Blood pressure is an important cardiovascular parameter. Currently, the cuff-based sphygmomanometer is a popular, reliable, measurement method, but blood pressure monitors without cuffs have become popular and are now available without a prescription. Blood pressure monitors must be approved by regulatory authorities. Current cuffless blood pressure (CL-BP) monitors are not suitable for at-home management and prevention of hypertension. This paper proposes simple criteria for over-the-counter CL-BP monitoring. First, the history of the sphygmomanometer and current standard blood pressure protocol are reviewed. The main components of CL-BP monitoring are accuracy during the resting condition, accuracy during dynamic blood pressure changes, and long-term stability. In this proposal we recommend intermittent measurement to ensure that active measurement accuracy mirrors resting condition accuracy. A new experimental protocol is proposed to maintain long-term stability. A medically approved automated sphygmomanometer was used as the standard device in this study. The long-term accuracy of the test device is based on the definition of propagation error, i.e., for an oscillometric automated sphygmomanometer (5 ± 8 mmHg) ± the error for the test device static accuracy (–0.12 ± 5.49 mmHg for systolic blood pressure and − 1.17 ± 5.06 mmHg for diastolic blood pressure). Thus, the long-term stabilities were − 3.38 ± 7.1 mmHg and − 1.38 ± 5.4 mmHg, which satisfied propagation error. Further research and discussion are necessary to create standards for use by manufacturers; such standards should be readily evaluated and ensure high-quality evidence.The online version contains supplementary material available at 10.1007/s12553-023-00726-6. Blood pressure (BP) is an important measure of health. It is created by the force of the blood pushing against the walls of blood vessels after the heart pumps. The heart must pump harder under conditions of high BP (hypertension). Hypertension is a serious health condition and increases the risks of heart, brain, kidney, and other diseases. It is a major cause of premature death worldwide and is present in more than one in four men and one in five women, or more than one billion people worldwide. The burden of hypertension is felt disproportionately in low- and middle-income countries, where two-thirds of cases occur, largely due to increased risk factors in those populations in recent decades .Booth published a valuable review on the history of monitoring BP , 3. In 1To monitor hypertension, a simple, easy-to-use device is preferable, and a cuffless sphygmomanometer is one such device. Due to the increasing popularity of cuffless devices, their safety and reliability are important. Post-market surveillance measures including regulatory inspections and regular calibration are warranted. The frequency of inspections and calibrations should meet legislative and regulatory requirements, and the manufacturer’s recommendations. Maintenance recommendations vary depending on device type, and the frequency and location of use. The following references outline procedures for medical inspections –6; we alVarious cuffless BP (CL-BP) monitors have been developed, as reviewed elsewhere –17. SectThe International Organization of Legal Metrology (OIML) recently published two recommendations, for non-invasive non-automated sphygmomanometers R 148  and non-CL-BP monitors appear to be an alternative to cuff-based sphygmomanometers because they are easy to operate, inexpensive, and may not require calibration. The next section presents existing commercial devices with and without evidence studies. The discussion focuses on the reliability of CL-BP values during dynamic BP changes and their long-term stability, as well as clinical applications of CL-BP monitors. Over-the-counter CL-BP devices have become popular and are available without a prescription. Here, we review the issues surrounding home-use CL-BP monitors in terms of accuracy at rest, dynamic response, and long-term use.Accuracy at rest follows the cuff-based sphygmomanometer under ISO 81060-2 , 16, 17.The requirement for a stable BP hampers the tracking of changes, particularly changes that occur over a few minutes; this hindrance is difficult to overcome because BP is typically unstable immediately after a change in BP. There are no reports on this topic. Therefore, we did not consider CL-BP monitors used as beat-to-beat monitors. In this report, we focus on the intermittent BP device as an alternative use of cuff-based sphygmomanometers and consider only the long-term stability. Furthermore, the initialization of BP measurement is important; for home use, long-term stability and reinitialization determination merit discussion. Thus, a simple protocol is proposed.Multiple manufacturers produce CL-BP devices based on various technologies, as listed in Table A brief explanation of the principle is as follows . The pulHypertension is a critical diagnosis . The LanCL-BP monitors have been evaluated in physiological studies and clinical trials. Physiological studies have investigated the reliability of the pulse transit time (PTT) at different measurement sites, such as the neck, fingers, and toes. Moreover, the relationship between BP and blood volume (in terms of blood vessel stiffness) has been evaluated –58. ThesThe establishment of a standard is important for ensuring the reliability of CL-BP monitors, but only the IEEE is actively engaged. However, the IEEE standards are only partly recognized by the FDA . AlthougThe proposal for long-term stability involves a two-step evaluation. First, accuracy at the resting stage is obtained by ISO81060-2, using the auscultation method. The obtained static accuracy is used to evaluate the long-term stability. Approved medical automatic oscillometric devices are used as gold standard devices for the evaluation because of their ease of handling and convenience for manufacturers. Long-term stability can be obtained as the error propagation consisting of the static accuracy of the device under test plus the static accuracy of the oscillometric BP device.The protocol for assessing accuracy at rest followed ISO 81060-2:2018 and is summarized below. CL-BP devices need to initialize using systolic and diastolic BPs obtained with a standard auscultation sphygmomanometer. The initial systolic BP (SBP) and diastolic BP (DBP) values are determined by the standard auscultatory method. Auscultatory measurements are recorded by two independent observers (unaware of each other’s readings) using a mercury sphygmomanometer and a binaural stethoscope. The measurements are performed with the participants in the sitting position, with their forearms at heart level. Phase I and V Korotkoff sounds are used to assess the SBP and DBP, respectively. All auscultatory BP measurements are performed on the arm used for measurement with the CL-BP monitor. Two criteria are used in the evaluation.Criterion 1.n individual paired measurements for all participants are within 5 ± 8 mmHg i-P(REF)i is the difference between the ith paired CL-BP monitor BP value minus the reference BP value. where Criterion 2.m participants, the standard deviation sm of the mean paired CL-BP monitor measurement and observers’ reading with the reference sphygmomanometer for each participant meet the criteria in Table For the SBP and DBP for each of m, j, and xj are the number of participants, the index for the individual participant, and the tested device error as calculated in (4), respectively; and d, k, and P(T)k-P(REF)k are the number of tested participants, the kth individual participant, and the difference between the paired CL-BP monitor’s BP values minus the reference BP values, respectively. where Accuracy measurements were performed 30 min after initialization. The obtained accuracy was defined as the device accuracy that met criteria 1 and 2.dut) ± SD(Xdut), where Xdut is the device under test; this means the accuracy of the developed device is tested with static error evaluation using an auscultation method.Using the above criteria, we define the error of the developed device as error =  M Obtain a measurement using the CL-BP monitor,(2) Obtain a measurement of reference BP using the oscillometric automated sphygmomanometer  , 60,(3) Wait at least 60 s,(4) Repeat steps (1) to (3),(5) Calculate the mean of the three CL-BP measurements and reference BP measurements. If the SBP and DBP values showed differences of > 12 and 8 mmHg, respectively, all data were excluded.The measurements were performed twice on the first 3 days. Subsequently, two measurements were performed daily, in the morning and at night; one measurement was performed in the morning from days 4 to 10; and one measurement was performed every 10 days until day 30. This protocol was modified from ISODIS 81060-3.2.The mean and SD of the obtained data were calculated over the 1-month measurement interval. If the differences between the first initialization BP and first measured BP was more than 12 and 8 mmHg for SBP and DBP, respectively, the participant was excluded from the study. The mean and SD values differ from the values at rest because an automated sphygmomanometer was used, instead of an auscultatory method.Because of error propagation, we propose another criterion. If an oscillometric reference sphygmomanometer is used as the standard, the error is the sum of the oscillometric automated sphygmomanometer error and the tested device error, as shown in Formula 5 with each error containing the mean ± SD.osc) ± SD (Xosc)) is within 5 ± 8 mmHg; thus, the total device error was 10 ± 11.3 mmHg. A mean error of 10 mmHg is large and we thus propose use of the CL-BP monitor’s accuracy obtained at rest. If the CL-BP monitor’s accuracy is 4 ± 6 mmHg, the allowable error for long-term stability is 9 ± 10 mmHg. We obtained different long-term accuracies depending on the resting accuracy of the CL-BP monitor.The reference error  and written informed consent was obtained from all participants. Experiments were performed in accordance with the Declaration of Helsinki.Initial SBP and DBP values were determined by the standard auscultatory method. After performance of the initial BP measurements required to classify participants into BP categories, Checkme Pro (SAN-EI MEDISYS Japan) was continuously used by the participants until three successive measurements were achieved . To ensure the short-term stability of device initialization, a 5-min rest period was allowed before validation measurements began. Three paired CL-BP monitor and auscultatory measurements were obtained, and the CL-BP monitor continuously measured BP throughout the procedure; BP values from the CL-BP monitor were determined by online analysis. A pause of 60 s was allowed between measurements to avoid the cuff inflation effect. The qualities of the ECG and PPG signals were checked periodically.During the initialization session, data from the CL-BP monitors were transferred to a computer; BP values were calculated using BP estimation software. Validation BP values from the CL-BP monitor were obtained by calculating the mean SBP and DBP over 20–30 s good-quality segments. The obtained values were compared with the paired auscultatory BP measurements. Three comparison values were obtained, and the means were used as the initial values. During initialization, if the SBP and DBP values differed by more than 12 and 8 mmHg, respectively, all data were excluded.The validation procedure was conducted in accordance with ISO 81060-2:2018 for the validation of BP measuring devices in adults. However, because of the characteristics of the CL-BP device, several adaptations were necessary. Three successive datasets were collected from 30 participants . The BP distributions are shown in Table Checkme Pro is an ambulatory vital sign-sensing device. The system consists of a finger PPG function that provides oxygen saturation measurement, as well as three embedded electrocardiography (ECG) leads with a control unit. The device is portable and equipped with a screen that displays beat-to-beat pulse waveform, ECG, and PTT changes. With the developed software, the PPG and ECG signals are transferred to the cloud via Bluetooth and the Internet. BP estimation is based on beat-to-beat determination of the PTT, calculated as the interval between the R-wave on ECG and the arrival of the corresponding pulse wave based on the PTT principle .Using our BP estimation software, SBP and DBP were calculated based on the relationship between BP and