The primary goal of this research is to identify the factors of intradialytic hypertension in hemodialysis patients and stabilize blood pressure (BP) even without antihypertensive medicines. There are various treatment alternatives for lowering BP in these patients, many of which do not require extra pharmacological therapy . These parameters provide good monitoring of BP, even with previously diagnosed hypertension. The adjustment of the extracellular volume with a low incidence of intradialytic hypotensive episodes is the most plausible explanation for this outcome.We did a systematic evaluation of all published articles since 1994 to evaluate antihypertensive drug outcomes in hemodialysis patients. All articles were searched in the English language using PubMed and Google Scholar databases. The screening techniques, study selection, data extraction procedures, and risk evaluation of bias were done using specified criteria and overseen by one of the senior writers with the application of quality assessment tools to the final articles. Data were searched using regular and MeSH  keywords. Although substantial developments have emerged in the medical field, there is still a significant knowledge gap in the sector, particularly when it comes to BP guidelines and therapy choices for hypertensive hemodialysis patients. Until additional data are available, we should treat hypertension in hemodialysis with the use of active pursuit of euvolemia using dry weight probing and reduction of salt excess. In addition to removing excess fluid and filtering waste products, hemodialysis (HD) replaces some of the basic functions of healthy kidneys. Because of this filtering effect, patients on HD should use caution when taking certain medications, such as antihypertensive drugs . People It has recently been reported that intra- and post-HD hypertension are independent risk factors for mortality in hypertensive HD patients. Over the last few years, numerous studies have examined the mechanisms of intradialytic hypertension and its management. Cardiovascular (CV) risks are higher in HD patients with hypertension. The level to which BP should be reduced or when and where to measure BP in such patients is not guided by any data. More than 72 million Americans have been diagnosed with hypertension, and 13% of them have stage 3 or higher CKD . As the Pre-HD systolic blood pressure (SBP) overestimates ambulatory blood pressure monitoring (ABPM) values, according to a meta-analysis of BP assessed at different times over HD . SBP of MethodsA systematic review of all published studies since 1994 was conducted to determine the effects of antihypertensive drugs in HD patients. All studies were consulted in English through PubMed and Google Scholar. The data were retrieved with the help of regular and MeSH  keywords. Two different authors have analyzed all the retrieved studies separately by considering all the predetermined criteria. Every study has been checked according to the Assessment of Multiple Systematic Reviews (AMSTAR) quality tool.Regular and MeSH KeywordsChronic renal failure: Chronic renal failure OR kidney insufficiency OR compromised renal function OR end-stage renal disease OR .Dialysis: Dialysis OR hemodialysis OR peritoneal dialysis OR removal of waste OR kidney failure OR "renal dialysis/adverse effects"[MeSH] OR "renal dialysis/pharmacology"[MeSH] OR "renal dialysis/therapeutic use"[MeSH] OR "renal dialysis/therapy"[MeSH]).Antihypertensive drugs: Alpha blocker OR beta blocker OR ACE inhibitor OR calcium channel blocker OR .Inclusion and Exclusion CriteriaFive inclusion criteria have been implemented to collect the data: (i) past 28 years of studies conducted with emphasis on newer studies; (ii) only patients who were on HD; (iii) studies exclusively on humans; (iv) hypertensive patients; and (v) studies written in the English language. Exclusion criteria included young patients < 25 years and patients on peritoneal dialysis.Quality EvaluationWe used Newcastle-Ottawa Scale for cohort and case-control studies. The National Institutes of Health (NIH) quality evaluation tool was used to conduct a cross-sectional study. Additionally, the quality of systemic reviews/meta-analyses was evaluated by AMSTAR-2. All low-quality items were overlooked, and only medium and high-quality items were incorporated. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram giving a brief overview of our data search can be seen in Figure DiscussionThere are no BP targets defined for patients undergoing HD, but most clinicians agree that intervention is warranted in cases of high BP. Until more definitive data are available, clinicians suggest keeping HD BP in the range of 130-160 mmHg/80-100. It is not recommended that further BP decreases are undertaken at this time. Katzarski et al. , increasIt is very hard to establish a specific range for hypertension in ESRD patients. After studying all the literature, we have concluded a specific range for hypertension. In young patients, if BP is equivalent to 140/90, then they will not be considered hypertensive patients. In patients aged more than 60 years, if the BP range is more than 160/90, then they will be considered hypertensive. Everyone agrees with non-pharmacological measures before starting antihypertensive drugs . The ranSeveral mechanisms contribute to BP control including volume optimization , vasodilInfluence of hydration statusDionisio et al. have found a correlation between interdialytic ambulatory BP and hydration state. Other studies have also discovered a correlation between hydration status and intradialytic BP measurements . The intThe short HD schedules with high ultrafiltration are associated with frequent hypotensive episodes and weight gain instead of achieving the desired dry weight: the patient becomes overweight and requires higher ultrafiltration and antihypertensive medication. As an alternative to antihypertensive medication, long dialysis and slow ultrafiltration can decrease hypotensive episodes and allow the patient to maintain a normal dry weight and control their BP without taking antihypertensive medication. It appears that optimizing hydration status is the best way to improve HD patients' BP values and survival rate.Effect of volume controlHigh BP is frequent and difficult to control in the HD population, explaining the high mortality rate in this population ,17. OtheRestriction of sodiumBecause of salt and volume management, 95% of patients in Laurent's  investigSodium overload raises intracellular sodium and calcium concentrations, causing an increase in vascular smooth muscle tonicity. Sodium reduction, on the other hand, may reverse this action, resulting in a fall in BP .The idea of dialysis adequacy has evolved and has been shaped by clinical experience, according to Weiner et al. We have long moved away from focusing solely on Kt/V , and now dialysis adequacy is a multifaceted approach that includes several domains aimed at restoring internal milieu homeostasis and improving the patient experience. Restoration of extracellular volume, adequate BP management, and hemodynamic stability in HD patients remain elusive even after more than 50 years of the invention of renal replacement therapy .Dialysis patients' sodium mass balance has progressed from a clinical dry weight approach to fluid management with diagnostic equipment to a new age of direct dialysis sodium and water control utilizing modern technology and analytics. Three primary components of total body sodium have been identified, which include circulating and systemically active sodium with its osmotic action, a sodium reservoir in the bones that exchanges slowly, and a reservoir of sodium in the interstitium of skin and muscles. Through local hypertonicity and sodium clearance processes, this pool is engaged in cell and biologic functions.23NaMRI and dialytic sodium balance) to enhance patient benefits and awareness [For a focused and individualized approach, new techniques for monitoring and regulating salt and water in dialysis patients are essential. By enhancing hemodynamic stability and dialysis tolerance, emerging advanced knowledge has the potential to enhance patient outcomes. Moreover, this is an example of translational medicine in which novel discoveries (e.g. tissue sodium buildup) are translated into creative tools  and cyclic guanidine monophosphate are two biochemical indicators.ESRD is a catabolic condition that leads to nephron loss, which causes weight gain with an unexpected reduction of lean body mass over time. Extracellular volume expansion and salt retention are caused by gradual nephron loss. Weight increase occurs as a result, while lean body mass is unexpectedly reduced.Hypervolemia occurs in chronic renal disease because of a decrease in glomerular filtration rate, which results in positive sodium balance and extracellular fluid expansion. This is coupled with excessive dietary sodium and fluid intake on many occasions. There is also secretion of ouabain-like inhibitors of Na,K-ATPase, which lead to elevation of intracellular calcium, causing an increase in vascular resistance.Sympathetic controlOveractivity of the renin-angiotensin system is another reason for hypertension in dialysis patients. It arises as a result of CKD-related localized renal ischemia and scarring, which leads to increased renin release and increased systemic vascular resistance. Increased sympathetic activity, which is caused by higher levels of angiotensin 2, also contributes to higher vascular resistance and systemic BP. It is also linked to asymmetric dimethylarginine, whose function is not fully known. Uremia, higher endothelin-1, erythropoietin administration for the treatment of CKD anemia, hyperparathyroidism, and elevated pulse pressure are among the other causes of hypertension in dialysis patients. Uremia, which is caused by CKD, triggers a neural reflex that stimulates the brainstem's cardiovascular centers. As a result of reduced renal clearance, endothelin 1, a strong vasoconstrictor, is accumulated inside the body.In individuals with chronic renal failure, erythropoietin given subcutaneously to treat chronic anemia raises BP by 10 mmHg. In individuals with CKD, hyperparathyroidism is another cause of high BP. Calcification of arterial trees accelerates vascular resistance, which leads to an increase in pulse pressure, which plays a role in the pathogenesis of hypertension. Because of their ineffectiveness, diuretics are rarely used as antihypertensive medication. Antihypertensive medication is chosen based on concomitant comorbidities, patient demographics, risk profile, and lifestyle.The study characteristics of 12 studies are presented in Table Limitations and further researchThere is a drawback in this study in terms of patient selection with comorbidities. Furthermore, we have not taken into account ethnic, sex, or nutrition disparities in the population. More research is needed to determine the true etiology of hypertension and then treat it appropriately.Intradialytic hypertension is a prevalent condition in the dialysis population . This variant indicates a significant chance of mortality. However, it is unclear whether this increased risk is due to per-session intradialytic hypertension or baseline systemic hypertension as determined by ABPM, a question that needs to be addressed further in future investigations. This change is caused by volume and salt overload, endothelial dysfunction, and the reticular activating system (RAS) and sympathetic nervous system (SNS) overactivity. This is the main reason hypertensive patients who were taking antihypertensive drugs have experienced hypotension episodes during HD. The management of intradialytic hypertension and hypotension necessitates a thorough implementation of current guidelines for the management of hypertension in HD patients. Most nephrologists believe to withhold antihypertensive drugs before dialysis to avoid hypotension episodes as a certain range of hypertension is less dangerous than intradialytic hypotension. Controlling sodium and volume overload, using prolonged or frequent dialysis to alleviate excessive intradialytic RAS and SNS activation, the wise use of specific antihypertensive classes, most commonly used calcium channel blockers, alpha-blockers, ACE inhibitors, and angiotensin receptor blockers to aliskiren and minoxidil, or even renal denervation in patients truly unresponsive to multiple drug therapy and dialysis optimization are all options until more specific evidence targeting mechanistic pathways of intradialytic hypertension becomes available.


