Aquatic assessment of the chelating ability of Silica-stabilized magnetite nanocomposite to lead nitrate toxicity with emphasis to their impact on hepatorenal, oxidative stress, genotoxicity, histopathological, and bioaccumulation parameters in Oreochromis niloticus and Clarias gariepinus.

BACKGROUND: In recent years, anthropogenic activities have released heavy metals and polluted the aquatic environment. This study investigated the ability of the silica-stabilized magnetite (Si-M) nanocomposite materials to dispose of lead nitrate (Pb(NO3)2) toxicity in Nile tilapia and African catfish. RESULTS: Preliminary toxicity tests were conducted and determined the median lethal concentration (LC50) of lead nitrate (Pb(NO3)2) to Nile tilapia and African catfish to be 5 mg/l. The sublethal concentration, equivalent to 1/20 of the 96-hour LC50 Pb(NO3)2, was selected for our experiment. Fish of each species were divided into four duplicated groups. The first group served as the control negative group, while the second group (Pb group) was exposed to 0.25 mg/l Pb(NO3)2 (1/20 of the 96-hour LC50). The third group (Si-MNPs) was exposed to silica-stabilized magnetite nanoparticles at a concentration of 1 mg/l, and the fourth group (Pb + Si-MNPs) was exposed simultaneously to Pb(NO3)2 and Si-MNPs at the same concentrations as the second and third groups. Throughout the experimental period, no mortalities or abnormal clinical observations were recorded in any of the treated groups, except for melanosis and abnormal nervous behavior observed in some fish in the Pb group. After three weeks of sublethal exposure, we analyzed hepatorenal indices, oxidative stress parameters, and genotoxicity. Values of alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), urea, and creatinine were significantly higher in the Pb-intoxicated groups compared to the control and Pb + Si-MNPs groups in both fish species. Oxidative stress parameters showed a significant decrease in reduced glutathione (GSH) concentration, along with a significant increase in malondialdehyde (MDA) and protein carbonyl content (PCC) concentrations, as well as DNA fragmentation percentage in the Pb group. However, these values were nearly restored to control levels in the Pb + Si-MNPs groups. High lead accumulation was observed in the liver and gills of the Pb group, with the least accumulation in the muscles of tilapia and catfish in the Pb + Si-MNPs group. Histopathological analysis of tissue samples from Pb-exposed groups of tilapia and catfish revealed brain vacuolation, gill fusion, hyperplasia, and marked hepatocellular and renal necrosis, contrasting with Pb + Si-MNP group, which appeared to have an apparently normal tissue structure. CONCLUSIONS: Our results demonstrate that Si-MNPs are safe and effective aqueous additives in reducing the toxic effects of Pb (NO3)2 on fish tissue through the lead-chelating ability of Si-MNPs in water before being absorbed by fish.

Noninvasive assessment of organ-specific and shared pathways in multi-organ fibrosis using T1 mapping.

Fibrotic diseases affect multiple organs and are associated with morbidity and mortality. To examine organ-specific and shared biologic mechanisms that underlie fibrosis in different organs, we developed machine learning models to quantify T1 time, a marker of interstitial fibrosis, in the liver, pancreas, heart and kidney among 43,881 UK Biobank participants who underwent magnetic resonance imaging. In phenome-wide association analyses, we demonstrate the association of increased organ-specific T1 time, reflecting increased interstitial fibrosis, with prevalent diseases across multiple organ systems. In genome-wide association analyses, we identified 27, 18, 11 and 10 independent genetic loci associated with liver, pancreas, myocardial and renal cortex T1 time, respectively. There was a modest genetic correlation between the examined organs. Several loci overlapped across the examined organs implicating genes involved in a myriad of biologic pathways including metal ion transport (SLC39A8, HFE and TMPRSS6), glucose metabolism (PCK2), blood group antigens (ABO and FUT2), immune function (BANK1 and PPP3CA), inflammation (NFKB1) and mitosis (CENPE). Finally, we found that an increasing number of organs with T1 time falling in the top quintile was associated with increased mortality in the population. Individuals with a high burden of fibrosis in ≥3 organs had a 3-fold increase in mortality compared to those with a low burden of fibrosis across all examined organs in multivariable-adjusted analysis (hazard ratio = 3.31, 95% confidence interval 1.77-6.19; P = 1.78 × 10-4). By leveraging machine learning to quantify T1 time across multiple organs at scale, we uncovered new organ-specific and shared biologic pathways underlying fibrosis that may provide therapeutic targets.

