BackgroundThe importance of optimal acid-base balance during renal transplant surgeries cannot be stressed enough. Optimal preload and electrolyte balance is important in maintaining this. There has been a debate on the choice of perioperative crystalloids in renal transplant surgeries over the past decades. Normal saline  is more likely to cause hyperchloremic acidosis when compared to balanced salt solutions (BSS) with low chloride content whereas BSS may cause hyperkalemia. We aim to compare the safety and efficacy of normal saline (NS), Ringer’s lactate (RL) and Plasmalyte (PL) on acid-base balance and electrolytes during living donor kidney transplantation.Materials and methodsPatients were randomized to NS group (n = 60), RL group (n = 60) and Plasmalyte group (n = 60). Arterial blood samples were collected for acid-base analysis after induction of anaesthesia (T0), prior to clamping the iliac vein (T1), 10 minutes after reperfusion of the donated kidney (T2) and at the end of surgery (T3). In addition, serum creatinine and 24-hour urine output were recorded on postoperative days one, two and seven.ResultsThere was a statistically significant difference (p < 0.001) in the pH at the end of surgery between the three groups with the NS group being more acidotic , although this was not clinically relevant. This was explainable by the parallel increase in chloride in the NS group. Early postoperative graft functions in terms of serum creatinine, urine output and graft failure requiring dialysis were not significantly different between the groups.ConclusionBalanced salt solutions such as Plasmalyte and Ringer’s lactate are associated with better pH and chloride levels compared to normal saline when used intraoperatively in renal transplant patients. This difference, however, does not appear to have any bearing on graft function. Plasmalyte seems to maintain a better acid-base and electrolyte balance, especially during the postreperfusion period. Intravenous fluid therapy is a ubiquitous, modifiable component of perioperative living donor kidney transplantation. Renal transplant surgery patients receive large volumes of intravenous fluids. On average, these patients are given around 3,000 mL of crystalloid intravenous fluids intraoperatively and around 2,500 mL in the first 24 hours after surgery. There is marked heterogeneity in clinical practice and no consensus on the appropriate choice and volume of fluid to be given in renal transplant surgical patients. For optimal graft function in the post-transplant period, adequate intravascular volume, electrolyte and homeostasis need to be maintained. To prevent renal insufficiency and electrolyte disturbances like hyperkalemia and hyperchloremia, a good understanding and management of fluid therapy are required. Normal saline has traditionally been the fluid of choice in the perioperative period of kidney transplantation. Normal saline infusion has been known to cause hyperchloremia . This hyLimited research and the absence of robust evidence on the appropriate type of intravenous fluid have resulted in an ongoing debate on the appropriate use of intravenous fluids for living donor kidney transplantation. The purpose of this study is to compare the effects of normal saline, Ringer's lactate and Plasmalyte on acid-base balance and electrolytes during living donor kidney transplantation.This study was commenced after approval from the Institute Ethics Committee (IEC/2016/937) and is registered in the Clinical Trials Registry (NCT03115060). Written informed consent was obtained from every patient included in the study. This prospective, randomized, double-blind study was conducted between April 2015 and December 2018 at the renal transplant centre in cooperation with the department of renal transplant surgery at a tertiary care centre in Chandigarh that caters to over 200 renal transplant recipients yearly.Inclusion criteria and randomizationPatients aged 20-60 years with the American Society of Anesthesiologists (ASA) physical status III and IV and scheduled for living-related kidney transplantation were included. Participants were excluded if they had (i) cardiovascular, respiratory, metabolic, hematologic, hepatic, or central nervous system diseases; (ii) pre-operative serum potassium level of more than 5.5 mEq/L; and (iii) refusal of study participation.Computer-based randomization (block randomization) was performed and allocation into one of three treatment groups was done using sealed envelopes. The patient and the investigator performing the analysis were blinded to the allocation. The perioperative staff was, however, not blinded to the type of fluid being administered. Patients were randomized in the preoperative room prior to transfer to the operation theatre to either receive 0.9% normal saline (NS), Ringer’s lactate (RL) or Plasmalyte (PL).Anaesthesia managementAll the participants received premedication overnight and in the morning on the day of surgery with tab pantoprazole 40 mg, tab metoclopramide 10 mg and tab alprazolam 0.25 mg. Upon arrival to the operation theatre, ASA standard monitors like five-lead electrocardiography, heart rate, blood pressure and pulse oximetry were attached along with entropy and neuromuscular transmission (NMT) monitoring. Before induction of anaesthesia, an 18-G intravenous (IV) cannula was secured in fistula free arm. After preoxygenation, general anaesthesia was induced using IV propofol (2-2.5 mg/kg), fentanyl (2 µg/kg) and atracurium (0.5 mg/kg), and maintained with desflurane in an oxygen-nitrous oxide mixture at a 1:1 ratio. Desflurane was adjusted to maintain a state entropy of 40-50. Additional doses of atracurium were given as necessary to maintain a train-of-four (TOF) stimulation count of 1. A central venous catheter was inserted after induction of anaesthesia in the right internal jugular vein under ultrasound guidance for central venous pressure (CVP) monitoring and the radial artery was cannulated in fistula free arm for invasive arterial monitoring. The patient was kept on controlled mechanical ventilation to maintain end-tidal carbon dioxide tension near 35 mmHg. Tidal volume was set at 8 mL per kilogram lean body weight with positive end-expiratory pressure of 5 mmHg. Forced-air warming was used to keep patients normothermic. After completion of the surgery, the neuromuscular blockade was reversed and the patient was extubated and shifted to the post-renal transplant intensive care unit. Intraoperatively, all patients received 0.5-1 mg/kg frusemide as instructed by the surgical team.Fluid managementIV crystalloids were given intraoperatively targeting pulse pressure variation (PPV) of 13% and a CVP of 12-14 mmHg as per our institute protocol, and the total volume of fluids administered in each group was recorded. After surgery, once urine output had been established, continuous infusion of IV fluids was administered targeting CVP of 14-16 mmHg in the post-renal transplant intensive care unit until discharge to the normal ward.Management of intraoperative hypotension and dyselectrolytemiaIntravenous dopamine was administered when hypotension, defined as a mean arterial blood pressure less than 20% baseline, persisted after repeated fluid boluses totalling 10 ml/kg. Intraoperative hyperkalemia with signs of ECG changes (elevation in T-waves) was treated initially with calcium-gluconate 1 gm administered slowly over 10 minutes. In severe cases , the dextrose-insulin infusion was administered.Data and measurementsThe following data were obtained from all the participants: age, sex, weight, height, total intraoperative fluid administered, total fluid administered until discharge from the post-operative intensive care unit, use of calcium-gluconate or dextrose-insulin infusions and use of inotropes.Arterial blood gases (ABG) were obtained after induction of anaesthesia (T0), prior to clamping the iliac vein (T1), 10 minutes after reperfusion of the donated kidney (T2) and at the end of surgery (T3). The following variables were obtained by ABG analysis: pH, partial pressure of carbon dioxide (pCO2), bicarbonate, base excess, sodium, potassium, chloride and lactate.Haemodynamics, renal condition, arterial blood gases, serum electrolytes and urine output were recorded intraoperatively and postoperatively. We gathered data on 24-hour urine output and serum creatinine on postoperative days one, two and seven. The follow-up period ended at this time point.Outcome MeasuresThe primary objective was to detect if there was any difference in the in vivo pH at the end of surgery between the three types of fluids. The secondary outcome measures were (1) acid-base balance at four intraoperative time points ; and (2) serum creatinine and urine output on day one, two and seven of surgery as a measure of renal function.Statistical analysisAn estimated sample size of 159 was calculated with the goal to demonstrate a moderate effect size of 0.25  with the pH difference at the end of surgery (T3) as the primary outcome measure. To cover for potential dropouts, we increased this sample size to 180. Continuous data have been represented as mean ± SD as they were normally distributed and analysis has been done using one-way ANOVA. Pairwise comparisons have been made post hoc where needed using Tukey honestly significant difference (HSD) for multiple comparisons. The final analysis has been done using SPSS .A total of 220 patients were screened and 180 were randomized and included in the study between April 2015 and December 2018  Table . AlthougBicarbonate was also lowest in the NS group at T2 (19.36 ± 1.11), which differed significantly from the other two groups . The 95% CI for the pH in the NS group was 7.27-7.32, RL group was 7.31-7.36 and PL group was 7.29-7.33, p < 0.001. The mechanism of acidosis produced by NS has been attributed to hyperchloremia -8. The sA 2015 systematic review, including 477 participants, on giving lower chloride solutions to renal transplant recipients also reported similar findings as our study [One of the limitations of our study includes the lack of a long-term follow-up in assessing graft survival. We did not prospectively assess 30-day mortality, although retrospectively all patients, in all groups, did arrive for scheduled follow-up visits even at 90 days post-transplant. This possibly means in our cohort the type of perioperative intravenous fluid did not significantly influence mortality. Assessing a biomarker such as neutrophil gelatinase-associated lipocalin (NGAL) or serum renalase either as part of the study or in the follow-up clinic may have given some additional information. We targeted CVP to ensure adequate preload as we were unable to convince the perioperative team on the robustness of PPV in the renal transplant population owing to poor evidence for the same and the prevailing institute management protocol at the time of study design.Balanced salt solutions such as Plasmalyte and Ringer’s lactate are associated with better pH and chloride levels compared to normal saline when used intraoperatively in renal transplant patients. The potassium kinetics also appear to be safe, further informing us that balanced salt solutions can be used safely during renal transplantation. This difference, however, does not appear to have any bearing on graft function. Plasmalyte seems to maintain a better acid-base and electrolyte balance, especially during the postreperfusion period.