P < 0.0001; DBP, P = 0.005). However, the reduction of arterial blood pressure induced by combined treatments was not higher than that induced by the single treatment, but more prolonged. All treatments showed strong antioxidative properties. Our data show that physical activity and a diet enriched with catechins individually have an important hypotensive effect, while the association did not produce a higher hypotensive effect than the single treatment, even if it was able to decrease blood pressure for a longer time. These findings have important implications for developing a protocol to apply in novel hypertension prevention procedures.Hypertension represents the main risk factor for the onset of cardiovascular diseases. Pharmacological treatments to control hypertension have been associated with new treatments involving physical activity and/or the intake of natural components . We here report the effects produced by a combination of a natural component (catechins) and a moderate exercise program on the development of hypertension in spontaneous hypertensive rats compared with those of each individual treatment. Arterial blood pressure and heart rate were measured with a non-invasive method in 28 rats randomly assigned to four groups: rats subjected to moderate physical exercise; rats with a catechins-enriched diet; rats subjected to moderate physical exercise combined with a catechins-enriched diet; control, untreated-rats left to age. All treatments were applied for 6 weeks. The statistical analysis revealed that the three treatments significantly reduced the weekly increase in arterial blood pressure observed in control rats (SBP,  According to the World Health Organization, hypertension is responsible for at least 45% of deaths due to heart disease and 51% of deaths due to stroke2. Unfortunately, its prevalence and negative impacts on health are growing due to increased life expectancy and other behavioral risk factors, such as poor diet, excessive alcohol consumption, lack of physical activity, excess weight, and exposure to persistent stress3. The therapeutic approach is based on pharmacological treatments integrated with lifestyle changes4. These approaches are generally effective but have limitations such as their cost5 and the fact that a high percentage of the patients does not follow the prescribed therapy or is drug intolerant7. For this reason, numerous attempts have been made to develop alternative procedures beyond pharmacological treatments and diet, which can stably reduce blood pressure8. In particular, it has been observed that the habit of performing a moderate but constant physical activity is associated with a lower incidence of hypertension and is also effective in reducing blood pressure values in hypertensive subjects10. A regular physical activity is also known to improve not only blood pressure values, but also other cardiovascular functions such as heart rate12 and peripheral vascular resistance14. Furthermore, exercise acts on reducing the effects on the sympathetic nervous system16 and contributes to decreasing the activity of the renin-angiotensin system17.High blood pressure represents the greatest risk factor for the onset of cardiovascular diseases19 whose dysfunction is often associated with an increased blood pressure22. Several studies have observed that such dysfunctions are due to an oxidative stress deriving from a reduction of nitric oxide production by endothelial cells24. Furthermore, studies performed in humans and experimental animals have highlighted that oxidative stress is a frequent feature in hypertensive subjects27.It has also been shown that physical activity improves the vascular endothelial functions28. A number of such antioxidants are found in fruits, vegetables, green tea, coffee, and chocolate and have been observed to have positive effects on the metabolic syndrome, the cardiovascular system, and blood pressure33. Attention has particularly focused on a special group of antioxidants, the catechins, that are molecules belonging to the category of flavonoids contained especially in teas34. Catechins constitute about 80–90% of total flavonoids in green tea, while they represent only 20–30% of total flavonoids in black tea35. Catechins administration has been shown to prevent the development of hypertension in the well-known animal model of spontaneously hypertensive rats (SHRs)37.Consequently, it has been proposed that antioxidant molecules can help in managing blood pressure and in treating hypertensionThe aim of the present work was to evaluate the effects of the combination of a catechins-enriched diet and a moderate exercise program on the development of hypertension in SHRs and to compare them with the action of each individually administered treatment.Male SHRs  were used. The animals arrived in our lab at the age of 4 weeks, when they were in normotensive conditions. Three days after their arrival in the housing, systolic, diastolic blood pressure (SBP and DBP respectively) and heart rate (HR) were measured Table . In housStarting from the 6th week of age, the animals were randomly assigned to four groups: (i) rats subjected to moderate physical exercise for 6 weeks , (ii) rats with a catechins-enriched diet for 6 weeks (n = 7), (iii) rats subjected to moderate physical exercise associated with a catechins-enriched diet for 6 weeks  and (iv) rats left to age without any treatment for 6 weeks .Malus pumila Miller cv. Annurca harvested less than 3 months, an apple extremely rich in different phenolic compounds such as catechins (117.6 mg/Kg of fresh weight), epicatechin, a catechin with -configuration (62.2 mg/Kg of fresh weight), and chlorogenic acid (130.9 mg/Kg of fresh weight)38, and with a stronger antioxidant activity than other varieties of apples39. The extract was produced according to the method of Napolitano et al.38 at the University of Naples and kindly provided to us. In our laboratory, the extract was stored at 4 °C, wrapped in aluminum foil to protect it from light and diluted daily in the water drunk by the animals. The extract was administered at the final concentration of 30 mg/kg b.w. and its administration began 2 days earlier than the start of the training protocol and ended on the day of the last training session. This extract concentration was tested through pilot experiments where we tried different dosages 20, 25, 30 and 35 mg/kg b.w. to test the antioxidative effect  These tests indicated that dosages below 30 mg/kg b.w. were not effective, while higher dosages did not increase the protection obtained with the dose of 30 mg/kg b.w., that was therefore chosen for our experiments.The catechins-enriched diet consisted of the administration of an extract of Throughout the treatment, the amount of water taken in by each rat was evaluated and all animals treated with a catechin-enriched diet ingested a comparable amount of water (about 25 ml/day).The animals were handled in accordance with the ARRIVE guidelines for the safety and use of laboratory animals (NIH publication no. 68-23 reviewed in 1985).The experimental protocol was approved by the Local University Ethics Committee and the Italian Ministry of Health (authorization no. 156/2017-PR).All methods were performed in accordance with the relevant guidelines and regulations.40.Starting from the 6th week of life, SHRs subjected to moderate intensity exercise were trained for 3 sessions a week on alternate days for 6 weeks, for a total of 18 sessions Table . In eachThe apparatus consisted of a plastic wheel (diameter 42 cm), closed at the rear and perforated along the entire external surface, so that air and light penetrated inside. At the front, the wheel was closed with a transparent plexiglass panel of the same diameter, which delimited a corridor along which the animal was forced to walk, following the clockwise or anticlockwise rotational movement of the wheel.In each session, the animal was taken from the breeding room to the training room, allowed to acclimatize for 10–15 min, and then collected manually from the housing cage and placed inside the training apparatus , the rotation speed , the rotation time (min), and to measure the space travelled (m) in real time.The acquired data were stored in order to be analyzed off-line.Before starting the training program, each rat was subjected to a short period of adaptation to the apparatus: it was left free to explore and move inside the wheel, without any connection to the software for about 15 min, then the wheel was moved slowly (4–5 m/min) to allow the rat to coordinate its gait with the rotation speed of the apparatus and establish the direction of rotation of the wheel preferred by the animal. When the rat was able to follow the movement of the wheel, walking continuously for at least 15 min, the training program began.All training sessions took place between 9:00 and 15:00, to reduce circadian influences and lasted 30 min . Every week the wheel speed was gradually and steadily increased for all the rats from the initial speed of 5 m/min until they reached 16 m/min at the end of the 18th session.The training program was structured as reported in Table At the end of each training session, the animal was manually placed in its housing cage and brought back to the animal housing until the next session.Figure 41. Measurements took place once a week  were measured using a Mouse and Rat Tail Cuff Method Blood Pressure Systems , which permits the blood pressure to be recorded through a photo-sensor positioned in a cuff that surrounds the animal’s tail. The rats were introduced in a plexiglass tube so that it was maintained in a prone position with the tail inserted in a cuff with the pressure sensor. This was connected to a compressed air cylinder through an arrangement of inlet and outlet valves, so as to allow the cuff to inflate and deflate at a constant speed. The tail blood pressure was continuously recorded by the pressure sensor and frequency and pressure signals were digitized on a desktop computer where they were recordedek Table , and fou42In addition, to estimate the myocardial workload we have calculated the rate pressure product (RPP), defined as the product