Cost-Effectiveness Analysis of the Clear Cell Likelihood Score Against Renal Mass Biopsy for Evaluating Small Renal Masses.

OBJECTIVE: To examine the cost-effectiveness of the clear cell likelihood score compared to renal mass biopsy (RMB) alone. METHODS: The clear cell likelihood score, a new grading system based on multiparametric magnetic resonance imaging, has been proposed as a possible alternative to percutaneous RMB for identifying clear cell renal carcinoma in small renal masses and expediting treatment of high-risk patients. A decision analysis model was developed to compare a RMB strategy where all patients undergo biopsy and a clear cell likelihood score strategy where only patients that received an indeterminant score of 3 undergo biopsy. Effectiveness was assigned 1 for correct diagnoses and 0 for incorrect or indeterminant diagnoses. Costs were obtained from institutional fees and Medicare reimbursement rates. Probabilities were derived from literature estimates from radiologists trained in the clear cell likelihood score. RESULTS: In the base case model, the clear cell likelihood score was both more effective (0.77 vs 0.70) and less expensive than RMB ($1629 vs $1966). Sensitivity analysis found that the nondiagnostic rate of RMB and the sensitivity of the clear cell likelihood score had the greatest impact on the model. In threshold analyses, the clear cell likelihood score was the preferred strategy when its sensitivity was greater than 62.7% and when an MRI cost less than $5332. CONCLUSION: The clear cell likelihood score is a more cost-effective option than RMB alone for evaluating small renal masses for clear cell renal carcinoma.

[Functional MRI assessment of microstructural and perfusion changes in the kidneys of rats with intrauterine growth restriction]. / åŠŸèƒ½ç£å ±æŒ¯è¯„ä¼°å®«å† å‘è‚²è¿Ÿç¼“ä»”é¼ è‚¾è„å¾®è§‚ç»“æž„åŠçŒæ³¨æ”¹å˜.

OBJECTIVES: To explore the value of functional magnetic resonance imaging (MRI) techniques, including intravoxel incoherent motion (IVIM), T1 mapping, and T2 mapping, in assessing the microstructural and perfusion changes in the kidneys of rats with intrauterine growth restriction (IUGR). METHODS: An IUGR rat model was established through a low-protein diet during pregnancy. Offspring from pregnant rats on a low-protein diet were randomly divided into an IUGR 8-week group and an IUGR 12-week group, while offspring from pregnant rats on a normal diet were divided into a normal 8-week group and a normal 12-week group (n=8 for each group). The apparent diffusion coefficient (ADC), true diffusion coefficient (Dt), pseudo-diffusion coefficient (D*), perfusion fraction (f), T1 value, and T2 value of the renal cortex and medulla were compared, along with serum creatinine and blood urea nitrogen levels among the groups. RESULTS: The Dt value in the renal medulla was higher in the IUGR 12-week group than in the IUGR 8-week group, and the D* value in the renal medulla was lower in the IUGR 12-week group than in both the normal 12-week group and the IUGR 8-week group (P<0.05). The T1 value in the renal medulla was higher than in the cortex in the IUGR 8-week group, and the T1 value in the renal medulla was higher in the IUGR 12-week group than in both the IUGR 8-week group and the normal 12-week group, with the cortical T1 value in the IUGR 12-week group also being higher than that in the normal 12-week group (P<0.05). The T2 values in the renal medulla were higher than those in the cortex across all groups (P<0.05). There were no significant differences in the T2 values of either the cortex or medulla among the groups (P>0.05). There were no significant differences in serum creatinine and blood urea nitrogen levels among the groups (P>0.05). Glomerular hyperplasia and hypertrophy without significant fibrotic changes were observed in the IUGR 8-week group, whereas glomerular atrophy, cystic stenosis, and interstitial inflammatory infiltration and fibrosis were seen in the IUGR 12-week group. CONCLUSIONS: IVIM MRI can be used to assess and dynamically observe the microstructural and perfusion damage in the kidneys of IUGR rats. MRI T1 mapping can be used to evaluate kidney damage in IUGR rats, and the combination of MRI T1 mapping and T2 mapping can further differentiate renal fibrosis in IUGR rats.