PTT, where an increase in BP enhances arterial wall tension, thus increasing arterial wall stiffness –63. Cons0, DBP0, T0, and γ are the PTT, initial SBP, initial DBP, initial PTT, and peripheral coefficient, respectively.where T, SBPEighteen participants  underwent this evaluation. Measurement of reference BP was performed using an oscillometric automated sphygmomanometer  . The proThe static accuracy was reasonably good and was maintained within ± 5 ± 8 mmHg Table . The corFour of 18 participants showed a 12-mmHg difference between initialization and the first measurement; they were excluded from the analysis. Static accuracies were − 0.12 ± 5.49 mmHg for SBP and − 1.17 ± 5.06 mmHg for DBP. The measurements obtained using the oscillometric automated sphygmomanometer were within 5 ± 8 mmHg. Based on the propagation of error, the accuracy criteria of the long-term stability of SBP and DBP measurements obtained using the oscillometric automated sphygmomanometer were − 5.12 ± 9.70 mmHg and − 6.17 ± 9.48 mmHg, respectively. The long-term accuracies of SBP and DBP were − 3.38 ± 7.1 mmHg and − 1.38 ± 5.4 mmHg, respectively; these values met the criteria (Supplementary Table versus reference BP readings), within 5, 10, and 15 mmHg for SBP and DBP, are presented in Fig. versus reference BP readings) to the total number of data points.The numbers of absolute BP differences  and an estimated probability of error of at least 85% are acceptable as a compromise, considering that performance is similar to currently available BP monitors [In both research protocols and manufacturer reviews, participant recruitment is an important consideration. If a device does not require reinitialization within approximately 1 month, the comparison study must be of 1-month duration. Because of the difficulty of recruitment, we enrolled fewer than 20 participants, some of whom did not meet the inclusion criteria. The recruitment of participants with high BP, particularly a high DBP, was difficult and constituted most of the additional screened participants; this is reflected in the overall distribution, as shown in the DBP plot, where most of the points are < 115 mmHg. Because the daily BP changes are close to the distribution in each range in DBP, the distribution conditions are fulfilled. A tolerable error of ≤ 10 mmHg  reduced the recommended sample size from 85 to 33. However, the regulatory authorities in the USA and Europe require validation with the longer, more robust 85-subject protocols, and all manufacturers selling products on these markets need to use the protocol described in the ANSI/AAMI/ISO 81060-2 standards (which are recommended by most clinicians).In addition, individual laboratory results should be closely monitored; often, accuracy requirements are not satisfied . Thus, sThe difference between the ISO/FDIS 81060-3 and our proposal is the use of a standard sphygmomanometer, either auscultatory or oscillometric. Moreover, the accuracy of the long-term stability mainly involves direct BP monitoring. The volume clamp method in the operating room and ICU is the target of ISO/FDIS 81060-3. Even a comparison study involving direct BP monitoring for more than 10 days is a heavy burden on medical staff.Moreover, the intra-correlation is used in the standard. This is reasonable and individuals have different daily activities. Without individual calibration, the intra-correlation coefficient is much more reliable than the standard statistics we used.A beat-to-beat evaluation can be conducted if a direct arterial BP monitor is used as a standard device. However, manufacturers need time and resources to conduct such evaluations. Additionally, several countries do not allow direct arterial BP monitoring in healthy individuals.At present, if manufacturers would like to distribute a device for use in continuous clinical practice , they must perform a comparison study with direct arterial BP monitoring. Another option involves the use of the volume clamp method as a standard, in accordance with ISO/FDIS 81060-3 Noninvasive Sphygmomanometers-Part 3: Clinical Investigation of the Continuous Automated Measurement Type. Therefore, the definition of a beat-to-beat evaluation in the proposed procedure was difficult, and further discussions of beat-to-beat evaluations are needed. New ideas for standardization protocols must be considered for the evaluation of dynamic changes.From a regulatory point of view, new devices must be highly precise. Embedded devices and medical software are used to avoid misdiagnoses , 74. RegWe proposed a protocol for evaluating the static accuracy and long-term stability of the CL-BP monitoring system. Due to experimental protocols, we were unable to perform a comparative study to evaluate the dynamic response. Our long-term validation study involving 15 participants did not meet the minimal validation criteria. Our revised proposal includes a new evaluation process for long-term stability assessments. Our study population size of 15 was small, but our results provide a roadmap for popularizing cuffless blood pressure monitors for screening purposes, and potentially other over-the-counter healthcare devices. Collectively, our findings will promote the formulation of a new standard.Below is the link to the electronic supplementary material.Supplementary Material 1


Low blood pressure and associated postural symptoms are well-recognized manifestations of anaphylaxis. Nonetheless, anaphylaxis can present with high blood pressure and is rarely reported in the literature. We report an unusual presentation of anaphylaxis with severe supine hypertension and orthostatic intolerance.A 43-year-old Asian female presented to the emergency department with generalized itching, hives, and postural dizziness after taking a slow-release diclofenac sodium 100 mg tablet. On admission, the patient was tachycardic with a supine blood pressure of 200/100 mmHg. She had urticaria and bilateral rhonchi. A clinical diagnosis of anaphylaxis was made. She was treated with intravenous hydrocortisone and chlorpheniramine, but intramuscular adrenaline was withheld owing to her high blood pressure. She was kept in the supine position, and her vital parameters were closely monitored. Although the respiratory and cutaneous symptoms improved with treatment, her blood pressure remained elevated. Forty minutes later, the postural dizziness recurred as she sat up on the bed and her blood pressure plummeted from 198/100 mmHg to 80/60 mmHg. She was put back in the supine position immediately, and the blood pressure was restored with three doses of intramuscular adrenaline and a fluid bolus. Her postural symptoms completely resolved after adrenaline, but her blood pressure remained elevated. Two weeks after the initial presentation, a diagnosis of essential hypertension was made, which probably had been undetected. In anaphylaxis, where the cardiovascular system is involved, a blood pressure reduction from baseline is expected in patients with preexisting hypertension. Despite cardiovascular involvement, our patients’ blood pressure on presentation to the emergency department was much higher than her pretreatment ambulatory blood pressure, thus making this presentation unusual.Diagnosis and treatment of anaphylaxis can be delayed in patients presenting with high blood pressure. Postural symptoms should alert the clinician to cardiovascular involvement despite elevated supine blood pressure. Early treatment with adrenaline should be considered in these patients with extreme caution. Anaphylaxis is a clinical diagnosis based on physical findings on presentation with or without a history of exposure to an allergen . The cliAnaphylaxis is characterized by sudden-onset skin or mucosal changes, respiratory or gastrointestinal manifestations, and blood pressure reduction occurring in any combination. Cardiovascular symptoms are potentially life-threatening manifestations of anaphylaxis and are observed more commonly in adults than in children . HypotenWe report a case of anaphylaxis presenting with severe hypertension and orthostatic intolerance. This report highlights the importance of suspecting anaphylaxis irrespective of the patient’s blood pressure, early treatment with adrenaline, and maintaining the supine posture until a complete recovery is achieved.A 43-year-old Asian female presented to the emergency department with generalized itching, hives, and postural dizziness 1 hour after taking slow-release diclofenac sodium (diclofenac sodium SR) 100 mg tablet for headache. She has a history of migraine, for which she had been taking diclofenac sodium SR. Two months prior to this episode, she had developed itching of her palms after taking a diclofenac sodium SR tablet, which had resolved spontaneously. Apart from one incident of food allergy to northern pilchard, she had no food or drug allergy. She had no history of asthma.At the onset of her symptoms, the patient had taken 4 mg of chlorpheniramine for itching and continued to do household chores. Although the itching subsided after about 15 minutes, she felt lightheaded and weak on standing, which prompted her to lie down. Her postural symptoms resolved within 5 minutes of lying down. Over the next 20 minutes, she developed a dry cough with difficulty breathing. Her chest symptoms were relieved after taking two puffs of salbutamol from a metered-dose inhaler prescribed for her daughter. Subsequently, as the itching recurred with hives, she decided to seek medical care. The patient again felt dizzy and lightheaded on getting up and therefore remained supine while traveling to the hospital.2) was 99% on room air. Examination revealed skin erythema, cutaneous edema, mild urticaria, and scattered rhonchi in both lungs. The rest of the system examination was normal.On admission to the emergency department, she was conscious and rational, with a pulse rate of 110 beats per minute and supine blood pressure of 200/100 mmHg. Her respiratory rate was 16 breaths per minute and oxygen saturation  adrenaline and intravenous fluid were withheld because of high blood pressure. As the patient was tachycardic, nebulized adrenaline or salbutamol was not given. Her cutaneous and respiratory symptoms improved with treatment, but pulse rate and blood pressure remained persistently high.Forty minutes later, she felt the need to pass urine and was advised to use a bedpan. However, as the patient insisted on using the washroom, she was asked to sit up on the bed without standing immediately. Her dizziness and lightheadedness recurred within minutes of sitting up, and a dramatic drop in her blood pressure from 198/100 mmHg to 80/60 mmHg was observed. She was put back in the supine position, and her legs were elevated. Intramuscular adrenaline 0.5 mg was administered immediately, and a fluid bolus was given. As the blood pressure remained low (80/62 mmHg), IM adrenaline was repeated twice, 5 minutes apart, until the systolic blood pressure was more than 100 mmHg. The patient was then transferred to the intensive care unit (ICU) for further observation. Her postural symptoms resolved completely after the administration of adrenaline. Her blood pressure fluctuated over the ensuing 24 hours with frequent high readings, and she remained tachycardic. Noteworthily, her blood pressure readings after treatment with adrenaline were not as high as the blood pressure at presentation. There were no hypotensive episodes. All her basic laboratory investigations, including full blood count (FBC), C-reactive protein (CRP), and renal function tests were normal. Serum tryptase was not done as the clinical criteria for the diagnosis of anaphylaxis were met. Two days later, when she was discharged from the hospital, her blood pressure was 165/95 mmHg.On discharge, a diagnosis of anaphylaxis to diclofenac sodium SR was made with a probable diagnosis of essential hypertension. She was prescribed an adrenaline autoinjector for emergency use and advised not to take diclofenac sodium or other nonsteroidal anti-inflammatory drugs (NSAIDs). Upon reviewing 2 weeks later, a 24-hour ambulatory blood pressure monitoring confirmed that she had previously undiagnosed hypertension. Interestingly, the highest recorded pretreatment systolic blood pressure (BP) was 170 mmHg, which was lower than her blood pressure on admission with anaphylaxis. All relevant imaging and hormonal investigations to identify a secondary cause for hypertension were found to be normal. She was commenced on telmisartan 40 mg and amlodipine 2.5 mg in the night and showed a good