Both functional and structural characteristics of social support and network were examined. Results showed that increasing total network size was related to 52% higher odds of uncontrolled hypertension . Higher network sizes on the provision of information support related to advice, emotional support related to decisions, and practical support related to sickness were associated with lower odds of uncontrolled hypertension. Every additional 1% of the percentage of network members having hypertension decreased 2% the odds of uncontrolled hypertension . A 1% additional network members who were living in the same household was associated with a decrease of 0.08 point of behavioral adherence score . Meanwhile, a 1% increase of network members who were friends on the provision of practical support related to sickness and jobs was related to an increase of 0.10 point and 0.19 point of behavioral adherence score . The current study suggested that further interventions to improve hypertension management should address the potential effects of social network characteristics.Relationships between social support characteristics with blood pressure control and recommended behaviors in Vietnamese hypertensive patients have not been investigated. This study is aimed at examining the role of social support characteristics in hypertension control and behaviors. Patients with hypertension ( People are now living longer but more vulnerable to noncommunicable diseases (NCDs) . HyperteChanging healthy behaviors seems not to be easy because it requires enormous efforts and motivations from each individual . MotivatIn the hypertensive community, several studies indicated the positive influence of both functional  and structural  social support and network characteristics of patients on the prevalence of hypertension, blood pressure control, or hypertensive complications. For example, a study in Korean older adults revealed that people with a larger social network size were less likely to suffer from hypertension , while aIn this study, we aimed to examine the role of social support and network characteristics in hypertension control and adherence of recommended behaviors among hypertensive patients managed at an urban hospital in Hanoi, Vietnam.Data of this analysis were from a cross-sectional study implemented at an urban hospital in Hanoi, Vietnam, from August to October 2019. There were approximately two thousand outpatients with hypertension who registered for hypertension management in this hospital. The protocol of this study was approved by the institutional review board of the hospital. We recruited outpatients aged 18 years or above who were confirmedly diagnosed with high blood pressure based on the guideline of the Vietnam Ministry of Health (persistently systolic blood pressure level of ≥140 mmHg and/or persistently diastolic blood pressure level ≥ 90 mmHg) . Other eTo calculate the sample size, we employed the formula to estimate a proportion with specified relative precision with confidence level = 95% and expected proportion of uncontrolled hypertension among treated hypertensive patients = 64.0% . The toA convenient sampling procedure was performed to recruit patients. First, patients who visited outpatient clinics during the study period for regular hypertension examination and treatment were screened the eligible criteria  by the physicians at the clinics. Then, when they completed all examination procedures (including blood pressure measures), patients were invited to become study participants by the research team and go to a private counseling room for protecting their confidentiality. They were provided a short description of the study and their rights as participants. A face-to-face interview was performed afterward, following by weight and height measures.The data collection team included undergraduate medical students from the Hanoi Medical University. Before collecting the data, they participated in intensive training sessions about interview skills with patients having high blood pressure, as well as the data collection procedure to ensure their consistency in data collection. They also participated in the pilot study with five patients to assure that they followed correctly the data collection guideline. A structured questionnaire was developed and piloted in these five patients to check the validity and reliability of the questionnaire. During the data collection, one student was in charge of the interview, and another student measured the weight and height of patients. Following variables were collected:When patients had regular medical examinations, their office blood pressure was measured by the hospital's physicians using the Japanese Alpk2 sphygmomanometer. After completing the interview, our data collector extracted this information from the patient's medical record. Patients having a systolic blood pressure level of ≥140 mmHg and/or diastolic blood pressure level ≥ 90 mmHg were classified into the “uncontrolled” group; otherwise, they were categorized into the “controlled” group .Eight items from the Condition-specific Recommendations and Adherence scale were used to assess the adherence of patients with different recommended behaviors for patients with hypertension . These b“In the last six months, who was the one that advises you when you had problems?” “In the last six months, who was the one that could offer their help when you were sick?” “In the last six months, who was the one that could offer their emotional support when you were feeling unwell?” “In the last six months, who was the one that could help you to perform the housework?” “In the last six months, who was the one that could discuss important matters with you?” In this study, we examined both functional and structural network characteristics of hypertensive patients by using a name generator method, which is one of the most common approaches to explore the individual's egocentric network , 37. An Patients were asked to call as many names as they could remember for each question. The name could be duplicated between questions but could not be duplicated within each question. We then calculate the participants' network size by summing the total number of unique alters in the questionnaire. We also asked patients to report some general characteristics of each network member, including gender, relationship with the participant , living place, contact frequency (daily/weekly/monthly/yearly), and whether having hypertension or not. Marital status and whether participating in social activities or not were also examined.Other information was collected including age, gender, education, occupation, living area, smoking and alcohol drinking status, comorbidities, weight, height, body mass index, and health-related quality of life. The Short-form 12 version 2 (SF-12v2) instrument investigates HRQoL of hypertensive patients regarding physical component (PCS-12) and mental component (MCS-12) , 40.We used the Stata software 14.0 for data analysis. Descriptive analyses were conducted to examine the differences in social network characteristics between patients with controlled/uncontrolled hypertension and between patients with behavioral adherence/nonadherence. Chi-squared tests and Mann–Whitney tests were performed as appropriate. Multivariate logistic and tobit regression models were used to explore the association of network variables with uncontrolled hypertension (yes/no) and behavioral adherence score. In this study, we conducted four models for each dependent variable. Model 1 was adjusted for age and sex, while model 2 was adjusted for age, sex, and quality of life (PCS-12 and MCS-12). Model 3 was additionally adjusted for body mass index and number of comorbidities, while model 4 was additionally adjusted for smoking and alcohol use. Multicollinearity was checked by using variance inflation factor (VIF). VIF results showed no multicollinearity among variables. Akaike information criterion (AIC) and Bayesian information criterion (BIC) were then calculated to examine the sensitivity of the models. The level of statistical significance was set at the 5% level.There were 220 hypertensive patients included in the study. The mean age was 64 years (SD 8.9 years). There were 10.9% of patients having lower secondary education level, 44.5% being current self-employed, and 40.5% being retired. Most participants (81.8%) were living with their partners and living in urban areas (85.5%). There were 54.6% reporting that participated in social activities. The majority of patients did not smoke (60.9%). The rate of uncontrolled hypertension was 40.5%, while the rate of adherence with recommended behaviors was 30.4%.p < 0.05) compared to those with controlled hypertension. Meanwhile, participants having adherence with recommended behaviors had a significantly higher percentage of network members who are friends on the provision of practical support-related jobs than that of their nonadherence counterparts (p < 0.05). Moreover, in the behavioral adherence group, the percentage of patients participating in the social activities (66.7%) was significantly higher than that of the behavioral nonadherence group .p > 0.05). Notably, patients participating in social activities had significantly higher behavioral adherence score compared to those not participating in such activities .Our study informs an insight into the relationship between functional and structural characteristics of social support and uncontrolled hypertension as well as adherence with recommended behaviors among hypertensive patients in the urban setting of Vietnam. The findings of this study indicated that both functional and structural network characteristics were associated with hypertension control and behavioral adherence. For example, higher network size on the provision of informational support, emotional support related to decisions, and practical support related to sickness was independently associated with a lower likelihood of uncontrolled hypertension. Moreover, social activity participation appeared to be independently related to a higher behavioral adherence score.In this study, we have observed that an overall large network size would increase the risk of uncontrolled blood pressure. However, our result differed from a prior study in Korean and American older adults, which showed that hypertensive patients having a large network size would have lower odds of uncontrolled hypertension , 30. It Regarding behavioral adherence, we found that patients having more practical support from friends were more likely to adhere to behavioral recommendations. Moreover, higher percentages of network members living in the same household would decrease adherence. In other words, the finding revealed that patients with a centralized network to household members were at higher risk of nonadherence. Another notable finding is that participating in social activities would increase the level of behavioral adherence. It should be noted that two-thirds of our samples were 60 years old or more. Previous literature suggested that older people should be encouraged to have an extensive social network and participate in social activities to promote their autonomy and social roles, which could increase their physical and mental health –45. ThesThe findings of this study pose several implications for public health and clinical practitioners. First, physicians should pay attention to the social relationships of hypertensive patients and the influences of these relationships with hypertensive treatment and behaviors. Awareness of patients' social support and social network can help to develop effective and tailored interventions based on the network characteristics for improving treatment outcomes and lifestyle behaviors. Second, our results support the development of tailored social network-based interventions to prevent uncontrolled blood pressure among hypertensive patients. Second, further studies should be warranted to examine the role of different network characteristics in the treatment progress and the development of hypertensive complications. Third, we believed that social support and network characteristics also had an important role in the onset of hypertension , 46, whiThis study has strengths, including the use of several validated instruments such as SF-12v2 and Condition-specific Recommendations and Adherence scale, which allowed study findings to be comparable to previous research in the world. Moreover, we employed a name generator, which is among the most common method to explore the egocentric network of each person , 37. TheThe current study showed that higher network sizes on the provision of informational support, emotional support related to decisions, and practical support related to sickness were associated with a lower likelihood of uncontrolled hypertension. Findings also revealed that social support and network characteristics were related to hypertension control and adherence with recommended behaviors. Further interventions to improve hypertension management should address the potential effects of social network characteristics.


