Comparison of the effects of peritoneal dialysis and hemodialysis on spontaneous brain activity in CKD patients: an rs-fMRI study.

OBJECTIVE: To compare the effects of peritoneal dialysis and hemodialysis on spontaneous brain activity in patients with end-stage renal disease. METHODS: A total of 52 dialysis patients with end-stage renal disease, including 25 patients with chronic kidney disease undergoing hemodialysis (HD-CKD) and 27 patients with chronic kidney disease undergoing peritoneal dialysis (PD-CKD), and 49 healthy controls (normal control) were included. All participants underwent neuropsychological testing (Mini-Mental State Examination and Montreal cognitive assessment) and resting-state functional magnetic resonance imaging. Fractional amplitude of low frequency fluctuations and Regional Homogeneity algorithms were employed to evaluate spontaneous brain activity. Statistical analysis was performed to discern differences between the groups. RESULTS: When compared with the normal control group, the PD-CKD group exhibited significant alterations in fractional amplitude of low frequency fluctuations in various cerebellum regions and other brain areas, while the HD-CKD group showed decreased fractional amplitude of low frequency fluctuations in the bilateral pericalcarine cortex. The Regional Homogeneity values in the PD-CKD group were notably different than those in the normal control group, particularly in regions such as the bilateral caudate nucleus and the right putamen. CONCLUSION: Both peritoneal dialysis and hemodialysis modalities impact brain activity, but manifest differently in end-stage renal disease patients. Understanding these differences is crucial for optimizing patient care.

Performance and Interpretation of Sonography in the Practice of Nephrology: Core Curriculum 2024.

Ultrasonography is increasingly being performed by clinicians at the point of care, and nephrologists are no exception. This Core Curriculum illustrates how ultrasonography can be incorporated into clinical decision making across the spectrum of kidney disease to optimize the care nephrologists provide to patients. Sonography is valuable in outpatient and inpatient settings for the diagnosis and management of acute and chronic kidney disease, evaluation of cystic disease, urinary obstruction, pain, hematuria, proteinuria, assessment of volume status, and in providing guidance for kidney biopsy. As kidney disease advances, ultrasound is useful in the placement and maintenance of temporary and permanent access for dialysis. After kidney transplantation, ultrasonography is critical for evaluation of allograft dysfunction and for biopsies. Sonography skills expedite patient care and enhance the practice of nephrology and are relatively easily acquired with training. It is our hope that this curriculum will encourage nephrologists to learn and apply this valuable skill.

Amide Proton Transfer-Weighted Magnetic Resonance Imaging for Application in Renal Fibrosis: A Radiological-Pathological-Based Analysis.

INTRODUCTION: Renal fibrosis (RF), being the most important pathological change in the progression of CKD, is currently assessed by the evaluation of a biopsy. This present study aimed to apply a novel functional MRI (fMRI) protocol named amide proton transfer (APT) weighting to evaluate RF noninvasively. METHODS: Male Sprague-Dawley (SD) rats were initially subjected to bilateral kidney ischemia/reperfusion injury (IRI), unilateral ureteral obstruction, and sham operation, respectively. All rats underwent APT mapping on the 7th and 14th days after operation. Besides, 26 patients underwent renal biopsy at the Nephrology Department of Shanghai Tongji Hospital between July 2022 and May 2023. Patients underwent APT and apparent diffusion coefficient (ADC) mappings within 1 week before biopsy. MRI results of both patients and rats were calculated by comparing with gold standard histology for fibrosis assessment. RESULTS: In animal models, the cortical APT (cAPT) and medullary APT (mAPT) values were positively correlated with the degree of RF. Compared to the sham group, IRI group showed significantly increased cAPT and mAPT values on the 7th and 14th days after surgery, but no group differences were found in ADC values. Similar results were found in human patients. Cortical/medullary APT values were significantly increased in patients with moderate-to-severe fibrosis than in patients with mild fibrosis. ROC curve analysis indicated that APT value displayed a better diagnostic value for RF. Furthermore, combination of cADC and cAPT improved fibrosis detection by imaging variables alone (p < 0.1). CONCLUSION: APT values had better diagnostic capability at early stage of RF compared to ADC values, and the addition of APT imaging to conventional ADC will significantly improve the diagnostic performance for predicting kidney fibrosis.

Muscle ultrasound to diagnose sarcopenia in chronic kidney disease: a systematic review and bayesian bivariate meta-analysis.

