total study population was females, of which, 70.7% had uncontrolled hypertension, with a p-value of 0.007. Majority of the candidates were between the ages of 50 and 59 and there was a significant difference in age groups of controlled and uncontrolled hypertensive patients . Co-morbidities and duration of hypertension yielded no significant results. Awareness, treatment, and practices of lifestyle modifications amongst controlled or uncontrolled hypertension groups were not statistically significant. Age and female gender were the only risk factors significantly linked with uncontrolled hypertension.Overall, there was no significant difference in the statistics of controlled and uncontrolled hypertensive patients. This requires further investigation and evaluation to identify the unknown risk factors and co-morbid contributing to these findings. Most of the patients are on treatment and still not controlled, and this could be considered under treatment. Health professional's advice and counseling skills, social media, internet, and public awareness sessions can play an active role in the management of BP and its associated complications. •Data regarding the awareness of lifestyle modifications in the general hypertensive population of Pakistan is scarce.•Out of 425 hypertensive patients, 70.7% had uncontrolled hypertension. Age and female gender were the only risk factors significantly associated with uncontrolled hypertension.•Most of the patients are on treatment and still not controlled, and thus could be considered under treatment. Interventions should be considered and implemented to potentially increase the control rates. Morbidity and mortality associated with disease progression continue to be an uphill struggle. Worldwide 1 billion of the population are stricken by hypertension and among them 7 million die per year due to inadequate control or complications secondary to uncontrolled Blood Pressure (BP) .By 2025 HTN prevalence is expected to expand up to 1.56 billion  and apprHypertension may lead to renal failure, cerebrovascular and cardiovascular events . GloballDespite massive research guidelines, high blood pressure remains a major public health concern since barriers to treatment and control are on the rise. Lack of awareness is one of the serious impediments to managing hypertension. Unfortunately, local data regarding the awareness of lifestyle modifications in the general hypertensive population is scanty. Therefore, this study is designed to gauge awareness, beliefs, and practices related to hypertension amongst diagnosed subjects. This data can help us overcome the barrier at the patient level and provide better health care services to control BP and minimize the consequences of uncontrolled hypertension.2This was an observational cross-sectional study, carried out after seeking the Ethical review board's approval between January and June 2019 JMC.ERC.811.18), reported in line with the STROCSS criteria .18, repo. Using tThe survey included socio-demographic data including age, gender, occupation, and education and other variables like co-morbidity, duration of HTN, current BP readings, and body mass index (BMI). The European health examination survey (EHES) guidelines were adopted to measure the blood pressure . During Additionally, awareness, practices, treatment, and control of hypertension were also assessed. Concerning practices, individuals were evaluated for physical activity, smoking, and alcohol consumption, dietary intake of fruits and vegetables, and use of low-fat dairy products. According to the “International Physical Activity Questionnaire” , physicaData was entered and analyzed in IBM SPSS version 25.0 . N with percentages was computed for categorical variables while mean with standard deviation were observed for continuous data. A chi-square test was used for categorical variables to analyze the differences in demographic variables, awareness, practices, and treatment between controlled and uncontrolled hypertensive patients. A p-value of less than 0.05 was considered significant.3In total, 425 people were included in the study. Females made up 279 (65.6%) of the total study population. Gender had a significant p-value of 0.007 when hypotheses were tested. Majority of the candidates were between the ages of 50 and 59, accounting for 144 (33.9%) of the population, with those aged 60 and older accounting for 131 (30.8%). There was a significant difference in age groups, and a p-value of 0.019 supported this finding.168 (39.5%) of our sample size had no education, even at the primary level. Whereas 297 (69.9%) of our study population was unemployed at the time of the survey, 131 (44.1%) had reached retirement age. It was noted that 159 (37.4%) of the candidates were classified as overweight, while the remaining 147 (34.6%) were classified as obese. Family history revealed hypertension for 293 (68.9%) and diabetes mellitus for 198 (46.6%) participants. As promising as it appeared, the rest of the demographic data, including co-morbidities and duration of hypertension, yielded