response to treatment.The timeline of events is summarized in Fig. Prompt recognition and early treatment with adrenaline are imperative for the appropriate management of anaphylaxis. In the absence of any immediate confirmatory tests, the diagnosis of anaphylaxis is based on pattern recognition. Skin is the commonest organ involved in anaphylaxis (90% of episodes), followed by the respiratory system (70%). Cardiovascular system involvement is recognized among only 10–45% of patients [This patient presented with skin and respiratory symptoms following exposure to a known allergen, making anaphylaxis the most likely diagnosis. She had postural dizziness from the onset of her symptoms suggesting cardiovascular involvement. Once anaphylaxis is triggered by a specific antigen, the mast cells and basophils are activated through different immunological mechanisms. Both mast cells and basophils play a key role in initiating and amplifying the allergic reaction by releasing inflammatory mediators. The pro-inflammatory properties of these mediators lead to increased vascular permeability, vasodilatation, increased glandular secretions, and smooth muscle spasms . The vasAt this patient’s presentation, the recorded high blood pressure could be due to preexisting hypertension, anxiety leading to sympathetic activation, or both. Anaphylaxis-induced high blood pressure is another rare possibility . The symet al. [et al. hypothesized that these initial compensatory mechanisms could be dominant in some patients, resulting in hypertension. This hypothesis was based on a case review of 62 patients who had anaphylaxis, and 8 of them were found to have high blood pressure at presentation [Hypertensive anaphylaxis has been reported previously by Solmazgul et al. . Evidencet al. , 6, 8. Cet al. . These eentation . A studyentation . In the entation . The obsHowever, these compensatory mechanisms may not be adequate to maintain the blood pressure when posture changes from supine to upright . The proFigure et al., two of the eight patients who had hypertensive anaphylaxis were treated with IM adrenaline. Their pretreatment systolic BP was 150 mmHg, and both the anaphylaxis and hypertension recovered completely without adverse reactions after the administration of IM adrenaline. Others recovered without IM adrenaline [The safety of adrenaline administration in the presence of high blood pressure is an important concern. Adrenaline is the drug of choice in the management of anaphylaxis as laryngeal edema and vasodilatation are responsive only to adrenaline . Both arrenaline . As per renaline .We did not administer adrenaline at the outset in our patient, but it was given immediately upon the drop in blood pressure. The initial delay in administering adrenaline is likely the reason for her near-fatal collapse after 2 hours from the onset of her symptoms. Delayed use of adrenaline is associated with increased severity and fatalities in anaphylaxis . FurtherGlucagon is recommended as a second-line agent for patients with anaphylaxis who are unresponsive to adrenaline .Glucagon can be considered as an alternative therapy for adrenaline in the presence of high BP. However, positive inotropic effects of glucagon can precipitate severe hypertension. Though this is a less common side effect of the drug, more scientific data are required on the use of glucagon in hypertensive anaphylaxis. The benefit of glucocorticosteroids in the acute management of anaphylaxis is controversial , 15. AltAnaphylaxis can present with normal, low, or elevated blood pressure. The scarcity of corroborating reports in the literature on anaphylaxis presenting with high blood pressure makes this entity unfamiliar to clinicians, leading to underdiagnosis and delayed treatment. Postural symptoms despite high blood pressure should alert the clinician to cardiovascular involvement, and close monitoring in the supine position is essential. Early treatment with adrenaline should be considered in these patients with extreme caution. Further studies are required to better understand the pathophysiology and management of anaphylaxis associated with high blood pressure and orthostatic intolerance.


Women who experience maternal complications, including pre-eclampsia, have a higher risk of cardiovascular disease development. Although the mechanism remains unclear, there is a hypothesis that pregnancy would be a stress test for cardiovascular disease. This study aimed to investigate whether changes in blood pressure during pregnancy would be associated with developing hypertension, which is a main risk of cardiovascular disease. We conducted a retrospective study by collecting Maternity Health Record Books from 735 middle-aged women. Of these, 520 women were selected based on our criteria. 138 were defined as the hypertensive group according to the criteria of receiving antihypertensive medications or blood pressures of >140/90 mmHg at the survey. The rest 382 were defined as the normotensive group. We compared the blood pressures of the hypertensive group with those of the normotensive group during pregnancy and postpartum. Then, 520 women were divided into quartiles (Q1-Q4) according to their blood pressures during pregnancy. After the changes in blood pressure for each gestational month relative to nonpregnant measurements were calculated, the changes in blood pressure were compared among the four groups. Additionally, the rate of developing hypertension was evaluated among the four groups. The average age of the participants was 54.8 years (range: 40-85 years) at the time of the study and 25.9 years (range: 18-44 years) at delivery. There were significant differences in blood pressure during pregnancy between the hypertensive group and the normotensive group. Meanwhile, these two groups did not indicate any differences in blood pressure in postpartum. Higher mean blood pressure during pregnancy was associated with smaller changes in blood pressure during pregnancy. The rate of development of hypertension in each group of systolic blood pressure was 15.9% (Q1), 24.6% (Q2), 29.7% (Q3), and 29.7% (Q4). The rate of development of hypertension in each group of diastolic blood pressure (DBP) was 18.8% (Q1), 24.6% (Q2), 22.5% (Q3), and 34.1% (Q4). Changes in blood pressure during pregnancy are small in women who have a higher risk of hypertension. Levels of blood pressure during pregnancy may be reflected in individual stiffness of blood vessels by the burden of pregnancy. If so, levels of blood pressure would be used to facilitate highly cost-effective screening and interventions for women with a high risk of cardiovascular diseases.  During normal pregnancy, the cardiovascular system develops reduced vascular resistance and increased arterial compliance (2), which allow for adequate oxygen and nutrient transfer to the fetus through the placental circulation. Generally, both systolic blood pressure (SBP) and diastolic blood pressure (DBP) start to decrease at an early stage of normal gestation, reach a nadir at 16-20 weeks, and gradually return to the pregestational level (3). Satter et al. hypothesized that this burden of pregnancy is affected by the mother’s underlying vascular risk factors (4), and numerous epidemiological studies and several guidelines have indicated that women who experience maternal complications, such as pre-eclampsia, are at a higher risk of cardiovascular disease (CVD) development (18).Pregnancy causes dramatic changes in the hemodynamics and an approximately 50% increase in the cardiac output If pregnancy is a stress test for CVD in later life, we can identify the individual risks of CVD during pregnancy. Although previous researchers have evaluated the association between maternal complications and CVD development, data on maternal complications are insufficient for all women to evaluate their own risks of CVD.(19). Our results revealed retrospectively that a 10 mmHg increase in the averaged DBP during pregnancy was associated with a 1.70-fold increase in the risk of hypertension later in life. We also found that blood pressure during puerperium is not associated with the development of hypertension. These results suggest that blood pressure during pregnancy is associated with an individual’s underlying risk of CVD; nevertheless, the mechanism behind this association was not discussed in our previous study.In our previous study, we hypothesized that women with a greater number of CVD risk factors would be less able to adapt to their physiological changes, allowing blood pressures during pregnancy to reflect the risk of CVD In this study, we hypothesized that changes in blood pressure during pregnancy are associated with the risk of CVD. To evaluate this hypothesis, we conducted a retrospective study among middle-aged women and investigated whether changes in blood pressure during pregnancy would be a risk of developing hypertension, which is a main risk of CVD, by collecting Maternity Health Record Books, which contain pregnancy records.2. The presence of hypertension was determined based on the usage of antihypertensive medications or high blood pressure (over 140/90 mmHg) at the time of the study.This retrospective study evaluated data from the Iwaki Health Promotion Project, a longitudinal, observational study of adult men and women who live in the Iwaki area . The Iwaki cohort has been studied since 2005 and includes approximately 1,000 participants per year . Trained staff recorded the participants’ heights, weights, blood pressures, histories of tobacco and alcohol use, and histories of illnesses. The blood pressure was measured using standardized methods, while the body mass index (BMI) was calculated in kg/m(20).We used data from the Maternity Health Record Books of middle-aged women. All pregnant Japanese women receive a Maternity Health Record Book that contains their medical history and demographic information, including their body weight, abdominal circumference, uterine fundus height, blood pressure, and the presence or absence of proteinuria, glycosuria, and edema; these data are recorded every 1-4 weeks depending on the gestational week. Attending physicians also record information regarding the neonate and the course of delivery. These records are occasionally used as a reliable information of health checkup for infants and vaccination, and many Japanese women keep these books for decades after delivery. Several previous studies have used similar techniques to obtain perinatal data (21). We examined the first pregnancy of each participant, because it allowed for a longer observational period and because the incidence of hypertensive disorders of pregnancy (HDP) is the highest in the first pregnancy. Twenty-three women who developed HDP were excluded from the study, because HDP is a risk factor for hypertension later in life (15). The diagnosis of HDP was based on the criteria of the Japan Society for the Study of Hypertension in Pregnancy (2018) (22). Thirteen women were further excluded due to a lack of data. Data from the first singleton pregnancy of 520 participants were included in the final analysis. Of the 520 participants, 138 were divided into the hypertensive group according to the criteria of receiving antihypertensive medications or blood pressures of ≥140/90 mmHg. The remaining 382 were defined as the normotensive group, that is, the control group.We collected 1,366 Maternity Health Record Books from 735 parous women between 2011 and 2015. From them, we selected 556 participants who (1) were over 40 years old, (2) had a singleton pregnancy, (3) had records of at least five blood pressure measurements during pregnancy, (4) had delivered at least 5 years before the study, and (5) did not have hypertension before pregnancy . In thisThis study was approved by the Hirosaki University Graduate School of Medicine Ethics Committee  and was performed according to the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All patients provided informed consent for their participation in this study and the publication of their data.t-test and the chi-square test. The mean SBP/DBP values during gestational weeks 12-41 and in each trimester were obtained for each participant. Differences in the SBP/DBP in each gestational period and 1 month postpartum between the hypertensive and normotensive groups were also compared using Student’s t-test.Participants’ characteristics were compared between the hypertensive (developed hypertension later in life) group and the normotensive group using Student’s The mean values for SBP and DBP during gestational weeks 12-41 were obtained for each patient. The patients were grouped into quartiles (Q1-Q4) according to their mean SBP/DBP and the differences between blood pressures at 1 month postpartum and each gestational month were compared. We used data in 1 month postpartum as data in nonpregnant status at that time. Differences in blood pressure were converted into percentages, and the second, third, and fourth quartiles were compared with the first quartile using the Mann-Whitney U test.All statistical analyses were performed using SPSS version 22 , and differences were considered statistically significant at p < 0.05.The mean age, BMI, and SBP/DBP were higher in the hypertensive group than in the normotensive group. The proportion of women at menopause was higher in the hypertensive group than in the normotensive group. These differences were consistent with the characteristics of hypertension. Alcohol consumption is a known risk factor for hypertension; nevertheless, in this study, the percentage of habitual alcohol drinkers was higher in the normotensive group than in the hypertensive group. Almost all participants had a normal course of pregnancy.This study is the first to investigate whether changes in blood pressure during pregnancy would be a risk of developing hypertension. We found that blood pressure changes during pregnancy varied between individuals, and these differences were associated with the risk of developing hypertension.