Establishing targets for goal-directed anesthesia in renal transplantation: A cohort analysis of high-saliency surgical time courses.

Delayed graft function (DGF) increases morbidity and mortality in kidney transplant recipients. Operative parameters, including hemodynamic manipulation through vasopressors and fluids, can impact perfusion to the newly transplanted kidney and influence DGF incidence. We analyzed intraoperative time-series data in 5-minute intervals from kidney transplant recipient operations (N = 545) in conjunction with pretransplant characteristics and postsurgical outcomes, including DGF incidence, 60-day creatinine, and graft survival. Of the operations, 127 DGF events were captured in our cohort from a single academic transplant center (57/278 donations after brainstem death [DBDs], 65/150 donations after circulatory/cardiac death [DCDs], 5/117 live donations). In multiple regression, postanastomosis hypotension defined as mean arterial pressure (MAP) <75 mmHg was a risk factor for DGF independent of conventional predictors of DGF in DCD and DBD kidneys. DCD recipients with DGF had lower average postanastomosis MAP (DGF: 80.1 ± 8.1 mmHg vs no DGF: 76.4 ± 6.7 mmHg, P = .004). Interaction analysis demonstrated above-average doses of vasopressors and crystalloids were associated with improved outcomes when used at MAPs ≤75 mmHg, but they were associated with increased DGF at MAPs >75 mmHg, suggesting that the incidence of DGF can be highly influenced by intraoperative hemodynamic controls. This analysis of surgical time courses has identified potential new strategies for goal-directed anesthesia in renal transplantation.

Hypertension and Kidney Function After Living Kidney Donation.

Importance: Recent guidelines call for better evidence on health outcomes after living kidney donation. Objective: To determine the risk of hypertension in normotensive adults who donated a kidney compared with nondonors of similar baseline health. Their rates of estimated glomerular filtration rate (eGFR) decline and risk of albuminuria were also compared. Design, Setting, and Participants: Prospective cohort study of 924 standard-criteria living kidney donors enrolled before surgery and a concurrent sample of 396 nondonors. Recruitment occurred from 2004 to 2014 from 17 transplant centers (12 in Canada and 5 in Australia); follow-up occurred until November 2021. Donors and nondonors had the same annual schedule of follow-up assessments. Inverse probability of treatment weighting on a propensity score was used to balance donors and nondonors on baseline characteristics. Exposure: Living kidney donation. Main Outcomes and Measures: Hypertension (systolic blood pressure [SBP] ≥140 mm Hg, diastolic blood pressure [DBP] ≥90 mm Hg, or antihypertensive medication), annualized change in eGFR (starting 12 months after donation/simulated donation date in nondonors), and albuminuria (albumin to creatinine ratio ≥3 mg/mmol [≥30 mg/g]). Results: Among the 924 donors, 66% were female; they had a mean age of 47 years and a mean eGFR of 100 mL/min/1.73 m2. Donors were more likely than nondonors to have a family history of kidney failure (464/922 [50%] vs 89/394 [23%], respectively). After statistical weighting, the sample of nondonors increased to 928 and baseline characteristics were similar between the 2 groups. During a median follow-up of 7.3 years (IQR, 6.0-9.0), in weighted analysis, hypertension occurred in 161 of 924 donors (17%) and 158 of 928 nondonors (17%) (weighted hazard ratio, 1.11 [95% CI, 0.75-1.66]). The longitudinal change in mean blood pressure was similar in donors and nondonors. After the initial drop in donors' eGFR after nephrectomy (mean, 32 mL/min/1.73 m2), donors had a 1.4-mL/min/1.73 m2 (95% CI, 1.2-1.5) per year lesser decline in eGFR than nondonors. However, more donors than nondonors had an eGFR between 30 and 60 mL/min/1.73 m2 at least once in follow-up (438/924 [47%] vs 49/928 [5%]). Albuminuria occurred in 132 of 905 donors (15%) and 95 of 904 nondonors (11%) (weighted hazard ratio, 1.46 [95% CI, 0.97-2.21]); the weighted between-group difference in the albumin to creatinine ratio was 1.02 (95% CI, 0.88-1.19). Conclusions and Relevance: In this cohort study of living kidney donors and nondonors with the same follow-up schedule, the risks of hypertension and albuminuria were not significantly different. After the initial drop in eGFR from nephrectomy, donors had a slower mean rate of eGFR decline than nondonors but were more likely to have an eGFR between 30 and 60 mL/min/1.73 m2 at least once in follow-up. Trial Registration: ClinicalTrials.gov Identifier: NCT00936078.

Methods to increase equity, diversity, and inclusion in Canadian urology programs.