OBJECTIVE: The aim of this systematic review was to assess the diagnostic test accuracy of muscle ultrasound for sarcopenia among chronic kidney disease (CKD) populations. BACKGROUND: Sarcopenia has become a worldwide health issue, especially for CKD patients. Conventional techniques of muscle mass assessment often prove limited, thus prompts increasing interest in ultrasound suitability. METHODS: We searched the Cochrane Library, PubMed and Embase for literature published up to June 2023. Ultrasound diagnosis of sarcopenia in CKD patients was included. Two independent investigators used the Quality Assessment Tool for Diagnosis Accuracy Studies (QUADAS-2) to assess the quality. We extracted valuable information from eligible studies. Using a Bayesian bivariate model, we pooled sensitivity and specificity values and summary receiver operating characteristic (SROC) curves. RESULTS: Five articles, involving 428 participants at various stages of CKD were included. Three studies diagnosed by the cross-sectional area (CSA) of the rectus femoris, while two others by muscle thickness (MT) and shear wave elastography (SWE) from the same muscle, separately. Overall, CSA or SWE had a pooled sensitivity of 0.95 (95% CrI, 0.80, 1.00), and the specificity was 0.73 (95% CrI, 0.55, 0.88) for diagnosing sarcopenia in CKD patients. CONCLUSIONS: Ultrasound measurements of CSA and SWE were more sensitive for diagnosing sarcopenia in the CKD population than in the general population. Ultrasound assessment from a single peripheral skeletal muscle site may serve as a rapid screening tool for identifying sarcopenic individuals within the CKD population, if a specific cut-off value could be determined.

Chronic kidney disease and its association with cerebral small vessel disease in the general older hypertensive population.

BACKGROUND: Cerebral small vessel disease can be identified using magnetic resonance imaging, and includes white matter hyperintensities, lacunar infarcts, cerebral microbleeds, and brain atrophy. Cerebral small vessel disease and chronic kidney disease share many risk factors, including hypertension. This study aims to explore an association between chronic kidney disease and cerebral small vessel disease, and also to explore the role of hypertension in this relationship. METHODS: With a cross sectional study design, data from 390 older adults was retrieved from the general population study Good Aging in Skåne. Chronic kidney disease was defined as glomerular filtration rate < 60 ml/min/1,73m2. Associations between chronic kidney disease and magnetic resonance imaging markers of cerebral small vessel disease were explored using logistic regression models adjusted for age and sex. In a secondary analysis, the same calculations were performed with the study sample stratified based on hypertension status. RESULTS: In the whole group, adjusted for age and sex, chronic kidney disease was not associated with any markers of cerebral small vessel disease. After stratification by hypertension status and adjusted for age and sex, we observed that chronic kidney disease was associated with cerebral microbleeds (OR 1.93, CI 1.04-3.59, p-value 0.037), as well as with cortical atrophy (OR 2.45, CI 1.34-4.48, p-value 0.004) only in the hypertensive group. In the non-hypertensive group, no associations were observed. CONCLUSIONS: In this exploratory cross-sectional study, we observed that chronic kidney disease was associated with markers of cerebral small vessel disease only in the hypertensive subgroup of a general population of older adults. This might indicate that hypertension is an important link between chronic kidney disease and cerebral small vessel disease. Further studies investigating the relationship between CKD, CSVD, and hypertension are warranted.

Chest CT radiomics is feasible in evaluating bone changes in chronic kidney diseases.

BACKGROUND: Non-invasive imaging methods are still lacking for evaluating bone changes in chronic kidney diseases (CKD). PURPOSE: To investigate the feasibility of chest CT radiomics in evaluating bone changes caused by CKD. MATERIAL AND METHODS: In total, 75 patients with stage 1 CKD (CKD1) and 75 with stage 5 CKD (CKD5) were assessed using the chest CT radiomics method. Radiomics features of bone were obtained using 3D Slicer software and were then compared between CKD1 and CKD5 cases. The methods of maximum correlation minimum redundancy (mRMR) and least absolute shrinkage and selection operator (LASSO) were used to establish a prediction model to determine CKD. The receiver operating characteristic (ROC) curve was used to determine the performance of the model. RESULTS: Cases of CKD1 and CKD5 differed in 40 radiomics features (P <0.05). Using the mRMR and LASSO methods, five features were finally selected to establish a predication model. The area under the receiver operating characteristic curve of the model in the determination of CKD1 and CKD5 was 0.903 and 0.854, respectively, for the training and validation cohorts. CONCLUSION: Chest CT radiomics is feasible in evaluating bone changes caused by CKD.

Renal stiffness measured by shear wave elastography and its relationship with perirenal fat in patients with chronic kidney disease.