(23). Thus, highly cost-effective measures are needed to prevent and treat CVD. Many previous reports indicated the possibility that pregnancy itself would be a useful stress test for CVD (25). If pregnancy itself is used as a stress test for CVD, even normal pregnancy could expose the underlying risks of CVD. Nevertheless, previous studies have not discussed this theme in detail. Our previous research revealed that DBP during normotensive pregnancy was statistically associated with the risk of developing hypertension (19). In this study, we compared the changes in blood pressure during pregnancy between four quartiles divided by the mean value of blood pressure during pregnancy. Our results revealed that higher mean blood pressure during pregnancy was associated with smaller changes in blood pressure during pregnancy. Additionally, women whose blood pressures were high showed an apparent tendency to develop hypertension. We also showed that there were significant differences in blood pressure during pregnancy between the current hypertensive group and the normotensive group. However, in the nonpregnant status at that time, these two groups did not indicate any differences in blood pressure. These findings might indicate that women who have stiffened blood vessels are unable to have sufficient reduced levels of blood pressure during pregnancy. If this hypothesis is true, the information regarding blood pressure during pregnancy would be a useful predictive marker for the development of hypertension.CVD accounts for 30% of deaths worldwide and is associated with heavy medical and economic burdens This study had three limitations. First, we only evaluated data from women with Maternity Health Record Books. Approximately 30% of parous women brought these books, which may have resulted in selection bias. Second, participation in the Iwaki Health Promotion Project is voluntary, and the project’s participants may represent a subset of healthy patients with a low incidence of hypertension. To avoid selection bias, a longitudinal study using hospital records is needed in the future. Third, the participants of this study were from a rural area in Japan. Hence, it may not be possible to generalize our findings to other populations.In conclusion, we found that pregnant women with high blood pressure showed a small decrease in blood pressure during pregnancy and that these women developed hypertension at a high rate. These results can be used to facilitate highly cost-effective screening and interventions for women with a high risk of CVD. However, our study was small-scale and did not include basic research. Therefore, to elucidate the association between pregnancy and the risk of CVD, further studies are required.Hideki Mizunuma Deceased July 9, 2020.NoneThis work was supported by KAKENHI (18K16753), Japan Society for the Promotion of Science (JSPS).H. Mizunuma and K. Iino designed this study. T. Higuchi, H. Mizunuma, K. Tanaka, Y. Yokoyama, and K. Iino interpreted data. K. Iino collected and analyzed data. K. Iino and H. Mizunuma wrote the report. H. Mizunuma and S. Nakaji managed this study.This study was approved by the Hirosaki University Graduate School of Medicine Ethics Committee. Approval code; 2011-033, 2012-050, 2013-062, 2014-014, 2014-377-1.


A concerning number of kidneys  are discarded yearly while patients experience significant morbidity and mortality on the transplant waitlist. Novel solutions are needed to solve the shortage of kidneys available for transplant. Patient perceptions regarding the use of these less than ideal kidneys remain unexplored.To explore the perspectives of patients who have previously received a less than ideal kidney in the past and patients awaiting transplant who could potentially benefit from one.Qualitative description study.2 provinces in Canada participated (Saskatchewan and Manitoba).Patients with end-stage kidney disease who were awaiting kidney transplant and were either (a) aged 65 years and older, or (b) 55 years and older with other medical conditions .Criterion sampling was used to identify participants. Semi-structured, one-on-one interviews were conducted virtually, which explored perceived quality of life, perceptions of less than ideal kidneys, risk tolerance for accepting one, and educational needs to make such a choice. The interviews were transcribed verbatim and thematic analysis was used to analyze the data.15 interviews were conducted with usable data . Participants were a mean of 65.5 ± 8.8 years old. Four interrelated themes became prominent including (1) patient awareness and understanding of their situation or context, (2) a desire for information, (3) a desire for freedom from dialysis, and (4) trust. Subthemes of transparency, clarity, standardization, and autonomy were deemed important for participant education. The majority of pretransplant participants (n = 8/10) indicated that between 3 and 5 years off of dialysis would make the risk of accepting a less than ideal kidney feel worthwhile.The study setting was limited to 2 Canadian provinces, which limits the generalizability. Furthermore, the participants were homogenous in demographics such as ethnicity.These findings indicate that patients are comfortable to accept a less than ideal kidney for transplant in situations where their autonomy is respected, they are provided clear, standardized, and transparent information, and when they trust their physician. These results will be used to inform the development of a new national registry for expanding access to deceased-donor kidney transplant.Not registered. While aggregate statistics on discarded kidneys are not available in Canada, data indicate that nearly 1 in 5 kidneys available for transplant in the United States are discarded. Novel efforts for optimizing organ use are urgently needed to mitigate this mismatch.Kidney transplantation has revolutionized the treatment of end-stage kidney disease; however, the shortage of donor kidneys remains a critical barrier. In 2019, more than 3000 Canadians were on the kidney transplant waitlist, but only 54% received a transplant. Kidneys retrieved from expanded criteria donors (ECDs), defined as those obtained from deceased donors ≥ 60 years, or donors aged 50-59 years with 2 of following: cerebrovascular cause of death, terminal serum creatinine > 132.6 μmol/L (1.5 mg/dL), or history of hypertension, are more likely to be discarded.6 In an analysis of registry data (October 1999 to June 2005) nearly half  of ECD kidneys were not used. Further work has highlighted a significant variation in acceptance rates of lower quality organs between settings, suggesting that kidneys considered unusable by 1 transplant center, could be acceptable for another.7 Potential wastage must be critically examined, as many patients may derive a survival benefit from an ECD kidney transplant, when compared with remaining on dialysis while awaiting a better organ offer.9 Less-than-ideal (LTI) kidneys  may be of particular benefit for those who are older or at decreased likelihood of receiving a kidney.Kidneys are discarded for a myriad of reasons, with 2 of the top predictive factors being donor age and creatinine. CBS is exploring a national registry for patients who may be interested in receiving a transplant that is considered LTI but acceptable. A registry could optimize the use of deceased-donor kidneys by standardizing practice, providing a mechanism for offering/sharing organs, enhancing transparency and efficiency, and offering new transplant opportunities for dialysis patients.Canadian Blood Services (CBS) is a not-for-profit organization that collaborates with the Organ and Tissue Donation & Transplantation (OTDT) community to improve national system performance, including managing clinical programs that support interprovincial sharing of organs. there is a lack of data describing what Canadians with kidney disease think about LTI kidneys. Previous studies have investigated transplant candidates’ understanding and preferences on increased risk/marginal donors,1216 but use of LTI kidneys remains inconsistent and unexplored. A recent qualitative study in the United States explored perspectives on high kidney donor profile index (KDPI) kidneys (KDPI > 85). Interviews were conducted with clinicians , and patients (pretransplant and posttransplant) to characterize experiences on consent, education, and the decision-making process. A local study on LTI kidneys is necessary to underpin a national initiative to maximize and standardize use in Canada, with particular focus on patients who may be interested in such a registry. The purpose of this study was to specifically explore the perspectives of those who have previously received an LTI kidney and those who may benefit from this type of transplant. We also sought feedback on what education would be required to support an informed decision to accept an LTI kidney.Although patient-centered priorities are key for successful implementation of health care interventions, study was undertaken in 2 Canadian provinces (Saskatchewan and Manitoba). This study was approved by the University of Saskatchewan Behavioural Ethics Board and all participants provided informed consent (Beh #2764).A qualitative description was used, whereby potential participants were identified by transplant nephrologists at the Saskatchewan Transplant Program and Transplant Manitoba and provided with an invitation letter. A research team member contacted patients who expressed interest in learning more about the study.To explore the perspectives of those who may benefit from an LTI transplant, we included patients with end-stage kidney disease who were awaiting kidney transplant and were either (1) aged 65 and older, or (2) 55 and older with other medical conditions . These parameters were chosen as they best represented the perceptions of the population of interest . We also included patients who had received a kidney transplant which was described by their physician as ECD (or synonymous terms), to learn what patients would have liked to know with the benefit of hindsight. Criterion samplingSupplemental Appendix A) consisted of exploratory questions pertaining to 4 domains: perceived quality of life (QOL), perceptions of LTI kidneys, risk tolerance for accepting an LTI kidney, and educational needs. Questions to the pretransplant cohort were posed to evaluate perspectives on their condition, perceptions of LTI kidneys, transparency of the process and to speculate and evaluate how a hypothetical kidney may benefit them. To investigate risk tolerance, a case-based scenario was used.21 The posttransplant group was asked about their current perspective on their health status and the impact of their transplant, LTI kidneys in general, transparency of the process in relation to LTI kidneys, and to speculate on how a hypothetical kidney may serve someone other than themselves. Self-reported demographic data including mode of dialysis, residence location, gender, marital status, education, and ethnicity were collected. The one-on-one (1 time) interviews