of heart rate (HR) and systolic blood pressure (SBP) and expressed as RPP = SBP × HR/100043 utilizing DCFH-DA, a fluorescent hydrogen peroxide sensitive dye, that allows the measurement of intracellular oxidative species such as H2O2 in the rat cortex neurons. This probe is hydrolyzed inside the cell to DCFH carboxylate that remains trapped in the cell. The oxidation of DCFH leads to the formation of a fluorescent product, 2′-7′-dichlorofluorescein (DCF), that can be monitored with fluorescence microscopy. The fluorescence intensity of DCF is correlated directly to the intracellular reactive ROS level that we evaluated by an appropriate filter (522 nm) and quantified by normalized grey levels) (NGL)44. We decided to measure ROS in the brain where we usually evaluate oxidative stress, as hypertension causes serious damages to the brain and the technique we developed is particularly useful in this body district. For experimental convenience, we studied the ROS formation at the level of the pial surface in the parietal area through a closed cranial window whose preparation has been previously described45. Local administrations of DCFH-DA was performed mixing the drug with artificial cerebrospinal fluid to obtain a concentration of 250 mM43. The solution was superfused over the pial surface for 30 min and 5 and 15 min after we detected ROS formation. The measurements were carried out in anesthetized animals with an intraperitoneal injection of α-chloralose (60 mg/kg b.w.).The presence of ROS was detected 4 days after the end of each treatment and in rats just arrived in our housing (young rats) in order to assess the antioxidative properties of each treatment. The content of ROS has been evaluated by using an in vivo fluorometric technique introduced by Watanabe in 1998Data were expressed as means ± SEM. Since the data collected were normally distributed according to the Kolmogrov-Smirnov method, the comparisons were performed with parametric tests. One way ANOVA was done to compare ROS formation among the different groups considered.Two-way ANOVA for repeated measures was used to compare the distances travelled by the trained rats, SBP, DBP, HR and RPP data within each group and among the different groups, considering the time and treatment factors and the interaction "time by treatment". Post hoc tests were performed to analyse the significant differences among the groups at each time considered, using the Tukey’s multiple comparisons test.These analyses were conducted using GraphPad Prism 7.0 software (Software Inc. San Diego CA).We also evaluated the rate of variation in blood pressure during the 6 weeks of treatment and 4 days after the end of each treatment by calculating the difference in SBP and DBP with respect to the values measured at the rat’s arrival in our lab . With SPSS 21.0 package a contrast analysis was done and multiple comparisons were carried out with Bonferroni test.P < 0.05.Statistical significance was set at P < 0.001 vs. adult SHRs). Training or catechin-enriched diet or the combined treatment with training and catechin-enriched diet preserved the pial microvasculature by ROS formation. In all three experimental groups subjected to treatment ROS formation was 0.02 ± 0.002 NGL   showed ROS formation (0.07 ± 0.001 NGL) while in young SHRs (i.e. SHRs just arrived in our lab) ROS formation was significantly much lower  Fig. .Figure 33,18 = 692.4, P < 0.0001; for DBP:F3,18 = 383.7, P = 0.005), the time factor (weeks)  and the interaction between these two factors .A two-way ANOVA for repeated measures was performed by considering the treatment factor  with respect to controls, including the measurements taken 4 days after the end of treatment, when a statistically significant difference for SBP and DBP was still observed (P < 0.0001). In the control group, blood pressure increased by 118 ± 1.87 mmHg for SBP and 116.25 ± 4.18 mmHg for DBP from the age of 4 weeks  to 11 weeks, while in training rats this difference was reduced to 63.8 ± 1.16 mmHg for SBP and 65 ± 4.78 mmHg for DBP in the same period  and DBP (P < 0.0001) values as early as the first week of catechin administration and throughout the observation period (46 days). A statistically significant reduction in the measurements performed 4 days after the end of treatment was observed for SBP (P < 0.0001), but not for DBP . In the measurements recorded 4 days after the end of treatment, the SBP and DBP values of training + catechins-enriched diet rats were significantly lower than in the control group (P < 0.001 or lower)  Figs. .In training + catechins-enriched diet rats the arterial blood pressure increased from the values recorded in the normotensive condition up to the end of the sixth week of treatment by 80.9 ± 10.86 mmHg for SBP and 90.4 ± 4.05 mmHg for DBP (Tables P < 0.001) as was the case for the catechins-enriched diet group (P < 0.001). However, SBP and DBP in the training + catechins-enriched diet group did not show any significant difference with respect to the values measured soon after the end of the treatment .We performed the Tukey’s multiple comparison test among the different times considered within each experimental group. In particular, we analyzed the blood pressure values between the sixth week of treatment and four days after its end Figs. ,5. In th18,144 = 46.703, Eta-squared = 0.898, α = 1.00, P < 0.001) and DBP  and the Bonferroni post-hoc test highlighted significant differences as shown in Tables In order to compare the increase in SBP and DBP in the SHRs undergoing the different treatments, we performed a contrast analysis of the differences in the values of SBP and DBP recorded at the various times considered with respect to basal values  and a significant trend for RPP to reduce during the six weeks . Multiple comparisons are shown in Fig. Finally, the different treatments were found to have an effect on myocardial workload, estimated through rate pressure product . Vascular resistance can also be modified by locally released molecules from the endothelium, like nitric oxide that induces vasodilation. Several studies have highlighted that in hypertensive subjects the function of the endothelium is altered53 and that moderate physical exercise has a beneficial effect by increasing endothelial nitric-oxide synthase, improving the endothelial function and inducing vasodilation56.Our data show that physical activity reduces the increase in arterial blood pressure that is normally observed in SHRs starting from the fourth week of life. The treatment modifies the weekly increase in arterial blood pressure values over time, as shown by the differences from baseline values during the six weeks of treatment , had a different effect, causing a reduction in individual arterial blood pressure values shown by treated SHRs over the weeks with respect to controls, without however modifying the rate of increase in blood pressure. These treatments determined, as early as the first week, a hypotensive effect compared to controls Figs. ,5, whichBy comparing the trend of pressure changes over the weeks of treatment it is clear that training slowed down the increase in arterial blood pressure. Treatment with catechins did not modify the rate of the blood pressure increase, but it induced an initial reduction of arterial blood pressure values that was maintained over time, that resulted in lower blood pressure levels over the weeks with respect to controls.61. Our findings additionally show that the association between physical exercise and catechins-enriched diet does not potentiate the hypotensive effect, which turned out to be similar to that induced by the single administration of catechins or by training. As shown in Figs. 62. Our rats were subjected to increasing levels of physical activity (Table 64. It has even been suggested that high doses of antioxidants have adverse effects on the performance of athletes, outweighing their potential beneficial effects65. In our case, the combined effect of catechins and an intense physical activity actually worsened the response to the physiological increase of SHR arterial blood pressure and may additionally explain why training alone had in some case a better effect than its combination with catechins.These results suggest that physical exercise constantly modulates the blood pressure regulation centres, not only by preventing the spontaneous tendency of SHRs to increase blood pressure over time, but also by modifying the rate of such an increase. This can be explained by an effect produced by physical activity on the neuronal centres that regulate blood pressure. Differently, the diet enriched with catechins can have an administration-dependent effect, as catechins decrease blood pressure values when are administered, reducing the oxidative stress that is recognized to be involved in many physiological conditions, including physical activityHowever, the combination of training + catechins-enriched diet did have a hypotensive effect with respect to controls, that lasted until the end of our observation period. In fact, four days after the end of the administration a significant increase in blood pressure was measured in trained rats and in those with a catechins-enriched diet rats, while the blood pressure of rats subjected to the combined treatments was not significantly different. The reduction in DBP and SBP observed in control rats 4 weeks after the end of the treatment Fig. , is puzz66. These side effects of physical activity can be mitigated by the simultaneous administration of antioxidants like catechins, so that the hypotensive effect of physical activity could be prolonged, as is the case of our training + catechins-enriched diet group.In conclusion, our results show that catechins-enriched diet produces hypotensive effects on the arterial blood pressure only during the administration period, in a manner similar to that of moderate physical activity. However, in the group only subjected to training, the beneficial effects on blood pressure tended to decline over time, probably because of the oxidative stress induced by physical exercise, which mitigate the benefits on the cardiovascular systemSupplementary Information.


