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.

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 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.

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.

The Resident Report Card: A Tool for Operative Feedback and Evaluation of Technical Skills.

BACKGROUND: Competency-based medical education surgical curriculums will require frequent, recorded trainee performance evaluations. It is our hypothesis that written feedback after each operation can be used to chart surgical progress, can identify underperforming trainees, and will prove beneficial for resident learning. METHODS: The resident report card (RRC) is an online, easy-to-use evaluation tool designed to facilitate the creation and distribution of resident technical assessments. RRC data were collected from urologic trainees and analyzed using ANOVA and post hoc testing to confirm our hypothesis. A standardized survey was sent to residents, gauging their views on the RRC. RESULTS: Over a 5-y period, 958 RRCs with the resident listed as the primary operator were collected across 29 different procedures. Resident cohort and individual performance scores stratified by postgraduate year (PGY) were shown to significantly improve when all procedures (cohort, 6.5 ± 1.9 [PGY-1] to 9.1 ± 1.0 [PGY-5]; individual [resident M], 8.8 ± 1.8 [PGY-3] to 9.4 ± 0.7 [PGY-5], P < 0.01) and specific procedures (laparoscopic donor nephrectomy: cohort, 7.3 ± 1.3 [PGY-3] to 8.9 ± 1.0 [PGY-5]; individual [resident I], 7.2 ± 1.3 [PGY-3] to 9.5 ± 0.6 [PGY-5], P < 0.01) were analyzed. Individual residents were able to be compared to their own peer group and to the average scores across all evaluated residents. Surveyed residents were overwhelmingly positive about the RRC. CONCLUSIONS: The RRC adds further evidence to the fact that standardized, formative, and timely assessment can capture trainee performance over time and against comparator cohorts in an acceptable format to residents and academic training programs.

TGF-ß1 stimulates movement of renal proximal tubular epithelial cells in a three-dimensional cell culture via an autocrine TGF-ß2 production.

TGF-ßs are multifunctional cytokines, but their roles in human renal homeostasis are not fully understood. This study investigated the role of TGF-ß1 in the movement of human renal proximal tubular epithelial cells (PTECs) in a three-dimensional (3D) model. HKC-8 cells, a human PTEC line, were grown in a 3D collagen culture system. Cell movement was observed under a microscope. The gene expression was examined using PCR Arrays or qRT-PCR, and protein levels by Western blot. Here, we showed that the tight junction structure formed between adjacent cells of a HKC-8 cell colony in 3D cultures, and TGF-ß1 stimulated their movement, evidenced by the appearance of fingerlike pseudopodia in the leader cells at the edge of the colonies. The cell movement of these human PTECs was correlated with up-regulation of both MMP2 and MMP9 and down-regulation or inactivation of PLAUR and PTK2B. Analysis of TGF-ß signaling targets confirmed autocrine production of TGF-ß2 and its cleaving enzyme furin as well as SNAI1 by TGF-ß1stimulation. Knockdown of TGF-ß2 expression disrupted TGF-ß1-stimulated PTEC invasiveness, which was correlated with the down-regulation of MMP2 and MMP9. In conclusion, the activation of TGF-ß receptor autocrine signaling by up-regulated TGF-ß2 may play a pivotal role in TGF-ß1-induced human PTEC movement, which could be mediated at least by both MMP2 and MMP9.

Transcriptome-Based Analysis of Molecular Pathways for Clusterin Functions in Kidney Cells.

Clusterin (CLU) is a chaperone-like protein and plays a protective role against renal ischemia-reperfusion injury (IRI); however, the molecular pathways for its functions in the kidney are not fully understood. This study was designed to investigate CLU-mediating pathways in kidney cells by using bioinformatics analysis. CLU null renal tubular epithelial cells (TECs) expressing human CLU cDNA (TEC-CLU(hCLU) ) or empty vector (TEC-CLU(-/-) ) were exposed to normoxia or hypoxia (1% O2 ). Transcriptome profiling with a significant twofold change was performed using SurePrint G3 Mouse Gene Expression 8 × 60 K microarray, and the signaling pathways was ranked by using Ingenuity pathway analysis. Here, we showed that compared to CLU null controls, ectopic expression of human CLU in CLU null kidney cells promoted cell growth but inhibited migration in normoxia, and enhanced cell survival in hypoxia. CLU expression affected expression of 3864 transcripts (1893 up-regulated) in normoxia and 3670 transcripts (1925 up-regulated) in hypoxia. CLU functions in normoxia were associated mostly with AKT2/PPP2R2B-dependent PI3K/AKT, PTEN, VEGF, and ERK/MAPK signaling and as well with GSK3B-mediated cell cycle progression. In addition to unfolded protein response (UPR) and/or endoplasmic reticulum (ER) stress, CLU-enhanced cell survival in hypoxia was also associated with PIK3CD/MAPK1-dependent PI3K/AKT, HIF-α, PTEN, VEGF, and ERK/MAPK signaling. In conclusion, our data showed that CLU functions in kidney cells were mainly mediated in a cascade manner by PI3K/AKT, PTEN, VEGF, and ERK/MAPK signaling, and specifically by activation of UPR/ER stress in hypoxia, providing new insights into the protective role of CLU in the kidney. J. Cell. Physiol. 231: 2628-2638, 2016. © 2016 Wiley Periodicals, Inc.