PURPOSE: This study aimed to utilize shear wave elastography (SWE) to assess changes in renal stiffness and its influencing factors in patients with chronic kidney disease (CKD) across different estimated glomerular filtration rate (eGFR) categories. It also sought to determine the correlation between perirenal fat (PF) and renal stiffness at various stages of CKD. METHODS: A total of 190 CKD patients and 50 healthy controls were evaluated. Clinical parameters, conventional renal ultrasound measurements, PF, and renal stiffness trends were assessed separately. Factors independently associated with renal stiffness and PF were further analyzed. RESULTS: Renal parenchymal stiffness was significantly higher in the Albumin-CKD G1-2 (ALB-CKD G1-2) and CKD G3 groups than in the control group (p < 0.05). The parenchymal stiffness of the CKD G3 group was higher than that of the ALB-CKD G1-2 group (p < 0.05). The independent factors of renal parenchymal stiffness varied at different stages of disease development, with eGFR and PF being significant factors in the CKD G3 group. PF was elevated in the ALB-CKD G1-2 and CKD G3 groups compared to the control group, and the independent factors of PF varied across different stages, although waist circumference remained a common factor. CONCLUSION: Using SWE to detect renal elastic moduli can effectively assess changes in renal stiffness in patients with CKD with varying eGFRs. PF is an independent factor of renal stiffness in patients with CKD G3, providing a foundation for early diagnosis and clinical treatment.

Ultrasound localization microscopy of the human kidney allograft on a clinical ultrasound scanner.

Chronic kidney disease is a major medical problem, causing more than a million deaths each year worldwide. Peripheral kidney microvascular damage characterizes most chronic kidney diseases, yet noninvasive and quantitative diagnostic tools to measure this are lacking. Ultrasound Localization Microscopy (ULM) can assess tissue microvasculature with unprecedented resolution. Here, we optimized methods on 35 kidney transplants and studied the feasibility of ULM in seven human kidney allografts with a standard low frame rate ultrasound scanner to access microvascular damage. Interlobar, arcuate, cortical radial vessels, and part of the medullary organization were visible on ULM density maps. The medullary vasa recta can be seen but are not as clear as the cortical vessels. Acquisition parameters were derived from Contrast-Enhanced Ultrasound examinations by increasing the duration of the recorded clip at the same plane. ULM images were compared with Color Doppler, Advanced Dynamic Flow, and Superb Microvascular Imaging with a contrast agent. Despite some additional limitations due to movement and saturation artifacts, ULM identified vessels two to four times thinner compared with Doppler modes. The mean ULM smallest analyzable vessel cross section was 0.3 ± 0.2 mm in the seven patients. Additionally, ULM was able to provide quantitative information on blood velocities in the cortical area. Thus, this proof-of-concept study has shown ULM to be a promising imaging technique for qualitative and quantitative microvascular assessment. Imaging native kidneys in patients with kidney diseases will be needed to identify their ULM biomarkers.

Characterization of renal fibrosis in rats with chronic kidney disease by in vivo tomoelastography.

Chronic kidney disease (CKD) is characterized by structural changes, such as tubular atrophy, renal fibrosis, and glomerulosclerosis, all of which affect the viscoelastic properties of biological tissues. However, detection of renal viscoelasticity changes because diagnostic markers by in vivo elastography lack histopathological validation through animal models. Therefore, we investigated in vivo multiparametric magnetic resonance imaging (mp-MRI), including multifrequency magnetic resonance elastography-based tomoelastography, in the kidneys of 10 rats with adenine-induced CKD and eight healthy controls. Kidney volume (in mm3 ), water diffusivity (apparent diffusion coefficient [ADC] in mm2 /s), shear wave speed (SWS; in m/s; related to stiffness), and wave penetration rate (PR; in m/s; related to inverse viscosity) were quantified by mp-MRI and correlated with histopathologically determined renal fibrosis (collagen area fraction [CAF]; in %). Kidney volume (40% ± 29%, p = 0.009), SWS (11% ± 12%, p = 0.016), and PR (20% ± 15%, p = 0.004) were significantly increased in CKD, which was accompanied by ADC (-24% ± 27%, p = 0.02). SWS, PR, and ADC were correlated with CAF with R = 0.63, 0.75, and -0.5 (all p < 0.05), respectively. In the CKD rats, histopathology showed tubule dilation due to adenine crystal deposition. Collectively, our results suggest that collagen accumulation during CKD progression transforms soft-compliant renal tissue into a more rigid-solid state with reduced water mobility. We hypothesized that tubule dilation-a specific feature of our model-might lead to higher intraluminal pressure, which could also contribute to elevated renal stiffness. Tomoelastography is a promising tool for noninvasively assessing disease progression, detecting biomechanical properties that are sensitive to different pathologic features of CKD.

Fibrosis imaging with multiparametric proton and sodium MRI in pig injury models.