were conducted virtually using the Webex Cisco platform. A University of Saskatchewan  graduate student in public policy with experience in performing interviews, and not known to the participants (C.R.), conducted the meetings. The student, who did not have a background in transplantation, came to the project with an interest in deliberative dialogue and participatory policy-making. Field notes were made during the interview to provide context to the data. An honorarium of CAD $75 was provided to participants.A semistructured interview guide was created by 4 members of the research team . It was reviewed by the rest of the research team and the CBS steering committee . The interview guide, which was inductive in nature  created the initial codes and managed the data set. H.M., N.R., and C.R. met on multiple occasions allowing for reflection, discussion, code, domain, and theme relabelling, and refinement. During the first phase and second phase , the transcripts were read multiple times, and the audiotapes were reviewed as needed to verify the data. A variety of semantic and latent codes were applied through the first pass through the data, at which point it was determined that a code book would be useful for organizing the semantic codes according to domains. To manage the varying perspectives (prospective vs retrospective), the pretransplant and posttransplant groups were initially coded separately. During phase 3 (generating themes), codes were collapsed into draft themes and subthemes. In phase 4 , the themes were reviewed within each cohort (pretransplant vs posttransplant), and across the data set. During phase 5 (defining and naming them), the themes and subthemes were reviewed for internal homogeneity and external heterogeneity and related back to the research question. During phase 6, the report was produced and sent to the participants who were asked whether there was any additional information that should be added.Interviews were transcribed by the Canadian Research Hub and anonymized. Transcriptions were input into NVivo12  and reflexive thematic analysis, as described by Braun and Clarke,The research associate contacted the 37 patients that expressed an interested in learning more about the study. Of them 16 agreed to be interviewed , but 1 pretransplant participant’s audiotape was inaudible and therefore 10 were used in the analysis. Of those who did not participate, patients either did not answer the phone or declined. The reasons for not participating were not explored in further detail. After approximately 9 interviews, the content seemed to be largely repetitive and the key themes that emerged were reinforced through the subsequent interviews. After member checking, some participants reiterated existing information  but no information was volunteered that changed the interpretation of the data or the resulting report. The interviews lasted between 15 and 35 minutes . The participants ranged in age from 55 to 76 years and majority (73%) were male. very poor, 5 = very good), and to describe the reason for their QOL rating. To obtain a sense of impact of disease, posttransplant participants were also asked to indicate how their transplant has affected their QOL on a scale of 1-5    and 4.Four overarching themes became prominent after the data were analyzed. These included (1) patient awareness and understanding of their situation or context, (2) a desire for information, (3) a desire for freedom from dialysis, and (4) trust. These themes were consistent amongst both the pretransplant and posttransplant participants. The posttransplant cohort had the benefit of hindsight, and reinforced (with more confidence) the sentiments expressed by the pretransplant cohort. The posttransplant cohort also had firm interpretations on their improvement to QOL. Participants in this study expressed an awareness and understanding of their clinical situation and complexities of the transplant process, as well as the potential benefits and risks of (a) accepting a transplant and (b) accepting an LTI kidney. The benefits of accepting any type of transplant included freedom from dialysis , the ability to travel (cited 9 times), QOL improvement (7), health and life expectancy benefits (5), and a perceived return to normalcy (11). Risks of remaining on dialysis included associated illness (cited 10 times), lack of energy (14), inability to undertake activities, or lack of freedom (10).It[the risk]’s more centered on how long it would last than how effective it would work. . .I mean you’re not gonna go through all of that surgery and recovery and all of that and then only have six months. It’s not really worth it to go through all that.The risks of accepting a transplant were referenced 16 times throughout the data without query, and the risks of accepting an LTI kidney were mentioned 28 times with prompting. The potential for decreased longevity with an LTI kidney was the most concerning risk, accounting for 18 of the 28 references. According to participant 7 (pretransplant),One consistent trend within this theme was that patients were aware and accepting of the risks associated with LTI kidney transplant. Many patients articulated risks associated with transplant  and proceeded to engage rationally with that risk. Participant 3 (posttransplant): “I’d say there’s risks, there’s also benefits. You have to decide if you want to accept the risk and if somebody doesn’t—I mean it’s an individual choice—and that’s fine.”Participants also articulated an understanding of scarcity of kidneys for transplant and a reasonable understanding of the challenges of allocation. Interestingly, patients seemed to evaluate the risk of transplantation in reference to their age and scarcity of resource suggesting an understanding and calculation about how they would like to spend the “time they had left.”Participant 6 (pretransplant) said, “Well, people are dying waiting for an optimal kidney, and if this has a possibility of extending their lifespan even though it may not be an ideal kidney, compared to death, some quality of life would be of benefit.”supplementary materials), participants in the pretransplant group were asked how many dialysis free years would make the risk of accepting an LTI kidney feel worthwhile. The majority of participants (n = 8/10), responded with a number between 3 and 5 years, while 1 participant responded with a year or less. An outlier (participant 6) responded with 15 years. According to participant 12 (pretransplant): “In my case, I’m 74. If it gave me—I don’t know—anywhere from say without any other problems, five to ten years of more life might be acceptable, right?” The posttransplant recipients were instead asked whether they would make the same decision to accept an LTI kidney. Four out of 5 participants said yes and indicated they would sign up for such a registry.Using the case-based scenario , “You have to remember there’s a whole element of emotional turmoil associated with getting ones hopes elevated and then bashed. That’s a big issue.”Patients expressed a desire for the medical system to express, in clear and understandable terms, both the quality of kidneys presented to them, as well as their expected outcomes in receiving a transplant. Historically, terms such as ECD or marginal have been used as descriptors. When asked what patients perceived to be most appropriate for this type of kidney, clear terminology such as “less than ideal” was preferred by 8 of 15 participants. According to participant 11 (pretransplant), “It’s straightforward, it’s not wishy washy with fancy words.”Patients indicated a need for standardized education about the various types of kidneys, and potential outcomes associated with that choice. They articulated a need for this information to be presented to them during the assessment process. They recognized that they may be on the waitlist for significant periods of time, and they recommended that terminology remain consistent throughout the assessment process, waitlist, and transplant process. There was the sense that this standardization would contribute to patient comprehension, which also underpins both autonomy and trust in their physician and health care system.In addition to the desire for standardization from a “personal journey” perspective, uniformity was also perceived to be important for the registry, with consistent definitions and criteria for offers applied nationally. One of the interview guide questions asked participants to consider a scenario where an LTI kidney offer was declined by 1 program, only to be utilized for transplant by another. One participant expressed concern that lack of standardized criteria could lead to a missed opportunity. Participant 1 (pretransplant), “Especially if they turn around and offer it [the kidney] to somebody else.” This can be interpreted as a desire for national standardization to ensure that local standards do not result in missed opportunities.Several (8) participants expressed a desire for their personal health care decisions to be respected. This concern for autonomy was clear but qualified with a desire to be equipped with appropriate and understandable information on which to base personal health decision-making. Participant 8 (posttransplant) stated, “I think it [education about LTI kidneys] should all be done beforehand.”Participants in the pretransplant and posttransplant cohort perceived transplantation as the ultimate solution to become free from dialysis. Participant 8 (posttransplant) stated, “I just kind of want some relief and get the hell off of dialysis.” Even though most participants were of retirement age, they regarded dialysis as a significant prohibition to activities that would improve their quality of life, such as traveling, visiting with grandchildren, or pursuing personal interests. According to Participant 3 (posttransplant), “It just ties up your life so much. It’s like you’re existing, you’re not really living.” Participant 14 (pretransplant) said, “Now that I’m stuck this in place, I think even if you had the opportunity to have a kidney that was 50% or 60%, it’s better than no kidney.”overt mention of their trust in their physicians and the medical institution. This was consistent throughout both the pretransplant and posttransplant groups. In this context, we note institution in reference to “the medical system”—many patients stated or implied that they trust that organs will be distributed in a fair and equitable manner that maximizes utility. Notably, the posttransplant group were more inclined to highlight their trust in their transplant team, in addition to their physician.The final theme explicated in this study was sense of trust, which was consistent in the interviews but not universal. Of the 16 participants, 12 patients made an I would probably leave it in the hands of the medical professionals as to what would be considered a viable kidney to transplant or not. I think if it was up to the patients or if they had some input, there might be some people willing to accept basically any kidney at all and I think a medical professional would be in a better position to determine what would be suitable and appropriate than a patient.The majority of patients expressed that they generally trusted doctors to both screen out kidneys that were inappropriate for them and guide them through evaluating kidneys that the physician’s deemed viable. According to participant 9 (posttransplant), “No, I don’t need a guarantee, what I need is an opinion and that’s why I have a doctor is because I trust them.” Participant 9 (pretransplant) stated,(theme 1: patient awareness and understanding of context). The risks associated with surgery, immunosuppression, and recovery time were cited frequently, suggesting an awareness of the ongoing care required for older individuals, while balancing the desire for freedom from dialysis even though there may be a shortened duration of benefit. Of note, we anticipated the participants to be tentative in explaining their opinions on the novel concept of accepting an LTI kidneys and had expected this topic would require explanation and discussion. Participants, however, were decisive and confident in their responses; on average the interviews took about 25 minutes because participants were able to articulate these opinions clearly and succinctly.Four interrelated themes describe transplant patient perspectives on expanding access to deceased-donor kidneys. First, participants acknowledged that organs for transplant are a scarce resource and an