Rat Models of Cardiorenal Syndrome and Methods for Functional Assessment.

Cardiorenal syndrome (CRS) is a clinical disorder involving combined heart and kidney dysfunction, which leads to poor clinical outcomes. To understand the complex pathophysiology and mechanisms that lie behind this disease setting, and design/evaluate appropriate treatment strategies, suitable animal models are required. Described here are the protocols for establishing surgically induced animal models of CRS including important methods to determine clinically relevant measures of cardiac and renal function, commonly used to assess the degree of organ dysfunction in the model and treatment efficacy when evaluating novel therapeutic strategies.

Assessment of epidemiology and outcomes of adult patients with kidney-limited thrombotic microangiopathies.

Thrombotic microangiopathies (TMA) are usually associated with hematological features (RH-TMA). The epidemiology of TMA limited to kidneys (RL-TMA) is unclear Therefore, patients with TMA and native kidney biopsies were identified during 2009-2022 in 20 French hospitals and results evaluated. RL-TMA was present in 341/757 (45%) patients and associated with lower creatinine levels (median 184 vs 346 µmol/L) than RH-TMA. RL-TMA resulted from virtually all identified causes, more frequently from anti-VEGF treatment and hematological malignancies but less frequently from shigatoxin-associated hemolytic uremic syndrome (HUS), systemic sclerosis, gemcitabine and bacterial infection, and even less frequently when three or more causes/triggers were combined (RL-TMA: 5%; RH-TMA: 12%). RL-TMA was associated with significantly lower major cardiovascular events (10% vs 20%), kidney replacement therapy (23% vs 43%) and death (12% vs 20%) than RH-TMA during follow-up (median 28 months). Atypical HUS (aHUS) was found in 326 patients (RL-TMA: 43%, RH-TMA: 44%). Among the 69 patients with proven complement-mediated aHUS, eculizumab (anti-C5 therapy) was used in 43 (62%) (RL-TMA: 35%; RH-TMA: 71%). Among the 257 other patients with aHUS, including 51% with RL-TMA, eculizumab was used in 29 but with unclear effects of this treatment. Thus, RL-TMA represents a very high proportion of patients with TMA and results from virtually all known causes of TMA and includes 25% of patients with complement-mediated aHUS. Adverse outcomes of RL-TMA are lower compared to RH-TMA but remain significant. Anti-C5 therapy was rarely used in RL-TMA, even in proven complement-mediated aHUS, and its effects remain to be assessed.

Utilization of the corticomedullary difference in magnetic resonance imaging-derived apparent diffusion coefficient for noninvasive assessment of chronic kidney disease in type 2 diabetes.