INTRODUCTION: Women and ethnic minorities are underrepresented at all levels of training and practice in urology residency programs. Equity, diversity, and inclusion (EDI) is a growing field of interest in medical research and business literature, especially regarding recruitment. The objective of this review was to evaluate evidence-based strategies to increase EDI to improve urology residency recruitment. METHODS: A review was conducted using Ovid Medline to identify publications reporting strategies to increase women and underrepresented minorities (URM ) in healthcare fields. An evaluation of business models was incorporated. Identified strategies were sorted and ranked based on how many papers reported an increased proportion of women or URM in their program following implementation. RESULTS: We assessed 234 publications from 1972-2022. Eleven underwent full review. Six additional pieces of business literature were reviewed and incorporated. The following methods were most often identified to increase diversity: mentorship and holistic application review (six publications), as well as funded internship programs and diverse selection committees (four publications). Diversity statements and application blinding were highlighted by multiple business sources but were each only reviewed in one medical publication. CONCLUSIONS: Recommendations identified include mentorship, holistic application review by diverse selection committees with bias training, and development of funded internship programs. Standardized questions and rubrics were also well-studied. Business strategies, such as publishing diversity statements and application blinding, are less studied in medical education literature. This study is unique in its inclusion of both medical and business literature and highlights concrete strategies for urology residency programs to increase EDI during recruitment.

De novo urethral stricture disease in renal transplant recipients.

INTRODUCTION: With routine catheterization and low urine output pre-transplant, renal transplant recipients (RTRs) may be at risk of urethral stricture disease post-transplant. The objective of this study was to characterize new urethral stricture disease in males following renal transplant. METHODS: A retrospective chart review was carried out on all male RTRs at Vancouver General Hospital who developed urethral strictures from October 2009-2019. Descriptive analyses were conducted on patient characteristics. Comparative analyses against non-stricture RTRs were carried out. RESULTS: Of 636 RTRs, 18 (2.8%) developed a postoperative urethral stricture. Median time from transplant to stricture discovery was 56 days (range 8-618 days). One-third of stricture patients had prior risk factors for stricture formation. Post-transplant, 77.8% presented symptomatically, with 61.1% requiring intervention. Overall graft survival rate was 88.9% among the RTR stricture group; 16.7% experienced acute rejection and 22.2% had delayed graft function (DGF). There was no significant association between developing postoperative urethral stricture and urinary tract infection (Chi-squared [X2]=0.04, p=0.84; odds ratio [OR ] 0.81, 95% confidence interval [CI] 0.1-6.21), DGF (X2=0.14, p=0.70; OR 0.8, CI 0.26-2.48), or acute rejection (X2=2.02, p=0.14; OR 2.55, CI 0.71-9.12). CONCLUSIONS: De novo post-transplant urethral stricture rates appear to occur at a higher rate than the general population and contribute to patient morbidity. Stricture disease should be considered post-transplantation in patients with voiding dysfunction, even if they don't have prior risk factors. Multicenter studies should be considered to elucidate any relationship between urethral stricture and graft survival.

Automatic measurement of kidney dimensions in two-dimensional ultrasonography is comparable to expert sonographers.

Purpose: Length and width measurements of the kidneys aid in the detection and monitoring of structural abnormalities and organ disease. Manual measurement results in intra- and inter-rater variability, is complex and time-consuming, and is fraught with error. We propose an automated approach based on machine learning for quantifying kidney dimensions from two-dimensional (2D) ultrasound images in both native and transplanted kidneys. Approach: An nnU-net machine learning model was trained on 514 images to segment the kidney capsule in standard longitudinal and transverse views. Two expert sonographers and three medical students manually measured the maximal kidney length and width in 132 ultrasound cines. The segmentation algorithm was then applied to the same cines, region fitting was performed, and the maximum kidney length and width were measured. Additionally, single kidney volume for 16 patients was estimated using either manual or automatic measurements. Results: The experts resulted in length of 84.8±26.4 mm [95% CI: 80.0, 89.6] and a width of 51.8±10.5 mm [49.9, 53.7]. The algorithm resulted a length of 86.3±24.4 [81.5, 91.1] and a width of 47.1±12.8 [43.6, 50.6]. Experts, novices, and the algorithm did not statistically significant differ from one another (p>0.05). Bland-Altman analysis showed the algorithm produced a mean difference of 2.6 mm (SD = 1.2) from experts, compared to novices who had a mean difference of 3.7 mm (SD = 2.9 mm). For volumes, mean absolute difference was 47 mL (31%) consistent with ∼1 mm error in all three dimensions. Conclusions: This pilot study demonstrates the feasibility of an automatic tool to measure in vivo kidney biometrics of length, width, and volume from standard 2D ultrasound views with comparable accuracy and reproducibility to expert sonographers. Such a tool may enhance workplace efficiency, assist novices, and aid in tracking disease progression.