Requirement of clusterin expression for prosurvival autophagy in hypoxic kidney tubular epithelial cells.

Cellular autophagy is a prosurvival mechanism in the kidney against ischemia-reperfusion injury (IRI), but the molecular pathways that activate the autophagy in ischemic kidneys are not fully understood. Clusterin (CLU) is a chaperone-like protein, and its expression is associated with kidney resistance to IRI. The present study investigated the role of CLU in prosurvival autophagy in the kidney. Renal IRI was induced in mice by clamping renal pedicles at 32°C for 45 min. Hypoxia in renal tubular epithelial cell (TEC) cultures was induced by exposure to a 1% O2 atmosphere. Autophagy was determined by either light chain 3-BII expression with Western blot analysis or light chain 3-green fluorescent protein aggregation with confocal microscopy. Cell apoptosis was determined by flow cytometric analysis. The unfolded protein response was determined by PCR array. Here, we showed that autophagy was significantly activated by IRI in wild-type (WT) but not CLU-deficient kidneys. Similarly, autophagy was activated by hypoxia in human proximal TECs (HKC-8) and WT mouse primary TECs but was impaired in CLU-null TECs. Hypoxia-activated autophagy was CLU dependent and positively correlated with cell survival, and inhibition of autophagy significantly promoted cell death in both HKC-8 and mouse WT/CLU-expressing TECs but not in CLU-null TECs. Further experiments showed that CLU-dependent prosurvival autophagy was associated with activation of the unfolded protein response in hypoxic kidney cells. In conclusion, these data suggest that activation of prosurvival autophagy by hypoxia in kidney cells requires CLU expression and may be a key cytoprotective mechanism of CLU in the protection of the kidney from hypoxia/ischemia-mediated injury.

Advantages of replacing hydroxyethyl starch in University of Wisconsin solution with hyperbranched polyglycerol for cold kidney perfusion.

BACKGROUND: Efficient and effective perfusion during organ procurement is required for the best prevention of donor organ injury preceding transplantation. However, current organ preservation solutions, including hydroxyethyl starch (HES)-based University of Wisconsin (UW) solution, do not always yield the best outcomes. Our previous study demonstrated that replacing HES with hyperbranched polyglycerol (HPG) reduced donor heart injury during cold storage. The current research was designed to examine the advantages of HPG-based solution for cold kidney perfusion. METHODS: Perfusion efficiency of HPG versus UW solution was tested using mouse kidneys at 4°C. The blood washout was evaluated by using a semiquantitative scoring system and tissue damage by histologic analysis. The interaction of HPG or UW solution with human red blood cells (RBCs) was examined by measuring RBC sedimentation and aggregation. RESULTS: The lower viscosity of HPG solution was correlated with faster and more efficient perfusion through donor kidneys as compared with UW. HPG solution was also more effective than UW in removing RBCs from the kidney and was associated with less tissue damage to donor kidneys. In vitro UW solution caused significant RBC sedimentation and hyperaggregation, whereas HPG showed minimal impact on RBC sedimentation and prevented RBC aggregation. CONCLUSIONS: This experimental study demonstrated that compared with UW, HPG solution was more efficient and effective in the removal of the blood from donor kidneys and offered better protection from donor tissue damage, suggesting that the HPG solution is a promising candidate to supplant standard UW solution for donor kidney perfusion in transplantation.

Relationship of clusterin with renal inflammation and fibrosis after the recovery phase of ischemia-reperfusion injury.

BACKGROUND: Long-term outcomes after acute kidney injury (AKI) include incremental loss of function and progression towards chronic kidney disease (CKD); however, the pathogenesis of AKI to CKD remains largely unknown. Clusterin (CLU) is a chaperone-like protein that reduces ischemia-reperfusion injury (IRI) and enhances tissue repair after IRI in the kidney. This study investigated the role of CLU in the transition of IRI to renal fibrosis. METHODS: IRI was induced in the left kidneys of wild type (WT) C57BL/6J (B6) versus CLU knockout (KO) B6 mice by clamping the renal pedicles for 28 min at the body temperature of 32 °C. Tissue damage was examined by histology, infiltrate phenotypes by flow cytometry analysis, and fibrosis-related gene expression by PCR array. RESULTS: Reduction of kidney weight was induced by IRI, but was not affected by CLU KO. Both WT and KO kidneys had similar function with minimal cellular infiltration and fibrosis at day 14 of reperfusion. After 30 days, KO kidneys had greater loss in function than WT, indicated by the higher levels of both serum creatinine and BUN in KO mice, and exhibited more cellular infiltration (CD8 cells and macrophages), more tubular damage and more severe tissue fibrosis (glomerulopathy, interstitial fibrosis and vascular fibrosis). PCR array showed the association of CLU deficiency with up-regulation of CCL12, Col3a1, MMP9 and TIMP1 and down-regulation of EGF in these kidneys. CONCLUSION: Our data suggest that CLU deficiency worsens renal inflammation and tissue fibrosis after IRI in the kidney, which may be mediated through multiple pathways.