Blood group and tissue incompatibilities remain significant barriers to achieving transplantation. Although no patient should be labeled “un-transplantable” due to blood group or tissue incompatibility, all candidates should be provided with individualized and realistic counseling regarding their anticipated wait times for deceased donor or kidney paired donation matching, with early referral to expert centers for desensitization when needed. Vital is the careful selection of patients whose health status is such that desensitizing treatment is less likely to cause serious harm and whose anti-HLA antibody status is such that treatment is likely to accomplish the goal of increasing organ offers with an acceptable final crossmatch. Exciting new developments have re-energized the interest and scope of desensitization in the times ahead. For patients with end-stage renal disease (ESRD), kidney transplantation is the optimal therapeutic option associated with a higher quality of life and lower mortality than chronic hemodialysis. The best results are achieved with a kidney from a healthy ABO and HLA matched living donor. Living donation accounts for a third of all kidney transplants performed in the United States. Unfortunately, not every donor recipient pair is feasible because of human leukocyte antigen (HLA) sensitization or ABO incompatibility (ABOi). To overcome these barriers to transplant, strategies such as desensitization have been developed. Here in we discuss historical and current perspectives on desensitization and reflect on future directions.) . However, many of these data were collected before implementation of the Kidney Allocation System (KAS), and patients in the control group were not necessarily enrolled in paired exchange programs. Additionally, regardless of the treatment strategy, highly sensitized patients whose calculated panel reactive antibody (cPRA) is ≥98% remained difficult to transplant as desensitization proved to be challenging in those with high HLA or ABO antibody titers.Sensitization to HLA is observed in 30% of patients on the kidney-transplant waiting list and an additional 11% of donor recipient pairs are ABO incompatible . Similarde novo DSA formation (12.5%), demonstrating proteasome inhibitor-based desensitization consistently and durably reduced HLA Ab levels and may be a reasonable alternative to IVIg based plasmapheresis regimens in a select population (Enthusiasm (and need) for desensitization of highly sensitized patients has decreased in recent years. Desensitizing treatments are expensive, resource intensive, and place patients at risk for morbidity associated with higher doses of maintenance immunosuppression. Furthermore, these treatments remove circulating antibody or temporarily inhibit antibody production without significant effect on immunologic memory. Additionally, the survival data are not replicable. The 5-year data from the Mayo Clinic showed significantly worse patient and graft survival in those undergoing desensitization with plasmapheresis and low-dose intravenous immunoglobulin (PP/IVIg) versus HLA compatible transplant, as well as protocol biopsy-detected transplant glomerulopathy in 55% of desensitized versus 7% of HLA-compatible recipients . In addipulation . Given tKAS prioritizes organ offers for patients with high levels of anti-HLA sensitization providing sensitized patients with a cPRA of 20% and above additional points toward organ allocation priority, and highly sensitized candidates with a cPRA of 100%, 99%, and 98% provided 202.1, 50.09, and 24.4 additional points for allocation priority, with each point being equivalent to 1 year of wait-time . In addiIn the United States, the allocation of deceased donor kidneys is based on ABO matching as opposed to ABO compatibility. The waiting time for blood type B kidney transplant candidates is typically longer than for candidates with other blood types. The blood type B kidney transplant candidate waitlist has the highest proportion of ethno-racial minority candidates, who are less likely to receive a living donor kidney transplant compared to white candidates, exacerbating longer waiting times for patients in these populations. With the goal of improving equity by improving access to transplantation for minority populations in the United States, KAS now allows allocation of type A, non-A1 and type AB, non-A1B (commonly known as A2 and A2B) kidneys to blood type B candidates if anti-A titers are low, with the program’s titer threshold defined in written policy.Finally, KPD or paired kidney exchange has become increasingly utilized as an approach to overcome biologic incompatibility, wherein two or more incompatible donor-recipient pairs exchange kidneys and all recipients benefit by receiving compatible transplants. The scope of KPD has further expanded with introduction of non-directed donors and compatible pairs in the form of multi-way exchanges and kidney donor chains to name a few. This has allowed the practice of KPD in the United States to expand exponentially, from a handful of transplants per year when it first started in 2002 to over 1000 transplants in 2020. An additional novel approach has become the combination of both KPD and desensitization to facilitate compatible and successful transplantation. An HLA sensitized patient pair can be paired with a better immunological match in the KPD pool than the original donor and subsequently desensitized to achieve transplantation establishing KPD and desensitization are not mutually exclusive strategies. Importantly, the development and implementation of KPD programs has been demonstrated to mitigate racial and gender disparities in access to living donor kidney transplantation .While the above options have reduced the need for desensitization, it has not been made redundant. Despite KAS, the most highly sensitized >99.5% PRA candidates on the wait list still do not get their fair share of transplants. Only 9.7% (213/2204) of candidates with a calculated panel reactive antibody ≥99.9% received a transplant, and the most highly sensitized candidates were less likely to receive a living donor transplant. Among candidates with a CPRA ≥ 99.5% i.e. 100%), only 2.5% of transplants were from living donors . Nearly 4 years after KAS (6/30/2018), 1791 actively wait-listed candidates had a CPRA of ≥99.9% and 34.6% (620/1791) of these had ≥5 years of waiting time  is a recombinant cysteine protease that cleaves all four subclasses of human IgG into F(ab’)2 and Fc fragments, inhibiting CDC and antibody-dependent cellular cytotoxicity. The efficacy of Imlifidase as a desensitization strategy was evaluated in two independent phase I/II trials  to enable the detection and monitoring of ABO antigen-specific B cells much like the single antigen bead analysis in HLA testing. This approach therefore comprises a novel, general platform for screening B cell populations for binding to carbohydrate antigens, including, in this case, the human A and B blood group antigens .. Using this and other novel biomarkers to follow treatment response in addition to traditional DSA MFI/titer measurement may offer additional guidance into management before and after transplantation. Furthermore, the conventional HLA mismatch has been challenged recently by the concept of HLA epitope matching algorithms that claim to offer a more precise assessment donor recipient HLA compatibility. Molecular mismatch has been proposed as a prognostic biomarker categorizing individual donor recipient pairs into low and high risk where for every 10 eplet mismatches there is a 2-fold increased hazard of developing a DR or DQ antibody  in pretransplant serum have a threefold higher risk of graft loss than patients with DSA but low sCD30 levels . Using antibody . When inantibody . Furtherormation . This isIn non-kidney solid organs transplant candidates with a high wait list mortality where dialysis and living donors is not an option, desensitization for deceased organ donor transplants continues to have a role and lessons learned in desensitization in kidney transplantation paves the way for future innovations.When living donors are available, paired exchange should be attempted to avoid the cost and risk associated with desensitizing therapy as well as the posttransplant immune response that will likely translate into worse long-term graft survival. Paired exchange options should be exhausted, and a realistic estimate of wait time taking into account priorities for high cPRA patients under KAS should be considered. Proceeding with desensitization for those highly sensitized patients without living donors, where paired exchange is not possible and expected wait time is considered unacceptable, may be a reasonable consideration. Although no patient should be labeled “un-transplantable” due to blood group type or DSA, all candidates should be provided with individualized and realistic counseling regarding their anticipated wait times for deceased donor or kidney paired donation matching, with early referral to expert centers when needed. Careful patient selection, which involves the identification of individuals who can withstand desensitization treatment and have favorable antibody profiles amenable to successfully overcoming the incompatibility to allow transplantation, remains the cornerstone desensitization. One cannot emphasize enough the importance of careful antibody monitoring throughout the posttransplant period. Lessons learned from the past along with exciting developments in pipeline will pave the way for the future of desensitization.All authors contributed to the article and approved the submitted version.JL: consultant for Hansa (manufactures imfilidase).The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