An evaluation of the contribution of routine ultrasound when performed with multiphase CT in renal donor imaging assessment.

OBJECTIVES: We sought to examine the contribution of routine ultrasound when performed with computed tomography in identifying exclusion criteria in potential living kidney donors. METHODS: We performed a 10-year retrospective cohort study including all cases of potential renal donors at our center. For each case, the donor workup ultrasound (US) and multiphase computed tomography (MPCT) original reports and imaging were reviewed by a fellowship-trained abdominal radiologist in consultation with a transplant urologist and placed into one of 3 groups: (1) no significant US contribution, (2) US was useful to characterize an incidental finding (either US exclusive or US aided in CT interpretation) but did not impact donor eligibility, and (3) an US exclusive finding contributed to donor exclusion. RESULTS: A total of 432 potential live renal donors were evaluated (mean age 41, 263 women). In total, 340 (78.7%, group 1) cases had no significant US contribution. In 90 cases (20.8%, group 2), US helped to characterize one or more incidental findings but did not contribute to donor exclusion. In 1 (0.2%, group 3) case, an US exclusive finding (suspected medullary nephrocalcinosis) contributed towards donor exclusion. CONCLUSION: US provided limited contribution to renal donor eligibility decisions when performed routinely with MPCT. CLINICAL RELEVANCE: Routine ultrasound could potentially be omitted in the live renal donor workup, with alternative strategies including a selective approach to incorporating ultrasound and an expanded role of dual-energy CT. KEY POINTS: • Ultrasound is performed routinely with CT for renal donor assessment in some jurisdictions; however, this practice has come into question particularly with advances in dual-energy CT. • Our study found that routine use of ultrasound provided limited contribution, primarily assisting CT in characterization of benign findings with only 1/432 (0.2%) potential donors in a 10-year period excluded based in part on an ultrasound exclusive finding. • The role of ultrasound can be narrowed to a targeted approach for certain at-risk patients, and can be further reduced if dual-energy CT is utilized.

The Kidneys Are Not All Normal: Transplanted Kidneys and Their Speckle Distributions.

OBJECTIVE: Modelling ultrasound speckle to characterise tissue properties has generated considerable interest. As speckle is dependent on the underlying tissue architecture, modelling it may aid in tasks such as segmentation or disease detection. For the transplanted kidney, where ultrasound is used to investigate dysfunction, it is unknown which statistical distribution best characterises such speckle. This applies to the regions of the transplanted kidney: the cortex, the medulla and the central echogenic complex. Furthermore, it is unclear how these distributions vary by patient variables such as age, sex, body mass index, primary disease or donor type. These traits may influence speckle modelling given their influence on kidney anatomy. We investigate these two aims. METHODS: B-mode images from n = 821 kidney transplant recipients (one image per recipient) were automatically segmented into the cortex, medulla and central echogenic complex using a neural network. Seven distinct probability distributions were fitted to each region's histogram, and statistical analysis was performed. DISCUSSION: The Rayleigh and Nakagami distributions had model parameters that differed significantly between the three regions (p ≤ 0.05). Although both had excellent goodness of fit, the Nakagami had higher Kullbeck-Leibler divergence. Recipient age correlated weakly with scale in the cortex (Ω: ρ = 0.11, p = 0.004), while body mass index correlated weakly with shape in the medulla (m: ρ = 0.08, p = 0.04). Neither sex, primary disease nor donor type exhibited any correlation. CONCLUSION: We propose the Nakagami distribution be used to characterize transplanted kidneys regionally independent of disease etiology and most patient characteristics.

The Living Kidney Donor Safety Study: Protocol of a Prospective Cohort Study.