Chronic kidney disease (CKD) is common and has huge implications for health and mortality. It is aggravated by intrarenal fibrosis, but the assessment of fibrosis is limited to kidney biopsies, which carry a risk of complications and sampling errors. This calls for a noninvasive modality for diagnosing and staging intrarenal fibrosis. The current, exploratory study evaluates a multiparametric MRI protocol including sodium imaging (23 Na-MRI) to determine the opportunities within this modality to assess kidney injury as a surrogate endpoint of fibrosis. The study includes 43 pigs exposed to ischemia-reperfusion injury (IRI) or unilateral ureteral obstruction (UUO), or serving as healthy controls. Fibrosis was determined using gene expression analysis of collagen. The medulla/cortex ratio of 23 Na-MRI decreased in the injured kidney in the IRI pigs, but not in the UUO pigs (p = 0.0180, p = 0.0754). To assess the combination of MRI parameters in estimating fibrosis, we created a linear regression model consisting of the cortical apparent diffusion coefficient, ΔR2*, ΔT1, the 23 Na medulla/cortex ratio, and plasma creatinine (R2  = 0.8009, p = 0.0117). The 23 Na medulla/cortex ratio only slightly improved the fibrosis prediction model, leaving 23 Na-MRI in an ambiguous place for evaluation of intrarenal fibrosis. Use of multiparametric MRI in combination with plasma creatinine shows potential for the estimation of fibrosis in human kidney disease, but more translational and clinical work is warranted before MRI can contribute to earlier diagnosis and evaluation of treatment for acute kidney injury and CKD.

Exploration of Interstitial Fibrosis in Chronic Kidney Disease by Diffusion-Relaxation Correlation Spectrum MR Imaging: A Preliminary Study.

BACKGROUND: Renal interstitial fibrosis is one of the most common pathways in the progression of chronic kidney disease (CKD). Noninvasive evaluation of interstitial fibrosis would help monitoring CKD progression and prognosis prediction. PURPOSE: To evaluate the severity of renal interstitial fibrosis by diffusion-relaxation correlation spectrum imaging (DR-CSI). STUDY TYPE: Prospective. SUBJECTS: Forty patients with CKD and 10 healthy controls (average age 49.2 ± 14.8 years, 18 females). FIELD STRENGTH/SEQUENCE: 3-T, DR-CSI with 36 axial spin-echo echo-planar diffusion-weighted images (6 b-values, 6 echo times). ASSESSMENT: Interstitial fibrosis level (IFL) was assessed from biopsy results (IFL = 1, fibrosis percentage <25%, defined as mild; IFL = 2, 25%-50%, moderate; IFL = 3, >50%, severe). Estimated glomerular filtration rate (eGFR) was calculated using serum creatinine. The regions of interest included cortex for both kidneys. The diffusivity-T2 spectrum was assessed considering three compartments (threshold: T2 30-40 msec, diffusivity 5-9 µm2 /msec, according to visible peaks): A (low diffusivity, short T2), B (low diffusivity, long T2), and C (high diffusivity). Volume fractions Vi (i = A, B, C) were calculated. STATISTICAL TESTS: Intra-class coefficient (ICC, >0.6 as good) to assess inter-reader agreement of DR-CSI Vi . Spearman's correlation to assess relationship of Vi to IFL and eGFR. Receiver operating characteristic analyses with the area under the curve (AUC) to discriminate patients with moderate-severe fibrosis from mild ones. Statistical significance criteria: P-value <0.05. RESULTS: ICCs were good for all Vi . Correlations were found between IFL and VB (r = 0.424, significant) and VC (r = -0.400, significant), and between eGFR and VB (r = -0.303, P = 0.058) and VC (r = 0.487, significant). Regarding VB and VC , the AUCs were 0.903 and 0.824. DATA CONCLUSION: DR-CSI help distinguish patients with moderate or severe renal interstitial fibrosis from mild ones. EVIDENCE LEVEL: 2 Technical Efficacy: Stage 2.

Utility of shear wave-based ultrasound elastography in chronic kidney disease and related pathological quantitative analysis.

OBJECTIVES: The purpose of this study was to investigate the effects of tissue fibrosis and microvessel density on shear wave-based ultrasound elastography (SWUE) of chronic kidney disease (CKD). In addition, we were looking to see whether SWUE could predict stage of CKD, correlating with the histology on kidney biopsy. METHODS: Renal tissue sections from 54 patients diagnosed with suspected CKD were subjected to immunohistochemistry (CD31 and CD34), and the degree of tissue fibrosis was assessed using Masson staining. Before renal puncture, both kidneys were examined using SWUE. Comparative analysis was used to assess the correlation between SWUE and microvessel density, and between SWUE and the degree of fibrosis. RESULTS: Fibrosis area according to Masson staining (p < 0.05) and integrated optical density (IOD) (p < 0.05) were positively correlated with CKD stage. The percentage of positive area (PPA) and IOD for CD31 and CD34 were not correlated with CKD stage (p > 0.05). When stage 1 CKD was removed, PPA and IOD for CD34 were negatively correlated with CKD stage (p < 0.05). Masson staining fibrosis area and IOD were not correlated with SWUE (p > 0.05), PPA and IOD for CD31 and CD34 were not correlated with SWUE (p > 0.05) and, finally, no correlation between SWUE and CKD stage was found (p > 0.05). CONCLUSION: The diagnostic value of SWUE for CKD staging was very low. The utility of SWUE in CKD was affected by many factors and its diagnostic value was limited. KEY POINTS: • There was no correlation between SWUE and the degree of fibrosis, or between SWUE and microvessel density among patients with CKD. • There was no correlation between SWUE and CKD stage and the diagnostic value of SWUE for CKD staging was very low. • The utility of SWUE in CKD is affected by many factors and its value was limited.