With a rapidly aging population, adequate blood pressure (BP) control is critical for hypertension management and prevention of cardiovascular events. Impressive cardiovascular benefits have been observed with intensive BP control  in the SPRINT  study, even in patients 75 years of age or older. A most recent meta-analysis including 51 randomized trials with over 350,000 participants from the BPLTTC  showed that BP lowering is effective in older people for reducing major cardiovascular events. The STEP (Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients) study—a multicenter, randomized, controlled trial conducted in China, provided important evidence that intensive BP treatment  benefits older hypertensive patients (aged 60–80 years) and reduced the incidence of cardiovascular events than standard treatment (target 130 mmHg to <150 mmHg). Because Asian people have a higher burden of hypertension and stroke than Caucasian people, intensive BP treatment has more advantages in reducing the risk of cardiovascular events including stroke in Asian hypertensive patients than in Caucasian people. Home BP monitoring is helpful to facilitate hypertension management for older patients. It should also be noted that clinical decision-making should be on a patient basis, such as fragility, diabetes, stroke, and other comorbidities, with tailored BP targets. Here we review the important clinical trials of BP control in elderly hypertension, interpretate the main findings of STEP, and also discuss the perspectives of managing hypertension in Asia. Hypertension is a global public health burden and a major cause of morbidity and mortality worldwide and in Asia, but it remains inadequately controlled . SeveralSystolic blood pressure (SBP) is well-recognized to be more important than diastolic blood pressure (DBP) as an independent risk predictor for cardiovascular diseases . The appPoint of viewClinical relevanceThe STEP study showed that intensive BP treatment targeting SBP < 130 mmHg markedly reduced the incidence of cardiovascular events in older hypertensive patients aged 60-80 years.Future directionThe cardiovascular benefits and risks of intensive BP treatment need to be clarified in future studies for the elderly hypertensive patients with comorbidities such as prior stroke, diabetes mellitus, heart failure, and renal impairments, or aged over 80 years old.Consideration for the Asian populationBecause Asian people have a higher burden of hypertension and stroke than Caucasian people, intensive BP treatment has more advantages in reducing the risk of cardiovascular events including stroke in Asian hypertensive patients than in Caucasian people.A number of clinical trials conducted in Asian patients have showed that lowering SBP is associated with reduced cardiovascular risk. The Systolic Hypertension in China (Syst-China) trial investigated the effects of antihypertensive treatment on cardiovascular risk in 2394 Chinese hypertensive patients aged 69–79 years with an averaged BP of 170.5/86 mmHg at baseline . After aP < 0.001) during a median follow-up of 3 years, but this was not accompanied by a significant decrease in the cardiovascular events and renal failure [Other studies have investigated whether the target for SBP control influences the impact of treatment on cardiovascular events. In the Valsartan in Elderly Isolated Systolic Hypertension (VALISH) trial conducted in 3260 Japanese patients aged 70–84 years with isolated systolic hypertension, SBP was reduced by 5.6 mmHg in the strict <140 mmHg) vs. moderate 140–150 mmHg) SBP control groups , reducing the risk by 26%, and also reducing the risk of most of the individual outcomes, including stroke and acute coronary syndrome reduced by 33%. The mean number of antihypertensive medications administered per patient was 1.9 in the intensive-treatment group and 1.5 in the standard-treatment group.STEP study is another milestone in the history of establishing active antihypertensive therapy to prevent cardiovascular diseases. Strengths of the STEP trial included the large sample size, the diverse patient population with coexisting chronic diseases including diabetic mellitus, the high rate of follow-up (97.3%), and the use of home BP monitoring.Of note, the STEP study used a smartphone-based application (app) to examine home BP as an adjunct to office blood pressure during the follow-up period. Every patient was provided with a validated automated home blood-pressure monitor  and required to obtain home BP readings at least 1 day per week during follow-up. The monitor’s Bluetooth function enabled patients to upload readings to a data center via the app. The percentage of patients who used the app to transmit home BP readings was 95.8%; the remaining patients did not use the app during the follow-up period. Overall, the between-group differences in BP were significant, persistent, and consistent across the office and home BP measurements. Throughout the trial, the mean home morning SBP was 129.6 mmHg in the intensive-treatment group and 137.5 mmHg in the standard-treatment group, with an average between-group difference of 7.9 mmHg; the mean home morning DBP was 78.3 mmHg and 81.8 mmHg, respectively , and 64.8% of the pateints had a Framingham risk score of 15% or higher. However, the Framingham Risk Score was formulated primarily in White populations and may overestimate the risk of cardiovascular disease in Chinese adults.The participants in the STEP study are relatively uncomplicated, healthy patients aged 60–80 years with hypertension. The mean age was 66.2 years, and 24% were aged 70–80 years. The mean body mass index was about 25.5 kg/mSPRINT excluded persons with diabetes mellitus, whereas the STEP trial did not. A subgroup analysis of the STEP showed a consistently beneficial, although nonsignificant, effect of intensive treatment in patients with diabetes mellitus. Of note, the statistics were underpowered, as in the Action to Control Cardiovascular Risk in Diabetes-Blood Pressure (ACCORD-BP) trial , which fBoth STEP and SPRINT trials excluded persons with a history of stroke. The Secondary Prevention of Small Subcortical Strokes (SPS3) trial found no significant benefit in lowering SBP to <130 mmHg compared with <150 mmHg for overall risk of another stroke, but a significant benefit was noted in reduced risk of intracerebral hemorrhage . FurtherIn the STEP trial, there was a beneficial, although nonsignificant, tendency on the risk of death from cardiovascular causes  in the intensive-treatment group, which might be explained by an inadequate statistic power; no effect on the risk of death from any cause was observed  . In contThe STEP and SPRINT studies set the intensive-treatment targets at <130 mmHg and <120 mmHg, respectively. During the 3.34-year follow-up period, in the intensive-treatment group of STEP study, the percentage of patients who reached the SBP target (110 to <130 mmHg) was 67.2% at 1 year of follow-up, 70.4% at 2 years, and 77.2% at 3 years [People may ask, did SPRINT go lower? The STEP trial used the conventional way in outpatient clinic setting and measured by trained physicians or nurses. The same validated office BP measurement device (the Omron HBP-1100 U) was used for all collaborating clinical centers in STEP, which may minimizes the potential investigator bias in the determination of blood pressure. The SPRINT used a particular methodology that many felt resulted in lower than usual clinic BP measurement. The office BP was measured with the use of an automated device when the trial staff was not present when the measurement was taken, which is known to reduce the “white coat” effect. However, in clinical practice automated devices may not be available and a strict protocol for correct measurement may not be followed, and thus BP may be overestimated.Drawz et al. evaluated the concordance between BPs obtained in routine clinical practice and those obtained using the SPRINT protocol, in a prognostic study of 3074 participants with 3 or more outpatient and trial BP measurements linking electronic health record (EHR) data . The outSystolic hypertension is the predominant form of hypertension in patients aged over 50–60 years, whereas DBP tends to decrease because of age-related changes in arterial vasculature, leading to a pulse pressure widening (the difference between SBP and DBP). Given that complicated comorbidities in elderly patients, the BP lowering is a challenge. There are several considerations during the target BP management.First, a number of observational studies indicate that lower SBP induced coronary arterial or cerebral arterial hypoperfusion, leading to increased risk of stroke  or cardiP = 0.03). Primary outcome risk was compared between the hypotension and non-hypotension group. In the whole patient population (8511), there were 14 (5.4%) in the hypotension group and 329 (4.0%) in the non-hypotension group having primary composite outcome, respectively, and the hazard ratio was 1.36 . It should be mentioned that patients enrolled in clinical trials tend to be less fragile and biologically active than patients seen in clinical practice; thus, the rate of adverse events reported in the trial may be lower than one would see in the real world.Second, are more adverse events an acceptable trade-off? In the STEP study, the incidences of dizziness, syncope, and fracture and the results for renal outcomes did not differ significantly between the two treatment groups, nor did the incidences of angioedema, headache, cough, and hives. However, the incidence of hypotension (defined as SBP < 110 mmHg or DBP < 50 mmHg) was more common in the intensive-treatment group than in the standard-treatment group  . HoweverCurrent hypertension guidelines have recommended the appropriate BP-lowering strategy to reduce the risk of cardiovascular events in older patients. The target is 130–139 mmHg in the European guideline  and <130The major features and themes of the Asian guidelines are similar to European and US guidelines, but there are several subtle differences. For example, the 2018 Chinese Hypertension Guideline recommended that SBP should be targeted to <150 mmHg, and further <140 mmHg, if tolerated; in elderly patients aged over 80 years old, a SBP target of <150 mmHg is recommended . The JapLower BP control is important in not only Western population but also Asian population. Althouth the awareness, treatment, and control rates of hypertension are generally improving, BP control remains inadequate worldwide and in Asia. Reasons for poor BP control include low awareness of hypertension among physicians and patients, under-treatment, and tolerability problems with antihypertensive drugs.Approximate 50–80% of people are unaware of the hypertensive condition and/or its potentially fatal impact on cardiovascular events. The control rates (defined as below 140/90 mmHg) in all subjects with hypertension are approximate 15% in China, 40% in Japan, 41% in Korea, and 50% in USA and Europe . Poor knPractical issues have therefore been raised with regard to the active BP treatment strategy. A lower BP control may prevent cardiovascular disease events in high-risk patients and reduce health care costs, as compared with standard control, but it would be more demanding to reach and may result in an increased risk of potential adverse events and higher costs, such as more frequent clinic visits, laboratory tests, and medications. Considering this point, Richman et al showed that intensive control of SBP prevented cardiovascular disease events and prolonged life span, at a cost below common willingness-to-pay thresholds . SimilarAsian people have a higher burden of hypertension and stroke as well as a steeper blood pressure-vascular event relationship than Caucasian people . The parFinding the best antihypertensive target is quite an important task. In our opinion, lower SBP is better if adverse events can be monitored, avoided, or managed. Certainly, it would be prudent to aim for a more conservative goal in elderly patients who are frail and at risk for falls, or in patients with a DBP of 60–65 mmHg and co-existing coronary artery disease or peripheral artery stenosis. Home BP monitoring is helpful to facilitate hypertension management for older patients. For the elderly hypertensive patients with comorbidities such as prior stroke, diabetes mellitus, heart failure, and renal impairments, or aged over 80 years old, further trials could assess the cardiovascular benefits of intensive BP treatment.The evidence, from the SPRINT trial, STEP trial, and the individual participant-level meta-analysis in BPLTTC, demonstrates that now is an time to act to return elevated blood pressure to its status as a continuous-variable risk factor, instead of treating it as a dichotomous disease. Blood pressure should be managed as an integrated part of a patient’s risk profile .