Background: Living kidney donation is considered generally safe in healthy individuals; however, there is a need to better understand the long-term effects of donation on blood pressure and kidney function. Objectives: To determine the risk of hypertension in healthy, normotensive adults who donate a kidney compared with healthy, normotensive non-donors with similar indicators of baseline health. We will also compare the 2 groups on the rate of decline in kidney function, the risk of albuminuria, and changes in health-related quality of life. Design Participants and Setting: Prospective cohort study of 1042 living kidney donors recruited before surgery from 17 transplant centers (12 in Canada and 5 in Australia) between 2004 and 2014. Non-donor participants (n = 396) included relatives or friends of the donor, or donor candidates who were ineligible to donate due to blood group or cross-match incompatibility. Follow-up will continue until 2021, and the main analysis will be performed in 2022. The anticipated median (25th, 75th percentile, maximum) follow-up time after donation is 7 years (6, 8, 15). Measurements: Donors and non-donors completed the same schedule of measurements at baseline and follow-up (non-donors were assigned a simulated nephrectomy date). Annual measurements were obtained for blood pressure, estimated glomerular filtration rate (eGFR), albuminuria, patient-reported health-related quality of life, and general health. Outcomes: Incident hypertension (a systolic/diastolic blood pressure ≥ 140/90 mm Hg or receipt of anti-hypertensive medication) will be adjudicated by a physician blinded to the participant's donation status. We will assess the rate of change in eGFR starting from 12 months after the nephrectomy date and the proportion who develop an albumin-to-creatinine ratio ≥3 mg/mmol (≥30 mg/g) in follow-up. Health-related quality of life will be assessed using the 36-item RAND health survey and the Beck Anxiety and Depression inventories. Limitations: Donation-attributable hypertension may not manifest until decades after donation. Conclusion: This prospective cohort study will estimate the attributable risk of hypertension and other health outcomes after living kidney donation.

Contexte: Chez les personnes en bonne santé, faire don d'un rein est généralement considéré comme sûr. Il convient toutefois de mieux comprendre les effets à long terme de ce don sur la pression artérielle et la fonction rénale. Objectifs: Déterminer le risque d'hypertension chez les adultes sains et normotendus qui donnent un rein par rapport à des non-donneurs sains et normotendus ayant des indicateurs de santé de base similaires. Nous comparerons également le taux de réduction de la fonction rénale, le risque d'albuminurie et les changements dans la qualité de vie liée à la santé entre les deux groupes. Cadre type d'étude et participants: Étude de cohorte rétrospective menée sur 1 042 donneurs de rein vivants, recrutés avant la chirurgie dans 17 centres de transplantation (12 au Canada et 5 en Australie) entre 2004 et 2014. Le groupe des non-donneurs (n=396) était constitué de parents ou amis du donneur, ou de candidats donneurs non admissibles à faire un don en raison d'une incompatibilité de groupe sanguin ou lors du test de compatibilité croisée. Le suivi s'est poursuivi jusqu'en 2021 et l'analyse principale sera effectuée en 2022. Le temps de suivi médian prévu (25e percentile, 75e percentile, maximum) après le don est de 7 ans (6, 8, 15 ans). Mesures: Les donneurs et les non-donneurs ont complété le même calendrier de mesures à l'inclusion et pendant le suivi (une date simulée de néphrectomie a été attribuée aux non-donneurs). Des mesures annuelles de pression artérielle, de débit de filtration glomérulaire estimé (DFGe), d'albuminurie, de qualité de vie liée à la santé autodéclarée et de santé générale ont été obtenues. Issues principales: L'hypertension incidente (pression artérielle systolique/diastolique ≥ 140/90 mm Hg ou prise d'un médicament antihypertenseur) sera jugée par un médecin aveugle au statut de don du participant. Nous évaluerons le taux de variation du DFGe à partir de 12 mois après la date de la néphrectomie et la proportion de participants qui développeront un rapport albumine/créatinine ≥ 3 mg/mmol (≥ 30 mg/g) pendant le suivi. La qualité de vie liée à la santé sera évaluée à l'aide du questionnaire de santé RAND de 36 questions et de l'Inventaire d'anxiété et de dépression de Beck. Limites: L'hypertension attribuable au don pourrait ne pas se manifester avant des décennies après le don. Conclusion: Cette étude de cohorte prospective permettra d'estimer le risque d'hypertension attribuable au don et d'autres effets sur la santé du donneur après un don de rein.

Kidney Ultrasound for Nephrologists: A Review.

Ultrasound imaging is a key investigatory step in the evaluation of chronic kidney disease and kidney transplantation. It uses nonionizing radiation, is noninvasive, and generates real-time images, making it the ideal initial radiographic test for patients with abnormal kidney function. Ultrasound enables the assessment of both structural (form and size) and functional (perfusion and patency) aspects of kidneys, both of which are especially important as the disease progresses. Ultrasound and its derivatives have been studied for their diagnostic and prognostic significance in chronic kidney disease and kidney transplantation. Ultrasound is rapidly growing more widely accessible and is now available even in handheld formats that allow for bedside ultrasound examinations. Given the trend toward ubiquity, the current use of kidney ultrasound demands a full understanding of its breadth as it and its variants become available. We described the current applications and future directions of ultrasound imaging and its variants in the context of chronic kidney disease and transplantation in this review.

The functions of clusterin in renal mesenchymal stromal cells: Promotion of cell growth and regulation of macrophage activation.