Sternal wound infection (SWI) post cardiac surgery remains an important cause of extra morbidity, mortality and cost. The objective was to identify risk factors for SWI in a cardiac centre in Eastern Saudi Arabia as part of the investigation into Surveillance variance in the local rates of SWI.We included cases and controls from a cross section of patients who underwent major cardiac surgery between 2017 and 2020 matched for age, sex and time of surgery. An explanatory logistic regression model was fitted to estimate the risk factors.N = 204 . factors significantly associated with SWI in the final multivariate model: hospital stay OR , Graft Conduit BIMA versus No Graft OR , transfusion of both packed cells plus other blood products versus no transfusion OR , HbA1c OR (1.09 Cl 0.84–1.41), BMI OR , perioperative blood glucose OR , surgery time OR .The diverse aetiology, cross-disciplinary nature of SWI prevention, and despite improved prevention and control practices, including related care bundles with their proven value, SWI remain a serious challenge in cardiac surgery. Multidisciplinary consensus guidelines are well overdue. Sternal wound infection following cardiac surgery is a relatively rare but serious complication associated with increased morbidity, mortality and cost , 2. TherThe reported incidence of SWI varies widely 2–10%), with a low incidence in studies of deep SWI excluding superficial and donor site infections. Variation in incidence is probably due to the various case definitions, classifications, geographical locations, hospital settings, duration of follow-up and time of publication –7. In Sa%, with aPublished predictors of SWI encompassed all stages of surgical care: preoperative, intraoperative and postoperative. This includes risk factors such as pre-morbidities, elective versus urgent procedures, standard of operation room aseptic and surgical techniques, type of CABG graft conduit, and environment of both operation and recovery rooms. The postoperative course, need for reoperation and blood transfusion, length of intensive care stay and duration of mechanical ventilation were recorded. Additionally, as most SWI cases are diagnosed after discharge from the hospital, the quality of home and outpatient wound care is a reported predictor , 12. TheS. aureus, and systematic decontamination when time or other reasons preclude screening. S. aureus should be treated with nasal mupirocin and chlorhexidine for the skin [Recently, Emilo Bouza and associates published a multidisciplinary consensus guideline that included the following proven intervention to reduce SWI: glycaemic control, smoking cessation, weight reduction, incision site preparation with depilatory cream or electric razor to remove the hair and chlorhexidine rather than povidone-based products, screening and eradication of the skin .Modern infection prevention and control practices, including care bundles, have reduced the rates of SWI, but their implementation and enforcement is an ongoing challenge. Despite the abovementioned consensus preventive interventions, we noted variance in our rates of SWI, and the process was out of control in the SWI control chart. Following the implementation of several quality improvement projects, we conducted this focused study to further examine the local risk factors, quantify their relative impact and prioritize them accordingly.Our objective was to identify possible preventive interventions and to evaluate the effectiveness of the current interventions in reducing the incidence of SWI. The prespecified hypothesis was that a range of specific preoperative and environmental factors would explain the incidence of SWI in our setting. It is generally accepted that SWI rates above 2% are an indication of inadequate surgical practice. This is particularly important in deep sternal wound infections (mediastinitis) given their high mortality rate of 10–40%. The heralding era of value-based purchasing and potential non-reimbursement of SWI, which has already happened elsewhere, will add to the provider’s costs associated with long hospital stays and complex therapy .We used a matched case–control design to compare the exposure of patients who underwent major cardiac surgery to a range of risk factors, chosen based on hypothesis, and who went on to develop SWI (cases) with those from the same source population who did not (controls). The source population is an open cohort of patients who underwent cardiac surgery during the defined time period 2017–2020.The matching ratio was 1:3, and cases were matched to control for unmeasured confounders. Explanatory covariates included a range of preoperative, intraoperative and postoperative risk factors, which were chosen from root cause analysis, brain storming and published literature of known predictors of SWI. Institutional approval to conduct the study was obtained. The Saud Al-Babtain Cardiac Centre has served the Eastern Province of Saudi Arabia and neighbouring areas since 2001 with a total capacity of 64 beds, and it is located within the 500 bed Dammam Medical Complex.1 January 2017 and 31 December 2020 were recruited as the source population. Both exposure and outcome data were available at the time of data collection. We had no comorbid or gender restrictions. Exclusion criteria: age < 18 years, isolated pericardial surgery, short procedure, and cardiac surgery without full median sternotomy.The Cardiac Surgery database (Dendrite version 1.7) was interrogated in November 2021, and all patients who underwent major cardiac surgery, including CABG, valve replacement, and repairs of all kinds , between Cases of SWI between 2017 and 2020 were ascertained through the Health Care Associated Infection Surveillance records. The cases were diagnosed according to the CDC/NHSN case definition, which includes total SWI: superficial and deep infections. The controls were selected from the same source population. Hospital-based controls were deemed appropriate and convenient, as they best represent the catchment population of the hospital, and the collection of exposure variables would be more convenient. The case definition is robust, and the collection of variables from hospital records reduced the likelihood of measurement and recall bias.We initially planned to select 4 controls who did not develop SWI after their cardiac surgery for every case who did. This ratio and the matching were chosen to maximize the power and efficiency of detecting the effect estimates of the exposure covariates’ odds ratio. Additionally, matching allowed control of unmeasured confounders and convenient sampling of the controls. However, we obtained only randomly selected controls to cases at a ratio of 3:1 because of the lack of enough matched female controls in our study population. Independent of exposure, we selected and individually matched controls for sex, age and time of surgery. Gender was randomly matched first, then age ± 2 years, and finally time of surgery ± 2 years , 15.The outcome variable was binary, with the case of SWI or control coded as indicator variables one and zero, respectively. Our candidate explanatory variables included 23 covariates, both continuous and categorical. Some are derived variables from the raw data. In addition, we scaled some continuous variables to clinically relevant groups. Additionally, we added two design variables, strata and time, to allow conditional logistic regression analysis. The continuous variables were age, inpatient days, HbA1c, weight, BMI, EuroSCORE II, perioperative blood glucose, haemoglobin, white cell count and surgery time. The categorical variables included sex, mortality, procedure, graft conduit, diabetes, smoking, pre-morbidity, antibiotic prophylaxis, infection control supply status, enrolment in an ongoing antibiotic prophylaxis study, environmental issues in the operating room, surgeon ID code, blood transfusion, and re-exploration.The sources and measurements of our variables included the dendrite database, where data were retrieved directly from medical and laboratory records, and infection control surveillance records were obtained separately. There are dedicated personnel who enter clinical and laboratory data into the database. Laboratory data were obtained from a single inhouse laboratory, observing the CLSI standards, which did not change its methods within the study period. Additionally, the infection control staff is well trained in surveillance methods and uses a robust inpatient and outpatient surveillance system based on the NHSN case definition. There were no differences between cases and controls in the way of measuring the outcome and exposure variables. Potential confounders included HA1c, weight, BMI, pre-morbidities, blood transfusion and re-exploration. The anticipated effect modifiers were age and sex.Cases of SWI were ascertained within the continuous surveillance system for hospital-acquired infections using internationally recognized methods and documentation guidance (NHSN/CDC), the case is defined as SWI related to surgery within 30–90 days from the operation, and include superficial, subcutaneous, and organ space infections. The latter uses both clinical and microbiological criteria to confirm the diagnosis and is concurrent during hospital stay with outpatient follow-up. This makes misclassification unlikely. Additionally, the exposure variables consist of clinical and laboratory data documented in the participants’ medical records and hence are not subject to recall bias. Furthermore, we chose cases and controls completely independent of exposure. In addition, the design of our study and source of variables did not have issues of potential participation and non-participation, as we had no questionnaires and, of course, we had no follow up-related potential sources of bias in this case–control design. Therefore, overall, the potential for selection and misclassification bias is small. Thus, we assume that neither the external nor infernal validity of our study is likely to be compromised.The sample size was determined by the number of cases during the study period. There were 51 cases and 153 matched controls, which made our total study size 204. Additionally, we entered this sample number into the CDC EpiInfo sample size calculator. It calculated a detection ability of an OR difference of 2.60 for population exposure of 20% and 6.06 for exposure of 2% at 80% power and 5% alpha.Statistical Analysis Software (SAS)–version 9.4 was used to analyze all the data after importation from the final Excel workbook, where they were stored after collection from the sources. We used the t-test, ChiSq-test and conditional logistic regression to compare patients