In paired comparison, TXCI samples expressed ADAMTS-4 in INT and PTC more often than TX0. ADAMTS-4 plasma concentration varied significantly across CKD stages, being highest in CKD 2 and 3 compared to other groups (p = 0.0064). Hemodialysis patients had higher concentrations of ADAMTS-4 compared to peritoneal dialysis (p < 0.00001). Conclusion: ADAMTS-4 might have a significant role in CKD as a potential novel diagnostic indicator.Background: We have previously shown that metzincin protease ADAMTS-4 accompanies renal fibrogenesis, as it appears in the blood of hemodialysis patients. Methods: Native kidney (NKB) and kidney transplant (TXCI) biopsy samples as well as plasma from patients with various stages of CKD were compared to controls. In paired analysis, 15 TXCI samples were compared with their zero-time biopsies (TX0). Tissues were evaluated and scored  for NKB and Banff ci for TXCI). Immunohistochemical (IHC) staining for ADAMTS-4 and BMP-1 was performed. Plasma ADAMTS-4 was detected using ELISA. Results: ADAMTS-4 IHC expression was significantly higher in interstitial compartment (INT) of NKB and TXCI group in peritubular capillaries (PTC) and interstitial stroma (INT). Patients with higher stages of interstitial fibrosis (ci > 1 and IFTA > 1) expressed ADAMTS-4 in INT more frequently in both groups ( Chronic kidney disease (CKD) is a heterogeneous disorder with multiple causes that endangers the structure and function of the kidney. Its occurrence is on a steady rise since the 1990s and has recently reached a global age-standardized prevalence of 9.1% ,3. CKD iThe regenerative capacity of the nephron and peritubular capillaries is not well understood; however, the existence of a renal stem cell was proposed . The seaOur previous research has also shown for the first time that metzincin protease family member ADAMTS-4  appears in the peripheral blood of human patients with ESRD . As ADAMDiscovery of a biomarker that could identify patients with early-stage CKD is of great importance, as it could lead to timely clinical interventions and more favorable patient outcomes. Thus far, there is only a limited number of papers reflecting on the role of ADAMTS-4 in kidney biology. This small-scale study strengthens the hypothesis that the ECM modulator ADAMTS-4 has a role in human CKD. Lessons learned about its role in the atherosclerotic milieu could prove valuable for decoding the intricate pathways ADAMTS-4 modulates in CKD. Therefore, we investigated the changes in expression and localization of ADAMTS-4 in the kidney  and also the changes in concentration of ADAMTS-4 released to the plasma of patients with different stages of CKD. Expression levels in renal tissue compartments were correlated to CKD progression, and changes of its plasma concentrations were monitored across the same groups. This prospective observational study was approved by the Ethics Committee of the University Hospital Center Zagreb (EP-16/106-2). All participants provided a signed informed consent. Blood and tissue samples were collected from patients between January 2018 and June 2019 at the Department of Nephrology, Arterial Hypertension, Dialysis and Transplantation, UHC Zagreb. v/v) 1:9. Plasma was obtained by centrifugation (15 min at 4 °C and 3000× g), and aliquots of each sample were stored at −80 °C until analysis. Experimental groups included: 32 patients in CKD stages 1–5, 5 hemodialysis (HD), 7 peritoneal dialysis (PD) patients, 30 kidney transplant patients (TX), and a control group of 5 healthy volunteers (CTRLpl) (Blood samples were drawn into tubes with anticoagulant substance containing 3.8% sodium citrate to form an anticoagulant-to blood ratio ((CTRLpl) .Kidney biopsy tissue samples were obtained from patients with CKD: 19 patients who underwent native kidney biopsy for clinical diagnosis of kidney disease (NKB group: 9 in CKD stages 1–2 and 10 in CKD stages 3–5) and 34 patients at different timepoints after kidney transplantation (TXCI group), who underwent kidney transplant biopsy for clinical evaluation (impairment of kidney function or proteinuria). As controls (CTRL group), 8 cadaveric kidney donors without evidence of CKD , who underwent transplant nephrectomies, were used . In 15 sKidney tissue samples biopsies underwent immunohistochemical (IHC) staining for ADAMTS-4 and BMP-1. Histopathology and immunohistochemistry analyses were performed in Clinical Department for Pathology and Cytology of University Hospital Center Zagreb. All patient clinical data were obtained from the hospital information system, and clinical data of kidney transplant donors for zero-time kidney biopsies were taken from kidney donor reports.Native kidney biopsy was performed by standard procedures  using ulTissue ADAMTS-4 and BMP-1 expression levels were determined on formalin-fixed, paraffin embedded (FFPE) tissue sections by IHC. Selected tissues were cut into 4 µm sections, placed on charged slides, and dried at 60 °C for one hour. Slides were cooled to room temperature, deparaffinized with Clarify , and rinsed in water in a Dako Omnis platform . Epitopes were retrieved with treatment with Dako Flex TRS Low  for 30 min at 97 °C. Slides were incubated with primary rabbit polyclonal ADAMTS-4 antibody  at a dilution 1:200 for 60 min, followed by Dako GV800 HRP-conjugated secondary antibody  for 20 min. For BMP-1 expression, detection slides were incubated with primary rabbit polyclonal antibody against BMP-1  at a dilution 1:50 for 60 min. Thereafter, primary antibody signal amplifier ) was applied for 10 min, followed by Dako GV800 HRP-conjugated secondary antibody  for 20 min. 3,3′-diaminobenzidine chromogen  was applied for 5 min, contrasted with hematoxylin, and cover-slipped. Stained slides were analyzed using an optical microscope . As positive control for ADAMTS-4, middle-sized intralobular artery in kidney biopsy sample was used. ADAMTS-4 was IHC positive in artery wall in the same pattern as previously described by Dong et al. [a) interstitial—peritubular capillaries (PTC) and interstitial stroma (INT), (b) glomerular—glomerular capillaries (GC) and Bowman space (BW), (c) tubules—proximal (PXT) and distal (DT). For both molecules (ADAMTS-4 and BMP-1), staining was defined as 0—negative or 1—positive for each of the six separate observation areas . Positive staining was defined if staining was present in more than 1% of observed area [IHC analyses were performed in three main kidney tissue compartments:  according to manufacturer’s instructions. Results were obtained with a plate reader (Molecular Devices–SpectraMax i3x) at 450 nm. All samples and standards were analyzed in duplicates and samples with an individual coefficient of variation (CV) greater than 25% were retested in duplicates. All procedures and evaluation of the results were conducted by researchers blinded to clinical and pathological patient data. t-test and ANOVA One-Way Analysis of Variance test for more than two independent groups. A two-tailed p-value < 0.05 was used as indicator of statistical significance. All analyses were carried out using MedCalc software (version 19.2.6).Normality of distribution of continuous variables was tested using D’Agostino-Pearson test. Categorical variables were presented as absolute numbers and percentages. Normally distributed continuous variables were presented as mean and standard deviation and non-normally distributed as median and interquartile range. The frequencies of ADAMTS-4 and BMP-1 proteins in the examined kidney biopsy samples of CTRL, NKB and TXCI group as well as for TX0-TXCI sample pairs were obtained by direct counting based on the positive/negative immunohistochemistry staining. Data distribution differences were compared using Fisher’s exact test with Yates correction. Plasma ADAMTS-4 concentration in the group of 8 patients with CKD was presented as multiple variables graphs with box-and-whisker plot for median. The difference in means between the two groups were analyzed by Student’s Immunohistochemistry analysis included kidney tissue biopsy samples from 19 patients who underwent native kidney biopsy (NKB), 34 patients with transplanted kidney who underwent biopsy due to a clinical indication (TXCI), and 8 cadaveric kidney donors who underwent transplant nephrectomies (CTRL). Study group characteristics are presented in Distribution of patient frequencies for ADAMTS-4 and BMP-1 IHC staining in their kidney biopsy samples (positive IHC staining frequency is presented) in each of six separate observation areas  for CTRL and groups with chronic kidney disease  is shown in BMP-1 was present in proximal tubules of 88% and glomerular Bowman space of 37% subjects in CTRL group and was totally absent in interstitial compartment and glomerular capillaries. ADAMTS-4 was present in tubular (both in PXT and DT) and glomerular (both in GC and BW) compartments of samples without CKD. Only 13% of subjects expressed ADAMTS-4 in interstitial stroma and none in peritubular capillaries. p = 1 and CTRL vs. TXCI, 87.5% vs. 97%, p = 0.348 for PXT, respectively, CTRL vs. NKB, 0% vs. 31.5%, p = 0.279 and CTRL vs. TXCI, 0% vs. 14.7%, p = 0.563; for DT, respectively). Similar was determined for BW . Even when we compared CKD subgroups (CKD 1–2 or CKD 3–5) with CTRL for each area, frequencies of BMP-1 positivity were similar , with only one exception for DT area, where frequency of BMP-1 staining was significantly higher in NKB-CKD 1–2 than in CTRL . Additionally, the CKD subgroups (CKD 1–2 and 3–5) from both groups (NKB or TXCI) were not different among each other regarding frequency of patients positivity for BMP-1 in each of the above-mentioned areas .In CKD, BMP-1 was also present only in tubular compartment (PXT and DT) and BW in both study groups, NKB and TXCI, respectively. Frequencies of BMP-1 IHC staining in tubules were not significantly different between CTRL and groups with CKD, NKB, or TXCI, respectively  and glomerular capillaries , being significantly higher in both groups with CKD (NKB or TXCI). In CKD, ADAMTS-4 IHC staining was detected in all six observation areas. When comparing frequencies of patients, regarding ADAMTS-4 IHC