Clusterin (CLU) increases resistance to renal ischemia-reperfusion injury and promotes renal tissue repair. However, the mechanisms underlying of the renal protection of CLU remain unknown. Mesenchymal stromal cells (MSCs) may contribute to kidney cell turnover and injury repair. This study investigated the in vitro functions of CLU in kidney mesenchymal stromal cells (KMSCs). KMSCs were grown in plastic culture plates. Cell surface markers, apoptosis and phagocytosis were determined by flow cytometry, and CLU protein by Western blot. There were no differences in the expression of MSC markers (positive: CD133, Sca-1, CD44, CD117 and NG2, and negative: CD34, CD45, CD163, CD41, CD276, CD138, CD79a, CD146 and CD140b) and in the trilineage differentiation to chondrocytes, adipocytes and osteocytes between wild type (WT) and CLU knockout (KO) KMSCs. CLU was expressed intracellularly and secreted by WT KMSCs, and it was up-regulated by hypoxia. CLU did not prevent hypoxia-induced cell apoptosis but promoted cell growth in KMSC cultures. Furthermore, incubation with CLU-containing culture medium from WT KMSCs increased CD206 expression and phagocytic capacity of macrophages. In conclusion, our data for the first time demonstrate the function of CLU in the promotion of KMSCs proliferation, and it may be required for KMSCs-regulated macrophage M2 polarization and phagocytic activity.

Contemporary risk factors for ureteral stricture following renal transplantation.

INTRODUCTION: Allograft ureteral strictures after renal transplantation impact graft function and increase patient morbidity. They can be challenging to treat and may require complex surgical repair. Therefore, the objective of this study was to identify contemporary risk factors for the development of post-renal transplant ureteral strictures. METHODS: A retrospective analysis was performed on all renal transplant patients at Vancouver General Hospital from 2008-2019. Demographics, clinical parameters, and outcomes were compared between patients who did and did not develop ureteral strictures. Putative risk factors for ureteral stricture were analyzed using logistic regression. RESULTS: A total of 1167 patients were included with a mean followup of 61.9±40.8 months. Ureteral strictures occurred in 25 patients (2.1%). Stricture patients had no demographic differences compared to non-stricture patients but had significantly higher rates of postoperative complications, longer hospital stays, and decreased renal function one year post-transplant (all p<0.05). On multivariable analysis, cold ischemia time >435 minutes (odds ratio [OR] 43.9, confidence interval [CI] 1.6-1238.8, p=0.027), acute rejection (OR 3.0, CI 1.1-7.4, p=0.027), and postoperative complications (OR 112.4, CI 2.4-5332.6, p=0.016) were risk factors for stricture. CONCLUSIONS: Renal transplant patients with ureteral stricture experience greater morbidity and reduced post-transplant renal function compared to non-stricture patients. Our findings support attempts to reduce cold ischemia time, acute rejection, and postoperative complications to mitigate this potential complication. Our study is limited by the low incidence of ureteral stricture resulting in a small sample of stricture patients. Future research in a larger, multicenter setting is warranted.

Clinical validation of an audio-based uroflowmetry application in adult males.

INTRODUCTION: Uroflowmetry is a common test to evaluate lower urinary tract symptoms. Audio-based uroflowmetry is a novel, alternative approach that determines urine flow by measuring sound. Available as a smartphone application, it has potential for screening and monitoring common urological pathologies, particularly in out-of-office environments. This study is the first to evaluate audio-based uroflowmetry in a clinical setting against the gold standard. METHODS: Adult male patients (n=44) attending a general urology clinic were recruited. Audio-based uroflowmetry and conventional uroflowmetry were performed concurrently. Pearson correlation and Bland-Altman analysis were used to compare performance with respect to max flow, time to max flow, and total voiding time. Symmetric mean absolute percentage error (SMAPE) was used to compare curve shapes. Repeatability was evaluated separately in three healthy volunteers using repeat measures correlation. RESULTS: Among urology clinic patients, the correlation for max flow was 0.12. Correlation for time to max flow was 0.46, with limits of agreement of -120-165%. Correlation for total voiding time was 0.91, with limits of agreement of -41-38%. The SMAPE for curve shape was 32.6%, with corresponding accuracy of 67.4%. Among healthy volunteers, the repeat measures correlation for max flow was 0.72. CONCLUSIONS: Audio-based uroflowmetry was inconsistent in evaluating flow rate, attributable to high variability and difficult standardization for acoustic signals. Performance improved with respect to temporal variables, as well as flow curve shape. Further work evaluating intra-patient reliability and pathology-specific performance is required to fully evaluate audio-based uroflowmetry as a screening or monitoring tool.

Correlation of surface-enhanced Raman spectroscopic fingerprints of kidney transplant recipient urine with kidney function parameters.