Diagnostic accuracy of ultrasound-based multimodal radiomics modeling for fibrosis detection in chronic kidney disease.

OBJECTIVES: To predict kidney fibrosis in patients with chronic kidney disease using radiomics of two-dimensional ultrasound (B-mode) and Sound Touch Elastography (STE) images in combination with clinical features. METHODS: The Mindray Resona 7 ultrasonic diagnostic apparatus with SC5-1U convex array probe (bandwidth frequency of 1-5 MHz) was used to perform two-dimensional ultrasound and STE software. The severity of cortical tubulointerstitial fibrosis was divided into three grades: mild interstitial fibrosis and tubular atrophy (IFTA), fibrotic area < 25%; moderate IFTA, fibrotic area 26-50%; and severe IFTA, fibrotic area > 50%. After extracting radiomics from B-mode and STE images in these patients, we analyzed two classification schemes: mild versus moderate-to-severe IFTA, and mild-to-moderate versus severe IFTA. A nomogram was constructed based on multiple logistic regression analyses, combining clinical and radiomics. The performance of the nomogram for differentiation was evaluated using receiver operating characteristic (ROC), calibration, and decision curves. RESULTS: A total of 150 patients undergoing kidney biopsy were enrolled (mild IFTA: n = 74; moderate IFTA: n = 33; severe IFTA: n = 43) and randomized into training (n = 105) and validation cohorts (n = 45). To differentiate between mild and moderate-to-severe IFTA, a nomogram incorporating STE radiomics, albumin, and estimated glomerular filtration (eGFR) rate achieved an area under the ROC curve (AUC) of 0.91 (95% confidence interval [CI]: 0.85-0.97) and 0.85 (95% CI: 0.77-0.98) in the training and validation cohorts, respectively. Between mild-to-moderate and severe IFTA, the nomogram incorporating B-mode and STE radiomics features, age, and eGFR achieved an AUC of 0.93 (95% CI: 0.89-0.98) and 0.83 (95% CI: 0.70-0.95) in the training and validation cohorts, respectively. Finally, we performed a decision curve analysis and found that the nomogram using both radiomics and clinical features exhibited better predictability than any other model (DeLong test, p < 0.05 for the training and validation cohorts). CONCLUSION: A nomogram based on two-dimensional ultrasound and STE radiomics and clinical features served as a non-invasive tool capable of differentiating kidney fibrosis of different severities. KEY POINTS: • Radiomics calculated based on the ultrasound imaging may be used to predict the severities of kidney fibrosis. • Radiomics may be used to identify clinical features associated with the progression of tubulointerstitial fibrosis in patients with CKD. • Non-invasive ultrasound imaging-based radiomics method with accuracy aids in detecting renal fibrosis with different IFTA severities.

Capability of arterial spin labeling and intravoxel incoherent motion diffusion-weighted imaging to detect early kidney injury in chronic kidney disease.

OBJECTIVES: To prospectively investigate the capability of arterial spin labeling (ASL) and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) for the identification of early kidney injury in chronic kidney disease (CKD) patients with normal estimated glomerular filtration rate (eGFR). METHODS: Fifty-four CKD patients confirmed by renal biopsy (normal eGFR group [eGFR ≥ 90 mL/min/1.73 m2]: n = 26; abnormal eGFR group [eGFR < 90 mL/min/1.73 m2]: n = 28) and 20 healthy volunteers (HV) were recruited. All subjects were examined by IVIM-DWI and ASL imaging. Renal blood flow (RBF) derived from ASL, true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f) derived from IVIM-DWI were measured from the renal cortex. One-way analysis of variance was used to compare MRI parameters among the three groups. The correlation between eGFR and MRI parameters was evaluated by Spearman correlation analysis. Diagnostic performances of MRI parameters for detecting kidney injury were assessed by receiver operating characteristic (ROC) curves. RESULTS: The renal cortical D, D*, f, and RBF values showed statistically significant differences among the three groups. eGFR was positively correlated with MRI parameters (D: r = 0.299, D*: r = 0.569, f: r = 0.733, RBF: r = 0.586). The areas under the curve (AUCs) for discriminating CKD patients from HV were 0.725, 0.752, 0.947, and 0.884 by D, D*, f, and RBF, respectively. D, D*, f, RBF, and eGFR identified CKD patients with normal eGFR with AUCs of 0.735, 0.612, 0.917, 0.827, and 0.733, respectively, and AUC of f value was significantly larger than that of eGFR. CONCLUSION: IVIM-DWI and ASL were useful for detecting underlying pathologic injury in early CKD patients with normal eGFR. KEY POINTS: • The renal cortical f and RBF values in the control group were significantly higher than those in the normal eGFR group. • A negative correlation was observed between the renal cortical D, D*, f, and RBF values and SCr and 24 h-UPRO, while eGFR was significantly positively correlated with renal cortical D, D*, f, and RBF values. • The AUC of renal cortical f values was statistically larger than that of eGFR for the discrimination between the CKD with normal eGFR group and the control group.