staining positivity between the CTRL and groups with CKD (NKB or TXCI) for all areas, statistically significant difference was found only in interstitial compartment  and was also marginally significant in INT , both being higher in advanced stage of CKD (CKD 3–5). The same was not observed within TXCI group.When comparing ADAMTS-4 expression between CKD subgroups (CKD 1–2 vs. CKD 3–5) within NKB or TXCI, significant difference was found only in PTC area of NKB group . Interestingly, when we compared among equivalent CKD subgroups of NKB and TXCI, similar ADAMTS-4 expression frequency was found in all six observed areas , which was not observed for PTCs. Similarly, when dichotomizing NKB group by IFTA stage as IFTA ≤ 1 or IFTA > 1, significantly more patients with IFTA > 1 expressed ADAMTS-4 in INT  and in PTCs .To further elucidate potential correlation of ADAMTS-4 with progression of chronic kidney disease, we correlated ADAMTS-4 IHC staining in interstitial compartment of kidney tissue (PTC and INT) with chronic kidney tissue interstitial fibrosis scores: chronic interstitial score (ci) per Banff classification for TXCI group and IFTA stage for NKB group. When dichotomizing TXCI group by ci score as ci ≤1 or >1, significantly more patients with ci > 1 expressed ADAMTS-4 in INT area  and TXCI group . Such association was not found for the BMP-1 molecule .As an additional unexpected observation, ADAMTS-4 IHC expression in proximal tubules was found to be associated with presence of acute tubular injury (ATI) in native and transplant kidney biopsy samples. ADAMTS-4 expression in PXT was significantly more frequent in patients with ATI than without in NKB  “zero time “samples (TX0) performed at the day of transplantation (15 TX0-TXCI pairs) are presented in p < 0.001, p = 0.00169 in INT, 15/15 vs. 0/15, respectively; p < 0.0001 for PTCs) and glomerular capillaries . In paired analysis, subjects in TXCI group had significantly higher CKD stage and ci score than in TX0 group . ADAMTS-4 plasma concentration varied significantly between CKD stages, being highest in CKD stages 2 and 3, taken together and compared to all other CKD stages  or to all studied groups taken together  Interestingly, when analyzing only dialysis groups, none of the patients in PD group had detectable ADAMTS-4 in plasma, which differed significantly from the HD group . Additionally, ADAMTS-4 plasma values in HD group were not different even after a regular 4 h hemodialysis procedure .Distribution of ADAMTS-4 concentration in plasma of the group of eight patients with CKD  and controls (CTRLpl) is presented in In this study, to the best of our knowledge, for the first time, ADAMTS-4 was characterized in kidney tissues and plasma of patients with CKD. Previous research of ADAMTS-4 in kidney diseases is scarce. Wang et al. reported an elevated ADAMTS-4 expression in patients with early stage membranous nephropathy; however, because of the use of tissue lysates, the exact origin of the protein could not be determined . A singlThe underlying pathology of CKD and ESRD is renal fibrosis, which initiates mainly in the peritubular capillaries of the interstitial compartment ,24. OtheThese effects might be partially explained by the role ADAMTS-4 has in the processing of extracellular matrix . ExpressThe analysis of plasma ADAMTS-4 revealed its expression across all stages of CKD, however, with significant variations. As the disease progresses, the expression levels peak at CKD stages 2 and 3 and afterwards sharply decrease towards ESRD. It could be speculated that higher systemic concentrations of ADAMTS-4 might be the result of inflammation that underlies kidney diseases. This is especially the case in primary glomerular disease; however, larger studies are needed for any further conclusions. In renal replacement therapies, ADAMTS-4 was detected in patients on hemodialysis before but also after dialysis. This finding is in concordance with previous research and could be explained by the fact that ADAMTS-4 is a large uremic toxin, which is poorly filtrated using a standard dialysis filter . InteresThis study characterized ADAMTS-4 proteinases for the first time in kidney tissue samples and plasma of patients with various stages of CKD. Based on its significantly higher IHC expression in peritubular capillaries and interstitial space of patients with CKD compared to controls, its stepwise abundance along with progression of interstitial fibrosis, which was also confirmed on the paired biopsy samples of the 15 transplanted kidneys, ADAMTS-4 might be a novel marker of CKD. Our preliminary results of plasma analysis also confirmed the presence of circulating ADAMTS-4 in CKD patients, being highest in stages 2 and 3, with subsequent disappearance until stage 5, which can fit into the dynamics of the development of the disease. Further prospective studies in larger cohorts are needed to validate the results of the present study.


Introduction: Sepsis-associated acute kidney injury (SA-AKI) represents a relevant cause of mortality and morbidity in critically ill children. Since with the “inflammatory theory” the authors have been witnessed an important role of inflammatory mediators in the pathophysiology and in the prognosis of SA-AKI, making the need of adjunctive therapies in association with kidney replacement therapies mandatory. Hemoperfusion with CytoSorb is a safe and well-tolerated therapy in septic shock: the very high surface area of the absorber means it is able to efficiently remove cytokines and other medium size molecules involved in cytokine storm, thus playing a synergistic effect with Continuous Kidney Replacement Therapy (CKRT).Materials and Methods: We retrospectively analyzed data from a cohort of eight critically ill children treated from January 2018 to March 2020 describing the impact of CKRT plus hemoperfusion with CytoSorb on renal outcome in critically ill children with septic shock.Results: We evidenced a significant reduction in interleukin (IL)-6 an IL-10 after hemoperfusion with CytoSorb in our pediatric population. Furthermore, we were able to show a significant improvement of creatinine and blood urea nitrogen (BUN) after blood purification and at pediatric intensive care units (PICU) discharge. We have observed a median of 2.5 CKRT days after stop of hemoperfusion . None of our patients required CKRT 30 days after PICU discharge (PICU-D). None of them developed CKD.Conclusion: Hemoperfusion with CytoSorb is a valuable therapeutic option in combination with CKRT in SA-AKI. More studies are warranted to confirm our results and in particular to define the role of this adjuvant therapy as a preemptive strategy to protect renal function in pediatric septic shock. Sepsis-associated acute kidney injury (SA-AKI) refers to impairment of renal function in sepsis and septic shock. In the pediatric setting, a large multicenter study reported that AKI developed in 26.9% and severe AKI in 11.6% of patients admitted to pediatric intensive care units (PICU) . BecauseIn vitro experiments demonstrated that CytoSorb efficiently removes a broad spectrum of inflammatory mediators including toxic pathogen associated molecular patterns (PAMPS) and damage associated molecular patterns (DAMPS), cytokines, and mycotoxins from blood  filters can impact on cytokines removal firstly by adsorption and this ability is more evident in the first hours of the hemofilter life . The abiom blood . Previouic shock –21].To our knowledge, few published studies focused on SA-AKI and renal outcome in septic patients who have received hemadsorption with CytoSorb, and none of them included pediatric patients . Therefo2 according to body weight, blood volume 60, 93, and 152 ml, respectively], combined with the adsorber in continuous veno-venous hemofiltration (CVVH) or continuous veno-venous hemodiafiltration (CVVHDF) modality, using a pre-/post-filter reinfusion and an effluent dose of 2,000 ml/h/1.73 m2. The cartridge was inserted in the CKRT circuit in series with the hemofilter in a post-filter position , 0.2–0.6–1 mposition ; both CKposition . Acute kposition  and indi1,Q3) before (T0) and after (T1) hemoperfusion of creatinine (mg/dl) , blood urea nitrogen (BUN) (mg/dl) ; lactate (mmol/L) ; urinary output (ml/kg/h) ; IL-6 (pg/ml) ; IL-10 (pg/ml) .We present data of eight critically ill children with septic shock. Patients' characteristics at PICU admission and at start of blood purification  are reported in p < 0.05) before (T0) and after (T1) hemoperfusion for creatinine (p = 0.012); IL-6 (p = 0.012); IL-10 (p = 0.043)  (p = 0.017). Creatinine HD median 0.35  (p = 0.050). BUN PICU median 12.5  (p = 0.021). We noticed a statistical difference (= 0.043)   . Further= 0.043)  represen1 0.25, Q3 18.75). None of our patients required CKRT 30 days after the PICU-D.The need for diuretics after the ending of CKRT has been observed in three out of eight patients (37.5%) and the need for anti-hypertensive drugs at HD has been noticed in three out of eight patients (37.5%). We have observed a median of 2.5 CKRT days after stop of hemoperfusion  . Three oIt has been recognized that kidney involvement in septic shock is not only related to intrarenal hemodynamic dysfunction, but is also a consequence of the dangerous effects of medium size molecules  which have a toxic effect on tubular cells when concentrated in the ultrafiltrate, acting on the luminal surface of the tubules . For theOur findings show that hemoperfusion significantly contributes to clearance of two of the most important cytokines (IL-6 and IL-10) involved in SA-AKI. We have observed a positive impact of this blood purification strategy on some important renal biomarkers: creatinine has shown a significant improvement at the stop of hemoperfusion but also at PICU and HD and the same positive variation has been observed for BUN at PICU-D. Unfortunately, we have not monitored other biomarkers of renal damage where we could more sensitively detect renal function improvements also in those patients who did not meet the full criteria for AKI. However, considering the progressive and sustained improvement in renal function in