Routine monitoring of kidney transplant function is required for the standard care in post-transplantation management, including frequent measurements of serum creatinine with or without kidney biopsy. However, the invasiveness of these methods with potential for clinically significant complications makes them less than ideal. The objective of this study was to develop a non-invasive tool to monitor the kidney transplant function by using Surface-Enhanced Raman Spectroscopy (SERS). Urine and blood samples were collected from kidney transplant recipients after surgery. Silver nanoparticle-based SERS spectra of the urine were measured and evaluated using partial least squires (PLS) analysis. The SERS spectra were compared with conventional chemical markers of kidney transplant function to assess its predictive ability. A total of 110 kidney transplant recipients were included in this study. PLS results showed significant correlation with urine protein (R2 = 0.4660, p < 0.01), creatinine (R2 = 0.8106, p < 0.01), and urea (R2 = 0.7808, p < 0.01). Furthermore, the prediction of the blood markers of kidney transplant function using the urine SERS spectra was indicated by R2 = 0.7628 (p < 0.01) for serum creatinine and R2 = 0.6539 (p < 0.01) for blood urea nitrogen. This preliminary study suggested that the urine SERS spectral analysis could be used as a convenient method for rapid assessment of kidney transplant function.

Clusterin regulates macrophage expansion, polarization and phagocytic activity in response to inflammation in the kidneys.

Clusterin (CLU) is a multifunctional protein localized extracellularly and intracellularly. Although CLU-knockout (KO) mice are more susceptible to renal ischemia-reperfusion injury (IRI), the mechanisms underlying the actions of CLU in IRI are not fully understood. Macrophages are key regulators of IRI severity and tissue repair. Therefore, we investigated the role of CLU in macrophage polarization and phagocytosis. Renal IRI was induced in wild-type (WT) or CLU-KO C57BL/6 mice by clamping the renal pedicles for 30 min at 32°C. Peritoneal macrophages were activated via an intraperitoneal injection of lipopolysaccharide (LPS). Renal tissue damage was examined using histology, whereas leukocyte phenotypes were assessed using flow cytometry and immunohistochemistry. We found that monocytes/macrophages expressed the CLU protein that was upregulated by hypoxia. The percentages of macrophages (F4/80+ , CD11b+ or MAC3+ ) infiltrating the kidneys of WT mice were significantly less than those in CLU-KO mice after IRI. The M1/M2 phenotype ratio of the macrophages in WT kidneys decreased at day 7 post-IRI when the injury was repaired, whereas that in KO kidneys increased consistently as tissue injury persisted. In response to LPS stimulation, WT mice produced fewer M1 macrophages, but not M2, than the control did. Phagocytosis was stimulated by CLU expression in macrophages compared with the CLU null controls and by the exogenous CLU protein. In conclusion, CLU suppresses macrophage infiltration and proinflammatory M1 polarization during the recovery period following IRI, and enhances phagocytic activity, which may be partly responsible for tissue repair in the kidneys of WT mice after injury.

Evaluation of hyperbranched polyglycerol for cold perfusion and storage of donor kidneys in a pig model of kidney autotransplantation.

Hyperbranched polyglycerol (HPG) is a biocompatible polyether polymer that is a potential colloid component in a preservation solution for suppressing interstitial edema during cold storage of a donor organ. This study evaluated the outcomes of kidney transplants after cold perfusion and storage with a HPG-based preservation solution (HPGS) in a pig model of kidney autotransplantation. The left kidneys of farm pigs (weighing 35-45 kg) were perfused with and stored in either cold HPGS or standard UW solution (UWS), followed by transplantation to the right side after right nephrectomy. The survival and function of transplants were determined by the urine output, and serum creatinine (SCr) and blood urea nitrogen (BUN) of recipients. Transplant injury was examined by histological analysis. Here, we showed that there was no significant difference between HPGS and UWS in the prevention of tissue edema, but HPGS was more effective than UWS for initial blood washout of kidney perfusion and for the prevention of cold ischemia injury during cold storage. After autotransplantation, the kidneys preserved with HPGS (HPG group) had better functional recovery than those with UWS (UW group), indicated by significantly more urine output and lower levels of SCr and BUN. The survived grafts in HPG group had less tissue damage than those in UW group. In conclusion, as compared to the UWS the HPGS has less negative impact on kidney cold ischemia during cold storage, resulting in improving immediate functional recovery after transplantation, suggesting that HPG is a promising colloid for donor kidney preservation.

Clusterin Deficiency Predisposes C57BL/6j Mice to Cationic Bovine Serum Albumin-Induced Glomerular Inflammation.