Evaluation of interstitial fibrosis in chronic kidney disease by multiparametric functional MRI and histopathologic analysis.

OBJECTIVES: To investigate the diagnostic value of functional MRI to assess renal interstitial fibrosis in patients with chronic kidney disease (CKD). METHODS: We prospectively recruited 80 CKD patients who underwent renal biopsies and 16 healthy volunteers to undergo multiparametric functional MRI examinations. The Oxford MEST-C classification was used to score the interstitial fibrosis. The diagnostic performance of functional MRI to discriminate interstitial fibrosis was evaluated by calculating the area under the receiver operating characteristic (ROC) curves. RESULTS: IgA nephropathy (60%) accounted for the majority of pathologic type in the CKD patients. Apparent diffusion coefficient (ADC) from diffusion-weighted imaging (DWI) was correlated with interstitial fibrosis (rho = -0.73). Decreased renal blood flow (RBF) derived from arterial spin labeling (rho = -0.78) and decreased perfusion fraction (f) derived from DWI (rho = -0.70) were accompanied by increased interstitial fibrosis. The T1 value from T1 mapping correlated with interstitial fibrosis (rho = 0.67) (all p < 0.01). The areas under the ROC curve for the discrimination of ≤ 25% vs. > 25% and ≤ 50% vs. > 50% interstitial fibrosis were 0.87 (95% confidence interval, 0.78 to 0.94) and 0.93 (0.86 to 0.98) by ADC, 0.84 (0.74 to 0.91) and 0.94 (0.86 to 0.98) by f, 0.93 (0.85 to 0.98) and 0.90 (0.82 to 0.96) by RBF, and 0.91 (0.83 to 0.96) and 0.77 (0.66 to 0.85) by T1, respectively. CONCLUSIONS: Functional MRI parameters were strongly correlated with the interstitial fibrosis of CKD. Therefore, it might a powerful tool to assess interstitial fibrosis of CKD noninvasively. KEY POINTS: • In CKD patients, the renal cortical ADC value decreased and T1 value increased significantly compared with healthy volunteers. • Functional MRI revealed significantly decreased renal perfusion in CKD patients compared with healthy volunteers. • The renal cortical ADC, f, RBF, and T1 values were strongly correlated with the interstitial fibrosis of CKD.

Value of multiparametric magnetic resonance imaging for evaluating chronic kidney disease and renal fibrosis.

OBJECTIVES: To identify optimized MRI markers for evaluating chronic kidney disease (CKD) and renal interstitial fibrosis (IF). MATERIALS AND METHODS: This prospective study included 43 patients with CKD and 20 controls. The CKD group was divided into mild and moderate-to-severe subgroups based on pathological results. Scanned sequences included T1 mapping, R2* mapping, intravoxel incoherent motion imaging, and diffusion-weighted imaging. One-way analyses of variance were used to compare MRI parameters among groups. Correlations of MRI parameters with estimated glomerular filtration rate (eGFR) and renal IF were analyzed using age as covariates. The support vector machine (SVM) model was used to evaluate the diagnostic efficacy of multiparametric MRI. RESULTS: Compared to control values, renal cortical apparent diffusion coefficient (cADC), medullary ADC (mADC), cortical pure diffusion coefficient (cDt), medullary Dt (mDt), cortical shifted apparent diffusion coefficient (csADC), and medullary sADC (msADC) values gradually decreased in the mild and moderate-to-severe groups, while cortical T1 (cT1) and medullary T1 (mT1) values gradually increased. Values of cADC, mADC, cDt, mDt, cT1, mT1, csADC, and msADC were significantly associated with eGFR and IF (p < 0.001). The SVM model indicated that multiparametric MRI combining cT1 and csADC can distinguish patients with CKD from controls with high accuracy (0.84), sensitivity (0.70), and specificity (0.92) (AUC: 0.96). Multiparametric MRI combining cT1 and cADC exhibited high accuracy (0.91), sensitivity (0.95), and specificity (0.81) for evaluating IF severity (AUC: 0.96). CONCLUSION: Multiparametric MRI combining T1 mapping and diffusion imaging may be of clinical utility in non-invasive assessment of CKD and IF. CLINICAL RELEVANCE STATEMENT: This study shows that multiparametric MRI combining T1 mapping and diffusion imaging may be clinically useful in the non-invasive assessment of chronic kidney disease (CKD) and interstitial fibrosis; this could provide information for risk stratification, diagnosis, treatment, and prognosis. KEY POINTS: • Optimized MRI markers for evaluating chronic kidney disease and renal interstitial fibrosis were investigated. • Renal cortex/medullary T1 values increased as interstitial fibrosis increased; cortical shifted apparent diffusion coefficient (csADC) correlated significantly with eGFR and interstitial fibrosis. • Support vector machine (SVM) combining cortical T1 (cT1) and csADC/cADC effectively identifies chronic kidney disease and accurately predicts renal interstitial fibrosis.