Promotion of cell proliferation by clusterin in the renal tissue repair phase after ischemia-reperfusion injury.

Renal repair begins soon after the kidney suffers ischemia-reperfusion injury (IRI); however, its molecular pathways are not fully understood. Clusterin (Clu) is a chaperone protein with cytoprotective functions in renal IRI. The aim of this study was to investigate the role of Clu in renal repair after IRI. IRI was induced in the left kidneys of wild-type (WT) C57BL/6J (B6) vs. Clu knockout (KO) B6 mice by clamping the renal pedicles for 28-45 min at the body temperature of 32°C. The renal repair was assessed by histology and confirmed by renal function. Gene expression was examined using PCR array. Here, we show that following IRI, renal tubular damage and Clu expression in WT kidneys were induced at day 1, reached the maximum at day 3, and significantly diminished at day 7 along with normal function, whereas the tubular damage in Clu KO kidneys steadily increased from initiation of insult to the end of the experiment, when renal failure occurred. Renal repair in WT kidneys was positively correlated with an increase in Ki67(+) proliferative tubular cells and survival from IRI. The functions of Clu in renal repair and renal tubular cell proliferation in cultures were associated with upregulation of a panel of genes that could positively regulate cell cycle progression and DNA damage repair, which might promote cell proliferation but not involve cell migration. In conclusion, these data suggest that Clu is required for renal tissue regeneration in the kidney repair phase after IRI, which is associated with promotion of tubular cell proliferation.

Reduction of chronic rejection of renal allografts by anti-transforming growth factor-ß antibody therapy in a rat model.

There is no effective treatment for chronic rejection (CR) that largely limits long-term survival of kidney transplants. Transforming growth factor (TGF)-ß is a fibrogenic factor for tissue fibrosis. This study was to test the efficacy of an anti-TGF-ß antibody in preventing the CR of renal allografts in a preclinical model. Male Lewis rats (RT1¹) were orthotopically transplanted with donor kidneys from male Fischer 344 (RT11v1) rats and were treated with either anti-TGF-ß or a control antibody. The CR of renal allografts was assessed by semiquantitative histological analyses, and intragraft cytokines and fibrosis-related genes ware examined by PCR arrays. Compared with the control antibody, anti-TGF-ß antibody treatment significantly reduced recipients' proteinuria (P = 0.0002), and CR in renal transplants, which was indicated by the fewer injured renal tubules, glomeruli, and interlobular arterioles or arteries, and by less mononuclear cell infiltration and interstitial fibrosis in the anti-TGF-ß antibody-treated group (P < 0.05), but not significantly attenuate the ratios of different infiltrating leukocytes. These pathological changes were associated with downregulation of TGF-ß1, TGF-ß2, and proinflammatory cytokines, or with upregulation of anti-fibrotic HGF, BMP5, and BMP7. The therapeutic effect of the anti-TGF-ß antibody was further confirmed by its prevention of graft dysfunction, indicated by lower levels of serum creatinine and blood urea nitrogen or higher creatinine clearance in anti-TGF-ß antibody-treated recipients compared with those in control recipients (P < 0.05). In conclusion, the anti-TGF-ß antibody (1D11) treatment significantly reduces CR of renal allografts in rats, suggesting the therapeutic potential of this antibody therapy for treating CR of kidney transplants in patients.

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.

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.

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.

Prolonged renal allograft survival by donor interleukin-6 deficiency: association with decreased alloantibodies and increased intragraft T regulatory cells.

Both humoral and cellular immune responses are involved in renal allograft rejection. Interleukin (IL)-6 is a regulatory cytokine for both B and Foxp3 (forkhead box P3)-expressing regulatory T (Treg) cells. This study was designed to investigate the impact of donor IL-6 production on renal allograft survival. Donor kidneys from IL-6 knockout (KO) vs. wild-type (WT) C57BL/6 mice (H-2(b)) were orthotopically transplanted to nephrotomized BALB/c mice (H-2(d)). Alloantibodies and Treg cells were examined by fluorescence-activated cell sorting analysis. Graft survival was determined by the time to graft failure. Here, we showed that a deficiency in IL-6 expression in donor kidneys significantly prolonged renal allograft survival compared with WT controls. IL-6 protein was upregulated in renal tubules and endothelium of renal allografts following rejection, which correlated with an increase in serum IL-6 compared with that in those receiving KO grafts or naive controls. The absence of graft-producing IL-6 or lower levels of serum IL-6 in the recipients receiving IL-6 KO allografts was associated with decreased circulating anti-graft alloantibodies and increased the percentage of intragraft CD4(+)CD25(+)Foxp3(+) Treg cells compared with those with WT allografts. In conclusion, the lack of graft-producing IL-6 significantly prolongs renal allograft survival, which is associated with reduced alloantibody production and/or increased intragraft Treg cell population, implying that targeting donor IL-6 may effectively prevent both humoral and cellular rejection of kidney transplants.

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.

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.