BACKGROUNDS: Accumulating data demonstrated that the cortico-medullary difference in apparent diffusion coefficient (ΔADC) of diffusion-weighted magnetic resonance imaging (DWI) was a better correlation with kidney fibrosis, tubular atrophy progression, and a predictor of kidney function evolution in chronic kidney disease (CKD). OBJECTIVES: We aimed to assess the value of ΔADC in evaluating disease severity, differential diagnosis, and the prognostic risk stratification for patients with type 2 diabetes (T2D) and CKD. METHODS: Total 119 patients with T2D and CKD who underwent renal MRI were prospectively enrolled. Of them, 89 patients had performed kidney biopsy for pathological examination, including 38 patients with biopsy-proven diabetic kidney disease (DKD) and 51 patients with biopsy-proven non-diabetic kidney disease (NDKD) and Mix (DKD + NDKD). Clinicopathological characteristics were compared according to different ΔADC levels. Moreover, univariate and multivariate-linear regression analyses were performed to explore whether ΔADC was independently associated with estimated glomerular filtration rate (eGFR) and urinary albumin creatinine ratio (UACR). The diagnostic performance of ΔADC for discriminating DKD from NDKD + Mix was evaluated by receiver operating characteristic (ROC) analysis. In addition, an individual's 2- or 5-year risk probability of progressing to end-stage kidney disease (ESKD) was calculated by the kidney failure risk equation (KFRE). The effect of ΔADC on prognostic risk stratification was assessed. Additionally, net reclassification improvement (NRI) was used to evaluate the model performance. RESULTS: All enrolled patients had a median ΔADC level of 86 (IQR 28, 155) × 10-6 mm2/s. ΔADC significantly decreased across the increasing staging of CKD (P < 0.001). Moreover, those with pathological-confirmed DKD has a significantly lower level of ΔADC than those with NDKD and Mix (P < 0.001). It showed that ΔADC was independently associated with eGFR (ß = 1.058, 95% CI = [1.002,1.118], P = 0.042) and UACR (ß = -3.862, 95% CI = [-7.360, -0.365], P = 0.031) at multivariate linear regression analyses. Besides, ΔADC achieved an AUC of 0.707 (71% sensitivity and 75% specificity) and AUC of 0.823 (94% sensitivity and 67% specificity) for discriminating DKD from NDKD + Mix and higher ESKD risk categories (≥50% at 5 years; ≥10% at 2 years) from lower risk categories (<50% at 5 years; <10% at 2 years). Accordingly, the optimal cutoff value of ΔADC for higher ESKD risk categories was 66 × 10-6 mm2/s, and the group with the low-cutoff level of ΔADC group was associated with 1.232 -fold (95% CI 1.086, 1.398) likelihood of higher ESKD risk categories as compared to the high-cutoff level of ΔADC group in the fully-adjusted model. Reclassification analyses confirmed that the final adjusted model improved NRI. CONCLUSIONS: ΔADC was strongly associated with eGFR and UACR in patients with T2D and CKD. More importantly, baseline ΔADC was predictive of higher ESKD risk, independently of significant clinical confounding. Specifically, ΔADC <78 × 10-6 mm2/s and <66 × 10-6 mm2/s would help to identify T2D patients with the diagnosis of DKD and higher ESKD risk categories, respectively.

Assessment of renal quality with quantitative contrast-enhanced ultrasound (CEUS) for differentiating kidney histopathology before procurement.

Purpose: This study aimed to investigate the use of contrast-enhanced ultrasonography (CEUS) to assess the kidneys' quality before procurement. Methods: This prospective study included 74 donors and 148 recipients of kidneys. 119 kidneys underwent quantitative analysis. Before organ procurement, potential kidney donors underwent CEUS, though organ procurement involved a zero-point puncture biopsy. CEUS parameters of the renal cortex and medulla were evaluated, including rise time (RT), time to peak (TTP), the area under the curve (AUC), wash-in slope (WIS), peak intensity (PI), and mean transit time (MTT). Donors' kidneys were classified based on their pathological. Additionally, short-term clinical indicators of renal recipients were collected and analyzed to determine whether the patients had delayed recovery of renal allograft function. Results: This experiment included 148 cases of kidney information, divided into two groups based on the Remuzzi score of the kidneys. However, 29 kidneys were excluded from the quantitative analysis due to loss or low quality of CEUS images. Comparing the time-intensity curve (TIC) of renal cortical region of interest (ROI), we found that the group with lower pathological scores exhibited higher PI (P=0.002), AUC(P=0.003), and WIS (P=0.009). TIC comparison results for renal medulla ROI revealed that the group with lower pathological scores had higher PI (P=0.010), AUC (P=0.023), and WIS (P=0.024). Conclusions: This study highlighted the potential of CEUS as a non-invasive, safe, and real-time examination method that correlates with the Remuzzi score and renal pathology. Therefore, it can be used as a prospective preoperative non-invasive evaluation method for the donor's kidney.