with SWI and their matched controls for selected perioperative risk factors.We visualized, cleaned, corrected, recoded, scaled, and filled-in missing values by multiple imputation, as data were assumed to be missing at random (MAR). After initially filling in missing values by reviewing the sources, the remaining missing values were HbA1c  and surgery time . No missing outcome variables. Multiple imputation was used due to the relatively large missing values. Sensitivity testing with incomplete data, single imputation, and full information maximum likelihood (FIML) was used for comparison.Then, we obtained descriptive statistics and a correlation matrix and compared the distribution of covariates between cases and controls. Finally, we fitted several univariate and a final multivariate logistic regression model. We used conditional analysis in all models.Descriptive statistics included summaries and plots of all the exposure variables using univariate and frequency procedures for continuous and categorical variables, respectively. Additionally, differences in exposure between cases and controls were compared with t-tests and Chi-sq tests. Furthermore, a correlation matrix was obtained to detect any potential colinear variables, cut-off (r =  > 0.7).p values < 0.10 were selected to progress to the final multivariate logistic model. We entered all determinant variables individually into 3 blocks. Confounding and interactions were identified. The total number of covariates was 23, and the final complete multivariate model included 12 significant covariates with p < 0.5 from univariate analysis, including confounders. Two colinear variables were removed. Model diagnostics were used to assess and compare the models and their goodness of fit (GOF).Univariate analysis yielded variables associated with SWI, and those with Among 985 eligible patients who underwent major cardiac surgery with median sternotomy, two were excluded because of age under 18 years. There were 51 cases of SWI, no exclusive donor site infection, and 153 randomly selected matched controls from the remaining 932 patients who met the inclusion criteria. Thus, the total sample size was 204 patients. The distribution of missing data was stable among groups, and the maximum was 16% and 19% in the HbA1c variable among cases and controls, respectively, while the surgery time missing values were identical in each group at 12%. The clinical and demographic characteristics of the participants are summarized in Table p values < 0.10 and unadjusted estimates, are shown in Table We initially considered the following variables: preoperative and total inpatient days, mortality status, surgical procedure, graft conduit, diabetes status, HbA1c, BMI, blood glucose within 24 h of surgery, weight, smoker status, premorbid status, EuroSCORE-II, participation in an ongoing antibiotic prophylaxis study, shortage of chlorhexidine gluconate skin prep (CHG), operating room (OR) environmental issues, surgeon ID, Hb, WBC, blood transfusion, re-exploration, and duration of surgery. The variables associated with SWI in univariate analysis, with p value > 0.10. The procedure and operating room environment were excluded because of collinearity with the graft conduit and the shortage of CHG, respectively.Eight variables were removed at this stage: preoperative hospital days, mortality status, smoking status, surgeon ID, Hb and WBC, all with a In Table /M2 and < 30 kg/M2, EuroSCORE < 2, > 2 < 6 and > 6 were entered in the model. They did not reveal more information than their respective scale forms except BMI > 30 kg/M2.Scaled continuous variables along clinically relevant groups: HbA1c percentage < 6 > 6 < 10 and > 10%, BMI > 30 kgWe included the following confounders in the final model: weight is a confounder of BMI, blood transfusion confounded re-exploration, all at > 10% change of the regression coefficient size compared to the univariate values. Additionally, the matching variables age and gender significantly modified the effects of graft and procedure variables.Eighty-five microbiology samples obtained from SWI cases revealed skin commensal 44/52%), gut bacteria and Pseudomonas aeruginosa (28/33%), and no growth in (13/15%). Commensals were mainly Staphylococcus species, including a few cases of MRSA, while gut bacteria were mainly Klebsiella pneumoniae, Escherichia Choli and Pseudomonas aeruginosa, as detailed in Table 4/52%, gup value of < 0.26. Additionally, Cox & Snell and Nagelkerke GOF R square were 0.28 and 0.41, respectively. All suggest that our final logistic model is a good fit for the data. In addition, the overall classifying accuracy of the model is good, with an ROC of 84%.The Hosmer and Lemeshaw test was insignificant at a As the missing values were relatively high for HbA1c  and Operation time  variables and distributed between cases and controls, 16% and 20% for HbA1c and 12% each for operation time, respectively. Nonetheless, we obtained 2 models using single, mean/median imputed data sets and FIML analyses. All produced comparable models to our final model shown in Table Our study revealed that inpatient days, graft conduit, HbA1c, weight, BMI, EuroSCORE II score, perioperative blood glucose, blood transfusion, re-exploration and surgery time are associated with developing SWI.Our results are consistent with previously published data. Despite implementation of the surgical wound infection prevention bundle, modifiable risk factors were still identified as predictors in our model. For example, perioperative blood glucose predicted SWI despite being within the recommended range of 140–180 mg/dl (mean 174.7 mg/dl in SWI cases and 155.7 mg/dl in controls), which suggests that tighter control, rather than moderate, is required in selected patient groups than recommended for the perioperative level by authoritative guidelines. In addition, innovative multidisciplinary implementation of proven intervention is required. , 17, 18Risk factors not reaching statistical significance, which were previously consistently reported in the literature as predictors, were most likely not identified because of the underpower of our study and/or bias towards the null due to matching with 3 variables. These include duration of preoperative admission, smoker and diabetes status, and premorbid conditions. In addition, we chose 3 variables: shortage of CHG skin prep products, participation of an ongoing surgical antibiotic prophylaxis, and presence of operation room pressure, temperature and/or humidity concerns around the time of surgery (within 72 h), all of which did not predict SWI in the final model. An exploratory analysis using an unsplit imputation data set (not shown) revealed that all these factors were significant except smoking and operation room environmental issues with a larger sample size.Pathogens isolated in SWI were in line with previously published data from Saudi Arabia and elsewhere, and the prevalence of multidrug resistant organisms was small .p < 0.000, but the 95% CI was too wide. Our study is an addition to the few published studies on determinants of SWI in the MENA region and is likely to be generalizable.The strength of this study is evaluating 23 potential risk factors of SWI in a good fit logistic regression model. Twelve were associated with SWI in univariate regression analysis, and 8 remained significant or trending in the final model. This is similar to the risk factors published in Western European countries. In addition, shortages in CHG skin prep supplies, and hence use of Bovidone-based alternatives during the COVID-19 pandemic, were associated with a 16-fold increase in SWI (OR 17.73), McNamar’s test Weaknesses of this work include the relatively small sample size (determined by the study period needed). The low sensitivity of the OR environment and CHG shortage variables, as they are not strictly individual-level variables, did not show significant effects. Additionally, we did not study important predictors of SWI due to nonavailability, which is generally less studied. The latter include variation in operative techniques, hemostasis materials, diathermy use and postdischarge home wound care. These are likely to be sources of residual confounding.Practically, this study helped to inform an ongoing quality improvement project in our setting by prioritizing the tacking of certain risk factors. Additionally, we highlighted the need for improved perioperative glycemic control, review selection for bilateral internal memory grafts and rationalize blood transfusion, all recognized causes of delayed sternal healing and risk of SWI. Some centers have established dedicated teams and multidisciplinary protocols to supervise perioperative glycemic control. This should, however, be individualized and not impact critically ill patients who would suffer more from hypoglycemia, as shown in the NICE-SUGAR study . HoweverIn conclusion, the advent of value-based contracting and nonremuneration of surgical wound infections should focus healthcare providers’ minds on the reduction of SWI and hence the need for more robust multidisciplinary research and evidence-based prevention efforts, specially on the poorly studied potential risks mentioned above. Our study suggested that the implementation of preventive interventions for SWI need to be improved.