BACKGROUND: Membranous nephropathy (MN) is a specific entity of glomerulonephritis, and its glomerular inflammation is characterized by the deposition of immune complexes in the glomerular basement membrane and proteinuria. However, the molecular mechanisms underlying the glomerular inflammation of MN are not fully understood. This study was designed to investigate the role of clusterin (CLU) in the development of MN using a mouse model of cationic bovine serum albumin (cBSA)-induced MN. METHODS: Both wild-type C57BL/6j (WT) and CLU-knockout C57BL/6j (CLU-KO) mice were immunized with cBSA. The kidney function was determined by the levels of serum creatinine (SCr), blood urea nitrogen (BUN) and urinary protein. MN and glomerular deposits of CLU, complement C3 and immunoglobulins (Igs) were determined by histological analyses. Serum proteins were analyzed by the enzyme-linked immunosorbent assay, Western blot and liquid chromatography-mass spectrometry. RESULTS: Here, we showed that after cBSA immunization, SCr and proteinuria were increased in CLU-KO mice but not in WT mice. Similarly, severe glomerular atrophy and mesangial expansion along with C3 deposit were only found in the kidneys of CLU-KO mice but not in WT mice. However, there were no differences of serum IgG and complement 3 levels between CLU-KO and WT mice. In the serum of WT mice, CLU bound to anti-cBSA IgG, complements (eg, C8), proteinase/protease inhibitors and antioxidative proteins to form a complex, and incubation with WT serum reduced the complement-dependent lysis of podocytes in cultures. CONCLUSION: Our data suggest that a CLU deficiency induces cBSA-initiated glomerular inflammation of MN in a disease-resistant strain of mice, suggesting an anti-glomerular inflammatory function of CLU in the resistance to MN development. This function may be at least in part due to the formation of CLU-anti-cBSA Igs complex that prevents glomerular inflammation or injury in the disease-resistant mice.

The COSMIC Bubble Helmet: A Non-Invasive Positive Pressure Ventilation System for COVID-19.

Goal: COSMIC Medical, a Vancouver-based open-source volunteer initiative, has designed an accessible, affordable, and aerosol-confining non-invasive positive-pressure ventilator (NIPPV) device, known as the COSMIC Bubble Helmet (CBH). This device is intended for COVID-19 patients with mild-to-moderate acute respiratory distress syndrome. System Design: CBH is composed of thermoplastic polyurethane, which creates a flexible neck seal and transparent hood. This device can be connected to wall oxygen, NIPPVs including Continuous Positive Airway Pressure and Bi-level Positive Airway Pressure, and mechanical ventilators. Discussion: Justification of CBH design components relied on several factors, predominantly the safety and comfort of patients and healthcare providers. Conclusion: CBH has implications within and outside of the pandemic, as an alternative to invasive mechanical ventilation methods. We have experimentally verified that CBH is effective in minimizing aerosolization risks and performs at specified clinical requirements.

Perioperative Complications During Living Donor Nephrectomy: Results From a Multicenter Cohort Study.

BACKGROUND: While living kidney donation is considered safe in healthy individuals, perioperative complications can occur due to several factors. OBJECTIVE: We explored associations between the incidence of perioperative complications and donor characteristics, surgical technique, and surgeon's experience in a large contemporary cohort of living kidney donors. DESIGN: Living kidney donors enrolled prospectively in a multicenter cohort study with some data collected retrospectively after enrollment was complete (eg, surgeon characteristics). SETTING: Living kidney donor centers in Canada (n = 12) and Australia (n = 5). PATIENTS: Living kidney donors who donated between 2004 and 2014 and the surgeons who performed the living kidney donor nephrectomies. MEASUREMENTS: Operative and hospital discharge medical notes were collected prospectively, with data on perioperative (intraoperative and postoperative) information abstracted from notes after enrollment was complete. Complications were graded using the Clavien-Dindo system and further classified into minor and major. In 2016, surgeons who performed the nephrectomies were invited to fill an online survey on their training and experience. METHODS: Multivariable logistic regression models with generalized estimating equations were used to compare perioperative complication rates between different groups of donors. The effect of surgeon characteristics on the complication rate was explored using a similar approach. Poisson regression was used to test rates of overall perioperative complications between high- and low-volume centers. RESULTS: Of the 1421 living kidney donor candidates, 1042 individuals proceeded with donation, where 134 (13% [95% confidence interval (CI): 11%-15%]) experienced 142 perioperative complications (55 intraoperative; 87 postoperative). The most common intraoperative complication was organ injury and the most common postoperative complication was ileus. No donors died in the perioperative period. Most complications were minor (90% of 142 complications [95% CI: 86%-96%]); however, 12 donors (1% of 1042 [95% CI: 1%-2%]) experienced a major complication. No statistically significant differences were observed between donor groups and the rate of complications. A total of 43 of 48 eligible surgeons (90%) completed the online survey. Perioperative complication rates did not vary significantly by surgeon characteristics or by high- versus low-volume centers. LIMITATIONS: Operative and discharge reporting is not standardized and varies among surgeons. It is possible that some complications were missed. The online survey for surgeons was completed retrospectively, was based on self-report, and has not been validated. We had adequate statistical power only to detect large effects for factors associated with a higher risk of perioperative complications. CONCLUSIONS: This study confirms the safety of living kidney donation as evidenced by the low rate of major perioperative complications. We did not identify any donor or surgeon characteristics associated with a higher risk of perioperative complications. TRIAL REGISTRATIONS: NCT00319579: A Prospective Study of Living Kidney Donation (https://clinicaltrials.gov/ct2/show/NCT00319579)NCT00936078: Living Kidney Donor Study (https://clinicaltrials.gov/ct2/show/NCT00936078).

