The role of artificial intelligence measured preoperative kidney volume in predicting kidney function loss in elderly kidney donors: A multicenter cohort study.

BACKGROUND: The increasing use of kidneys from elderly donors raises concerns due to age-related nephron loss. Combined with nephrectomy, this loss of nephrons markedly increases the risk of developing chronic kidney disease (CKD). This study aimed to investigate the prognostic value of preoperative kidney cortex volume in predicting the loss of kidney function in elderly donors, by developing an artificial intelligence (AI)-based model for precise kidney volume measurement and applying it to living kidney donors. MATERIALS METHODS: A multicenter retrospective cohort study using data from living donors who underwent donor nephrectomy between January 2010 and December 2020 was conducted. An AI segmentation model was developed and validated to measure kidney cortex volume from pre-donation computer tomographic (CT) images. The association between measured preoperative kidney volumes and post-nephrectomy renal function was analyzed through a generalized additive model. RESULTS: A total of 1074 living kidney donors were included in the study. Validation of the developed kidney cortex volume model showed a Dice similarity coefficient of 0.97 and a Hausdorff distance of 0.76 mm. The measured cortex volumes exhibited an age-related decrease, which correlated with declining kidney function. Elderly donors showed greater decreases in estimated glomerular filtration rates (eGFR) post-donation compared to young donors (P=0.041). Larger preoperative remnant kidney cortex volume was associated with significantly less decline of eGFR post-donation than those with smaller preoperative remnant kidney cortex volume (P<0.001). CONCLUSION: This study highlights the critical role of preoperative kidney cortex volume in the donor assessment process, particularly for elderly donors. The fully automated model for measuring kidney cortex volume provides a valuable tool for predicting post-donation renal function and holds promise for enhancing donor evaluation and safety.

The impact of simulator training of vascular anastomosis and video assessment for surgical residents.

INTRODUCTION: The rapid increase of minimally invasive surgery and the shortened training period for surgical residents has resulted in limited opportunities to acquire proficiency in open surgical techniques, such as vascular anastomosis. However, vascular anastomosis remains an essential skill in every surgery for bleeding control. This study aimed to validate the effectiveness of surgical education model for vascular anastomosis and assess the impact on the comprehension, skill, and confidence of surgical residents in performing vascular anastomosis. METHODS: A total of 21 surgical residents with 1st to 3rd years of experience at Seoul National University Hospital participated in a four-week vascular anastomosis training program. The program included an educational lecture and the performance of an end-to-side anastomosis on a procedural model, with evaluations being conducted using the Objective Structured Assessment of Technical Skills (OSATS) and the End Product Rating Score (EPRS) in pre- and post-training surveys. RESULTS: Significant improvement was observed in the OSATS score (from 9.22 ± 2.4 in week 1 to 12.87 ± 3.1 in week 4; P < 0.001) and the EPRS score (from 12.47 ± 4.1 in week 1 to 17.57 ± 2.2 in week 4; P < 0.001). Additionally, the surgical performance time significantly decreased from 20.99 ± 4.6 minutes to 16.33 ± 4.2 minutes (P = 0.019) CONCLUSIONS: Simulator training of in vitro vascular anastomosis, when accompanied by expert-led instruction, can effectively enhance the surgical proficiency, confidence, and overall surgical outcomes of residents, as inferred from the observed improvements in OSATS and EPRS scores. The results suggest that integration of this training model into surgical curricula could be a promising strategy for enhancing vascular surgical training.

Cysteine as an Innovative Biomarker for Kidney Injury.