Background: Currently, following the new advances in cancer treatments and the increasing prevalence of kidney disease in the population, more kidney biopsies are being performed. The aim of our study is to analyze clinical and histological characteristics of patients with active solid organ malignancy who underwent kidney biopsy. This is a multi-center collaborative retrospective study supported by groups GLOSEN/Onconephrology from the Spanish Society of Nephrology. Clinical, demographical and histological data were collected. Results: A total of 148 patients with cancer who underwent a kidney biopsy from 12 hospitals were included. 64.3% men and mean age of 66.9 years old. The indications for biopsy were acute renal injury (67.1%), proteinuria (17.1%), exacerbated chronic kidney disease (8.2%), and chronic kidney disease (7.5%). Most frequent malignances were lung (29.1%) and abdominal (25%), with 49.7% metastatic cancer. As oncospecific treatment, 28% received chemotherapy, 29.3% immunotherapy, 19.3% specific therapies, and 2.1% conservative treatment. At the time of kidney biopsy, median creatinine was of 2.58 mg/dL [1.81–4.1 (IQ 25–75)], median urine protein-to-creatinine ratio of 700 mg/g [256–2463 (IQ 25–75)] and 53.1% presented hematuria. The most frequent renal biopsy diagnoses were: acute interstitial nephritis (39.9%), acute tubular necrosis (8.8%), IgA nephropathy (7.4%) and membranous nephropathy (6.1%). Median follow-up was 15.2 months [5.7–31.4 (IQ 25–75)]. Conclusions: There is a new trend in kidney disease and cancer patients in terms of diagnosis and treatment. Acute interstitial nephritis has established itself as the most common kidney injury in patients with cancer who underwent a kidney biopsy. Renal biopsy is a valuable tool for diagnosis, treatment, and prognosis of solid organ cancer patients with kidney damage. The relationship between cancer and kidney disease is bidirectional, which increases mortality and morbidity in a pool of high complexity patients . RecentlAt a onconephrology clinic, nephrologists must usually answer the question about the etiology of the renal event in the patient with cancer. The cancer itself could be responsible for the renal disease. However, the oncospecific treatment could also be related to the kidney injury. Furthermore, sometimes, the nephrologist, depending on the renal diagnostic suspicion, should recommend the discontinuation (or not) of the oncologic drugs.A total of 15–17% of patients who are treated with checkpoint inhibitors develop acute kidney injury ,7, mainlThe recommendations for kidney biopsy in patients with cancer have been recently updated . CurrentCollecting retrospective data on histologic patterns and clinical evolution of patients with cancer who underwent kidney biopsy could help the nephrology community to understand the change in kidney damage linked to the transformation of oncology that is happening nowadays . The aimWe conducted a retrospective multicenter observational study of patients with solid organ neoplasia who underwent a renal biopsy of the native kidney in Spain between January 2010 and March 2021. Patients were followed up until May 2021. All of the patients older than 18 years old who underwent a kidney biopsy while presenting a solid organ malignancy were eligible except those with a previous kidney transplant. Biopsies performed the year before the diagnosis of neoplasia were included. We included patients from nephrology departments belonging to the Spanish Glomerular Study Group and/or Spanish Onconephrology Study Group. The Ethical Committee of Vall d’Hebron University Hospital approved the study protocol (PR(AG)260/2019).Clinical and laboratory data were evaluated at the time of kidney biopsy. Demographic and clinical data, including age, sex, ethnicity, high blood pressure, diabetes mellitus, cardiovascular disease, and regular chronic medications, were collected. Oncological disease characteristics were also recorded, as well as laboratory parameters. Baseline creatinine was defined as the last measurement before the renal event that motivated the biopsy. AKI was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria .p-value < 0.05 was considered statistically significant.The data were analyzed using IBM SPSS Statistics Version 25.0. IBM Corp., Armonk, NY, USA. The Kolmogorov–Smirnov test was applied to determine whether quantitative variables were normally distributed. The results were expressed as frequencies for categorical variables and as mean ± standard deviation (SD), or median and interquartile range (IQR), for continuous variables. The comparison of continuous variables between two groups was performed by either a Student’s T or Mann–Whitney U, depending on the distribution of the variable. A Cox survival analysis adjusted for clinical conditions was performed to identify risk factors associated with mortality. A two-sided A total of 148 patients from 12 Spanish hospitals were included in the study ] as shown in 2 glomerular filtration rate) and the median urine protein/creatinine ratio was 700 mg/g, while 23% of patients presented with nephrotic-range proteinuria. Furthermore, 53.1% presented hematuria, 10.8% eosinophiluria, and 6.8% hemolytic anemia and/or low platelet count. Autoimmunity workup revealed that 6.8% of patients presented positivity for antineutrophil cytoplasmic antibodies and 10.1% showed decreased serum levels of C3 and/or C4; these data are summarized in Briefly, the most frequently used therapies were chemotherapy (28%), immunotherapy (29.3%), and specific targeted therapies (19.3%). Overall, 54 patients included were treated with checkpoint inhibitors (CPI), and in 22.3% of them, two CPI drugs were administered. At the time of kidney biopsy, median creatinine was 2.58 mg/dL  ]. The diagnosis of renal disease preceded the diagnosis of neoplasia in only six patients. The most frequent kidney histological diagnosis was acute interstitial nephritis (AIN) (39.9%), followed by acute tubular necrosis (8.8%), IgA nephropathy (7.4%), membranous nephropathy (6.1%), and thrombotic microangiopathy (5.4%) . Acute i= 0.001) .The nephrologist’s opinion about the etiology of the renal event was recorded. According to this, 56% of the diagnoses were secondary to the antineoplastic treatment that the patients were receiving at the time of the kidney biopsy. The most frequently responsible drugs were: immunotherapy (CTLA4 + PD1/PD1/PD-L1), MEK/B RAF inhibitor, and tyrosine kinase inhibitor in patients who developed biopsy-proven AIN. Acute tubular necrosis was related to oxaliplatin, alectinib, and capecitabine, while VEGF  was responsible for thrombotic microangiopathy.A total of 13% of the renal events were secondary to the cancer itself, highlighting several cases: dominant IgA post-infectious glomerulonephritis after abscess secondary to resection of pulmonary metastasis, membranous nephropathy in the case of bladder and anal epidermoid neoplasia, amyloidosis in intestinal cancer, as well as diverse extracapillary glomerulonephritis and thrombotic microangiopathy secondary to gastrointestinal cancer.Finally, in 31% of patients, kidney pathology was not related to cancer or its treatment. .n = 39) was secondary to treatment with immunotherapy, and the remaining 34% (n = 20) was mainly due to antibiotics and other anticancer drugs, as detailed in There were 59 patients diagnosed with AIN: 66%  relapsed at a median time of 3.6 months ([2.4–5.2 (IQ 25–75)]. In more than half (n = 6), the recurrence occurred within the corticosteroid withdrawal, and in two cases, the relapse was related to CPI re-start despite steroids.After kidney biopsy, 104 patients out of the 148 were specifically treated according to the renal diagnosis. A total of 59 (100%) patients with acute interstitial nephritis were treated with steroids; 21 (35.6%) of them received intravenous methylprednisolone pulses. In two cases, mycophenolate mofetil was also administered. The median duration of steroids treatment was 3.7 [1.8–9.3 (IQ 25–75)] months. The subanalysis of the 52 cases of AIN secondary to oncological treatment evidenced that 21%  and the other with anti-PD1. In the first case, the patient received treatment with empirical corticosteroids until the result of the kidney biopsy, which was withdrawn with subsequent complete remission. In the second case, immunotherapy (nivolumab) was removed, and the patient was treated for one month with corticosteroids at 0.5 mg/kg/day, and complete remission was achieved. The other seven patients were: four antiPLAR positive, one antiPLAR negative, and two unknown. In primary membranous nephropathy, the treatment administered in three cases was rituximab. , Table 6n = 2), steroid (n = 1) and plasmapheresis (n = 1). Two of those required temporary dialysis despite the treatment. The renal damage was associated with gemcitabine in two patients and anti-VEGF in the rest.Half of the patients with thrombotic microangiopathy (8) received immunosuppressive treatments: eculizumab (n = 8) were treated with corticosteroids; four of them were treated with cyclophosphamide and three with rituximab.All patients with extracapillary glomerulonephritis . Median creatinine at the end of the follow-up was 1.4 mg/dL [1.03–2.15 (IQ 25–75)], and 39.1% of patients had died. Of note, three months after the kidney biopsy, 33.8% of the patients had a serum creatinine > 1.5 mg/dL, while this percentage was 15.5% in baseline kidney function. At the end of the follow-up or before their death, 43.9% of the patients showed a serum creatinine > 1.5 mg/dL. The Cox survival analysis identified the presence of metastasis as a risk factor for mortality in our study (p = 0.006).The mean follow-up was 15.2 months [5.7–31.4 (IQ 25–75)]. A total of 29 patients (18.9%) required kidney replacement therapy. There was an association between the presence of hematuria and the presence of nephrotic proteinuria with the requirement of renal replacement therapy . Evaluation by a nephrologist with expertise in onconephrology could help find an etiological diagnosis of renal dysfunction in patients with cancer, avoiding diagnostic delays and improving renal prognosis. A better renal outcome would probably be linked to an increased number of future oncospecific treatments, generally limited by renal function . The proAs previously known, the prevalence of CKD in patients with cancer is increasing compared with the general population . In our It is interesting to mention that three months after the kidney biopsy, only 33.8% presented a creatinine > 1.5 mg/dL, possibly due to the pathological diagnosis of kidney disease and its appropriate targeted treatment, highlighting the importance of accurate nephrological evaluation in patients with cancer and de novo kidney disease.The main reason for submitting a cancer patient to kidney biopsy was acute kidney failure ,26,27: cOur study has several limitations. It is a retrospective study of a single medium-sized European country, so it may not apply to other regions with diverse populations and very different health systems. The information was obtained through the review of the clinical history, which could cause a lack of data. The strong point of the study, however, is that it is a multicenter study assessing the kidney biopsies performed in patients with cancer in the last ten years. Furthermore, this study is the first that analyzes only patients with cancer that underwent kidney biopsy, and it represents what is happening in real-world life medical practice.Nowadays, there is a new trend in kidney disease and cancer patients. In our multicenter study, acute interstitial nephritis has been identified as the most common kidney disease histologic pattern in this population, followed by acute tubular necrosis and IgA nephropathy. Kidney biopsy in this group of patients provides valuable diagnostics and drives treatment, leading to a better renal prognosis in these patients. More studies are needed to increase the knowledge of the diagnosis, treatment, and prognosis of oncologic patients with kidney damage.