no significant results. A remarkable 400 (94.1%) were aware that excessive salt consumption is a risk factor for hypertension. Furthermore, 362 (85.2%) were aware that hypercholesterolemia played a significant role in the pathophysiology of hypertension. Lack of exercise, smoking, and alcohol abuse was identified as risk factors for developing hypertension by 59.5%, 48.2%, and 41.6%, respectively. In terms of practices, 324 (76.2%) had low physical activity, 395 (92.9%) were not current smokers, 421 (99.1%) were non-alcoholics, 196 (46.1%) consumed fruits 5–7 days per week, 230 (54.1%) included veget ables 1–4 days weekly in their diet, and 321 (75.5%) were habitual of using low-fat dairy products in their diet. However, none of these were significant in either the controlled or uncontrolled hypertension groups. Taking into account the treatment regimen of the participants in this study, it was discovered that 216 (50.8%) were using angiotensin-converting enzyme (ACE) inhibitors, while calcium channel blockers came in second with a frequency of 198 (46.6%). Although the vast majority of 269 (63.3%) had only one anti-hypertensive drug in their management, it was shocking to see that the number of anti-hypertensive drugs had no substantial role in controlling hypertension (p = 0.422). .Based on the results of multivariate logistic regression analysis, age (p = 0.03) and female gender (p = 0.03) were identified as statistically significantly risk factors of uncontrolled BP .Table 3M4The health system is endeavoring to combat the burden of infectious diseases that have subjugated the subcontinent. During this time of struggle, the rising trends in hypertension and its consequences are further creating an exigent situation for the healthcare departments. This study assisted us in evaluating the degree of awareness and adherence to healthy lifestyle practices amongst hypertensive participants. Healthy lifestyle behavior plays an important role not only in the control of hypertension but also in minimizing its complications. In addition, this study elaborates the influence of multiple risk factors and demographics along with the knowledge, attitude, and treatment on the patients with controlled as well as uncontrolled hypertension.According to our study, the prevalence of hypertension was 65.6% in women as compared to 34.4% in males, therefore showing a significant difference in both genders. This is continuous with the findings of Mirzae. M et al.  and TabrAs per the results of this study, the most common age group affected with hypertension was between 50 and 59 with a prevalence of 33.9% corroborating with the study of Penpid. S et al.  and SanuLiterature reveals a strong association between levels of education with hypertension ,27. BettBMI plays a vital role in the evolution of hypertension. Obesity is a strong predisposing factor towards increased blood pressure and occurs secondary to lower physical activity and consumption of unhealthy food with less nutrition and more cholesterol ,30. Our This study exhibits that majority of the hypertensive patients were well aware of certain risk factors such as salt reduction, physical inactivity, high cholesterol, alcohol, and smoking. However, no significant difference was observed between the levels in controlled and uncontrolled groups. This is possibly due to lack of applied knowledge, dissent towards the treatment strategies, recalcitrant towards lifestyle modifications, and other preventive measures. Moreover, deficiency of proper health care services and untrained management staff may also contribute to this result.22 showing no correlation between the two. This may be due to retarded effect of nicotine, or by tolerance and adaptation towards nicotine thereby negating it as a contributing factor towards hypertension. Different studies have generated different outcomes regarding this correlation therefore, it remains a conflict so far [Moreover, the population is aware of the health effects of smoking but many of them fail to identify its association with raised BP. This was supported by the result that only 48.7% were cognizant of the fact that smoking can increase the risk of hypertension. Results were consistent with Tesema et al. (56.9%) , but a gt so far .Our study revealed no valuable difference between physical activity and hypertension among the control and uncontrolled group. This finding corresponds with the result compiled by Katibeh et al. revealing no remarkable correlation . PhysicaThis study did not reveal a substantial outcome of fruits, vegetables, low-fat products among both groups. This may be due to a better lifestyle modification by the patients diagnosed with hypertension and the data collected after the correction of dietary habits. Moreover, a healthy diet such as fruits and vegetables may improve the illness, but other elements such as non-compliance towards pharmacological management along with the refusal to remaining lifestyle modification may be the dominating component towards this result. Nevertheless, the adoption of the DASH diet  in