BACKGROUND: Kidney transplantation is a widely used treatment for end-stage kidney disease. Nevertheless, the incidence of acute kidney injury (AKI) in deceased donors poses a potential hazard because it significantly increases the risk of delayed graft function and potentially exerts an influence on the kidney allograft outcome. It is crucial to develop a diagnostic model capable of assessing the existence and severity of AKI in renal grafts. However, no suitable kidney injury markers have been developed thus far. METHODS: We evaluated the efficacy of the molecular probe NPO-B, which selectively responds to cysteine, as a new diagnostic tool for kidney injury. We used an in vitro model using ischemia/reperfusion injury human kidney-2 cells and an in vivo ischemia/reperfusion injury mouse model. Additionally, cysteine was investigated using urine samples from deceased donors and living donors to assess the applicability of detection techniques to humans. RESULTS: This study confirmed that the NPO-B probe effectively identified and visualized the severity of kidney injury by detecting cysteine in both in vitro and in vivo models. We observed that the fluorescence intensity of urine samples measured using NPO-B from the deceased donors who are at a high risk of renal injury was significantly stronger than that of the living donors. CONCLUSIONS: If implemented in clinical practice, this new diagnostic tool using NPO-B can potentially enhance the success rate of kidney transplantation by accurately determining the extent of AKI in renal grafts.

2023 Korean Society of Echocardiography position paper for diagnosis and management of valvular heart disease, part I: aortic valve disease.

This manuscript represents the official position of the Korean Society of Echocardiography on valvular heart diseases. This position paper focuses on the clinical management of valvular heart diseases with reference to the guidelines recently published by the American College of Cardiology/American Heart Association and the European Society of Cardiology. The committee tried to reflect the recently published results on the topic of valvular heart diseases and Korean data by a systematic literature search based on validity and relevance. In part I of this article, we will review and discuss the current position of aortic valve disease in Korea.

2023 Korean Society of Echocardiography position paper for the diagnosis and management of valvular heart disease, part II: mitral and tricuspid valve disease.

This manuscript represents the official position of the Korean Society of Echocardiography on valvular heart diseases. This position paper focuses on the diagnosis and management of valvular heart diseases with referring to the guidelines recently published by the American College of Cardiology/American Heart Association and the European Society of Cardiology. The committee sought to reflect national data on the topic of valvular heart diseases published to date through a systematic literature search based on validity and relevance. In the part II of this article, we intend to present recommendations for diagnosis and treatment of mitral valve disease and tricuspid valve disease.

A comparative analysis of clinical outcomes between conversion to mTOR inhibitor and calcineurin inhibitor reduction in managing BK viremia among kidney transplant patients.

BK virus-associated nephropathy (BKVAN) exerts a substantial impact on allograft survival, however, the absence of robust clinical evidence regarding treatment protocols adds to the complexity of managing this condition. This study aimed to compare the two treatment approaches. The study population consisted of patients who underwent kidney transplantation between January 2016 and June 2020 at two tertiary hospitals in Korea. Patients diagnosed with BK viremia were evaluated based on their initial viral load and the treatment methods. The 'Reduction group' involved dose reduction of tacrolimus while the 'Conversion group' included tacrolimus discontinuation and conversion to sirolimus. A total of 175 patients with an initial viral load (iVL) ≥ 3 on the log10 scale were evaluated within two iVL intervals (3-4 and 4-5). In the iVL 4-5 interval, the Reduction group showed potential effectiveness in terms of viral clearance without statistically significant differences. However, within the iVL 3-4 interval, the Reduction group demonstrated superior viral clearance and a lower incidence of biopsy-proven acute rejection (BPAR) than the Conversion group. The renal function over 12 months after BKV diagnosis showed no statistically significant difference. Reducing tacrolimus compared to converting to mTORi would be a more appropriate treatment approach for BK viral clearance in kidney transplantation. Further research is warranted in a large cohort of patients.

Evaluation of left ventricular filling pressure by echocardiography in patients with atrial fibrillation.