CONTEXTE: Bien que le don vivant d'un rein soit sécuritaire chez un individu en santé, plusieurs facteurs sont susceptibles d'engendrer des complications périopératoires. OBJECTIF: Nous avons exploré l'association entre l'incidence des complications périopératoires et les caractéristiques du donneur, la technique chirurgicale employée et l'expérience du chirurgien au sein d'une vaste cohorte contemporaine de donneurs vivants d'un rein. TYPE D'ÉTUDE: Une étude de cohorte multicentrique où certaines données (notamment les renseignements concernant le chirurgien) ont été recueillies rétrospectivement, après l'inclusion complète des sujets (donneurs vivants d'un rein). CADRE: Des centres de transplantation au Canada (n=12) et en Australie (n=5). SUJETS: Des individus ayant fait don d'un rein entre 2004 et 2014, et les chirurgiens qui ont procédé à la néphrectomie. MESURES: Les notes médicales au dossier, opératoires et à la sortie de l'hôpital, ont été recueillies de façon prospective; les données concernant les renseignements périopératoires (peropératoires et postopératoires) ayant été extraites des notes une fois l'inclusion du sujet complétée. Les complications ont été catégorisées selon la classification de Clavien-Dindo, puis caractérisées comme étant mineures ou majeures. En 2016, les chirurgiens ayant pratiqué les néphrectomies ont été invités à répondre à un sondage en ligne au sujet de leur formation et de leur expérience. MÉTHODOLOGIE: Des modèles de régression logistique multivariée utilisant des équations d'estimation généralisées ont été employés pour comparer les taux de complications périopératoires entre les différents groupes de donneurs. L'effet exercé sur le taux de complications par les caractéristiques du chirurgien a été exploré selon une approche similaire. Une régression de Poisson a été utilisée pour évaluer et comparer les taux globaux de complications entre les centres à volume élevé et les centres à faible volume. RÉSULTATS: Des 1 421 candidats répertoriés, 1 042 individus ont subi une néphrectomie, desquels 134 (13 % [IC 95 %: 11­15 %]) ont vécu un total de 142 complications périopératoires (55 peropératoires; 87 postopératoires). La complication peropératoire la plus fréquente était une lésion à l'organe, alors qu'un iléus s'est avéré la principale complication postopératoire. Aucun donneur n'est décédé en période périopératoire. La plupart des complications rencontrées étaient mineures (90 % des 142 complications répertoriées [IC 95 %: 86­96 %]). Toutefois, 12 donneurs (1 % des 1 042 donneurs [IC 95 %: 1­2 %]) ont souffert de complications majeures. Aucune différence significative du point de vue statistique n'a été observée entre les groupes de donneurs et le taux de complications. Des 48 chirurgiens admissibles, 43 (90 %) ont répondu au sondage en ligne. Les taux de complications périoperatoires n'ont pas varié de façon significative en fonction des caractéristiques des chirurgiens, ou selon le volume de patients de l'hôpital. LIMITES: La façon d'inscrire les renseignements médicaux (opératoires ou à la sortie de l'hôpital) dans les dossiers des patients n'est pas normalisée et varie d'un chirurgien à l'autre. Certaines complications pourraient ne pas avoir été notées. Le sondage en ligne destiné aux chirurgiens a été rempli rétrospectivement, il reposait sur des déclarations volontaires et n'avait pas fait l'objet d'une validation. Nous ne disposions d'une puissance statistique que pour détecter les effets importants des facteurs associés à un risque accru de complications périopératoires. CONCLUSION: Cette étude confirme le caractère sécuritaire d'un don vivant de rein, comme en témoigne le très faible taux de complications périopératoires majeures. Nous n'avons pu établir de caractéristiques, du donneur ou du chirurgien, qui soit associées à un risque accru de complications périopératoires.