Deep learning imaging features derived from kidney ultrasounds predict chronic kidney disease progression in children with posterior urethral valves.

BACKGROUND: We sought to use deep learning to extract anatomic features from postnatal kidney ultrasounds and evaluate their performance in predicting the risk and timing of chronic kidney disease (CKD) progression for boys with posterior urethral valves (PUV). We hypothesized that these features would predict CKD progression better than clinical characteristics such as nadir creatinine alone. METHODS: We performed a retrospective cohort study of boys with PUV treated at two pediatric health systems from 1990 to 2021. Features of kidneys were extracted from initial postnatal kidney ultrasound images using a deep learning model. Three time-to-event prediction models were built using random survival forests. The Imaging Model included deep learning imaging features, the Clinical Model included clinical data, and the Ensemble Model combined imaging features and clinical data. Separate models were built to include time-dependent clinical data that were available at 6 months, 1 year, 3 years, and 5 years. RESULTS: Two-hundred and twenty-five patients were included in the analysis. All models performed well with C-indices of 0.7 or greater. The Clinical Model outperformed the Imaging Model at all time points with nadir creatinine driving the performance of the Clinical Model. Combining the 6-month Imaging Model (C-index 0.7; 95% confidence interval [CI] 0.6, 0.79) with the 6-month Clinical Model (C-index 0.79; 95% CI 0.71, 0.86) resulted in a 6-month Ensemble Model that performed better (C-index 0.82; 95% CI 0.77, 0.88) than either model alone. CONCLUSIONS: Deep learning imaging features extracted from initial postnatal kidney ultrasounds may improve early prediction of CKD progression among children with PUV. A higher resolution version of the Graphical abstract is available as Supplementary information.

A back propagation neural network approach to estimate the glomerular filtration rate in an older population.

BACKGROUND: The use of creatinine-based glomerular filtration rate (GFR)-estimating equations to evaluate kidney function in elderly individuals does not appear to offer any performance advantages. We therefore aimed to develop an accurate GFR-estimating tool for this age group. METHODS: Adults aged ≥ 65 years who underwent GFR measurement by technetium-99 m-diethylene triamine pentaacetic acid (99mTc-DTPA) renal dynamic imaging were included. Data were randomly split into a training set containing 80% of the participants and a test set containing the remaining 20% of the subjects. The Back propagation neural network (BPNN) approach was used to derive a novel GFR estimation tool; then we compared the performance of the BPNN tool with six creatinine-based equations (Chronic Kidney Disease-Epidemiology Collaboration [CKD-EPI], European Kidney Function Consortium [EKFC], Berlin Initiative Study-1 [BIS1], Lund-Malmö Revised [LMR], Asian modified CKD-EPI, and Modification of Diet in Renal Disease [MDRD]) in the test cohort. Three equation performance criteria were considered: bias (difference between measured GFR and estimated GFR), precision (interquartile range [IQR] of the median difference), and accuracy P30 (percentage of GFR estimates that are within 30% of measured GFR). RESULTS: The study included 1,222 older adults. The mean age of both the training cohort (n = 978) and the test cohort (n = 244) was 72 ± 6 years, with 544 (55.6%) and 129 (52.9%) males, respectively. The median bias of BPNN was 2.06 ml/min/1.73 m2, which was smaller than that of LMR (4.59 ml/min/1.73 m2; p = 0.03), and higher than that of the Asian modified CKD-EPI (-1.43 ml/min/1.73 m2; p = 0.02). The median bias between BPNN and each of CKD-EPI (2.19 ml/min/1.73 m2; p = 0.31), EKFC (-1.41 ml/min/1.73 m2; p = 0.26), BIS1 (0.64 ml/min/1.73 m2; p = 0.99), and MDRD (1.11 ml/min/1.73 m2; p = 0.45) was not significant. However, the BPNN had the highest precision IQR (14.31 ml/min/1.73 m2) and the greatest accuracy P30 among all equations (78.28%). At measured GFR < 45 ml/min/1.73 m2, the BPNN has highest accuracy P30 (70.69%), and highest precision IQR (12.46 ml/min/1.73 m2). The biases of BPNN and BIS1 equations were similar (0.74 [-1.55-2.78] and 0.24 [-2.58-1.61], respectively), smaller than any other equation. CONCLUSIONS: The novel BPNN tool is more accurate than the currently available creatinine-based GFR estimation equations in an older population and could be recommended for routine clinical use.