BACKGROUND: Echocardiography is widely used to evaluate left ventricular (LV) diastolic function in patients suspected of heart failure. For patients in sinus rhythm, a combination of several echocardiographic parameters can differentiate between normal and elevated LV filling pressure with good accuracy. However, there is no established echocardiographic approach for the evaluation of LV filling pressure in patients with atrial fibrillation. The objective of the present study was to determine if a combination of several echocardiographic and clinical parameters may be used to evaluate LV filling pressure in patients with atrial fibrillation. RESULTS: In a multicentre study of 148 atrial fibrillation patients, several echocardiographic parameters were tested against invasively measured LV filling pressure as the reference method. No single parameter had sufficiently strong association with LV filling pressure to be recommended for clinical use. Based on univariate regression analysis in the present study, and evidence from existing literature, we developed a two-step algorithm for differentiation between normal and elevated LV filling pressure, defining values ≥ 15 mmHg as elevated. The parameters in the first step included the ratio between mitral early flow velocity and septal mitral annular velocity (septal E/e'), mitral E velocity, deceleration time of E, and peak tricuspid regurgitation velocity. Patients who could not be classified in the first step were tested in a second step by applying supplementary parameters, which included left atrial reservoir strain, pulmonary venous systolic/diastolic velocity ratio, and body mass index. This two-step algorithm classified patients as having either normal or elevated LV filling pressure with 75% accuracy and with 85% feasibility. Accuracy in EF ≥ 50% and EF < 50% was similar (75% and 76%). CONCLUSIONS: In patients with atrial fibrillation, no single echocardiographic parameter was sufficiently reliable to be used clinically to identify elevated LV filling pressure. An algorithm that combined several echocardiographic parameters and body mass index, however, was able to classify patients as having normal or elevated LV filling pressure with moderate accuracy and high feasibility.

Shifts in Clinical Characteristics, Treatment, and Outcome for Rheumatic Mitral Stenosis: Insights From a 20-Year Multicentre Registry Study in Korea.

BACKGROUND: The rapid economic development of South Korea provides a unique model to study changes in the clinical characteristics, treatment approaches, and clinical outcomes of patients with rheumatic mitral stenosis (MS) relative to socioeconomic growth. METHODS: From the Multicenter mitrAl STEnosis with Rheumatic etiology (MASTER) registry, 2,337 patients diagnosed with moderate or severe rheumatic MS between January 2001 and December 2020 were analyzed. Patients were grouped into consecutive 5-year intervals based on their year of diagnosis. Clinical characteristics, echocardiographic data, and clinical outcomes were assessed. RESULTS: Over 20 years, the severity of mitral stenosis increased from 79.1% to 90.2%; similarly, the average age at diagnosis increased from 54.3 to 63.0 years (all P < 0.001). Comorbidities such as hypertension and atrial fibrillation increased (6.3% to 29.5% and 41.4% to 46.9%, respectively; all P for trend < 0.05). The rate of mitral intervention within five years after diagnosis increased from 31.2% to 47.4% (P for trend < 0.001). However, clinical outcomes of rheumatic mitral stenosis deteriorated over time in the composite outcomes (log-rank test, P < 0.001). Conversely, the incidence of stroke remained stable (60.6-73.7%; P < 0.001), which might be attributed to the increased use of anticoagulation therapy. CONCLUSION: This study observed an increase in patient age, comorbidities, and valve disease severity as the country transitioned from a developing to developed status. Despite a rise in mitral valve interventions, clinical outcomes deteriorated over 20 years, highlighting the need for modified treatment approaches to improve patient outcomes.

The time-dependent changes in serum immunoglobulin after kidney transplantation and its association with infection.

Introduction: Kidney transplant recipients often experience significant alterations in their immune system, which can lead to increased susceptibility to infections. This study aimed to analyze time-dependent changes in serum immunoglobulin and complement levels and determine the risk factors associated with infection. Methods: A retrospective analysis of serum samples from 192 kidney transplant recipients who received transplantations between August 2016 and December 2019 was conducted. The serum samples were obtained at preoperative baseline (T0), postoperative 2 weeks (T1), 3 months (T2), and 1 year (T3). The levels of serum C3, C4, IgG, IgA, and IgM were measured to evaluate immune status over time. Results: The analysis revealed significant decreases in IgG and IgA levels at T1. This period was associated with the highest occurrence of hypogammaglobulinemia (HGG) and hypocomplementemia (HCC), as well as an increased incidence of severe infection requiring hospitalization and graft-related viral infections. Using a time-dependent Cox proportional hazards model adjusted for time-varying confounders, HGG was significantly associated with an increased risk of infection requiring hospitalization (HR, 1.895; 95% CI: 1.871-1.920, P-value<0.001) and graft-related viral infection (HR, 1.152; 95% CI: 1.144-1.160, P-value<0.001). Discussion: The findings suggest that monitoring serum immunoglobulin levels post-transplant provides valuable insights into the degree of immunosuppression. Hypogammaglobulinemia during the early post-transplant period emerges as a critical risk factor for infection, indicating that serum immunoglobulins could serve as feasible biomarkers for assessing infection risk in kidney transplant recipients.