our cohort and that no one of our survived patients required CKRT at 30 days or had a clinical picture of CKD, we can postulate that together with CKRT the adjunctive action of hemoperfusion played a significant role on renal outcome in our cohort trough a massive removal of medium-sized molecules which lead toxic effect on tubular cells.Two of three patients who did not survived were newborns confirming the high morbidity and mortality in small children with severe septic shock and with need of extracorporeal support , 28.Our study provides important information on the potential role of CytoSorb hemoperfusion plus CKRT in preventing and treating SA-AKI in children with septic shock. We would outline some limitations; our cohort was very small and under-powered to draw definitive conclusion by our statistical evaluation. Some important aspects need to be elucidated with further studies, primarily the best timing to start with this type of adjunctive therapy and the potential removal of antibiotics or other useful drugs with the two devices. As it has been debated for CKRT about right time and the potential role of CKRT without AKI as a preemptive strategy to protect renal function and gain hemodynamic stability, the same concept should be applied for hemoperfusion with CytoSorb as it has emerged that removal of inflammatory mediators from the bloodstream is thought to possibly improve clinical outcomes . We woulAlthough we acknowledge that definitive conclusions cannot be drawn from this a small cohort, we highlight that our experience shows that hemoperfusion with CytoSorb is a valuable therapeutic option in SA-AKI. The use of adsorption columns is attractive, since these devices can be combined with CKRT for the concomitant treatment of fluid overload and AKI, and at the same time, play an important role in managing cytokine storm associated with organs damage in septic shock. More evidence is required to better define the role of CytoSorb therapy in this clinical setting in the proper time of onset of this adjuvant therapy.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Ethical Committee Children Hospital Bambino Gesù. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.GB drafted the manuscript. GL and FS analyzed and interpreted the data and written the manuscript with GB. AC, CC, and IG discussed the results and reviewed the manuscript. All authors have read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Takayasu’s arteritis (TA) is a chronic, progressive, inflammatory arteritis. We presented the case of cesarean section in a patient with TA.A 31-year-old pregnant woman with TA underwent a planned cesarean section at 34 weeks of pregnancy. She had stenosis of the cerebral and coronary arteries and heart failure due to aortic regurgitation. Spinal anesthesia was performed. In addition to standard monitoring, arterial blood pressure in the dorsalis pedis artery and regional cerebral tissue oxygen saturation were monitored. Intraoperative arterial blood pressure was maintained using continuous infusion of noradrenaline with a careful intermittent bolus infusion of phenylephrine. All the procedures were successfully performed without significant complications.In a pregnant woman with TA, severe stenosis of the cerebral and coronary arteries, and heart failure due to valvular heart disease, careful anesthetic management by selecting catecholamines and assessing the perfusion pressure for critical organs is important. Takayasu’s arteritis (TA) is a disease characterized by non-specific inflammation of the aorta and its main branches . The incThe patient in this case report was a 31-year-old woman . She was diagnosed with TA at the age of 23 years and started treatment with steroids and immunosuppressive drugs. She had a spontaneous pregnancy and was admitted to our hospital at 23 weeks of pregnancy because of cardiovascular disease associated with TA. Her gravidity was two times, including artificial abortion at 18 years, and she was nulliparity. After admission to our hospital, daily vital signs, weight measurement, and cardiac ultrasonography once every 2 weeks were performed. As the pregnancy progressed, some signs of cardiac failure, such as postprandial chest tightness, cardiac enlargement, and pericardial effusion, became apparent. A cesarean section was planned at 34 weeks and 1 day of pregnancy, considering the risk of increased systemic vascular resistance and exacerbation of heart failure by straining, hyperventilation, and labor induction.She had a medical history of bare-metal stent placement for a stenotic lesion in the left main trunk of the coronary artery at the age of 23 years and drug-eluting stent placement for a stenotic lesion in the circumflex branch at the age of 24 years. She was undergoing aspirin and clopidogrel antithrombotic therapy after drug-eluting stent implantation; however, clopidogrel was discontinued after 23 weeks of pregnancy in preparation for delivery, and antithrombotic therapy with aspirin alone was continued. She was also undergoing nifedipine and carvedilol therapy for hypertension.The patient’s pulse in the bilateral radial arteries was not palpable due to inflammatory changes in the arteries associated with TA; however, the bilateral dorsalis pedis arteries were palpable. Blood pressure could not be measured in the upper arm. Her blood pressure was 131/65 mmHg, measured on the lower legs, and her pulse rate was 82 beats/min on admission. Her oxygen saturation levels using a pulse oximeter were available and 99% in fingers of both hands.2, sinus of Valsalva diameter of 41.9 mm, and ascending aortic diameter of 40.7 mm. These findings indicated severe aortic regurgitation associated with aortic root dilatation.Imaging examinations, including head computed tomography, head magnetic resonance imaging, and brain single-photon emission computed tomography, revealed severe stenosis of the left common carotid artery, bilateral vertebral arteries, and bilateral subclavian arteries, with preserved blood flow from the right common carotid artery to the entire brain via the circle of Willis arteries Fig. . Transth2) using the INVOS™ 5100C system (Covidien Japan K.K.).Cesarean section was planned under spinal anesthesia. In addition to standard monitoring, we monitored arterial pressure, cardiac output at the dorsalis pedis artery using the FloTrac™ sensor (Edwards Lifesciences), and regional cerebral tissue oxygen saturation (rSO2 temporarily decreased from 56 to 50% on the right and from 63 to 52% on the left; however, there were no abnormal neurological findings. A single dose of 0.1 mg of phenylephrine was administered, and the patient’s blood pressure improved rapidly. Intraoperatively, the systolic blood pressure was maintained at 110–120 mmHg, the mean blood pressure was 60–70 mmHg, and the heart rate was 70–80 beats/min. After 10 min of regional anesthetics administration, a loss of cold sensation occurred in the Th5–S dermatomes. The infant was delivered 3 min after the initiation of surgery. Intravenous 10 units of oxytocin were administered immediately after placental delivery. Favorable uterine contractions were obtained; however, the patient’s blood pressure and heart rate did not change. The infant had Apgar scores of 8 and 9 points at 1 and 5 min, respectively, and weighed 1888 g. The umbilical artery blood pH was 7.364, pCO2 was 38.3 mmHg, base excess was − 3.2 mmol/L, and lactate was 2.8 mmol/L. The operative time was 57 min; blood loss was 1470 mL, including amniotic fluid; and the volume of fluid infusion was 693 mL of extracellular fluid preparation and 750 mL of hydroxyethyl starch preparation (Fig. A continuous dose of nicorandil was initiated after admission at 2 mg/h, followed by a continuous dose of noradrenaline at 0.02 μg/kg/min. Spinal anesthesia was performed with a 26-G pencil-point needle from the third and fourth lumbar intervertebral spaces, and 1.8 mL of 0.5% hyperbaric bupivacaine was administered with 10 μg of fentanyl and 100 μg of morphine. Immediately after the regional anesthetics administration, the systolic blood pressure decreased to 73 mmHg, and the mean blood pressure was 42 mmHg. rSOIn this case, stenosis of the left common carotid artery, bilateral vertebral artery, and bilateral subclavian artery was observed. Moreover, the patient had a history of treatment for coronary artery stenosis, and severe aortic regurgitation and pericardial effusion were observed. Therefore, we believed it was important to select the correct anesthetic method, to maintain perioperative cerebral blood flow, to maintain coronary artery blood flow, and to manage heart failure.First, regarding the selection of anesthetic method, all the reports so far have reported on epidural anesthesia, spinal anesthesia, or a combination of both –9. In pr2; however, we recommend to carefully evaluate the result depending on which arterial was used for measurement.For the treatment of hypotension during cesarean section under spinal anesthesia, phenylephrine tends to cause maternal bradycardia, whereas noradrenaline is not likely to cause bradycardia , 12. A c2 monitoring were performed for patients with cervical vascular stenosis or obstruction and valvular disease as monitored in our case [2 monitoring was useful for detecting transient decrease of cerebral perfusion in a patient who developed dysarthria, tinnitus, and stiff neck during cesarean section [2 was observed in accordance with a decrease of blood pressure immediately after spinal anesthesia. Although neurological abnormalities were not observed, rSO2 may be monitored for cerebral blood flow assessment in pregnant women with TA.Finally, there are several reports wherein invasive arterial blood pressure measurement and rSOour case –6. Lee e section . In our In anesthetic management of cesarean section in a parturient with TA, anesthesiologists should carefully select the anesthetic method and drug administration while considering oral administration of antiplatelet drugs, heart disease, and maintenance of organ blood flow associated with vascular lesions, followed by the measurement of blood pressure and monitoring.