Noninvasive Assessment of Diabetic Kidney Disease With MRI: Hype or Hope?

Owing to the increasing prevalence of diabetic mellitus, diabetic kidney disease (DKD) is presently the leading cause of chronic kidney disease and end-stage renal disease worldwide. Early identification and disease interception is of paramount clinical importance for DKD management. However, current diagnostic, disease monitoring and prognostic tools are not satisfactory, due to their low sensitivity, low specificity, or invasiveness. Magnetic resonance imaging (MRI) is noninvasive and offers a host of contrast mechanisms that are sensitive to pathophysiological changes and risk factors associated with DKD. MRI tissue characterization involves structural and functional information including renal morphology (kidney volume (TKV) and parenchyma thickness using T1- or T2-weighted MRI), renal microstructure (diffusion weighted imaging, DWI), renal tissue oxygenation (blood oxygenation level dependent MRI, BOLD), renal hemodynamics (arterial spin labeling and phase contrast MRI), fibrosis (DWI) and abdominal or perirenal fat fraction (Dixon MRI). Recent (pre)clinical studies demonstrated the feasibility and potential value of DKD evaluation with MRI. Recognizing this opportunity, this review outlines key concepts and current trends in renal MRI technology for furthering our understanding of the mechanisms underlying DKD and for supplementing clinical decision-making in DKD. Progress in preclinical MRI of DKD is surveyed, and challenges for clinical translation of renal MRI are discussed. Future directions of DKD assessment and renal tissue characterization with (multi)parametric MRI are explored. Opportunities for discovery and clinical break-through are discussed including biological validation of the MRI findings, large-scale population studies, standardization of DKD protocols, the synergistic connection with data science to advance comprehensive texture analysis, and the development of smart and automatic data analysis and data visualization tools to further the concepts of virtual biopsy and personalized DKD precision medicine. We hope that this review will convey this vision and inspire the reader to become pioneers in noninvasive assessment and management of DKD with MRI. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

Artificial intelligence-assisted quantification and assessment of whole slide images for pediatric kidney disease diagnosis.

MOTIVATION: Pediatric kidney disease is a widespread, progressive condition that severely impacts growth and development of children. Chronic kidney disease is often more insidious in children than in adults, usually requiring a renal biopsy for diagnosis. Biopsy evaluation requires copious examination by trained pathologists, which can be tedious and prone to human error. In this study, we propose an artificial intelligence (AI) method to assist pathologists in accurate segmentation and classification of pediatric kidney structures, named as AI-based Pediatric Kidney Diagnosis (APKD). RESULTS: We collected 2935 pediatric patients diagnosed with kidney disease for the development of APKD. The dataset comprised 93 932 histological structures annotated manually by three skilled nephropathologists. APKD scored an average accuracy of 94% for each kidney structure category, including 99% in the glomerulus. We found strong correlation between the model and manual detection in detected glomeruli (Spearman correlation coefficient r = 0.98, P < .001; intraclass correlation coefficient ICC = 0.98, 95% CI = 0.96-0.98). Compared to manual detection, APKD was approximately 5.5 times faster in segmenting glomeruli. Finally, we show how the pathological features extracted by APKD can identify focal abnormalities of the glomerular capillary wall to aid in the early diagnosis of pediatric kidney disease. AVAILABILITY AND IMPLEMENTATION: https://github.com/ChunyueFeng/Kidney-DataSet.