This study aims to understand the difference in the influence of urinary sodium and potassium excretion on blood pressure in patients of different sexes with hypertension by analyzing the relationship between urinary sodium and potassium excretion and blood pressure.  In this cross-sectional study, 606 hospitalized patients with essential hypertension were recruited from 16 hospitals in the Shanxi Province between June 2018 and December 2019. These patients were grouped by sex, with 368 males and 238 females. Basic information and relevant serum biochemical indexes of patients in the two groups were recorded. The 24-hour urinary sodium and potassium excretion were measured, and 24-hour ambulatory blood pressure monitoring was performed simultaneously. This was done to analyze and compare the relationship between urinary sodium and urinary potassium excretion and blood pressure in adult hospitalized patients of different sexes with hypertension. P < 0.001). There was no significant difference in 24-hour urinary potassium excretion between male patients with hypertension and female patients. Spearman correlation analysis showed that 24-hour urinary sodium excretion was positively correlated with 24-hour SBP and nSBP in male patients (P < 0.05), while 24-hour urinary potassium excretion was negatively correlated with 24-hour SBP and nSBP in male patients (P < 0.05). The 24-hour urinary sodium in female patients was significantly positively correlated with 24-hour SBP, 24-hour DBP, SBP, dDBP, nSBP, and nDBP (P < 0.01). The 24-hour urinary potassium was significantly negatively correlated with nSBP (P < 0.05). Multiple stepwise linear regression showed that 24-hour urinary sodium excretion was still significantly positively correlated with 24-hour SBP and nSBP in male patients with hypertension after adjusting for various confounding factors.  The 24-hour urinary sodium excretion in male patients with hypertension was significantly higher than that in female patients ( High urinary sodium and low urinary potassium excretion are closely related to elevated blood pressure in adult patients with hypertension, and there are sex differences. Hypertension is one of the most common chronic noncommunicable diseases worldwide and has become the most important risk factor for coronary heart disease, stroke, chronic kidney disease, and death , 2. At pAt present, although there are many studies at home and abroad on the relationship between urinary sodium, potassium excretion, and blood pressure, the relationship between these patients of different genders with hypertension is rare. This study attempted to analyze the relationship between urinary sodium and potassium excretion and blood pressure in adult patients with hypertension of different sexes in the Shanxi area and then to understand the difference in the influence of urinary sodium and potassium excretion on blood pressure in patients from this area; therefore, providing a new theoretical basis for the prevention and treatment of blood pressure.In this cross-sectional study, 606 hospitalized patients , aged between 18 and 80 years, with essential hypertension were recruited from 16 hospitals in the Shanxi Province between June 2018 and December 2019. According to the scientific statement of the Chinese Medical Doctors Association on the diagnostic criteria and antihypertensive targets of hypertension in China, the diagnostic criteria for hypertension are systolic blood pressure ≥140 mmHg (1 mmHg = 0.133 kPa) or diastolic blood pressure ≥90 mmHg  and female patients [40.16 (27.81–55.46) mmol] .The 24-hour urinary sodium excretion in male patients [176.57 (144.00∼215.95) mmol] was higher than that in female patients [164.00 (129.75∼198.50) mmol], and the difference was significant , but the 24hDBP, dDBP, and nDBP of the male group were significantly higher than those of the female group (P < 0.001)  .P < 0.05). The 24-hour urinary potassium excretion was significantly negatively correlated with 24-hour SBP and nSBP (P < 0.05). Spearman correlation analysis in the female group showed that 24-hour urinary sodium was significantly positively correlated with 24-hour SBP, 24-hour DBP, dSBP, dDBP, nSBP, and nDBP (P < 0.01), while 24-hour urinary potassium was significantly negatively correlated with nSBP (P < 0.05)  .P < 0.05), and 24-hour urinary potassium excretion was negatively correlated with 24-hour SBP, dSBP, and nSBP in male patients with hypertension (P < 0.05). The 24-hour urinary sodium was still significantly positively correlated with 24-hour SBP, 24-hour DBP, dSBP, dDBP, nSBP, and nDBP in female patients with hypertension (P < 0.01), while 24-hour urinary potassium was significantly negatively correlated with 24-hour SBP, dSBP, and nSBP (P < 0.05)  .The prevention of cardiovascular and cerebrovascular diseases is an important public health strategy to improve national health and further increase life expectancy. Among cardiovascular and cerebrovascular diseases, hypertension, in particular, has a high incidence worldwide, so the prevention and treatment of hypertension is a top priority. In the past 20 years, China has carried out several national sample surveys on people over 18, and the results of three sample surveys conducted from 2002 to 2015 show that the prevalence of hypertension among the overall population is on the rise , 21. In Sodium and potassium are the most abundant cations, both extracellular and intracellular, and they are inextricably linked to maintaining the homeostasis of the organism. High sodium intake directly causes sodium and water retention and increases circulating blood volume, resulting in an increased return to the heart and cardiac output, resulting in increased blood pressure. Increased sodium levels will amplify the baroreflex of sympathetic nerve activity and lead to a strong sympathetic nervous response and eventually an increase in blood pressure . High soThe sodium and potassium in the human body are mainly excreted by the kidneys, and the intake is approximately equal to the excretion in urine when the diet is stable. Therefore, the intake of the body is estimated by the excretion of urinary sodium and potassium in 24 hours when the diet is stable. In this study, 24-hour urine samples were collected to analyze the relationship between urinary sodium and urinary potassium excretion and blood pressure for the first time. The results showed that the average salt intake of adult patients with hypertension in Shanxi Province was 10.65 g/d. In males, the intake was 11.15 g/d, and in females, it was 9.79 g/d. This is significantly higher than the World Health Organization's recommendation of no more than 5 g of salt per person per day . The average potassium intake per capita was 1.72 g/L, the average potassium intake for males was 1.77 g/d, and the average potassium intake for females was 1.63 g/d. Both are lower than the amount of 2 g recommended in the Dietary Guidelines for Chinese Residents (2016). The 24-hour ambulatory blood pressure monitoring, which was used in the present study, has been widely used in clinical practice. It provides more comprehensive and real-time blood pressure information and is able to identify different types of hypertension . The 24-hour ambulatory blood pressure monitoring records blood pressure day and night to obtain the 24-hour average blood pressure. It is a relatively objective and accurate detection method for evaluating the blood pressure levels with strong reliability and repeatability. In addition, it is possible to analyze the circadian rhythm of blood pressure and the trend of blood pressure changes, which may guide treatment plans and evaluate antihypertensive efficacy and reduce the risk of target organ damage. The study of this research group showed that in both male and female patients with essential hypertension, 24-hour urinary sodium excretion was significantly positively correlated with increased blood pressure, while 24-hour urinary potassium excretion was significantly negatively correlated with increased blood pressure. After adjusting for confounding factors such as age, BMI, history of diabetes, and history of hyperlipidemia, multiple linear stepwise regression analysis showed that the regression relationship between 24-hour urinary sodium and potassium excretion and 24-hour ambulatory blood pressure parameters was still statistically significant. This correlation was more significant in female patients with hypertension.A previous study has confirmed that being female is also one of the important factors affecting the mechanism of high sodium and low potassium promoting hypertension . ProspecHigh sodium and low potassium intake is a controllable factor in blood pressure development in adult patients with hypertension of different sexes. In the prevention and treatment of hypertension in the future, we should vigorously publicize the health significance of a balanced diet of sodium and potassium, carry out reasonable diet management according to different sexes, and develop individualized antihypertensive programs. This study first analyzed the relationship between urinary sodium, potassium excretion, and blood pressure in different gendered patients with hypertension, which is innovative in guiding blood pressure management in these patients. Moreover, the sample size of the study is large, the subjects are regionally representative, and the results of the study have great reference value. However, electrolyte excretion is highly variable in daily life and has many influencing factors. In this study, 24-hour urine samples were used in a single day, which is a deficiency of this study. With sufficient conditions, we can collect urine for 24 hours for several days to obtain more accurate data.High urinary sodium and low urinary potassium excretion are closely related to elevated blood pressure in adult patients with hypertension in Shanxi, and there are gender differences. There was a stronger positive correlation between high urinary sodium excretion and blood pressure in women than in men. Low urinary potassium excretion was significantly negatively correlated with 24-hour mean systolic blood pressure and nighttime systolic blood pressure in patients with hypertension. Gender differences should be considered in the prevention, treatment, and dietary intervention of patients with hypertension.