understanding of how their age will affect their opportunity to receive and benefit from a kidney transplant 21 Participants also articulated a desire for freedom from dialysis citing disadvantages such as the inability to travel or pursuing personal interests which would improve their quality of life . Given that our study population was older with comorbidities, this finding is noteworthy, as it indicates that the dialysis-associated costs to these patients could be as significant as the inability to participate in the economy or socialize might be to a younger patient. It also supports the use of LTI kidneys for transplant to facilitate freedom from dialysis for patients in older age groups.Patients were able to use their comprehension to assess a cost-benefit analysis for accepting an LTI kidney, and most participants indicated they would accept an LTI kidney now if it gave them 3-5 years of freedom from dialysis, while accepting that long-term graft survival may be reduced. This is in line with other work showing that patients are willing to accept higher risk organs, particularly when their clinical situation is deteriorating.theme 2: desire for information). Participants repeatedly indicated that education presented with transparency, clarity, and standardization was important to them. Information provided in this way contributes to trust in the health care system (theme 4: trust) while retaining the autonomy to make supported choices about their health (theme 2: desire for information). In our study, as in others, patients had a strong desire to be involved in the decision-making process.25 Standardization emerged as a theme to ensure an “equal footing” between patients within a program as well as nationally to ensure that local opportunities are not missed. This suggests that the proposed national program should consider the application of standardized terminology and teaching to allow for informed decision-making by both health care providers and patients. Participants require such education both during the assessment period and when they are offered a kidney. During the time of the offer, they would appreciate information about the nature of the kidney being offered and the anticipated clinical course from accepting the organ. Like other work, participants indicated that specific features about the donor and the plausible risks may impact their choice,26 and that they generally trusted doctors to screen out kidneys that were inappropriate for them and guide them through the decision-making process. This suggests that while patients desire information and agency in their interaction with the medical system, special attention and careful dialogue is preferable from a patient perspective; thoughtless interaction with patients can lead to significant disappointment and emotional turmoil.Valuable insights were garnered on the type of education required for patients considering an LTI transplant  Saskatchewan Transplant Program at the time . A future study, however, is needed to explicitly explore the perspectives of patients who identify as First Nations or Métis, or other populations who may be under-represented on the waitlist, or who may have different perspectives based on varying levels of trust of the health care system. While this study provided insights from Canadian patients on LTI kidneys, it was only was just a starting point. Further consultations are needed to guide the development of a new registry, such as delving further into specifics about the ideal timing of the education, and patient understanding of risks and benefits of receiving an LTI kidney.Participants in this study exhibited a self-awareness and understanding of their clinical situation and context and were able to articulate a risk-benefit calculation for accepting an LTI transplant. In order to feel most comfortable with decision-making, they require clear and digestible education that remains consistent until the time of their transplant offer. They need their education and transplant offers to be honest and transparent to allow them to exercise their autonomy while maintaining trust in their physician and the system. When these conditions exist, patients are willing to accept LTI kidneys to obtain freedom from dialysis. Transparency, clarity, and consistency, and respect for autonomy should be key tenets in the movement toward more successful use of LTI kidneys.Click here for additional data file.Supplemental material, sj-docx-1-cjk-10.1177_20543581221100291 for Waitlisted and Transplant Patient Perspectives on Expanding Access to Deceased-Donor Kidney Transplant: A Qualitative Study by Canute Rosaasen, Nicola Rosaasen, Rahul Mainra, Aaron Trachtenberg, Julie Ho, Christina Parsons, Sean Delaney and Holly Mansell in Canadian Journal of Kidney Health and Disease


Clinical studies on ambulatory blood pressure (BP) have shown that increases in BP values, particularly at nighttime, are associated with cardiovascular (CV) morbidity and mortality , 2. AccoIn this Research Topic, we have included several articles trying to further elucidate the relationship between sleep disorders (particularly OSA), systemic arterial hypertension, and CV disease. OSA is indeed the most common sleep-related disorder and is associated with hypertension and CV comorbidities. It affects 10% of adult females and 20% of males with prevalence that can rise up to 40–90% in specific subgroups like patients with severe obesity .Bock et al. it was hypothesized that central adiposity measured by the waist-to-hip ratio (WHR), which appears to be more closely related to the presence of OSA as compared to the body mass index (BMI)  , might bArachchige and Steier. They comprehensively described all possible types of OSA treatment available nowadays, including several non-CPAP strategies, such as hypoglossal nerve stimulation and transcutaneous approaches . This device can be used in treating SDB in patients with heart failure (HF) and provide information about their residual respiratory events  on blood pressure (BP) and vascular function. IMST is performed on a portable hand-held device and entails repeated inspiratory efforts against a resistance. It is a simple and time-efficient breathing exercise consistently reported to reduce systolic BP, sympathetic nervous system activity, and endothelial dysfunction in small, selected groups of healthy and high-risk populations at a short-term follow-up (Lastly, in the field of OSA treatment and its CV complications, the study protocol by ollow-up . NeverthSleep disorders, hypertension and cardiovascular diseases” Research Topic met its objectives by making a significant contribution to a number of different areas of this field, even though there are still many aspects that need to be resolved and better understood regarding the association between sleep disorders and cardiovascular diseases. We hope that the readers will find this Research Topic inspiring and helpful in both research and clinical management of OSA.Overall, we think that the “All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.


Open thoracoabdominal aortic aneurysm (TAAA) repair is a complex and challenging operation with a high incidence of serious complications, and high perioperative mortality and morbidity. Left heart bypass (LHB) is a circulatory support system used to perfuse the distal aorta during TAAA operation, and the advantages of LHB include guaranteeing distal perfusion, reducing the use of heparin, and diminishing the risk of bleeding and postoperative neurological deficits. In China, the circuit for TAAA repair is deficient, and far from the perfusion requirements. We designed a modular multifunctional LHB circuit for TAAA repair. The modular circuit consisted of cannulation pipelines, functional consumables connection pipelines, and accessory pipelines. The accessory pipelines make up lines for selective visceral perfusion and kidney perfusion, suckers and rapid infusion. The circuit can be assembled according to surgical requirements. The ultrafilter and heat exchanger are integrated into the circuit to fulfill the basic demands of LHB. The LHB circuit also has pipelines for selective visceral perfusion to the celiac artery and superior mesenteric artery and renal perfusion pipelines. Meanwhile, the reserved pipelines facilitate the quick switch from LHB to conventional cardiopulmonary bypass (CPB). The reserved pipelines reduce the time of reassembling the CPB circuit. Moreover, the rapid infusion was integrated into the LHB circuit, which can rapid infusion when massive hemorrhage during the open procedures such as exposure and reconstruction of the aorta. The ultrafiltration can diminish the consequent hemodilution of hemorrhage and rapid infusion. A hemoperfusion cartridge also can be added to reduce the systemic inflammatory during operation. The circuit can meet the needs of LHB and quickly switch to conventional CPB. No oxygenator was required during LHB, which reduce the use of heparin and reduce the risk of bleeding. The heat exchanger contributes to temperature regulation; ultrafiltration, arterial filter, and rapid-infusion facilitated the blood volume management and are useful to maintain hemodynamic stability. This circuit made the assembly of the LHB circuit more easily, and more efficient, which may contribute to the TAAA repair operation performed in lower volume centers easily. 26 patients who received TAAA repair under the modular multifunctional LHB from January 2018-March 2022 were analyzed, and we achieved acceptable clinical outcomes. The in-hospital mortality and 30-day postoperative mortality were 15.4%, and the postoperative incidences of paraparesis (4%), stroke (4%), and AKI need hemodialysis (12%) were not particularly high, based on the limited patients sample size in short research period duration. Open thoracoabdominal aortic aneurysm (TAAA) repair is a complex and challenging operation including extensive exposure and reconstruction of the thoracoabdominal aorta and vital aortic branches . Open TALeft heart bypass (LHB) and cardiopulmonary bypass (CPB) with or without hypothermic circulatory arrest are important perfusion-assisted techniques strategy for organ protection in TAAA repair. LHB is a widespread circulatory support system used to perfuse the distal aorta during TAAA operation, and the advantages of LHB include guaranteeing distal perfusion, reducing the use of heparin and diminishing the risk of bleeding and postoperative neurological deficits , 9. The We designed a modular multifunctional LHB circuit that can be assembled according to surgical requirements for TAAA repair.The LHB circuitry is modified to accommodate surgical needs specific to the surgical procedure. The LHB circuit is used for patients undergoing Crawford extent II TAAA repair to extend from the left subclavian artery down to the aortic bifurcation organ perfusion. LHB can provide isothermic self-oxygenated blood while the proximal anastomosis is being completed, so the cardiac function and pulmonary function should meet systemic oxygenation and perfusion.The circuit consists of reusable equipment and disposable. The pipelines of the LHB circuit mainly consist of three supplied sterile and individually wrapped bags as shown in The LHB circuit mainly includes three parts: cannulation pipelines, functional consumables connection pipelines, and accessory pipelines. The accessory pipelines make up lines for selective visceral perfusion, kidney perfusion, suckers and rapid infusion.The cannulation pipelines are shown in adapter, which can be connected to a pressure monitor, and an arterial sampling connector. The sealed port E and port E’ were a pair of ports for an ultrafilter. Both the port T1 in the T-type adapter on the right side is connected to a pressure monitor, and also connect to the port T1  with 30 mg heparin was added to the hard-shell reservoir A in  as a pricoagulation time (ACT) and mixed venous oxygen saturation (SvO2) are examined when the central venous line is placed successfully.All patients are intubated with a double-lumen endobronchial tube for later single right-lung ventilation. The blood pressures of the right radial or brachial for the upper limb monitoring, and the dorsal pedis artery for the lower limb in the opposite of the fusion cannulation in the iliac artery or femoral artery. A large-bore triple lumen central venous line is placed in the right internal jugular vein for central venous pressure monitoring, fluid infusion, anesthetics and vasoactive medications infusion, followed