Olaris Global Panel (OGP): A Highly Accurate and Reproducible Triple Quadrupole Mass Spectrometry-Based Metabolomics Method for Clinical Biomarker Discovery.

Mass spectrometry (MS)-based clinical metabolomics is very promising for the discovery of new biomarkers and diagnostics. However, poor data accuracy and reproducibility limit its true potential, especially when performing data analysis across multiple sample sets. While high-resolution mass spectrometry has gained considerable popularity for discovery metabolomics, triple quadrupole (QqQ) instruments offer several benefits for the measurement of known metabolites in clinical samples. These benefits include high sensitivity and a wide dynamic range. Here, we present the Olaris Global Panel (OGP), a HILIC LC-QqQ MS method for the comprehensive analysis of ~250 metabolites from all major metabolic pathways in clinical samples. For the development of this method, multiple HILIC columns and mobile phase conditions were compared, the robustness of the leading LC method assessed, and MS acquisition settings optimized for optimal data quality. Next, the effect of U-13C metabolite yeast extract spike-ins was assessed based on data accuracy and precision. The use of these U-13C-metabolites as internal standards improved the goodness of fit to a linear calibration curve from r2 < 0.75 for raw data to >0.90 for most metabolites across the entire clinical concentration range of urine samples. Median within-batch CVs for all metabolite ratios to internal standards were consistently lower than 7% and less than 10% across batches that were acquired over a six-month period. Finally, the robustness of the OGP method, and its ability to identify biomarkers, was confirmed using a large sample set.

Validation of TRI-SCORE for Outcome Prediction After Isolated Tricuspid Valve Surgery in Asian Patients.

BACKGROUND: TRI-SCORE was recently developed in Europe as a risk model for predicting in-hospital death after isolated tricuspid valve surgery. We aimed to validate TRI-SCORE in an Asian population and investigate its value for predicting long-term outcomes. METHODS AND RESULTS: The TRI-SCORE was calculated for 202 patients (65±11 years, 61% women, 81% functional tricuspid regurgitation) who underwent isolated tricuspid valve surgery for severe tricuspid regurgitation at 2 Korean centers and was based on 8 parameters: age, New York Heart Association class, right-sided heart failure signs, furosemide daily dose, glomerular filtration rate, bilirubin, left ventricular ejection fraction, and moderate/severe right ventricular dysfunction. The primary outcome was all-cause death during follow-up; the secondary outcome was in-hospital death. During a median follow-up duration of 50 (interquartile range, 21-82) months after isolated tricuspid valve surgery, 23 (11.4%) patients experienced the primary outcome, and 7 (3.5%) patients experienced the secondary outcome. Observed all-cause death and in-hospital death increased by up to 50% in those with higher scores. Patients with the primary outcome had a higher TRI-SCORE (4.5±2.4 versus 2.9±2.1; P=0.001) than those without. The TRI-SCORE showed a significant association with the primary outcome (concordance index, 0.77, cutoff value, 4) and in-hospital death (area under the curve, 0.84; cutoff value, 3). Using the Kaplan-Meier analysis, patients with a high TRI-SCORE exhibited a poor outcome for all-cause death at follow-up (log-rank P<0.001) and in-hospital death (log-rank P=0.004). CONCLUSIONS: TRI-SCORE was validated in an Asian population and helped predict long-term outcomes after isolated tricuspid valve surgery.