A large-scale retrospective study enabled deep-learning based pathological assessment of frozen procurement kidney biopsies to predict graft loss and guide organ utilization.

Lesion scores on procurement donor biopsies are commonly used to guide organ utilization for deceased-donor kidneys. However, frozen sections present challenges for histological scoring, leading to inter- and intra-observer variability and inappropriate discard. Therefore, we constructed deep-learning based models to recognize kidney tissue compartments in hematoxylin & eosin-stained sections from procurement needle biopsies performed nationwide in years 2011-2020. To do this, we extracted whole-slide abnormality features from 2431 kidneys and correlated with pathologists' scores and transplant outcomes. A Kidney Donor Quality Score (KDQS) was derived and used in combination with recipient demographic and peri-transplant characteristics to predict graft loss or assist organ utilization. The performance on wedge biopsies was additionally evaluated. Our model identified 96% and 91% of normal/sclerotic glomeruli respectively; 94% of arteries/arterial intimal fibrosis; 90% of tubules. Whole-slide features of Sclerotic Glomeruli (GS)%, Arterial Intimal Fibrosis (AIF)%, and Interstitial Space Abnormality (ISA)% demonstrated strong correlations with corresponding pathologists' scores of all 2431 kidneys, but had superior associations with post-transplant estimated glomerular filtration rates in 2033 and graft loss in 1560 kidneys. The combination of KDQS and other factors predicted one- and four-year graft loss in a discovery set of 520 kidneys and a validation set of 1040 kidneys. By using the composite KDQS of 398 discarded kidneys due to "biopsy findings", we suggest that if transplanted, 110 discarded kidneys could have had similar survival to that of other transplanted kidneys. Thus, our composite KDQS and survival prediction models may facilitate risk stratification and organ utilization while potentially reducing unnecessary organ discard.

Kidney involvement in systemic lupus erythematosus: From the patient assessment to a tailored treatment.

In the last few years, several studies have provided new evidence for the diagnosis, management, and follow-up of patients with lupus nephritis. Evidence showing dissociation between clinical and histological findings has prompted reevaluation of the role of the kidney biopsy as a tool for diagnosis and follow-up. In therapeutics, four immunosuppressive schemes now have supporting evidence for use as initial therapy. Current challenges include individualized selection of the best immunosuppressive regimen, an unmet need for non-invasive biomarkers of disease activity to inform treatment responses and guide subsequent therapy, holistic patient management in this complex, multisystem disease, and ultimately the development of more targeted therapies directed at specific effector pathways driving glomerular inflammation and damage in order to improve treatment response. In this communication, we review the diagnostic and therapeutic approach to lupus nephritis, as well as evaluation of response to therapy and disease control.

Learning more from the inter-rater reliability of interstitial fibrosis assessment beyond just a statistic.

Interstitial fibrosis assessment by renal pathologists lacks good agreement, and we aimed to investigate its hidden properties and infer possible clinical impact. Fifty kidney biopsies were assessed by 9 renal pathologists and evaluated by intraclass correlation coefficients (ICCs) and kappa statistics. Probabilities of pathologists' assessments that would deviate far from true values were derived from quadratic regression and multilayer perceptron nonlinear regression. Likely causes of variation in interstitial fibrosis assessment were investigated. Possible misclassification rates were inferred on reported large cohorts. We found inter-rater reliabilities ranged from poor to good (ICCs 0.48 to 0.90), and pathologists' assessments had the worst agreements when the extent of interstitial fibrosis was moderate. 33.5% of pathologists' assessments were expected to deviate far from the true values. Variation in interstitial fibrosis assessment was found to be correlated with variation in interstitial inflammation assessment (r2 = 32.1%). Taking IgA nephropathy as an example, the Oxford T scores for interstitial fibrosis were expected to be misclassified in 21.9% of patients. This study demonstrated the complexity of the inter-rater reliability of interstitial fibrosis assessment, and our proposed approaches discovered previously unknown properties in pathologists' practice and inferred a possible clinical impact on patients.