by the insertion of an 8.5F catheter sheath for fluid and blood rapid infusion. Transesophageal echocardiography (TEE) is also monitored to assess the hemodynamics and cardiac function changes. Cerebral oximetry is measured with near-infrared spectroscopy (NIRS), and the depth of anesthesia is also evaluated using the bispectral index (BIS). A temperature probe is positioned in the patient’s nasopharynx for temperature monitoring. Moreover, a urethral catheter integrated with a temperature probe is placed for urine output and temperature management. Self-adhesive defibrillation electrodes were located on the chest wall, and an external defibrillator is a standby. Cell-saving and rapid-infusion devices are set up so that shed blood can be salvaged and volume can be rapidly replaced, respectively. The baseline of activated The inferior left pulmonary vein is the routine site of atrial cannulation for the outflow line, and the proximal abdominal aorta, the iliac artery, or the femoral artery is selected to establish an inflow line. Heparin is administered intravenously at a dose of 1.5 mg/kg cannulation performs until the patient’s ACT is verified to be more than 280 s. A 22- or 24-Fr angled-tip venous cannula is connected to the outflow line of the LHB circuit, which is named C1 in The LHB is initiated at a flow rate of 0.5 L/min after the ACT > 280 s, and the cannulation is performed and connected to the circuit correctly. Pay more attention to the drainage and perfusion pressure, the drainage is evaluated by the movement of cannulation in the pulmonary vein caused by the vacuum, and the perfusion pressure is read from the pressure monitor. The cannulation of pulmonary vein and artery are adjusted to maintain sufficient blood can be drained from the left heart to perfuse the lower body. The distal aortic perfusion mainly relays on the LHB flow rate when an aortic cross-clamp is applied. The flow rate is 2.5–3.5 L/min to keep the patient’s mean arterial pressure (MAP), both the upper limb and lower limb, maintain in the range of 70–90 mm Hg. The reserved pipeline marked B in Overall, the rapid infusion system the 8.5F catheter sheath can afford high to 1,000 ml/min warming fluid delivery to fulfillment of the volume demands of patients. Whereas the reserved rapid infusion modular will be applied, when the fusion flow is hard to successfully maintain the target MAP due to massive blood volume lost in the condition of catastrophic bleeding or aneurysm rupture. Our reserved hard-shell reservoir and pipelines can afford a more rapid infusion rate. Like the structure in The intercostal and/or lumbar arteries, which are the main feeding artery of the spinal cord, should be revascularized with one branch of the aortic graft. During the reimplantation period, the MAP is kept relatively high  as part of a spinal protection strategy. Meanwhile, the temperature sustains at a relatively lower level near 34°C, which is another spinal cord protection strategy. It is better to enhance the hematocrit by ultrafiltration, and blood transfusion. Rewarming the patient to keep the Nasopharyngeal temperature near 36°C when the intercostal and/or lumbar arteries anastomosis is completed.Selective visceral perfusion and kidney perfusion are essential principles for TAAA repair during the abdominal aorta reconstruction, which aims to minimize the duration of abdominal-organ ischemia and reduce the incidence of renal and hepatic insufficiency, coagulopathy, and bowel ischemia. Selective visceral artery perfusion is performed with the oxygenated isothermic blood continuously delivered from the LHB circuit through a Y-type three-way connector of the perfusion line E in . A Y-braA renal perfusion system is used to maintain selective renal hypothermia for the preservation of renal function. The renal perfusion is conducted with the renal perfusion system, which is set up with a separated tube connected with a solution inlet, a Y-branch off the line connected with two10-Fr balloon catheters, which is placed in the renal arteries to accept the cold crystalloid perfusion. Cold crystalloid (lactated Ringer’s solution with mannitol and methylprednisolone or HTK solution in 4°C) is delivered with boluses of 200–400 mL intermittent by another roller pump, The cold crystalloid is administered every 6 min with a flow rate of 300 ml/min for 1–2 min, and the perfusion pressure should be less than 200 mmHg. Ultrafiltration and rewarm can be performed to alleviate the hemodilution and hypothermia due to the massive cold crystalloid solution perfusion. The urine volumes of renal in the periods of renal perfusion and post reimplantation should be evaluated, and diuretics can be administrated.The switch is implemented in the condition that the pulmonary function and cardiac function are far from covering the need for LHB. Our LHB circuit is integrated with reserved pipelines that can be switched to conventional CPB easily. Stop the LHB circulation, cut line C into two two-port C1 and C2, and C1 connects to venous cannulation or cavoatrial cannulation as venous drainage while port C2 connects to another arterial cannulation as perfusion line after cannulate is completed. move down the hard-shell reservoir A in , which i1 (No. ChiCTR2200058222).We retrospectively analyzed the clinical data of patients undergoing TAAA repair under LHB from 2017 to 2022. This retrospective study was approved by the Committee on the Medical Ethics of Xiangya Hospital, Central South University (No. 202101022), and the requirement for informed consent was waived because of the retrospective design. Trial registration was performed in the Chinese Clinical Trial RegistryWe analyzed 26 patients that received TAAA repair under the modular multifunctional LHB from January 2018-March 2022 in Xiangya Hospital, Central South University. The demographic characteristics and extent type of TAAA were shown in The results of blood product transfusion were listed in t-tests for the preoperative and the first day of postoperative data. The results showed that Hb and Platelets were significantly decreased after surgery, and NT-proBNP, Urea, creatinine (Cre), direct bilirubin (DBil), Total bile acid (TBA), lactate dehydrogenase (LHD), creatine kinase (CK), Myoglobin (Mb), prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FIB), D-Dimer (D2) were rapidly increased. No significant difference was found in the comparison of the levels of Troponin I, Uric acid, alanine aminotransferase (ALT), and aspartate aminotransferase (AST), and creatine kinase-MB isoenzyme (CK-MB). The details were listed in Finally, 22 patients were cured and discharged from the hospital, one of the 26 patients died in the operation due to bleeding, and three died in the hospital after the repair. No more patients died during the 30-day postoperative. Two patients required re-exploration for bleeding. The permanent spinal cord deficit appeared in two patients, and one was paraparesis while another one recovered. One patient had a stroke after surgery. Three patients who got acute renal injury (AKI) need hemodialysis. Pneumothorax was the most frequent adverse event after repair with nine patients. The causes of death were postoperative rupture, multiple organ dysfunction syndromes, and severe infection, and all of them were Extent II with a long length of surgery and LHB duration. The postoperative mechanical ventilation time was 20.6 ± 16.1 h, the length of ICU stay was 72.5 ± 46.5 h, and hospital stay time was 13.8 ± 7.1 days for the patients cured and discharged . MeanwhiAs a non-high-volume center, we achieved acceptable clinical outcomes for patients who received open TAAA repair under LHB. The in-hospital mortality and 30-day postoperative mortality were 15.4%, and the postoperative incidences of paraparesis (4%), stroke (4%), and AKI need hemodialysis (12%) were not particularly high, based on the limited patient’ sample size in short research period duration. The mortality was 15.4%, which may blame the following factors. The characteristics of patients indicated that high to 69% of patients suffering from type II TAAA, which involves the reconstruction of descending thoracic aorta and abdominal aortic aorta with long-lasting anastomoses and a massive trauma for the patient. Moreover, more patients failed endovascular repair and re-intervention after endovascular repair cases, which made the surgical procedure more complicated. The integrated management of LHB including spinal cord protection and selective visceral perfusion and renal perfusion may contribute to the favorable results of our research.The morbidity and mortality of the open TAAA repair continue to remain considerable, despite the advances in open surgical techniques. In-hospital mortality ranges between 2.3%  and 32.7Both open surgical and endovascular repair of TAAA achieved excellent midterm results regarding mortality and the overall survival of patients . TAAA haLHB and CPB with or without hypothermic circulatory arrest, which is a highly invasive procedure may contribute to morbidity and mortality . A meta-Overall, LHB is achieved using a temporary bypass from the left atrium to either the distal descending thoracic aorta or the femoral artery with a closed-circuit in-line centrifugal pump . LHB canLHB, which requires limited anticoagulation, and mild passive hypothermia, could significantly diminish the influence on physiological functions. LHB appears to provide the greatest benefit to patients undergoing the more extensive repairs and reduced the incidence of spinal cord deficits in patients undergoing extent II repairs . The comThe traditional LHB circuit for the TAAA repair typically involves a simple circuit consisting of inflow and outflow lines, and a centrifugal head. The blood volume fluctuation is significant, and massive fluid and blood replacement are required rapidly, as a consequence of severe bleeding during extensive exposure and reconstruction of the thoracoabdominal aorta and its aortic branches. So excessive hemodilution, hypotension, and hypothermia may occur, even resulting in overwhelming hemodynamics changes. These conditions are a common phenomenon in the early stage of a low-volume center. Ultrafilter, heater exchanger, arterial filter, and rapid-infusion circuit were added to the classical LHB circuit to diminish to hazard the of profuse bleeding due to operation. The heater exchanger contributes to the temperature regulation; The ultrafilter, arterial filter, and rapid-infusion system facilitated the blood volume management and are useful to maintain hemodynamic stability.oxygenator. The cost difference between the new circuit versus the traditional circuit is unclear due to the limited data. The closed-circuit system of LHB cannot respond to sudden hemodynamic fluctuations during aortic clamping or catastrophic bleeding, so the rapid-infuser system and another infusion system should be implemented. Recent research found the reservoir-added centrifugal pump circuit system was an effective perfusion system for blood infusion to reduce hemodynamic fluctuations  is a common complication and is a significant risk factor for mid-term survival in patients undergoing TAAA repair. Preventing AKI can modify the mid-term survival after TAAA repair . Researcotection . The visotection . The midotection .The advantages of LHB include augmentation of distal perfusion and reduction of left ventricular strain by decreasing preload and afterload . MoreoveIn conclusion, the modular LHB circuit system is an effective, practical, and multifunctional perfusion system. The circuit can meet the needs of LHB and quickly switch to conventional CPB. This circuit also made the assembly of the LHB circuit more easily, and more efficient, which may contribute to the TAAA repair operation performed in lower volume centers easily.The original contributions presented in this study are included in the article/The studies involving human participants were reviewed and approved by Committee on the Medical Ethics of Xiangya Hospital, Central South University. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.CZ and LH: conceptualization. XC, QH, and FL: methodology. XC and CZ: software. CZ, QH, and EW: validation. ZY and CZ: formal analysis, writing—review and editing. QH, EW, and LD: investigation. CZ: resources, data curation, project administration, funding acquisition, and visualization. LH and JH: writing—original draft preparation. LH: supervision. All authors have read and agreed to the published version of the manuscript.