An increased risk for complication was independently associated with obtaining a single kidney core (vs. 2 and 3 cores) (p = 0.021). Conclusions: KB is an invasive and safe procedure with a low percentage of complications. Obtaining an extra kidney core for research does not increase the risk of complications during the intervention, which remains low in concordance with previously published reports.Background and objectives: Kidney biopsy (KB) is the “gold standard” for the diagnosis of nephropathies and it is a diagnostic tool that presents a low rate of complications. Nowadays, biobank collections of renal tissue of patients with proven renal pathology are essential for research in nephrology. To provide enough tissue for the biobank collection, it is usually needed to obtain an extra kidney core at the time of kidney biopsy. The objective of our study is to evaluate the complications after KB and to analyze whether obtaining an extra core increases the risk of complications. Material and methods: Prospective observational study of KBs performed at Vall d’Hebron Hospital between 2019 and 2020. All patients who accepted to participate to our research biobank of native kidney biopsies were included to the study. Clinical and laboratory data were reviewed and we studied risk factors associated with complications. Results: A total of 221 patients were included, mean age 56.6 (±16.8) years, 130 (58.8%) were men, creatinine was 2.24 (±1.94) mg/dL, proteinuria 1.56 (0.506–3.590) g/24 h, hemoglobin 12.03 (±2.3) g/dL, INR 0.99 (±0.1), and prothrombin time (PT) 11.86 (±1.2) s. A total of 38 patients (17.2%) presented complications associated with the procedure: 13.1% were minor complications, 11.3% ( Kidney biopsy (KB) is the “gold standard” technique for the diagnosis of renal pathologies . ApproxiIn general, the previously published series demonstrated minor complications in 10–20% of cases and major complications in 1–6% of KB . Most seThis is a prospective and observational study in which native KB performed at the Vall d’Hebron Hospital from January 2019 to December 2020 have been included. Since January 2019, our hospital has a biobank of native kidney biopsies approved by the Ethical committee for clinical research—Vall d’Hebron institute of Research (CEIC-VHIR) (PR (AG) 252/2018), as well as by the Department of Health of the Generalitat de Catalunya. In our hospital, ultrasound-guided KB is performed by an interventional radiologist in the presence of a clinical nephrologist. The thickness of the needle usually used is 16G and the choice of the side of the kidney biopsy is an individualized decision of the radiologist in each case. Furthermore, the indications of trans-jugular renal biopsy in our center are: patients with combined liver biopsy, a single kidney, or hemostasis alterations that confer a high risk of bleeding. This technique is performed by an angio-radiologist approaching the posterior right inferior renal vein through the right jugular vein. The contraindications of this technique are the presence of an internal jugular vein thrombosis or a serious coagulation disorder that contraindicates the puncture of a central venous access. In general, two kidney cores were obtained and subsequently processed in the pathology department by the usual techniques  for histological diagnosis. All study subjects signed the informed consent. An extra third kidney core biopsy was obtained and stored in RNA later solution when possible. RNAlater Solution is an aqueous stabilizing solution that permeates most tissues rapidly to stabilize and protect RNA in fresh samples, eliminating the need for immediate freezing. Renal tissues were stored in RNAlater solution at −20 °C. The inclusion criteria were patients who signed informed consent, older than 18 years old, and the realization of native kidney biopsy. The exclusion criteria were patients who did not signed informed consent, younger than 18 years old, and renal transplant patients.A total of 33 variables were analyzed: 23 (69.7%) clinical and 10 (30.3%) analytical. Demographic variables (sex and age), anthropomorphic characteristics ), medical pathological history (hypertension (defined as >140/90 mmHg) and diabetes mellitus), chronic medication (antiplatelet and/or anticoagulant), analytical variables , as well as the histological diagnosis. In addition, the type of technique used for the kidney biopsy (ultrasound-guided vs. trans-jugular), the kidney from which the biopsy was obtained (right vs. left), the number of kidney cores obtained, and kidney and cortical size in centimeters were collected (cm) and systolic and diastolic blood pressure in mmHg were also collected. Finally, the complications derived from the KB were recorded. Complications were classified as minor, corresponding to patients who presented mild hematoma without transfusion requirement or cause prolonged admission. Major complications included patients with severe hematoma that required a longer hospital stay, anemia requiring transfusion, hematuria or hemodynamic instability, need of arterial embolization, arteriovenous fistula, and death. With the purpose of classifying patients into major or minor complications, the most severe complication was the one registered.t-test for independent data and U Mann–Whitney test for variables that do not follow a normal distribution. The comparison between means with more than two categories was performed with an ANOVA test and the Tukey test for multiple comparisons between different groups. A binary logistic regression multivariate analysis was performed with the presence of post-kidney biopsy complications as dependent variable. A multinomial logistic multivariate analysis was performed with the presence of major complications, minor complications, and absence of complications as dependent variables. Statistical significance was considered when p was less or equal than 0.05.For the statistical analysis, the computer program IBM SPSS Statistics version 20.0 was used. The quantitative variables with normal distribution were presented as mean and standard deviation. Variables that do not follow a normal distribution were presented as median and interquartile range. Qualitative variables were expressed as a percentage. For the comparison of qualitative variables, we used the chi square test and for the comparison of the means between two samples, we used the Student’s A total of 221 patients were included  with a m2), proteinuria 1.56 (0.506–3.59) g/24 h, mean hemoglobin 12.03 (±2.3) g/dL, 250,995  platelets, INR 0.99 (±0.1), PT 11.86 (±1.2) seconds. A total of 100 patients (45.2%) presented microhematuria in the urinary sediment before the KB. A total of 15 (6.8%) patients were under anticoagulation treatment and 36 patients (16.3%) were on antiplatelet treatment. Both anticoagulation and antiplatelet treatments were stopped in all patients at least 5 days before the KB. Regarding the technique used for renal biopsy, in 213 (96.4%) patients it was ultrasound-guided and the remaining n = 8 (3.8%) were performed by a transjugular procedure. In 152 (68.8%) patients, three renal tissue cores were obtained, in 62 (28.1%) patients, two cores, and in 7 (3.2%) patients, a single core was obtained. A sample for the biobank was obtained in a total of 180 (81.4%) patients, in 138 cases (76.7%), 3 renal cores were obtained, in 40 patients (22.2%), 2 renal cylinders, and in 2 cases (1.1%) obtaining a unique renal core was sufficient to obtain material for the biobank. Reasons for a research biopsy core not being obtained were operator choice in patients presenting a bleeding complication during the procedure before collection of research tissue . We analyzed and compared the patients’ characteristics according to the number of kidney cores that were obtained in the procedure  patients were men, 128 (57.9%) patients had hypertension, and 52 (23.5%) were diabetic. The mean weight was 75.8 (±24.6) kg and a BMI of 27.6 (±5.01) (kg/mrocedure . p = 0.002). Furthermore, in patients with three cores, the left kidney was more frequently biopsied as compared with the right side .We found differences in the terms of renal function and the side of punction. Thus, patients where one core was obtained presented worse baseline renal function as compared with the patients where two or three cores were obtained , followed by nonspecific diagnosis , nephroangiosclerosis , diabetic nephropathy , IgA nephropathy , membranous nephropathy , and non-allergic interstitial nephritis   .n = 25) of patients required blood transfusion, 12 patients post-KB, and 13 patients pre-KB. The indications of blood transfusion pre-KB were level of hemoglobin < 8 g/dL to ensure a higher level of safety prior to the invasive procedure. A total of 5.3% (n = 38) of patients with complications, presented macrohematuria. Most of the complications were minor complications , mild hematomas that represented 13.1% of the total number of kidney biopsies performed  complications associated with the procedure were recorded. A total of 11.3% (rmed see . n = 3), which corresponds to 7.9% of the total complications. A total of five patients  required embolization and in one case  the complication was an arterio-venous fistula. We did not observe any cases of nephrectomy or death. The patients who presented complications (major and minor) were classified and compared with those who did not present any type of complication (Severe hematomas were diagnosed in 1.4% (lication . p = 0.034), had lower body weight (p = 0.022), higher platelet count (p = 0.038), lower PT (p = 0.05), and required a higher percentage of blood transfusions (p = 0.003). A tendency of lower pre-kidney biopsy hemoglobin level was observed in patients who presented complications (p = 0.057). There was no evidence of a higher number of complications in patients from whom three renal tissue cores were obtained in comparison to patients with one or two cores (p = 0.012). In addition, we also compared the baseline characteristics of the population according to the degree of complications  (We observed that the patients who presented complications were younger (ication) . p = 0.028 and p = 0.02, respectively), they were more likely to have undergone transjugular kidney biopsy (p = 0.006), and required a higher number of blood transfusions peri-procedure (p < 0.001).We found that patients with major complications presented a longer INR and PT  as a dependent variable . p = 0.021). A second multivariate logistic regression model was performed in which the dependent variable was the presence of major complications, adjusting for the same variables as the previous model. However, in this case, no statistically significant risk factors for major complications were identified. Furthermore, we performed another multivariate multinomial analysis for independent risk factors for presenting minor complications vs. major complications vs. absence of complications (p = 0.035) and obtaining single kidney core (p = 0.026) were independent risk factors of presenting minor complications. Regarding major complications, we did not find any independent risk factors.The model was adjusted by variables that were statistically significant in the previous univariate analysis: age, hemoglobin level, number of renal tissue cores, number of platelets, PT, and weight. Obtaining a single kidney core (vs. 2 and 3 cores) was identified as independent risk factors of bleeding  associated with the procedure. Only 4.1% of the total showed major complications, and it should be noted that no case of nephrectomy or death was detected. In our cohort, obtaining a single kidney core (vs. two and three cores) was identified as an independent risk factor of bleeding.For the purpose of analyzing the complications after KB, it is important to take into account the protocol of the procedure of each center to be able to interpret correctly the results of the studies. Thus, it is important to consider the thickness of the needle used for the puncture and the number of cores that are usually obtained. Several studies that have been focused on post-kidney biopsy complications detailed these relevant aspects ,33,34,35However, in a few studies, the KB protocol details are not explained ,14,36. TPrevious studies focused on post-kidney biopsy complications obtained similar percentages to those observed in the present study. Pombas et al., in a Spanish cohort of 661 kidney biopsies, diagnosed 16.6% of complications . The perIn previous studies, the transfusion requirement was lower, with percentages ranging from 1.2% to 5% ,14,24,28Finally, obtaining of a single renal tissue core was also identified as a risk factor for complications as compared to those with two or three kidney cores. A plausible explanation for this finding is that in the patients who presented a bleeding complication, it was mainly detected at the first puncture, and for that reason, only a single kidney core was obtained. Another possible explanation suggested that increased bleeding risk  per se could have contributed to perform only one biopsy, with more bleeding complications thereafter.As mentioned above, in our study, obtaining more kidney cores was not identified as a risk factor for complications secondary to KB. A study called TRIDENT (Transforming Research in Diabetic Nephropathy) is currently ongoing, in which a cohort of biopsied diabetic patients with diabetic nephropathy is analyzed; an extra kidney core has been obtained for research studies purposes . To dateOur study had some limitations. One of the main limitations of our study is that it is a single center study that accounts for a small sample size. For this reason, one can surmise that several variables were not statistically significant in the analysis. Another limitation is that it is an observational prospective study, and it is not a randomized clinical trial (RCT). Thus, enlarging the sample size, performing a multicenter extra renal core biopsy study, or designing an RCT could help to ascertain the security of obtaining extra cores in KB. In addition, other complications risk factors, such as increased bleeding time and specific coagulation factors, have not been assessed.Kidney biopsy is an essential tool for the diagnosis and management of patients with renal involvement. Performing this procedure is safe thanks to the improvement of the technique over the years, which has achieved a low rate of complications. Furthermore, obtaining an extra renal core for research, which implies one more puncture during the biopsy procedure, did not increase the risk of presenting complications in our study. Future multicenter studies that include a larger cohort are necessary to evaluate the existence of other risk factors for presenting associated complications in this type of population.