The adherence to the intervention was moderate, with an attrition rate of 12%. A modified version reducing visits and explorations will likely improve compliance and can be used to assess the long-term maintenance of these benefits in managing resistant hypertension by diverse healthcare providers.Hypertension is a common chronic medical condition. Treatment is not satisfactory in a significant proportion of patients with primary hypertension, despite the concurrent use of three or more medications with different mechanisms of action. Such treatment-resistant hypertension is a clinical challenge associated with poor prognosis and needs further investigation. The efficacy of lifestyle changes has not been established yet in patients with resistant hypertension, and educational efforts appear clinically irrelevant in patients who must achieve behavioral changes without supervision. A 6-month multidisciplinary pilot intervention enrolled 50 patients with established resistant hypertension. The aims were: (1) to examine whether intensive and supervised lifestyle changes contribute to decreasing blood pressure in this condition, and (2) to identify which components affect compliance and feasibility. The program provided intensive changes in nutrition, physical exercise, and control of sleep disturbances supervised by nutritionists, physiotherapists, and psychologists. Nurses and pharmacists followed up on adherence to the antihypertensive medication. The primary outcome was 24 h blood pressure control. Data in patients with full compliance (n = 30) indicate that lifestyle modifications in resistant hypertension significantly reduced 24 h both systolic and diastolic blood pressure ( Despite improvements in hypertension awareness and treatment, the associated risk of death is rising because target organ damage remains when blood pressure (BP) goals are not achieved . ClinicaIn defiance of guidelines for pharmacological treatment and assessment of drug combinations, multi-drug treatment is not as effective as desirable ,13,14. AAdopting a healthy cardiovascular lifestyle with increased exercise, dietary modification, and weight loss is often recommended as the first step for treating high BP with remarkable efficacy in unmedicated or drug-controlled patients with hypertension ,25,26,27Behavioral interventions need decisions about their feasibility to select and adapt appropriate methods rather than being derived from highly controlled efficacy studies. We designed a prospective cross-sectional pilot study in patients with RHT, a population target with unique particularities, through a 6-month program providing comprehensive care. The organization of the study included a multidisciplinary team of nurses, pharmacists, nutritionists, physiotherapists, psychologists, and physicians with the necessary skills. Those involved in implementing the program performed monthly visits and procedures to compare baseline and post-intervention BP measurements. Personalized sessions emphasized healthy lifestyle changes, including exercise programs and nutritional counseling. The implications of how the intervention would fit with daily-life activities, perceived sustainability, and costs within organizational goals focused on our concerns. The organization and procedures were approved by the Institutional Review Board [PR(AG)207/2015] and were monitored by the local Ethics Committee of the Vall d’Hebron Hospital. All procedures were conducted in accordance with the Good Clinical Practice Guidelines of the Health Department of Generalitat de Catalunya and were in compliance with the Declaration of Helsinki. All participants provided written informed consent. Details will be made available upon reasonable request. Rationale about feasibility and gains in the precision and the mean and variance of BP measurements indicated the justifications for a minimum sample size of 24 cases .Those with secondary causes of hypertension or clinically severe diabetes and/or ischemic heart disease were considered ineligible among contacted patients. Other initial exclusion criteria included the use of illicit drugs, including ethanol in excess, and previous prescription of weight-loss pills and medications that can raise BP. Fifty patients with true RHT were enrolled among those regularly attending our clinic with BP values > 130/80 mmHg when three or more different classes of antihypertensive drugs, including a diuretic at optimized dosages, were prescribed or the need for four or more drugs to achieve BP < 130/80 mmHg. As RHT was a diagnosis of exclusion, ambulatory BP monitoring was not only an essential component in the evaluation but also reinforced lifestyle modifications. Self-reports and reports from attending nurses and pharmacists confirmed excellent adherence to antihypertensives.Recruited patients with RHT were reevaluated at baseline to ensure the diagnosis, and the lead clinician reviewed medications and supervised clinical adherence according to guidelines . All enrt-test, chi-square test, or McNemar test, and analyses of differences conducted with SPSS 24  were significant when p-values were <0.05. Plots from GraphPad Prism 6.01  illustrated changes in BP measurements. Because the response was not uniform, we also used R (version 4.0.2) to calculate the Pearson pairwise correlation matrices, MetaboAnalystR  according to the food frequency questionnaire. The mean decrease in calorie intake from baseline to post-intervention was modest, −256 kcal/day , but associated with relatively increased servings per day of vegetables, fruits, nuts, and legumes. Participants exhibited substantial weight loss with significant changes in BMI that were not appreciated by measurements of waist circumference a,b. Of nPatients with RHT, who do not respond well to multiple antihypertensive medications, need unique consideration. Mortality, the prevalence of end-organ damage, weight excess, and cardiovascular risk are higher than in effortlessly controlled hypertensive patients . There iIt is relevant to identify effective behavioral changes for lowering BP, but the impact of lifestyle changes on this population is unclear. The few available data are promising and demonstrate that programs for patients that have to achieve behavioral changes on their own perform poorly ,39,40. HWeight loss has been demonstrated to play a significant role in managing resistant hypertension ,48. ObesOur practice-based evidence confirmed the efficacy of behavioral interventions and provided numerically larger BP reductions than those observed with invasive procedures ,23,49,50As this pilot study was planned as a 6-month intervention, the data on persistence and long-term effectiveness is lacking, which represents a limitation. In addition, the sample size should be increased to accommodate more and all types of patients  and to assess the heterogeneity that we have observed in response to treatment.To conclude, maximizing lifestyle intervention is a beneficial therapeutic strategy in patients with RHT with the ability to achieve significant BP reductions. Interventions, likely associated with weight loss and fitness, yield positive outcomes and should not be disregarded in patients with poor fitness, weight excess, and major cardiovascular damage. The success of these interventions depends not only on the patient’s consent and motivation but also on their willingness to attend visits with the multidisciplinary team and adhere to the program. This requires strong coordination and communication among the members of the multidisciplinary team in order to ensure that the program is feasible and sustainable for the patient. It is crucial for the patient to receive ongoing support and guidance in order to maintain long-term healthful behaviors.


Bilateral ureteropelvic junction obstruction is a common cause of secondary hypertension in the pediatric population, often due to congenital malformation. On the other hand, it is less frequently encountered in the adult population and is usually due to an acquired condition, most commonly by a bilaterally obstructing nephrolithiasis causing hydronephrosis and subsequent hypertension. The aim of this study was to investigate and highlight the underlying mechanisms by which acute bilateral ureteropelvic junction obstruction causes hypertensive crisis and why early detection and prompt treatment are necessary to mitigate the effects of elevated blood pressure on target organs.A 41-year-old African American man with hypertensive cardiomyopathy presented with anuria. He was found to have elevated blood pressure with evidence of target organ damage on laboratory examination, demonstrated by sudden elevation of his serum creatinine level. He was initially treated with oral and intravenous antihypertensives, with minimal improvement. The work-up was unremarkable apart from the imaging finding of acute bilateral ureteropelvic junction obstruction from obstructing nephrolithiasis causing hydronephrosis. Bilateral ureteral stents were placed for decompression, with resolution of the hypertensive crisis and improvement of renal function.This case highlights the importance of prompt diagnosis and treatment of underlying acute bilateral ureteropelvic junction obstruction to mitigate the deleterious effects of sudden blood pressure elevation on target organs. Primary hypertension among adults is a common disease entity encountered in the clinical setting and is usually influenced by multiple factors, including age, lifestyle, comorbidities, genetics, and race. On the other hand, hypertension in a young adult should receive prompt evaluation for possible secondary underlying causes to mitigate the long-term complications of elevated blood pressure. These include, but are not limited to, the investigation of possible renal and vascular pathologies, endocrine issues, or drug side effects .Ureteropelvic junction (UPJ) obstruction, as a cause of secondary hypertension, commonly occurs in children secondary to a congenital malformation , 3. It cTo determine the underlying mechanisms by which acute bilateral UPJ obstruction causes hypertensive crisis and why early detection and prompt treatment are necessary to mitigate the effects of elevated blood pressure on target organs.A 41-year-old African American man was brought to the emergency department for evaluation due to 4-day history of progressive decrease in urine output associated with bilateral flank pain. He denied having fever, shortness of breath, dysuria, hematuria, lower-extremity swelling, skin tightening, painful extremities on cold exposure, fatigue, or recent weight loss.The patient’s past medical history was significant for hypertension and chronic systolic heart failure (left ventricular ejection fraction 15%). The patient had been admitted a year prior for new-onset acute systolic heart failure due to uncontrolled hypertension that was diagnosed when he was in his early twenties and was never treated. He was discharged with losartan, spironolactone, hydralazine, isosorbide dinitrate, and carvedilol, for which he reported good compliance. His family and social history were noncontributory.On presentation, he had blood pressure of 262/147 mmHg, heart rate of 102 beats/min, respiratory rate of 18 breaths/min, and oxygen saturation of 97% on ambient air. He was alert and oriented and was not in acute respiratory distress. He had faint bilateral crackles at the lung bases. No jugular vein distension or peripheral edema was noted. His heart rhythm was normal, and there were no murmurs or gallops. He had generalized abdominal tenderness without guarding. The urinary bladder was palpable. No costovertebral angle tenderness was shown. The remainder of the examination was unremarkable.His blood chemistry showed a serum creatinine level of 14.1 mg/dL, increased from his baseline level of 1.6 mg/dL, and a blood urea nitrogen (BUN) level of 57 mg/dL with a BUN-to-creatinine ratio of 4.04. Urinalysis showed microscopic hematuria. Chest radiography revealed mild pulmonary edema. His hemoglobin level was 13 g/dL. He was managed with intravenous labetalol (10 mg), oral carvedilol 25 mg), and oral hydralazine (25 mg), which slightly decreased his high blood pressure by approximately 40 mmHg for his systolic blood pressure (SBP) and 10 mmHg for his diastolic blood pressure (DBP). A straight catheter was inserted, with no urine flow noted. Furthermore, a bladder scan was performed, which showed no urine in the bladder. An ultrasound of the kidneys showed bilateral UPJ obstruction from bilateral obstructing nephrolithiasis measuring 1.4 cm at the right UPJ and 1 cm at the left UPJ, causing moderate right and severe left hydronephrosis  activity and activation of the renin–angiotensin–aldosterone system (RAAS) .The RAAS plays a role in the development of hypertension among patients with hydronephrotic kidneys, as evidenced by increased plasma renin activity . In the The patient in this case developed bilateral nephrolithiasis, which was asymptomatic, eventually causing acute UPJ obstruction and subsequent hydronephrosis. This simultaneous acute bilateral obstruction caused the rapid development of hydronephrosis leading to downstream effects that culminated in a hypertensive crisis. The elevated blood pressure led to target organ damage, including flash pulmonary edema, because of the increased hydrostatic pressure. There was rapid resolution of the elevated blood pressure after relief of the obstruction using bilateral nephrostomy tubes. The patient’s serum creatinine level also greatly improved after relief of the obstruction.Among patients presenting with acute bilateral UPJ obstruction complicated by a hypertensive crisis, prompt treatment is necessary to ameliorate target end-organ damage. According to the American Urological Association (AUA), an obstructed renal system is a urological emergency, and thus immediate intervention is needed . Recomme