Ovarian cancer is one of the most common gynecologic cancers with the highest mortality rate in China. Acute kidney injury (AKI) is a postoperative complication associated with all-cause mortality. The incidence and risk factors for AKI after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) have not been fully elucidated. The purpose of this study was to determine the incidence and associate ed risk factors of AKI among those patients undergoing CRS-HIPEC.This retrospective study collected demographic, tumor-related, preoperative, intraoperative, and postoperative data from 282 advanced ovarian cancer patients who underwent CRS-HIPECs. AKI was defined and staged according to the clinical practice guideline of Kidney Disease Improving Global Outcomes (KDIGO) in 2012. The prognosis of AKI was determined according to the change in serum creatinine 90 days after the operation. We conducted univariate and multivariate logistic regression analyses to assess the association between variables of interest and the occurrence of AKI.2 ; Baseline eGFR<60 mL/min/1.73 m2 ; and concomitant medications of angiotensin convert enzyme inhibitor or angiotensin receptor blocker (ACEI or ARB) .Of 282 advanced ovarian cancer patients, 11.7% of them developed AKI. The Multivariate logistic regression analysis showed that the risk factors independently associated with AKI included cisplatin dose≥70mg/mOur study demonstrates that the incidence of AKI after CRS plus cisplatin-based HIPEC is not uncommon among advanced ovarian cancer patients. Cisplatin overdose, baseline kidney dysfunction, and use of ACEI or ARB are independent risk factors for the occurrence of AKI among those patients. Ovarian cancer has become one of the most common gynecologic cancers with the highest mortality rate in China , 2. As iHowever, there are also data indicating that the application of CRS plus HIPEC has some non-eligible complications, and most causes of systemic toxicity of it are related to renal toxicity and bone marrow failure , 8. The Our study aimed to assess the incidence and identify the associated risk factors of AKI in a group of Chinese advanced ovarian cancer patients undergoing the CRS plus cisplatin-based HIPEC.This is a retrospective cohort study. Patients who were consecutively diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC and IV epithelial ovarian cancer  and received the CRS plus cisplatin-based HIPEC were included in the database of Beijing Shijitan Hospital, Capital Medical University between January 2018 and December 2021. The patients who had confirmed end-stage renal disease before the CRS plus cisplatin-based HIPEC or who did not finish the whole process of the therapy were excluded. The ethical approval for this study was granted by the Institutional Ethical Review Board of Beijing Shijitan Hospital, Capital Medical University [sjtkyll-lx-2020-35]). The informed consent for inclusion in the present study was waived because it was a retrospective study and only de-identified information was used in this study.2, heated at between 41°C and 43°C for 60 min, and using an open coliseum technique, the regimens of HIPEC therapy for individual patients were mainly determined by consultant surgeons, and cisplatin dose over 70mg/m2 was regarded as a high dose of cisplatin therapy in the HIPEC treatment , concomitant medications 7 days before operation , body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), previous oncological related treatments (chemotherapy or chemotherapy plus surgery), American Society of Anesthesiologists (ASA) stages, operative details . We also collected data on preoperative serum concentrations of hemoglobin and albumin. The baseline eGFR was calculated by using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation with an adjusted coefficient of 1.1 for the Asian population and categorized as ≥60 and <60 ml/min/1.73 m2 . Serum cAKI was defined and staged according to the clinical practice guideline of Kidney Disease Improving Global Outcomes (KDIGO) in 2012  . DependiWe defined renal recovery as full recovery with Scr decreased to below threshold or to the baseline, partial recovery as serum creatinine decreased by 25% or more from peak concentration but remained higher than the threshold or baseline, and non-recovery as the patient still dependent on dialysis or serum creatinine decreased by less than 25% from peak concentration within 90 days following AKI .2, as well as ASA stages, some operative parameters, such as PCI score, number of visceral resections, level of peritonectomy, ascitic volumes, operative time, estimated blood loss volumes and hypotension, and chemotherapy regimen of HIPEC (we stratified our patients into two groups by the dose of cisplatin at 70mg/m2). All covariates with a P value of less than 0.10 on univariable analysis were entered into the multivariable model. We reported an odds ratio (OR) with a 95% confidence interval (95% CI) for each covariate of interest. Statistical significance was set at a value of p<0.05. Analyses were performed with SPSS version 21.0 statistical software .Continuous variables were expressed as mean with standard deviation (SD) or median with interquartile range (IQR); categorical variables were expressed as a number with a percentage. Differences between the AKI group and non-AKI group were compared using Chi-square tests for categorical variables and student’s t-test or Mann-Whitney U test, as appropriate, for continuous variables. We used univariate and multivariate logistic regression analysis to evaluate factors related to AKI, with AKI as the dependent variable, and all baseline variables as covariates, including age, comorbidities , concomitant medications , previous oncological treatments . Regarding intraoperative parameters, patients in the AKI group were more likely to have more visceral resections and estimated blood loss, and a higher proportion of cisplatin dose ≥70 mg/m2 compared with the non-AKI group (P<0.05). There were no significant differences in age, BMI, blood pressure, ASA stages, baseline serum level of hemoglobin and albumin, and some intraoperative parameters  between the two groups (P>0.05) , while 88.3% (n = 249) were non-AKI patients. Patients in the AKI group were more likely to have comorbid hypertension and diabetes mellitus, concomitant medications of ACEI or ARB (%), previous treatment of chemotherapy plus surgery, and a higher proportion of baseline eGFR <60 ml/min/1.73m(P>0.05) Table 1.2, she also had diabetes and hypertension, ARB was used to control the blood pressure, her HIPEC treatment dose of cisplatin was 60 mg/m2. The median time from surgery initiation to the occurrence of AKI was 3.5 (IQR 2.5 to 6.5) days. Of the 33 patients with AKI, full renal recovery was achieved in 10 (30.3%) patients, partial recovery in 14 (42.4%) patients, and failure to recover in 9 (27.3%) patients until 90 days after AKI.Among the patients who developed AKI, the majority of them were in mild-to-moderate severity (KDIGO stage 1: 16 (48.5% of AKI episodes), stage 2: 11 (33.3%), and stage 3: 6 (18.2%)), and only 1 patient received acute renal replacement therapy, she was 58 years old woman whose baseline eGFR was 51mL/min/1.73 m2 visceral resections≥3, cisplatin dose≥70mg/m2, intraoperative blood loss and hypotension(p<0.10); Multivariate logistic regression analysis showed that the risk factors independently associated with AKI included concomitant medications of ACEI or ARB , Baseline eGFR<60 mL/min/1.73 m2 , and cisplatin dose≥70mg/m2  (The results of univariate logistic regression were listed in P=0.012) Table 3.In this retrospective study, we found that the incidence of AKI was 11.7% in a group of Chinese advanced ovarian cancer patients undergoing the CRS plus cisplatin-based HIPEC. A high dose of cisplatin, baseline kidney dysfunction, and the use of ACEI or ARB were independent risk factors for the occurrence of AKI. By applying the KDIGO definition of AKI, our results determined some important risk factors in the early identification of AKI in advanced ovarian cancer patients undergoing CRS plus cisplatin-based HIPEC treatment. To the best of our knowledge, our study was also the first related report in the area of the association of CRS plus HIPEC and the occurrence of AKI among Chinese advanced ovarian cancer patients.As one of the serious complications in cancer patients, AKI has been proven to be associated with increased all-cause mortality and received great attention in clinical settings in recent years , 21. Pre2. In a multicenter phase I study, the nephrotoxicity would be increased significantly if the dose of cisplatin was greater than 70mg/m2, this dose of cisplatin was also regarded as a high dose for HIPEC treatment in the Chinese expert consensus on CRS plus HIPEC for peritoneal malignancies . Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.YB and YL designed the study. YD and PY collected data and performed the statistical analysis, YB and YD and wrote the manuscript draft. All authors contributed to data interpretation and editing of the final manuscript and approved the final version of the manuscript.