Research progress in functional magnetic resonance imaging assessment of lupus nephritis kidney injury.

Lupus nephritis is one of the most common and severe complications of systemic lupus erythematosus and is also a major predictor of poor prognosis and mortality. Lupus nephritis has the characteristics of insidious onset, complex pathological types, rapid progression of organ damage, and easy recurrence. Currently, kidney damage in lupus nephritis is usually assessed based on urine analysis, renal biopsy, and glomerular filtration rates. However, they all have certain limitations, making it difficult to diagnose lupus nephritis early and assess its severity and progression. With the rapid development of functional magnetic resonance, multiple functional imaging techniques are expected to provide more useful information for the pathophysiological development, early diagnosis, progression, prognosis, and renal function evaluation of lupus nephritis. This article reviews the principle of multiple functional magnetic resonance imaging and the research status of evaluating renal function in lupus nephritis.

European Society for Organ Transplantation (ESOT)-TLJ 3.0 Consensus on Histopathological Analysis of Pre-Implantation Donor Kidney Biopsy: Redefining the Role in the Process of Graft Assessment.

The ESOT TLJ 3.0. consensus conference brought together leading experts in transplantation to develop evidence-based guidance on the standardization and clinical utility of pre-implantation kidney biopsy in the assessment of grafts from Expanded Criteria Donors (ECD). Seven themes were selected and underwent in-depth analysis after formulation of PICO (patient/population, intervention, comparison, outcomes) questions. After literature search, the statements for each key question were produced, rated according the GRADE approach [Quality of evidence: High (A), Moderate (B), Low (C); Strength of Recommendation: Strong (1), Weak (2)]. The statements were subsequently presented in-person at the Prague kick-off meeting, discussed and voted. After two rounds of discussion and voting, all 7 statements reached an overall agreement of 100% on the following issues: needle core/wedge/punch technique representatively [B,1], frozen/paraffin embedded section reliability [B,2], experienced/non-experienced on-call renal pathologist reproducibility/accuracy of the histological report [A,1], glomerulosclerosis/other parameters reproducibility [C,2], digital pathology/light microscopy in the measurement of histological variables [A,1], special stainings/Haematoxylin and Eosin alone comparison [A,1], glomerulosclerosis reliability versus other histological parameters to predict the graft survival, graft function, primary non-function [B,1]. This methodology has allowed to reach a full consensus among European experts on important technical topics regarding pre-implantation biopsy in the ECD graft assessment.

Early assessment of acute kidney injury in severe acute pancreatitis with multimodal DWI: an animal model.

OBJECTIVES: To evaluate the feasibility of multimodal diffusion-weighted imaging (DWI) for detecting the occurrence and severity of acute kidney injury (AKI) caused by severe acute pancreatitis (SAP) in rats. METHODS: SAP was induced in thirty rats by the retrograde injection of 5.0% sodium taurocholate through the biliopancreatic duct. Six rats underwent MRI of the kidneys 24 h before and 2, 4, 6, and 8 h after this AKI model was generated. Conventional and functional MRI sequences were used, including intravoxel incoherent motion imaging (IVIM), diffusion tensor imaging (DTI), and diffusion kurtosis imaging (DTI). The main DWI parameters and histological results were analyzed. RESULTS: The fast apparent diffusion coefficient (ADC) of the renal cortex was significantly reduced at 2 h, as was the fractional anisotropy (FA) value of the renal cortex on DTI. The mean kurtosis (MK) values for the renal cortex and medulla gradually increased after model generation. The renal histopathological score was negatively correlated with the medullary slow ADC, fast ADC, and perfusion scores for both the renal cortex and medulla, as were the ADC and FA values of the renal medulla in DTI, whereas the MK values of the cortex and medulla were positively correlated (r = 0.733, 0.812). Thus, the cortical fast ADC, medullary MK, FADTI, and slow ADC were optimal parameters for diagnosing AKI. Of these parameters, cortical fast ADC had the highest diagnostic efficacy (AUC = 0.950). CONCLUSIONS: The fast ADC of the renal cortex is the core indicator of early AKI, and the medullary MK value might serve as a sensitive biomarker for grading renal injury in SAP rats. CLINICAL RELEVANCE STATEMENT: The multimodal parameters of renal IVIM, DTI, and DKI are potential beneficial for the early diagnosis and severity grading of renal injury in SAP patients. KEY POINTS: • The multimodal parameters of renal DWI, including IVIM, DTI, and DKI, may be valuable for the noninvasive detection of early AKI and the severity grading of renal injury in SAP rats. • Cortical fast ADC, medullary MK, FA, and slow ADC are optimal parameters for early diagnosis of AKI, and cortical fast ADC has the highest diagnostic efficacy. • Medullary fast ADC, MK, and FA as well as cortical MK are useful for predicting the severity grade of AKI, and the renal medullary MK value exhibits the strongest correlation with pathological scores.