Long-term control of diabetes by tofacitinib-based immunosuppressive regimen after allo islet transplantation in diabetic rhesus monkeys that rejected previously transplanted porcine islets.

Porcine islet xenotransplantation has been highlighted as an alternative to allo islet transplantation. Despite the remarkable progress that has been made in porcine-islet pre-clinical studies in nonhuman primates, immunological tolerance to porcine islets has not been achieved to date. Therefore, allo islet transplantation could be required after the failure of porcine islet xenotransplantation. Here, we report the long-term control of diabetes by allogeneic pancreatic islet transplantation in diabetic rhesus monkeys that rejected previously transplanted porcine islets. Four diabetic male rhesus monkeys received the porcine islets and then allo islets (5700-19 000 IEQ/kg) were re-transplanted for a short or long period after the first xeno islet rejection. The recipient monkeys were treated with an immunosuppressive regimen consisting of ATG, humira, and anakinra for induction, and sirolimus and tofacitinib for maintenance therapy. The graft survival days of allo islets in these monkeys were >440, 395, >273, and 127, respectively, similar to that in allo islet transplanted cynomolgus monkeys that received the same immunosuppressive regimen without xeno sensitization. Taken together, it is likely that prior islet xenotransplantation does not affect the survival of subsequent allo islets under clinically applicable immunosuppressants.

Optimizing Percutaneous Mitral Valvuloplasty for Rheumatic Mitral Stenosis　- Clinical Significance of Changes in Mitral Valve Area.

BACKGROUND: Percutaneous mitral valvuloplasty (PMV) is a standard treatment for severe rheumatic mitral stenosis (RMS). However, the prognostic significance of the change in mitral valve area (∆MVA) during PMV is not fully understood.Methods and Results: This study analyzed data from the Multicenter mitrAl STEnosis with Rheumatic etiology (MASTER) registry, which included 3,140 patients with severe RMS. We focused on patients with severe RMS undergoing their first PMV. Changes in echocardiographic parameters, including MVA quantified before and after PMV, and composite outcomes, including mitral valve reintervention, heart failure admission, stroke, and all-cause death, were evaluated. An optimal result was defined as a postprocedural MVA ≥1.5 cm2without mitral regurgitation greater than Grade II. Of the 308 patients included in the study, those with optimal results and ∆MVA >0.5 cm² had a better prognosis (log-rank P<0.001). Patients who achieved optimal results but with ∆MVA ≤0.5 cm² had a greater risk of composite outcomes than those with optimal outcomes and ∆MVA >0.5 cm² (nested Cox regression analysis, hazard ratio 2.27; 95% confidence interval 1.09-4.73; P=0.028). CONCLUSIONS: Achieving an increase in ∆MVA of >0.5 cm2was found to be correlated with improved outcomes. This suggests that, in addition to achieving traditional optimal results, targeting an increase in ∆MVA of >0.5 cm2could be a beneficial objective in PMV treatment for RMS.

Pericardiocentesis versus window formation in malignant pericardial effusion: trends and outcomes.

OBJECTIVES: Malignant pericardial effusion (MPE) in patients with cancer is associated with poor prognosis. This study aimed to compare clinical outcomes in patients with cancer who underwent pericardiocentesis versus pericardial window formation. METHODS: In the present study, 765 consecutive patients with cancer (mean age 58.4 years, 395 men) who underwent pericardial drainage between 2003 and 2022 were retrospectively analysed. All-cause death and MPE recurrence were compared based on the drainage method (pericardiocentesis vs pericardial window formation) and time period (period 1: 2003-2012; period 2: 2013-2022). RESULTS: Pericardiocentesis was performed in 639 (83.5%) patients and pericardial window formation in 126 (16.5%). There was no difference in age, sex distribution, proportion of metastatic or relapsed cancer, and chemotherapy status between the pericardiocentesis and pericardial window formation groups. Difference was not found in all-cause death between the two groups (log-rank p=0.226) regardless of the period. The pericardial window formation group was associated with lower MPE recurrence than the pericardiocentesis group (6.3% vs 18.0%, log-rank p=0.001). This advantage of pericardial window formation was more significant in period 2 (18.1% vs 1.3%, log-rank p=0.005). In multivariate analysis, pericardial window formation was associated with lower MPE recurrence (HR: 0.31, 95% CI: 0.15 to 0.63, p=0.001); younger age, metastatic or relapsed cancer, and positive malignant cells in pericardial fluid were associated with increased recurrence. CONCLUSION: In patients undergoing pericardial drainage for MPE, pericardial window formation showed mortality outcomes comparable with pericardiocentesis and was associated with lower incidence of MPE recurrence.