adjunct to pharmacological therapy is an effective way of managing hypertension and its complications .Treatment provided was also similar between both the groups, again showing no considerable difference between the outcomes. The ACE inhibitor was the first-line drug used in many followed by calcium channel blocker. Our results generated poor control of this disease, regardless of the number of medications adjoined in the existing therapy. This is likely due to negligence and non-adherence towards the regimen and frequent changes of medications .5This study was carried out in a single center; further multicenter studies are required to strengthen these shreds of evidence for the lifestyle of hypertension. In this study we enrolled only hospital-based hypertensive participants; a community-based survey of hypertensive individuals will provide more significant results. Since it was a cross-sectional study, therefore, cannot predict the casualty rate and a proper association of hypertension with independent variables. Apart from the blood pressure readings, the entire results were derived based on information provided by the patient. There may be biasness on account of self-reported details. Moreover, detailed information about the adherence of the drug, economic status, and healthcare facilities was not taken into account.6There was no significant difference in the statistics of controlled and uncontrolled hypertensive patients. This requires further investigation and evaluation to identify the unknown risk factors and co-morbid contributing to these findings. Most of the patients are on treatment and still not controlled, and thus could be considered under treatment. Interventions should be considered and implemented to potentially increase the control rates. One example is to consider initiating two anti-hypertensive agents upon the diagnosis of hypertension and then to up-titrate dosage and add a third and fourth agent in short follow-up intervals until blood pressure control was achieved. Furthermore, health professional's advice and counseling skills, social media, internet, and public awareness sessions can play an active role in the management of BP and its associated complications.This study received ethical approval from Jinnah Medical and Dental College.None.All authors made substantial contribution to this article.1.Name of the registry:2.Unique Identifying number or registration ID:3.Hyperlink to your specific registration (must be publicly accessible and will be checked):N/A.Informed verbal consent was obtained from patients.Not commissioned, externally peer-reviewed.None declared.


This secondary analysis of a randomized clinical trial examines the risk of kidney or hepatic toxic effects among patients with impaired kidney function at baseline treated with remdesivir. We report on patients with impaired kidney function at baseline as a post hoc analysis to examine the risk of kidney or hepatic toxic effects with remdesivir administration.The Canadian Treatments for COVID-19 (CATCO) trial randomized patients to remdesivir or standard care between August 1, 2020, and April 1, 2021, as part of the global Solidarity trial.5 This study was approved by all ethics committees and followed the CONSORT reporting guideline. Patients with impaired kidney function (eGFR <30 mL/min/1.73 m2 at randomization)6 received open-label remdesivir or best-quality supportive care .We report all-cause mortality (unadjusted and adjusted for sex and baseline eGFR), adverse events, incidence of new ventilation or hemodialysis as proportions, and outcomes of day 5 eGFR and alanine aminotransferase levels, using medians (IQRs). There were no a priori levels of significance established. Given baseline imbalance, analysis of covariance was performed for the change in eGFR, adjusting for baseline eGFR. As sensitivity analysis, we report the results of binary outcomes for all patients in the main trial with eGFR 60 mL/min/1.73 m2; median age was 74  years  had a baseline eGFR less than 30 mL/min/1.73 m6) years . There w2 (n = 248) at randomization, there was no significant difference between those receiving remdesivir (n = 122) or standard care (n = 126) in hospital mortality , new mechanical ventilation , or new dialysis .The median duration of remdesivir administered in the intervention arm was 10  days . There were no significant differences in key outcomes between groups . Adjustm2 at baseline who received remdesivir, there was no increased risk of transaminitis or toxic kidney effects at day 5. There was also no significant difference in the need for invasive mechanical ventilation or new dialysis, or mortality. This study is limited by small numbers and baseline imbalance between groups. These findings suggest that remdesivir can be safely administered in patients with kidney dysfunction, balancing possible risks and benefits. The need for assessing kidney function in the absence of clinical suspicion before and during outpatient administration of remdesivir can be questioned.In patients with eGFR less than 30 mL/min/1.73 m