Magnetic Resonance Imaging to Evaluate Kidney Structure, Function, and Pathology: Moving Toward Clinical Application.

Recent advances in multiparametric magnetic resonance imaging (MRI) allow multiple quantitative measures to assess kidney morphology, tissue microstructure, oxygenation, kidney blood flow, and perfusion to be collected in a single scan session. Animal and clinical studies have investigated the relationship between the different MRI measures and biological processes, although their interpretation can be complex due to variations in study design and generally small participant numbers. However, emerging themes include the apparent diffusion coefficient derived from diffusion-weighted imaging, T1 and T2 mapping parameters, and cortical perfusion being consistently associated with kidney damage and predicting kidney function decline. Blood oxygen level-dependent (BOLD) MRI has shown inconsistent associations with kidney damage markers but has been predictive of kidney function decline in several studies. Therefore, multiparametric MRI of the kidneys has the potential to address the limitations of existing diagnostic methods to provide a noninvasive, noncontrast, and radiation-free method to assess whole kidney structure and function. Barriers to be overcome to facilitate widespread clinical application include improved understanding of biological factors that impact MRI measures, development of a larger evidence base for clinical utility, standardization of MRI protocols, automation of data analysis, determining optimal combination of MRI measures, and health economic evaluation.

Impact of race-independent equations on estimating glomerular filtration rate for the assessment of kidney dysfunction in liver disease.

BACKGROUND: Altered hemodynamics in liver disease often results in overestimation of glomerular filtration rate (GFR) by creatinine-based GFR estimating (eGFR) equations. Recently, we have validated a novel eGFR equation based on serum myo-inositol, valine, and creatinine quantified by nuclear magnetic resonance spectroscopy in combination with cystatin C, age and sex (GFRNMR). We hypothesized that GFRNMR could improve chronic kidney disease (CKD) classification in the setting of liver disease. RESULTS: We conducted a retrospective multicenter study in 205 patients with chronic liver disease (CLD), comparing the performance of GFRNMR to that of validated CKD-EPI eGFR equations, including eGFRcr (based on creatinine) and eGFRcr-cys (based on both creatinine and cystatin C), using measured GFR as reference standard. GFRNMR outperformed all other equations with a low overall median bias (-1 vs. -6 to 4 ml/min/1.73 m2 for the other equations; p < 0.05) and the lowest difference in bias between reduced and preserved liver function (-3 vs. -16 to -8 ml/min/1.73 m2 for other equations). Concordant classification by CKD stage was highest for GFRNMR (59% vs. 48% to 53%) and less biased in estimating CKD severity compared to the other equations. GFRNMR P30 accuracy (83%) was higher than that of eGFRcr (75%; p = 0.019) and comparable to that of eGFRcr-cys (86%; p = 0.578). CONCLUSIONS: Addition of myo-inositol and valine to creatinine and cystatin C in GFRNMR further improved GFR estimation in CLD patients and accurately stratified liver disease patients into CKD stages.