A 20-Year Analysis of Ruptured Abdominal Aortic Aneurysm Outcomes and Associated Factors in Korea.

BACKGROUND: Unlike western countries, which have reported distinct decreases in incidence of ruptured abdominal aortic aneurysm (rAAA) over the last few decades, epidemiologic studies in Korea have not shown significant changes in incidence or mortality of rAAA. The purpose of this study was to analyze the changes in rAAA treatment outcomes and various associated risk factors over the past 2 decades. METHODS: A 20-year retrospective multicenter review for rAAA cases from the period of January 2000 to December 2020 was undertaken. Preoperative, intraoperative and postoperative clinical data were extracted for patients diagnosed with rAAA. For analysis, outcomes from the early era, defined as patients treated between January 1, 2000, and December 31, 2010, were compared with outcomes from the late era, defined as patients treated between January 1, 2011, and December 31, 2020. RESULTS: The total in-hospital mortality was 34.1% in the early era compared to 44.8% in the late era. Patients in the late era were older than those in the early era (75.2 ± 10.3 years vs. 70.3 ± 8.9 years; P = 0.009). Treatment with rAAA endovascular aneurysm repair increased from 2.3% in early to 13.8% in late era (P = 0.031). In the early era, more patients were operated by experienced surgeons than the late era (78.1% vs. 45.9%; P = 0.002). The emergency room to operating room time did not show improvement over the 20 years. CONCLUSIONS: The results indicate that mortality rate of rAAA in Korea has not changed over the last 2 decades. The study suggests the need for national preventive strategies, improved systemic coordination, and potential centralization of vascular services to enhance survival rates for rAAA.

Outcomes of Severe Mitral Stenosis With the Revised Severity Criteria: Mitral Valve Replacement vs Percutaneous Mitral Valvuloplasty.

BACKGROUND: This study aimed to compare the outcomes, according to percutaneous mitral valvuloplasty (PMV) vs mitral valve replacement (MVR), of severe mitral stenosis (MS) with the updated criteria (MVA ≤ 1.5 cm2). METHODS: From the Multicenter Mitral Stenosis With Rheumatic Etiology (MASTER) registry of 3140 patients, we included patients with severe MS who underwent PMV or MVR between January 2000 and December 2021 except for previous valvular surgery/intervention, at least moderate other valvular dysfunction, and thrombus at the left atrium/appendage. Moderately severe MS (MS-MS) and very severe MS (VS-MS) were defined as 1.0 cm2 < MVA ≤ 1.5 cm2 and MVA ≤ 1.0 cm2, respectively. Primary outcomes were a composite of cardiovascular (CV) death and heart failure (HF) hospitalization. Secondary outcomes were a composite of primary outcomes and redo intervention. RESULTS: Among 442 patients (mean 56.5 ±11.9 years, women 77.1%), the MVR group (n = 260) was older, had more comorbidities, higher echoscore, larger left chambers, and higher right ventricular systolic pressure than the PMV group (n = 182). During a mean follow-up of 6.9 ± 5.2 years with inverse probability-weighted matching, primary outcomes did not differ, but the MVR group experienced fewer secondary outcomes (P = 0.010). In subgroup analysis of patients with MS-MS and VS-MS, primary outcomes did not differ. However, the MVR group in patients with VS-MS showed better secondary outcomes (P = 0.012). CONCLUSIONS: PMV or MVR did not influence CV mortality or HF hospitalization in both MS-MS and VS-MS. However, because of increased early redo intervention in the PMV group in VS-MS, MVR would be the preferable option without clear evidence of suitable morphology for PMV.