Long-term effects of contrast media exposure on renal failure progression: a retrospective cohort study.

BACKGROUND: With the constant need for technique improvement for ensuring correct diagnoses and precise treatment, imaging examinations that use contrast media have become unavoidable and indispensable. However, the long-term effects of contrast media on renal function remain unclear in populations with advanced renal failure. This study aimed to examine the relationship between contrast media exposure and long-term trends in renal function in patients with renal failure. METHODS: This retrospective cohort study included patients with a definitive diagnosis of chronic kidney disease who visited medical institutions in Japan between April 2012 and December 2020. The cohort was divided into contrast agent therapy and non-contrast agent therapy groups. The assessment indices were the number of contrast exposures and renal function decline. Renal function decline was calculated based on observed chronic kidney disease stage trends and glomerular filtration rate correspondence tables sourced from various guidelines. A stratified analysis focusing on changes in renal function while accounting for the acceleration of chronic kidney disease progression was also performed. RESULTS: After adjusting for patient background with propensity score matching, 333 patients each were included in both groups. The observation period was 5.3 ± 2.1 and 4.9 ± 2.2 years per case in the contrast-enhanced and non-contrast-enhanced groups, respectively. The baseline estimated glomerular filtration rate at the beginning of the observation period was 55.2 ± 17.8 mL/min/1.73 m2 in the contrast-enhanced groups (P = 0.65). Although only slightly different in both groups, the glomerular filtration rate change was 1.1 ± 3.3 mL/min/1.73 m2/year in the contrast agent therapy group and tended to be higher with contrast media exposure. Stratified analysis showed that the annual glomerular filtration rate changes in patients with more contrast media exposures and altered renal function were 7.9 ± 7.1 mL/min/1.73 m2/year and 4.7 ± 3.6 mL/min/1.73 m2/year in the contrast agent therapy and non-contrast agent therapy groups, respectively (1.69 times, P < 0.05). CONCLUSION: We were able to identify a clinical trend of successful measures for preventing adverse renal outcomes associated with contrast media exposure. However, increased frequency of contrast media exposure has a long-term effect on renal function in patients with altered it. Appropriate treatment choices related to contrast media may control chronic kidney disease.

Use of novel structural features to identify urinary biomarkers during acute kidney injury that predict progression to chronic kidney disease.

BACKGROUND: A significant barrier to biomarker development in the field of acute kidney injury (AKI) is the use of kidney function to identify candidates. Progress in imaging technology makes it possible to detect early structural changes prior to a decline in kidney function. Early identification of those who will advance to chronic kidney disease (CKD) would allow for the initiation of interventions to halt progression. The goal of this study was to use a structural phenotype defined by magnetic resonance imaging and histology to advance biomarker discovery during the transition from AKI to CKD. METHODS: Urine was collected and analyzed from adult C57Bl/6 male mice at four days and 12 weeks after folic acid-induced AKI. Mice were euthanized 12 weeks after AKI and structural metrics were obtained from cationic ferritin-enhanced-MRI (CFE-MRI) and histologic assessment. The fraction of proximal tubules, number of atubular glomeruli (ATG), and area of scarring were measured histologically. The correlation between the urinary biomarkers at the AKI or CKD and CFE-MRI derived features was determined, alone or in combination with the histologic features, using principal components. RESULTS: Using principal components derived from structural features, twelve urinary proteins were identified at the time of AKI that predicted structural changes 12 weeks after injury. The raw and normalized urinary concentrations of IGFBP-3 and TNFRII strongly correlated to the structural findings from histology and CFE-MRI. Urinary fractalkine concentration at the time of CKD correlated with structural findings of CKD. CONCLUSIONS: We have used structural features to identify several candidate urinary proteins that predict whole kidney pathologic features during the transition from AKI to CKD, including IGFBP-3, TNFRII, and fractalkine. In future work, these biomarkers must be corroborated in patient cohorts to determine their suitability to predict CKD after AKI.