Prediction of acute rejection in renal allografts using shear-wave dispersion slope.

OBJECTIVES: To evaluate the role of shear-wave dispersion slope for predicting renal allograft dysfunction. METHODS: We retrospectively reviewed 128 kidney transplant recipients (median age, 55 years [interquartile range, 43-62 years]; male, 68) who underwent biopsy for allograft evaluation from November 2022 to February 2023. Cortex and renal sinus fat stiffness and shear-wave dispersion slope were obtained at shear-wave elastography (SWE). Cortex-to-sinus stiffness ratio (SR) and dispersion slope ratio (DSR)-related clinical and pathologic factors were evaluated using multivariable linear regression analysis. We conducted univariate and multivariate analyses for multiparametric ultrasound (US) parameters for identifying acute rejection and calculated the area under the receiver operating curve (AUC) values. RESULTS: Of 128 patients, 31 (24.2%) demonstrated acute rejection. The SR value did not differ between patient groups (1.21 vs. 1.20, p = 0.47). Patients with acute rejection demonstrated a higher DSR than those without rejection (1.4 vs. 1.21, p < 0.01). Interstitial fibrosis and tubular atrophy grade (IFTA; coefficient, 0.11/grade; p = 0.04) and renal transplant and biopsy interval (coefficient, 0.00007/day; p = 0.03) were SR determinant factors, whereas only IFTA grade (coefficient, 0.10/grade; p = 0.01) for DSR. Multivariate analysis revealed mean resistive index (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.02-1.14, p = 0.01) and DSR value (OR 16.0, 95% CI 3.0-85.8, p = 0.001) as independent factors for predicting acute rejection. An AUC of 0.74 for detecting acute rejection was achieved by combining the resistive index and DSR value. CONCLUSION: Shear-wave dispersion slope obtained at SWE may help identify renal allograft dysfunction. CLINICAL RELEVANCE STATEMENT: Acute rejection in renal allografts is a major cause of allograft failure, but noninvasive diagnosis is a challenge. Shear-wave dispersion slope can identify acute rejection non-invasively. KEY POINTS: • The interstitial fibrosis and tubular atrophy grade was a determinant factor for stiffness ratio and shear-wave dispersion slope ratio between cortex and renal sinus fat. • Shear-wave dispersion slope ratio between cortex and renal sinus fat could identify acute rejection in renal allografts. • A shear-wave dispersion slope has a potential to reduce unnecessary renal biopsy for evaluating renal allografts.

Association of high intra-patient variability in tacrolimus exposure with calcineurin inhibitor nephrotoxicity in kidney transplantation.

Tacrolimus intra-patient variability (IPV) is a novel predictive marker for long-term kidney transplantation outcomes. We examined the association between IPV and calcineurin inhibitor (CNI) nephrotoxicity and the impact of pharmacogenes on CNI nephrotoxicity and IPV. Among kidney transplant recipients at our hospital between January 2013 and December 2015, the records of 80 patients who underwent 1-year protocol renal allograft biopsy and agreed to donate blood samples for genetic analysis were retrospectively reviewed. The cohort was divided into the low and high IPV groups based on a coefficient variability cutoff value (26.5%). In multivariate analysis, the IPV group was involved in determining CNI nephrotoxicity (HR 4.55; 95% CI 0.05-0.95; p = 0.043). The 5-year graft survival was superior in the low IPV group than in the high IPV group (100% vs 92.4% respectively, p = 0.044). Analysis of the time above therapeutic range (TATR) showed higher CNI nephrotoxicity in the high IPV with high TATR group than in the low IPV with low TATR group (35.7% versus 6.7%, p = 0.003). Genetic analysis discovered that CYP3A4 polymorphism (rs2837159) was associated with CNI nephrotoxicity (HR 28.23; 95% CI 2.2-355.9; p = 0.01). In conclusion, high IPV and CYP3A4 polymorphisms (rs2837159) are associated with CNI nephrotoxicity.